circabc.europa.eu - Public/Library... · Web viewA valid MSDS for each formulant is required. If the formulant is a mixture, each component has to be ... %H2SO4 or %NaOH In the

CA-Dec12-Doc.6.2.b

EUROPEAN COMMISSIONDIRECTORATE-GENERALENVIRONMENTDirectorate D - Water, Chemicals & BiotechnologyENV.D.3 - Chemicals & Nanomaterials

Technical Notes for Guidance

EU Evaluation Manual for the Authorisation of Biocidal Products

These Technical Notes for Guidance were endorsed during the 44th CA meeting for release for a 6-month consultation period of stakeholders.

All comments should be sent to [email protected] by 30 June 2012.

At the end of this consultation period, these Technical Notes for Guidance would, if appropriate, be revised on the basis of the comments received.

Meanwhile, Member States competent authorities and stakeholders could already apply the principles laid down in these Technical Notes for Guidance.

Commission européenne, B-1049 Bruxelles / Europese Commissie, B-1049 Brussel - Belgium. Telephone: (32-2) 299 11 11.

Office: BU9 6/163. Telephone: direct line (32-2) 2986933. Fax: (32-2) 2998558.

E-mail: [email protected]

Author, 01/03/-1,

The issue of data protection and data access plus literature search requriements should be given higher prominance in the document and perhaps given individual sections. NL: We agree, we will take this into account into the next version of the EvalMan.

Author, 01/03/-1,

There are lot of points where the English is difficult to follow or there are typos or words not normally used. The document would benefit from a peer-review before publication. NL: A native English speaker has improved the grammar and syntax. We have also addressed repetition in this version.

Author, 01/03/-1,

What is the relevance of this document with BPR coming into force next year? By the time all the comments have been considered and the document amended it may not finalised until the end of the year (2012) and then 9 months later BPR will be applicable. Is it useful and useable? NL: ECHA will revise the document in 2014 to the BPR. The current version is for BPD.

Author, 01/03/-1,

The issue of how to handle substances of concern should be considered further before such general statements are added to the document. NL: The outcome of the SoC workshop will be implemented in version 2.

Author, 01/03/-1,

It should be clear that this is a living document, because new decisions are always made and MSs have still little experience authorising products under the BPD. NL: we have included a sentence to point this out.

Author, 01/03/-1,

The link to relevant parts of the TGD/EDS etc should be more clearly made i.e. Section 5.4 of TNsG of dossier preparation. NL: we will address in the next version of the Eval Man.

Author, 01/03/-1,

In some cases the information is very basic and in some cases very detailed. Is the balance correct within the manual? NL: we will address in the next version of the Eval Man.

Author, 01/03/-1,

There is a lot of repetition in the document and perhaps further streamlining could be done. NL: A native English speaker has improved the grammar and syntax. We have also addressed repetition in this version.

EU Evaluation Manualfor the Authorisationof Biocidal Products

finalversion 1.0

EU Evaluation Manual for the authorisation of biocidal products v1.0

INDEX

I. About this manual............................................................................................................65I.a For whom is this manual intended?.............................................................................65I.b Why has this manual been compiled?.........................................................................65I.c How should I use this manual?...................................................................................65I.d Maintenance of this manual........................................................................................76

II. General principles of product authorisation........................................................................76II.a Legal framework..........................................................................................................76II.b Procedure of approach (incl. exposure based approach)...........................................76II.c Principles behind data requirements for product authorisation...................................87

II.c.1 Active substance.....................................................................................................87II.c.2 Substances of concern...........................................................................................98II.c.3 Product....................................................................................................................98II.c.4 Waiving...................................................................................................................98

II.d Efficacy........................................................................................................................98II.e Exposure assessment: Basic principles....................................................................109

II.e.1 Human exposure..................................................................................................109II.e.2 Exposure to live stock and pets............................................................................109II.e.3 Environmental exposure.......................................................................................109

II.f Effect/hazard assessment: Basic principles............................................................1110II.f.1 Physico-chemical hazards and effects................................................................1110II.f.2 Human health hazards and effects......................................................................1110II.f.3 Environmental hazards and effects.....................................................................1110

II.g Risk assessment: Basic principles..........................................................................12111. Applicant......................................................................................................................13122. Identity (product)..........................................................................................................1312

2.1 Active substance(s).................................................................................................14132.2 Formulants...............................................................................................................15142.3 Substances of concern............................................................................................15142.4 Other aspects of identity..........................................................................................15142.4.1. Multi-component and products adhered to a carrier........................................1514

3. Physico-chemical & technical properties (product)......................................................15143.1 General requirements..............................................................................................16153.2 Waiving....................................................................................................................16153.3 Special requirements...............................................................................................17163.4 Data requirements and evaluation..........................................................................1716

4. Analytical methods.......................................................................................................30294.1 Analytical methods for formulation analysis............................................................3029Generally, analytical methods for the residue analysis of the active substance are described in the CA-Report.............................................................................................3130

5. Efficacy........................................................................................................................33325.1 General introduction................................................................................................33325.2 Intended use............................................................................................................33325.3 Efficacy....................................................................................................................3332

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5.3.1 Data requirements..............................................................................................34335.3.2 Norms and criteria..............................................................................................35345.3.3 Resistance and other aspects that influence the efficacy...................................35345.3.4 Unacceptable effects..........................................................................................3534

Appendix A (chapter 5): Status of efficacy guidance for specific product types..............3736Appendix B (chapter 5): Paragraphs of the Common Principles (Annex VI of 98/8/EC) relevant for efficacy evaluation and decision making......................................................3938

6. Human health assessment..........................................................................................41406.1 Combination toxicity................................................................................................42416.2 Exposure assessment.............................................................................................4342

6.2.1 Sources of information for exposure calculations...............................................46456.3 Effect assessment...................................................................................................49486.4 Risk characterisation...............................................................................................5655

6.4.1 Tiered approach..............................................................................................57566.4.2 Risk reduction measures.................................................................................6059

Appendix A (chapter 6):......................................................................................................6160Appendix B (chapter 6):......................................................................................................6261

Examples regarding data requirements for specific product types..................................62617. Environmental assessment..........................................................................................6463

7.1 Mixture toxicity.........................................................................................................65647.2 Exposure assessment.............................................................................................6665

7.2.1 Exposure calculations.........................................................................................69687.2.1.1 Aquatic compartment (water and sediment)..............................................70697.2.1.2 Sewage treatment plant.............................................................................72717.2.1.3 Marine compartment (water and sediment)...............................................73727.2.1.4 Soil compartment (including groundwater for drinking water production). .74737.2.1.5 Air................................................................................................................78777.2.1.6 Birds and mammals (primary and secondary exposure)............................7877

7.3 Effect assessment...................................................................................................83827.3.1 Aquatic compartment (water and sediment).......................................................83827.3.1.1 Relevant toxicity data for PNEC derivation................................................84837.3.1.2 PNEC derivation.........................................................................................85847.3.2 Sewage treatment plant......................................................................................88877.3.2.1 Relevant toxicity data for PNEC derivation................................................88877.3.2.2 PNEC derivation.........................................................................................88877.3.3 Marine compartment (water and sediment)........................................................89887.3.3.1 Relevant toxicity data for PNEC derivation................................................89887.3.3.2 PNEC derivation.........................................................................................89887.3.4 Soil compartment................................................................................................90897.3.4.1 Relevant toxicity data for PNEC derivation................................................90897.3.4.2 PNEC derivation.........................................................................................91907.3.5 Birds and mammals............................................................................................93927.3.5.1 Relevant toxicity data for PNEC derivation................................................93927.3.5.2 PNEC derivation.........................................................................................93927.3.6 PBT/vPvB assessment.......................................................................................94937.3.7 Endocrine disruption...........................................................................................9695

7.4 Risk characterisation...............................................................................................96957.4.1 Tiered approach..................................................................................................97967.4.1.1 Aquatic compartment (water and sediment)....................................................97967.4.1.2 Sewage treatment plant.............................................................................98977.4.1.3 Marine compartment (water and sediment)...............................................98977.4.1.4 Soil compartment (including groundwater for drinking water production). .98977.4.1.5 Air.............................................................................................................10099

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7.4.1.6 Birds and mammals (primary and secondary exposure)........................1021017.4.2 Risk reduction measures................................................................................104103

Appendix – ENV 1: Quality assessment of data.............................................................105104Classification, Labelling and Packaging.........................................................................106105

Packaging....................................................................................................................1071068. Appendices..............................................................................................................108107

I Track record changes (including date of change)...............................................108107II Guidance which in the future should be included in the TNsGs..........................109108III Future work..........................................................................................................110109IV List of standard terms and abbreviations............................................................111110V Overview of product types.........................................................................................120VI Format PAR with SPC...............................................................................................123VII 124

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I. About this manual

I.a For whomwho is this manual intended?This manual is intended for experts working on the dossier evaluation of biocidal products under Directive 98/8/EC at the Competent Authorities of their EU Member State. In addition, the information in this manual may also be useful for industry.

I.b Why has this manual been compiled?Over the years, a lot of guidance on how to evaluate the (possible) risks of biocidal products and their constituents has been developed both inside and outside (e.g. OECD) the EU. This information is scattered over an ever increasing number of (guidance) documents. Next to this, several member states currently have their own authorisation procedure (and sometimes their own guidance), while others do not have such a system, yet. These factors can seriously hamper a consistent product evaluation within the EU.

Both the Biocidal Products Directive 98/8/EC and the upcoming Biocidal Products Regulation COM(2009)267 establish the principle of mutual recognition of authorisations within the EU. This means that a product which has been evaluated and authorised in one member state (reference member state, Ref-MS) should, in principle, also be authorised in another member state (concerned member state, CMS), provided that the authorisation holder wants to put it on the market in the CMS as well and that there are no specific national circumstances in the CMS that differ from those that were evaluated by the RMS.In order to facilitate the mutual recognition process, it is essential that all member states perform their risk evaluation in a similar way and base their judgement on the same principles. This will also increase the trust between member states to rely on each other’s dossier evaluations. Harmonisation is the key issue in whether or not mutual recognition will work.

This manual intends to give direction on which information should be used in a certain part of the evaluation process, where this information can be found and how it can be used in the risk evaluation. It is not the intention of this manual to duplicate existing guidance already presented on the site of the European Commission. In cases there is a relevant link available an asterisk (=*) is used. Frequently used links are presented in appendix VII (not an alphabetical list but in a sequence that was used). The site of the European Commission were most of the links can be found is: http://ec.europa.eu/environment/biocides/index.htm

I.c How should I use this manual?Chapter II gives a short and comprehensive overview of the general principles behind the product authorisation process and thus. This chapter is advised as a starting pointgood place to start when using this manual. Subsequently, in Chapters 1 – 9, the different aspects of a risk evaluation are elaborated in more detail and can be used as guidance by the people responsible for those specific aspectsparts of biocide the dossier evaluation.The appendices contain, amongst others, a glossary of standard terms and abbreviations, an overview of the product types, a a format for the Summary of Product Characteristics (SPC) including the summary of products characteristics (see product assessment report (PAR) in appendix VI) and an overview of helpfulthe frequently used internet links. Further used in this manual. Next to this, appendices are dedicated to track record changes to this Manual, guidance towhich in the future should be included in future the TNsG and agreements or text

6

Author, 01/03/-1,

Is this sentence / section really necessary? NL: we have amended the sentence

Author, 01/03/-1,

Perhaps some clear examples could be given here. NL: as this is the introduction, we have decided not to implement examples

Author, 01/03/-1,

This is true but these documents provide clear guidance on certain elements and therefore should be clearly referenced within this document. If you don’t link to the relevant parts of the document and an evaluation is only done using this method then the evaluation may be incorrect because the wrong methodology has been used. NL: we will take this into account in version 2 of the EvalMan, after endorsement

http://ec.europa.eu/environment/biocides/index.htm


proposals for inclusion in based on future versions of this Manualworkcollecting issues ( agreements or text proposals that should be included in the manual in the (near) future, but cannot be included at this moment, for instance because a thorough discussion between the member states is needed first or endorsement by the CA-meeting is pending).

I.d Maintenance of this manualThe Dutch Ministry of Housing, Spatial Planning and the Environment (VROM) provided the Dutch Board for the Authorisation of Plant Protection Products and Biocides (Ctgb) with funding for development of the Evaluation Manual. This includes the maintenance of the manual until 2013. This manual is a living document, therefore maintenance Maintenance will be performed once per year and will, where necessary, include updating the manual with newly agreed upon guidance that was agreed upon, removing old or, redundant guidance and checking the hyperlinks in the manual.

It is crucial for the status of the manual that other member states actively contribute to this process by pointing out guidance/technical agreements that are relevant in their opinion. It is anticipated that maintenance of the manual will be taken over by the European Chemical Agency (ECHA) in Helsinki, Finland, assince ECHA is expected to play an important role in the new Biocidal Products Regulation which comesdue to come into force on September 1st 2013.

II. General principles of product authorisation

II.a Legal frameworkCurrently, the legal basis for biocidal product authorisation is the national legislation in each individual member state, which is based on the EU Biocidal Products Directive 98/8/EC (BPD).This manual is describingdescribes how to evaluate a biocidal product dossier in accordance with article 8 of the BPD and the Common Principles, which can be found in Annex VI of the BPD. From September 1st 2013, the legal basis for biocidal product authorisations will be the Biocidal Products Regulation, which will be directly applicable in all EU Member States.

II.b Procedure of approach (incl. exposure based approach)In short, the evaluation of a biocidal product dossier is based on the following approach:- Check whether the active substance(s) within the product is/are included in Annex I of the BPD for the concerning Product Type (PT) and whether they are technically equivalent to the active substance(s) on Annex I. - Check whether the applicant has access to the Annex I dossier(s) of the active substance(s), either directly (being the data owner) or indirectly (through a Letter of Access, LoA).- Check whether the applicant is located in the EU- Check whether the requested product is similar to the product evaluatedalready included in the Annex I dossier and whether the intended uses have beenwas evaluated during the Annex I inclusion procedure. - Check for of substances of concern on the basis of classification and relevant concentration in the biocidal product.- Check thatwhether the requested use(s) do not differ from the use(s) that are evaluated in the Annex I dossier. The Summary of Product Characteristics (SPC) provideprovides

7

Author, 01/03/-1,

If the product was the product evaluated with the active substance dossier for Annex I inclusion what does that change? NL: if a similar or the same product has been evaluated under Annex I then a harmonised assessment is included in the CAR and this approach should be used.

Author, 01/03/-1,

Is that always the case in every Member State? Should this say that the ...evaluation of a biocidal priduct dossier should follow the approach below: ? NL: this is the harmonised approach. Text not amended

Author, 01/03/-1,

What does that mean for this document and it’s relevance? NL: this is included to specify that this document concerns BPD and not BPR

Author, 01/03/-1,

What does this title actually mean? Should it say the General principles to be considered when authorising products? NL: we find the title sufficiently addressing the content of the chapter

Author, 01/03/-1,

Shouldn’t this document hightlight that this is a living doucment? NL: we agree, text amended.

Author, 01/03/-1,

What does this mean? NL: We have amended the text to clarify its meaning


information on the requested use(s).- Check the Register for Biocidal Products (R4BP), https://webgate.ec.europa.eu/env/r4bp/user.login.cfm) as to whether there have already been evaluations of biocidal products with a similar use within the EU. This can provide you with useful information on how to proceed with the dossier evaluation.- If there are uncertainties regarding“unclarities” concerning the exact use of the biocidal product, ask the applicant for clarification (e.g. dosage, frequency, way of application, location of application). Subsequently, consider the exposure routes that result from this use and decide on which data are needed for the product (and, if necessary, for on the active substance).- Check thatif all the necessary data is available to beginstart the evaluation.- The dossier evaluation should start from the perspective of the use and the corresponding exposure pattern. Next, the exposure is compared to the hazard, which will in the end lead to an appropriate risk assessment (and if necessary risk reduction measures).

II.c Principles behind data requirements for product authorisation In the risk assessment for biocidal product authorisation, The approach in which exposure is a result of the practical use of the biocidal product and its the intrinsic properties of its constituents (e.g. water solubility, vapour pressure, etc.). Therefore,) requires the dossier for product authorisation must to contain information on both subjects. Prior to product authorisation the risks involved in with the use of the product need to be evaluated. Possible harmful components not only include the active substance, but also other components of the product with intrinsically harmful properties. effects. Although active substances included in Annex I have been evaluated, the composition and actual use of the biocidal product for which authorisation is sought may differ from those evaluated in the Competent Authority Report (CAR) for Annex I inclusion of the active substance.

For products containing Annex I included substances, the testing criteria are laid down in the Biocidal Products Directive 98/8/EC*. The dossier of the biocidal product should must meet the requirements laid down in Annexes IIA, IIB and relevant parts, IIIA and IIIB of this directive. Further explanations regarding data requirements are given in the TNsG*. on data requirements*. The TNsG on Dossier Preparation provides a form (the Form for check for completeness and quality of data compiled in Doc. III-B; in Appendix 4.3) that may be useful for evaluating the completeness of data

According to the TNsG on data requirements* for Active Substances and Biocidal Products “the applicant is responsible to search for data from all sources which he or she may reasonably be expected to have access to”. Generally, this could be achieved by a recent literature search, i.e. not older than one year.

A list of studies to be performed according to Applicability of Good Laboratory Practice (GLP) is available (Guidance regarding the Applicability of GLP to Data Requirements according to Annex IIB/IIIB of Directive 98/8/EC (PA&MRFG-Feb11-Doc.8a.i)).

II.c.1 Active substanceThe In the CAR the exact physical and chemical properties of the active substance and the possible risks of the active substance for specific uses have has been evaluated in the CAR. Therefore . For product authorisation it is required that either the active substance for the application in question must be is manufactured atfrom the same source as one considered at the time of the Annex I inclusion, or the applicant must proveit should be proven that the active substance used is identical or and technically equivalent to the active substance as

8

Author, 01/03/-1,

What does this mean? Should there not be a clearer link to the pages that the reader should consult? NL: we will address this in version 2 of the EvalMan as all references are now in this format.

Author, 01/03/-1,

The dossier of a biocidal product doesn’t have to meet the requriements of IIA or IIIA. They may submit their own active substance dossier that meets the requirement or submit a letter of access that meets the requriements. It should be clear to the reader that the active substance dossier doesn’t necessarily have to be submitted again. NL: all dossiers should meet this requirement and in section II.c.1 we specify that they can submit their own dossier or provide a letter of access to a dossier. Text not amended

Author, 01/03/-1,

Uncertainities? The word unclarity does not exist in English. NL: text adapted

Author, 01/03/-1,

Yes, but this shouldn’t currently (under the BPD) prevent an evaluation taking place. NL: we think all MS are aware of this. text not amended


evaluated in the CAR.The applicant should provide the competent authority access to the active substance dossier which was the basis for the Annex I inclusion. Access can be either direct (the applicant is the directly (data owner) or indirectly (through a Letter of Access (, LoA) from the data owner). If the applicant for the product does not have access to the Annex I dossier, a full active substance dossier has to be submitted. The Rapporteur Member State (RMS) will subsequently has to compare the endpoints in this dossier to the endpoints of the existing List of Endpoints (LoE) in the Annex I dossier. In principle, the List of Endpoints (LoE) of the Annex I dossier should be used for product authorisation, as long as the endpoint isdoes not product specific (i.e. related to formulation, use or inactive ingredients). depend on the product characteristics. Chapters 1 to 9 will specifically address give guidance on this issue for the differentrespective aspects of the dossier evaluation.

A proposal for harmonisation and the creation of a level playing field for the authorisation of products based on active substances included in Annex I(A), but using another dossier, is discussed in PA/MRFG. Reference to the finalised document will be inserted once the document has officially been published.

If the product under evaluation has shows a different use pattern than the product that was evaluated for Annex I inclusion of the active substance, there might be different exposure routes. In that case, additional data on the active substance(s) couldmight be considered necessary. IfIn the case where new data on active substance are submitted, the MS receiving the dossier of the product authorisationauthoriszation shall assess these.

II.c.2 Substances of concernA substance of concern is means any substance other thanwhich is not an active substance, which but has an intrinsically harmful effect on people, animals or the environment and which is present in a biocidal product in sufficient amounts or which arises from the use of the producta biocidal product gives rise to such an effect (Article 2, paragraph 1, under Directive 98/8/EC). Currently, the PA&MRFG is discussing how to deal with these substances within the biocidal product evaluation. The outcome of this discussion will be inserted in this paragraph once a conclusion is reached.

II.c.3 ProductAs stated in II.b, before starting the product evaluation, one should first check whether or not a similar the product was already evaluated during the Annex I inclusion stage and, if so, whether or not the intended use is are the same for the product under evaluation and the product in the Annex I dossier.If the products are not the same, data are needed for all product specific endpoints that depend on the product characteristics (see chapters 1 to 9 for further details). If the products are the same, but intended uses differ, additional data on the product might be necessary, depending on whether or not the exposure routes differ. Even if the product is the same as evaluated during the Annex I-inclusion stage it must be verifiedchecked that the applicant has access to the data, either directly or via LoA..

II.c.4 WaivingAnWaiving is the request by an applicant can request thatfor adaptation of the data requirements, when certain tests be waived on the grounds that they are not considered necessary or impossible to submit in view of the nature or the proposed uses of the biocidal

9

Author, 01/03/-1,

What if it is not the same data owner? What if data are protected? How can you use someone’s protected data in this way? NL: We agree. We have clarified that we imply that a similar methodology should be used. Text not amended

Author, 01/03/-1,

Perhaps an indication of when such a decision is reached could be added here. NL: we will include the outcome of the SoC working group in version 2 of the EvalMan

Author, 01/03/-1,

Maybe the terminology should be changed here to be the definition in the Directive i.e. Any substance, other than the active substance, which has an inherant capacity to cause an adverse effect to people..’ NL: we agree, text amended

Author, 01/03/-1,

What happens if there is product specific data? This should over-ride any specific active substance endpoint even if that endpoint is not dependent on the product characterisitics. NL: How product specific data have to be taken into account is dependant on the aspect. Therefore this should be addressed in the specific chapters. The section has been amended.

Author, 01/03/-1,

How do they do this? What does this mean?


product or are impossible to conduct. This data waiving request. Waiving should be accompanied by a justified scientific statement, which clarifies why the applicant is of the opinion that they arehe is not obliged to submit these data. At this moment, the acceptability of waiving statements is predominantly based on expert judgement, but the (draft) Biocidal Products Regulation will likely provide more detailed guidance.

II.d EfficacyPractical use of the biocidal product according to the manufacturer’s manual should result in an optimal efficacy without risk to thefor user(s), bystanders or the environment. To evaluate whether these requirements are met, it is necessary that the applicant must provide a detailed description of the proposed use of the product is provided. Tests in which the biocidal product is used according to the manufacturer’s instructions are required to prove that the efficacy of the biocidal product is as claimed by the applicant when used according to the instructions for use. The product should still be efficacious at the end of the shelf life. For more detailed information on efficacy requirements, see Chapter 5. This chapter also contains information on the intended use(s) as well as on resistance and other unacceptable effects.

II.e Exposure assessment: Basic principlesGiven the 23 product types in which biocidal products are used, the exposure scenarios of products are highly variable, both for environmental and human exposure. In order to appropriately assess theFor exposure to a biocidal assessment, it is important to be aware of the exact use of the product, adequate information on the exact use, amount of use, frequency of use, duration of use and type of use must be submitted. From these,following from that the assessor can determine dosage of the probable exposure route(s) and levels of exposure for both humans andproduct, the environment.frequency of use, the duration of exposure and the route(s) of exposure. These items should be described clearly and in detail in the dossier (in the SPC section of the dossier. If an adequate description is ) and if not submitted, consultation with the applicant is recommended in order to come to an appropriatea satisfying description is recommended.

II.e.1 Human exposureTo assess human exposure to biocidal products it is necessary to determine who will be exposed to the product. This may be limited to primary exposure of the users (either professionals or non-professionals) but in many applications (in)direct (secondary) exposure of bystanders can notcannot be excluded. Indirect exposure of bystanders may take place via residues of biocidal products (for instance on treated surfaces, and pets), but also via food which has been in contact with treated objects.. Particular attention is should be paid to exposure to children. . Another aspect which has to be taken into account is the route of exposure. The route of exposure mainly depends mainly on the use profile of the product, but physico-chemical properties of the product, such as volatility, should also be considered. In order to saveThe general strategy for saving time while remaining highly protective of human and effort without allowing for a health, a risk is named tiered approach is followed. In the and works as follows. In a first step (tier 1), a worst case scenario using default parameters is assumed. If such over-estimation does not give riseraise to any concern, then no further effort is should be invested in obtaining a more realistic estimate. If, however, a potential risk cannot be excluded necessary, a refined exposure assessment is performed, using more realistic data and – if available – more elaborate realistic models in the second (tier 2). Product specific exposure measurements are used in tier 3. For more information on human exposure assessment, see Chapter 6.

10

Author, 01/03/-1,

The term bystander is typically used in the context of PPPs and refers to a person being not the user but present during application. Hence being considered to be directly exposed via spray drift. Whereas the resident might be exposed after the application via transfer of rersidues from contaminated surfaces. In the context of biocidal products both scenarios are covered by the term “secondary exposure”. Therefore we suggest to use the terms “primary exposure” and “secondary exposure” as being the common terms used for Biocides. NL: we agree, amended.

Author, 01/03/-1,

Does this mean that all efficacy tests need to be submitted with some aged products or can you still use the shelf life studies to demonstrate the product remains effective? This section requires clearer guidance and information. NL: this just gives the basic principles. Clear guidance is given in the TNsG’s


Risk mitigation measures (RMM) such as e.g. containment, ventilation, exhaustion, or personal protection equipment (PPE) may reduce the exposure and thereby the risk for the users of the biocidal product (see also Chapter 6.4.2 for human health and 7.4.2 for environmental exposure reduction). According to Directive 98/24/EC, paragraph 6(2), PPE canshall not be a permanent measure but must be restricted to accidents, incidents or emergencies or where exposure cannot verifiably be reduced by other means, verifiably, according Directive 98/24/EC, paragraph 6 (2). If for non-professional users the wearing of PPE, including the use of gloves, would be the only possible method for reducing exposure, the product shall usually not be authorised.(see also Chapter 6.4.2. and 7.4.2).

II.e.2 Exposure to live stock and pets

When biocides are applied directly on animals or in their surroundings, the risk animal health and welfare has to animals should be be considered. A risk assessment of animals is needed (this can be relevant for a.o. PT 3 and PT 18). This assessment is not always done in the CAR, but is instead performed atleft to the product authorizationthorisation level (see § 1.10 Manual of Technical Agreements*).

II.e.3 Environmental exposureFor the evaluation of the environmental exposure to biocidal products several exposure scenarios are available in which many parameters are taken into consideration. Depending on the use parameterspattern, the route of entry into the environment can differ (e.g. run-off from soil into surface water, manure application on soil, etc.) and the constituents of the biocidal product can end up in various environmental compartments (sewage treatment plant (STP), soil, water, sediment, air). The exposed environmental compartmentThis also depends on the fate and behaviour of the constituents of the product.In order to make an useful assessment of the environmental exposure, it is necessary to obtain a full dossier on the physico-chemical properties of the product (see Chapter 3). Furthermore, not only the availability of a relevant emission scenario andis necessary, but the relevant input parameters mustalso have to be available (see Chapter 7.2).

II.f Effect/hazard assessment: Basic principlesAn important step in the risk assessment process is hazard identification. The purpose of hazard identification is to identify the inherent capacity of a biocidal product to causefor causing adverse effects. These can be physico-chemical, human health or environmental hazards. This is an important step in the risk assessment. The hazard assessment also forms the basis for the classification and labelling of the biocidal product (see Chapter 9). A product can be hazardous to human health, hazardous to the environment or both (as in physico-chemical hazards).

II.f.1 Physico-chemical hazards and effectsArticle 5(1)(b) of the Directive requires that a biocidal product must have no unacceptable physical or chemical effects. Such effects can arise from the intrinsic properties of the product, such as flammability and explosivity. Effects can also occur indirectly through, for example, chemical incompatibility between the biocidal product and other materials. More information can be found in Chapter 3.

II.f.2 Human health hazards and effects The humanHuman health hazards and effect assessment effects of a biocidal product should

11

Author, 01/03/-1,

What about the relevance of other PTs? NL: we have added a.o.

Author, 01/03/-1,

How is welfare defined? Is the benefit of using a product considered? E.g. the benefit of reducing flies in animal houses, a flea treatment?

Author, 01/03/-1,

Under what circumstances will it be allowed? Examples should be given here in order to enhance harmonisation. NL: Could be dependent on different policy issues in different MSs.

Author, 01/03/-1,

What constitues an emergency? NL: To prevent the exposure of workers to health risks from certain chemical agents and/or certain activities involving chemical agents, the production, manufacture or use at work of the chemical. The employer shall protect the safety and health of workers from an accident, incident or emergency related to the presence of hazardous chemical agents at the workplace.

Author, 01/03/-1,

How do you define permanent? NL: The workers who are permitted to work in the affected area shall be provided with appropriate protective clothing, personal protective equipment, specialised safety equipment and plant which they must use as long as the situation persits; that situation shall not be permanent.


focusbe focused on the effects arising specifically from the product itself. This assessment is based on studies with the product or frame formulation, together with information from the evaluation of active substances and substances of concern. This assessment can also be based on known effects of the components, even when specificWhere product data wereare not submitted or required. for an effect, the assessment must be based on the known effects of the components.

The human health riskeffects assessment comprises the following steps of the risk assessment procedure: • Hazard Identification: the aim of the hazard identification is to identify the effects of concern. • Dose (concentration) – response (effect) assessment: at this step the relevant no observed adverse effect level (NOAEL) is), shall, where possible, be determined.

PotentialThe human health effects are normally identified and investigated via addressed by laboratory studies, but useful data for human health risk assessment can also be obtained from epidemiological studies, such as, for example, human case reports and case studies and from studies available in publicthe open literature. However, the quality of these often varies between anecdotal information to full studies conducted according to Good Clinical/Laboratory Practice guidelines. Although toxicity endpoints are usually addressed by animal data, the evaluation of human data cancould supplement findings in animal studies, such as, for example, for skin sensitisation. More information can be found in Chapter 6.3.

II.f.3 Environmental hazards and effectsThe environmental effects assessment comprises the following steps of the risk assessment procedure: • Hazard Identification: the aim of the hazard identification step is to identify the effects of concern. • Dose (concentration) – response (effect) assessment: at this step the predicted no effect concentration (PNEC) is), shall, where possible, be determined.

The hazard identification is based on information about: • Physical and chemical propertiesdata • Fate and behaviour in the Environment (including degradation and mobility) • Effects on aquatic organisms (including sediment-dwellers) • Effects on terrestrial organisms (including mammals and birds)

For products consisting of an active substance with a simple diluent (e.g. water), the assessment of the active substance is sufficient to cover the risks from the product. A different approach is needed for products containing two or more active substances or when the product is a complex formulation, or when the product contains substances of concern. A formulation can also change the properties of the active substance in the environment (fate and behaviour, effects). An interaction between the active substances might result in additive, synergistic or antagonistic effects that would remain unaccounted for if the active substances were assessed separately. The same situation arises if the product contains a diluent enhancing the bioavailability of the active substance. It could then be argued that it is necessary to test the effects of products towards ecosystems whenever it is apparent that there is an interaction between the components of the product. For more information, see Chapter 7.3.

II.g Risk assessment: Basic principles Risk assessment for a biocidal product with a certain use(s) is based on comparing the identified effects/hazards of a biocidal product with the predicted exposure. This has to be

12

Author, 01/03/-1,

How would this assessment be carried out to give a realistic assessment? NL: this methodology is currently still under development. We will amend this in EvalMan version 2.


performed for certain physico-chemical aspects (e.g. explosivity), for human health and for the environment.To that end, Therefore, the first step of the risk assessment is to determine which possible negative effects a biocidal product may have on either human health or the environment. This depends on the intrinsic properties of the individual constituents of the biocidal product as well as the formulation itself, since, but a certain constituent may also affect the toxic properties or behaviour of the other constituents (see also Chapter 6.1. and 7.1. on combination toxicity).Whether the biocidal product actually has adverse effects in practice depends on the is determined by the exposure level of exposure to for humans and the environmentexposure concentrations in the different environmental compartments. Therefore, these concentrations are have to be estimated and subsequently compared to the effect concentrations that were are determined in the hazard/effects assessment.If a risk is identified, in certain cases, risk reduction measures can be proposed to reduce the risk (e.g. adequate protective clothing for operators or measures to prevent the biocidal product entering the soil).

For more information on human health risk characterisation, see Chapter 6.4, for environmental risk characterisation, see Chapter 7.4. For risk reduction measures, see Chapters 6.4.2 (human health), 7.4.2. (environment) and Chapter 8 (measures to be adopted).

13


1. ApplicantThe TNsG on data requirements describes the requirements concerning the applicant, manufacturer and/or formulator. The applicant has to have a permanent office with a legally responsible representative in the EU Community. Name, address, telephonetelephones and fax numbers, e-mail and other contact information forof the applicant should be provided.The name, address, telephone number and location of the formulating plant(s) of the manufacturer/formulator should also be provided. If the formulator is not the same as the manufacturer, contact information forof both should be provided.

2. Identity (product)Annex IIB of 98/8/EC and Annex IV B of 98/8/EC describe the requirements on common core data for biocidal products. Data regarding the composition should preferably be provided according to that the template. The classification of the active substances and of the ingredients are not mentioned in this table. That information will be derived from the material safety data sheets (MSDS) and other relevant Annexannex II data information.

The detailed quantitative and qualitative composition of the biocidal product, including the percentages by weight of the ingredients as well as their function must be documented in the SPC (see table below). This information is confidential and should not be disclosed to third parties

14

Author, 01/03/-1,

We welcome this information being added. However, we think there should be a general statement on confidentiality and data protection added to the begining of the guidance. NL: we agree and will include a section on this in version 2 of the EvalMan

Author, 01/03/-1,

Formatting NL: amended

Author, 01/03/-1,

Seems to be a problem with the formatting of this section. NL: amended


Instructions for completing the table:- If the formulant is a mixture, each component shouldshall preferably be specified

(IUPAC-/CAS name, - EC-/CAS no, etc.).

- The Please indicate the concentration of the active substance in the pure form (, that is the one that will be stated on the label) should be indicated.

- The concentrations should be stated in mass percentages (%w/w). For liquids, in addition to mass percentages, concentrations should be stated in grams per litre (g/L)) as well.

- WhetherPlease indicate whether a substance of concern is included should be indicated.

2.1 Active substance(s)

2.1.1: The source(s) of the active substance

A clear statement on how the Annex annex II data requirements are being addressed is required i.e.:

1) The applicant is the data owner of the Annexannex II package evaluated for Annexannex I inclusion or;

2) the applicant has access to the data evaluated for Annexannex I (a letter of access must be provided) or

3) the data protection period has expired for the data considered for Annexannex I inclusion or

4) the applicant has their own complete or partial Annexannex II dossier.

In the finallatter case it must be made clear for each annex point where matching studies are being provided and where non-protected data out of protection are being relied upon.

Information on each source of the active substance to be used in the biocidal product is required.

For each source of the active substance the following details are required:

Name and address of the manufacturer Name and address of the manufacturing plant The technical specification of the active ingredient as manufactured (in accordance

with the data requirements outlined in directive 98/8 and the TNsG).

A clear statement as to whether the source of the active substance was considered as part of the Annexannex I process is required. Any and allAll new sources of the active substance(s) must be accompanied by appropriate batch data and validated methods of analysis. A technical equivalence evaluation will be required for all new sources of active. Biocidal

15

Author, 01/03/-1,

The formulator of the biocidal product will not know this information and this will often be provided by the manufacturer of that formulant. NL: comment noted.


products can only be authorised with approved sources of the active ingredient and hence a completethe technical equivalence assessment must be conductedwill need to be completed before authorisation of the biocidal product is possible.

2.1.2: Content and composition of the active in the biocidal product

All relevant information regarding the active substance should be provided i.e. ISO name, CAS no., EC no., CIPAC no., IUPAC and/or CA names.

The amount of pure active substance and the amount of the technical material (based on the minimum purity as manufactured) in the formulation should be provided.

Where the active ingredient is present as a variant (e.g. a salt or an ester) then the amount of the variant and the acid equivalent amount must both be given.

A proposal for harmonisation and the creation of a level playing field for the authorisation of products based on active substances included in Annex I(A), but using another dossier is discussed in PA/MRFG. Reference to the finalised document will be inserted once the document has officially been published.

2.2 FormulantsAll relevant information, as stated in the TNsG on data requirements, should be provided for formulants (section B2.2). A valid MSDS for each formulant is required. If the formulant is a mixture, each component has to be specified (IUPAC-/CAS name, EC-/CAS no, etc.). If the applicant does not have access to detailed information on a formulant, the manufacturer can provide the specification to the CA directly. If a biocidal product contains a component that should be considered as a substance of concern, this should be indicated.In addition the function of each formulant in the biocidal product must be stated.

2.3 Substances of concernThe definition of a substance of concern is (source, Art. 2(1)e of Directive 98/8/EC):‘Any substance, other than the active substance, which has an inherent capacity to cause an adverse effect on humans, animals or the environment and is present or is produced in a biocidal product in sufficient concentration to create such an effect.’

If a biocidal product contains an ingredient that should be considered as a substance of concern, this should be indicated in the dossier.

2.4 Other aspects of identity2.4.1. Multi-component products and products adhered to a carrierFor multi-component products, every component should be specified, even if the components are packed separately. For example: an anti-fouling paint consisting of a base and activator, separately packed. The composition of both the base and the activator should be stated and the ratio in which these components are to be mixed should be stated.

In some cases a biocidal product can be adhered to or impregnated onto a carrier. In those cases, the biocidal product composition is to be specified both without the carrier and including the carrier. An example would be a fly paper consisting ofsticker, a biocidal product, adhered to a paper or plastic surface.

16

Author, 01/03/-1,

See comment earlier. Also, if a supplier of a formulant has already provided this information for one product in one member state do they have to do this again for another product in the same Member State? If the original evaluating MS has the inforamtion do the concerned MSs also need the information? NL: This evaluation manual does not address mutual recognition. We propose that this is to be discussed with other MS and the COM for a future update or a separate guidance document.

Author, 01/03/-1,

A level playing field of evaluation and treatment of applicants is important. NL: noted


3. Physico-chemical & technical properties (product)In Annex IIB of 98/8/EC and Annex IVB of 98/8/EC, core data requirements are stated. In the technical notes of guidance*, available on the JRC website, data requirements are specified in more detail.

3.1 General requirementsIn those cases where the biocidal product can be categorised as one of the FAO/WHO formulation types, the FAO Manual* can be used to as guidance for data requirements. However, many biocidal products cannot be categorised as such, therefore requirerequiring a product- specific approach.

Data provided in the dossier is to be summarised in the same way as for setting up the Competent Authority Reports, as established during the EU Review Programme.

Test method

MethodA reference to the test method used should be made here. In accordance with Article 8 (8) of Directive 98/8/EC tests must be conducted as per relating to the methods described in Annex V to Directive 67/548/EEC, which was replaced by the Council Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) on 1 June 2008. If a method is inappropriate or not described, other methods especially internationally recognised methods (e.g. UN, OECD or CIPAC, ISO, ASTM, EC and CEN) and, where indicated, in-house methods may be used. In-house methods musthave to be thoroughly described so the validity of the and should produce valid results can be assessed. When an EC method is available, but not used by the applicant, this mustshould be justified in the application.

ResultsAll relevant variables of a study must be stated. For instance, solvents used, temperature, test concentration, etc.. In most cases, if a CIPAC, EC or OECD method is used, the method will include a description on how results are to be reported.

Remarks / justificationDeviations from standard data requirements, or justification for non-submission should be provided here.

GLP (Y/N)For every study it should be stated whether it was performed according to GLP. The TNsG (chapter 6, 6.4) outlines exemptions for GLP requirements. It may be possible to submit a non-GLP study for the physical and chemical tests for the biocidal product. The acceptance of non-GLP studies can will only be considered only on a case -by -case basis (see TNsG).

3.2 WaivingWaivers may replace any study or data requirement, if scientifically sound. Waiving of data requirements is possible in the case:I. A data requirement is not relevant to the product and/or the intended useII. A study cannot be performed because the test is not feasibleIII. The outcome of a study can be accurately predicted based on a scientific argumentationIV.The outcome of the study is in no way relevant to the risk assessment, classification and

17

Author, 01/03/-1,

All tests should be conducted in a scientific manner and produce valid results. This should not just apply to in-house studies. NL: we have clarified the text.

Author, 01/03/-1,

Should there be a link to where these reports are stored? NL: we think that data storage should not be addressed in this EvalMan. Inclusion of references to other guidance on data storage for product authorisation will be reviewed for version 2 of the EvalMan


labelling or intended use.

Examples: The formulation does not contain any components that are classified as oxidising, making

it highly unlikely the formulation will require classification (I.) The dust content of a granule if exposure to dust is not in any way possible during

application (II.)

Waivers must always be supported by scientific argumentation.

3.3 Special requirementsFor formulations, which cannot be categorised according to FAO/WHO 2-letter codes, no set of data requirements is available. In general, a common sense approach should be followed. For example, a paint should remain within manufacturer specifications for viscosity and colour, making these properties interesting for a shelf-life study. The applicant may reason which properties are relevant to their product and provide supporting argumentation and waivers.

3.4 Data requirements and evaluationFor data core data requirements, please refer to the TNsG on data requirements and the TNsG on product evaluation. The table below includes additional information on the core data requirements that should be addressed in a product authorizationauthorisation dossier. Under methods, available standard methods are stated. Under results, the way the results should be presented is stated. Under remarks/justification any additional information on how to address the data requirement are mentioned.

Subsection(Annex Point/TNsG)

Methods Results Remarks/Justification

GLP(Y/N)

3.1

Appearance(IIB3.1/Pt. I-B3.1)

The aggregate state, the physical state, the colour and the odour of the biocidal product have to be described at 20 °C and 1013 hPa. This information could be received (if indicated) from the description in the specification and/or the material safety data sheet of the biocidal product

Not required

3.1.1

Physical state and nature

The physical state should be described in qualitative terms such as “powdery”, “viscous”, “suspension”, “emulsion”.

Not required

3.1.2

Colour

The colour has to be determined visually.

Not required

3.1.3

Odour

In general descriptive terms should be reported e.g. “garlic-like”.May be waived for products containing substances which are toxic by inhalation.

Not required

3.2 EC A14 (not) explosive The determination of explosive Required

18




GLP(Y/N)

Explosive properties(IIB3.2/Pt. I-B3.2)

properties should be conducted on the product.Explosive properties are associated with the presence of certain chemical groups in a molecule which can react to produce very rapid increases in temperature or pressure. Testing could be waived based on a consideration of the chemical structure, if none of the components of the biocidal product is explosive, if exothermic decomposition, determined by DSC is below 500 J/g or on results from the screening procedures described in Appendix 6 of the United Nations ‘Recommendations on the Transport of Dangerous Goods, Manual of Tests and Criteria, Fifth revised edition, 2009’ (as amended).

Testing could be waived for gas mixtures because EU Method A.14 is applicable for solid, pasty or liquid products only. The classification procedure needs not to be applied when the organic product or a homogenous mixture of organic substances contain chemical groups associated with explosive properties but the exothermic decomposition energy is less than 500 J/g and the onset of exothermic decomposition is below 500 °C.

3.3

Oxidising properties (IIB3.3/Pt. I-B3.3)

Solid: EC A17Liquid: EC A21Oxidising properties of gases: Tests or calculation methods

(not) oxidising in the sense of EC A17 or EC A21.

Testing could be waived if none of the components of the biocidal product is oxidising or if a structural analysis of the individual components of the product shows no chemical groups or bonds are present known to induce oxidising properties. Waiving could also be applicable regarding the results from the screening procedures described in Appendix 6 of the United Nations

Required

19




GLP(Y/N)

as described in ISO 10156 as amended or 10156-2 as amended.

‘Recommendations on the Transport of Dangerous Goods, Manual of Tests and Criteria, Fifth revised edition, 2009’ (as amended).

3.4

Flash-point and other indications of flammability or spontaneous ignition(IIB3.4/Pt. I-B3.4)

Flash point EC A9 In ˚ C May be waived if the product contains no flammable components.

Required

Autoflammability EC A15

EC A16

Auto-ignition temperature in ˚ C

Relative self-ignition temperature in ˚ C

May be waived if the product contains no components with an auto-ignition point <100 ˚ C e.g. no autoflammable components..

Required

Other indications of flammability

Flammability: EC A10

EC A11 (gases)

EC A12 (contact with water)

(not) highly flammable(in the sense of EU A.10)

(not) extremely flammable

not) highly flammable(in the sense of EU A.12)

May be waived if the product contains no flammable components.

For gases the lower explosion limit and the upper explosion limit, or a statement that the gas is non-flammable over a full range of mixtures with air, should be submitted.

These data are required only if the product is designed to liberate a gas on contact with water or if the data on the active substance or co-formulants show the individual components may release a gas on contact with water.Testing could be waived based on a consideration of the chemical structure or on results from the screening procedures described in Appendix 6 of the United Nations ‘Recommendations on the

Required

20


Transport of Dangerous Goods, Manual of Tests and Criteria, Fifth revised edition, 2009’ (as amended).

3.5 Acidity/Alkalinity(IIB3.5/Pt. I-B3.5)

pH:CIPAC MT75.3

Acidity / alkalinity:CIPAC MT191

%H2SO4 or %NaOH

In the case of preparations which are acidic (pH < 4) or alkaline (pH > 10) the acidity or alkalinity and the pH value must be determined and reported according to CIPAC Method MT 191 and MT 75.3 respectively.For formulations, applied as aqueous dilutions, the pH value of a 1 % dispersion or aqueous solution of the biocidal product has to be determined e.g. according to CIPAC method MT 75.3.

Required

3.6

Relative density/bulk density(IIB3.6/Pt. I-B3.6)

EC A.3

CIPAC MT186

The relative density of liquid preparations has to be determined according to EC method A.3. The bulk (tap) density of powders, granules and other solid preparations must be determined e.g. according to CIPAC method MT 186.

Required for relative density. Not required for bulk density.

3.7

Storage stability - stability and shelf life(IIB3.7/Pt. I-B3.7)

Effects of temperature CIPAC MT46.3

CIPAC MT39.3,MT 48, MT 51, MT 54

OECD 113

Test can be used for extrapolation of chemical stability to 2 years. However, this test is not suitable for extrapolation of palatability and physical stability. Extrapolation of data regarding relevant impurities is not applicable.

Low temperature stability may be addressed by incorporating freeze and thaw cycles in the shelf-life study.For suspensions, wet

Not required in the case the product is heat sensitive.

For solid preparations sold in flexible packs the effects that stacking these packs have on the physical and chemical properties on storage must be investigated. The pressures encountered should be typical of those in commercial practise and fully justified.

Test for low temperature stability should not be required for products which are – according

Not required.

Not Required.

21


sieve residue and suspensibility should be determined after storage.

to label claim – not to be stored or applied at 0°C or below, comparable to justification for waiving CIPAC MT46.

Effects of light Only required if the product is sensitive to light and/or heat.

Reactivity towards container material

GIFAP monograph No. 17

All relevant technical properties must be determined after storage.Duration and storage temperature must be reported.Packaging material used must be specified in detail.Acceptable: 1L HDPE bottle, LDPE/Al/paper bag. Not acceptable: plastic bottle, coated can.

For baits, palatability must be addressed after storage. After storage it should be investigated whether the product is still efficacious and sufficiently attractive to the target organism. See Efficacy section for the requirements on how to address palatability.

Required only in those cases that toxicologically or environmentally relevant breakdown products are formed during storage.

3.8

Technical characteristics(IIB3.8/Pt. I-B3.8)

Wettability/ WettabilityCIPAC MT53.3

Wettability must be complete within one minute (without stirring). If this requirement is not met, a justification is required this does not cause problems during application. Test should be performed at the highest concentration. The greater the amount of solid to water the more difficult it will be to wet.

Only required for water dispersable products (WG, SG, WP, etc)

Not required.

22


Suspensibility/Spontaneity of

dispersion

SuspensibilityCIPAC MT177CIPAC MT184

Spontaneity of dispersion CIPAC MT 160, CIPAC MT 174

Tests to be performed in CIPAC D water at the highest and lowest proposed concentration for use.If suspensibility is below 60% or higher than 110%, a justification is required that this will not pose problems during application. Appropriate label instructions and/or sprayability study may be required.

Requirement: content of active substance in the suspension is in the range between 60 – 105 %. The test should be performed at the highest concentration. The greater the amount of product to water the more difficult it will be to disperse. Formulation types: water dispersable products (WG, SC)

The determination of the suspensibility of substances dispersible in water is carried out using CIPAC MT 184. The relative measured content of the active substance in the suspension should be in the range of 60% to 105%. The test must be performed at the highest and lowest concentration recommended for use of the preparation. As changes in viscosity and surface tension interact with each other.

The spontaneity of dispersion of biocidal products dispersible in water has to be determined according to CIPAC methods MT 160 and MT 174 respectively. The content of the active substance in the suspension should be in the range of 60% to 105%.

Test method is required for water dispersible products.

Wet sieve analysis CIPAC MT 182CIPAC MT185

% residue on a 75 µm sieve.

The wet sieve test is applicable to water-dispersible biocidal products and can be determined e.g. according to the CIPAC methods MT 182 or MT 185 depending on the formulation type. A maximum residue of 2 % on a 75 µm sieve is allowed.

Not required.

Dry sieve analysis CIPAC MT 58.2, CIPAC MT 59.2, CIPAC MT 59.1 CIPAC MT 170

A maximum residue of 5 % on a 75 µm sieve is allowed. Not more than (0.005 x content of active substance in g/kg)% should be present as the active substance in the residue on the sieve.

Required for dusts, powders and granules, if no particle size distribution test is conducted.However, the particle size data must include data on the residue retained on a 75 µm sieve. For dustable powders the active content in the residue retained on the 75 µm sieve must always be determined.

23


Emulsifiability/Emulsion stability/ Re-emulsifiability

CIPAC MT36.3CIPAC MT180 (suspo-emulsions)

Re-emulsifiabilityCIPAC MT36.3

Tests to be performed in CIPAC A and D water at the highest and lowest proposed concentration for use. As surfactant concentration changes both high and low concentration this affects dispersion characteristics.

The acceptable limits demonstrating that an emulsion is stable are as follows :

MT 36.1: max 2 ml cream after 30 mins, trace of oil. If any separation is observed re-emulsification should be complete after 24 hours.

MT 180: Max 2 ml cream after 30 mins, trace of oil. If any separation is observed re-emulsification should be complete after 24 hours

If no stable emulsion is formed, a justification is required on why this will not negatively influence application of the biocidal product.. Appropriate label instructions and/or a sprayability study may be required.

Required for emulsifiable products that require emulsification before use and emulsions (emulsion stability test).

Re-emulsifiability is additionally required if separation appeared during the test of emulsion stability.

Not required.

Dissolution rate CIPAC MT176 (water soluble bag)For tablets:

The dissolution rate should be demonstrated regarding tablets and products used in water soluble bags in water and that the formulation dissolves or disperses

Required for products used in a water soluble bag and for all tablets.

Not required.

24


no specific method.

rapidly. The test should be performed at the highest concentration. As the greater the amount of solid to water the more difficult it will be to disperse,

25


Attrition/friability of granules; integrity of tablets

CIPAC MT178 CIPAC MT 178.2 (granules)

CIPAC MT193(tablets)

Requirements: 98%

Where the material has an attrition resistance of <98% then theparticle size of the dust must be determined and the risk tooperators and bystanders must be addressed.

Where the material has an attrition resistance of <98% thenevidence is required that the material may be satisfactorily applied through application equipment must be addressed.

Only required for granules and tablets.

Tablets must remain intact to avoid risk for the operator (dust formation) or the dose becoming at risk. For separately packed tablets only friability needs to be determined.Requirements: tablets may not break

Not required.

Persistence of foaming CIPAC MT47.2

State solvent, test concentration and mL foam after 1 minute.

Requirements: ≤60 mL after 1 minute.

Test should be performed at the highest concentrationThe level of foam should not exceed 60 mL after 1 minute. Where a preparation is outside these limits then evidence must be submittedshowing that there is

Not required for products that are not diluted for use (ready for use products).

Not required.

26


no unacceptable risk to operators following use of thepreparation through the appropriate application equipment.

Flowability/Pourability

CIPAC MT172

CIPAC MT148CIPAC MT 148.1

Flowability requirement: pass through the sieve after 5 and 20 liftings.As the product is heated to 54 oC for this test, CIPAC MT170 may not be suitable for testing heat sensitive products and products containing water or other volatiles.

The following is acceptable: The sample should flow through the sieve after a maximum of 5 liftings’.

Maximum 5 % residue and 0.25 % rinsed residue respectively may still remain in the measuring cylinder. The test can be performed in the commercial packaging if the standard lab test is failed. Higher residues may cause hazardous situations during waste disposal:. A justification is required for on why high residues would not pose an issue, or instructions should be provided on safe waste disposal.Higher residues may also affect the ability to prepare the biocidal product at the maximum in use rate and hence adversely affect the efficacy:. Appropriate evidence

Flowability: required for granules.

Pourability: required for dispersions.

Not required.

27


that the efficacy will not be adversely affected maybe required.

Dustiness CIPAC MT171

Where the apparent dust content is >1% (by weight), the particle size and nature of the dust must be investigated in order to evaluate the potential risk to operators andbystanders.

Where a granular material is described as 'dusty' thenevidence is required that the material may be satisfactorily applied through application equipment.

Only required for granular products that cannot be fully dissolved in water (WG, WP, etc.) and may be hazardous by inhalation.

Not required.

Dustability CIPACMT 34

The equipment used in CIPAC MT 34 is not readily available. Therefore data are required showing the preparation may be satisfactorily applied as a dust through the proposed application equipment and that there is no unacceptable compaction or caking following a heat test under pressure.

Required for DP formulations Not required

Dilution stability CIPACMT 179/MT41

The dilution stability is determined to ensure that water-soluble preparations dissolve readily and/or, when diluted, produce stable solutions without precipitation,flocculation, etc. The results submitted should fully describe

28

Author, 01/03/-1,

See comment earlier. NL: please see response given in comment 28


the appearance and amount of any separation or sediment.The test should be conducted at the maximum in use concentration specified on the label.

Acceptable limits :MT 41 ‘trace’ of sediment after 30 mins

MT 179 max 2% on 75 m sieve

Where a preparation is outside this limit then evidence must be submittedshowing the material separated will not block application equipment or present an unacceptable risk to the operator or affect the efficacy.

Additional

technical

properties

Burning rate smoke generators

The burning rate should be determined to establish how long it takes before the preparation stops generating smoke..

Requirements: the burning rate should correspond with the proposed use.

Not required.

Burning completeness smoke generators

Burning completeness must be determined by weighing the preparation before and after use. It should be demonstrated that by far the largest part of the active substance went up in

Not required.

29


smoke. This also requires determination of the concentration active substance in the residue.

Requirements: The preparation may, after use, present no risk for operator or environment, and disposal should –if applicable- be possible in accordance with the instructions for use.

Composition smoke of smoke generators

Smoke composition must be analysed for concentration active substance and decomposition products, if any, to guarantee that the produced smoke does indeed contain the active substance and no decomposition products.

Requirements: The preparation may after use present no risk to operator or environment.

Not required.

Spraying pattern aerosols

FEA 644 Homogeneity must be determined according FEA method 644.Spray diameter must be determined at 30 cm distance.

Requirements: none

Only for aerosols (not for spray pumps and non-pressurised vehicles).

Not required.

Sprayability In those cases where standardised tests are not suitable to support the claim a biocidal product can be safely used or if standard tests do not produce desired results, it is possible to submit a sprayability study or field study, in which application of the biocidal product is investigated. A In any way, a sprayability study

30


must be representative for the intended use and should preferably be performed using a worst-case scenario.

An example would be that a water dispersable granule does not result in a suspensibility (CIPAC MT184) of 60% or higher, meaning the spray fluid would be inhomogeneous and clogging of spray nozzles may occur. The sprayability study would then have to consist of a test at the lowest and highest dosage. Mass flow through the nozzle should be monitored (e.g. when the tank is full, ¾, ½, ¼ filled and nearly empty) and the sprayed fluid should be investigated on active ingredient contents.

3.9

Compatibility with other products(IIB3.9/Pt. I-B3.9)

ASTME1518-99

In those cases a product is mixed with another product, evidence must be provided showing that the mixed products can be safely used.

Only for products that may require mixing with other products, as stated on the product label.

Physical or chemical interactions may occur and should be documented. If all properties of the single products are known as far as a chemical reaction can be excluded without any doubt, scientific justification for the renouncement of the determination of the physical and chemical compatibility iswill be sufficient.

Not required

3.10

Surface tension(Pt. I-B3.10)

EC A5OECD 115

Temperature must be stated and surface tension must be reported in the unit mN/m.Test must be performed on the undiluted products at 25 oC.

Only for liquids

Only required if the product contains more than 10% organic solvent (hydrocarbons).

Required

3.11 OECD Test must be performed Only for liquids Required

31


Viscosity(Pt. I-B3.10)

114 at 20 and 40 oC.Kinematic viscosity is to be reported in m2/s.Dynamic viscosity is to be reported in mPa.s

Only required if the product contains more than 10% organic solvent (hydrocarbons).

3.12

Particle size distribution(Pt. I-B3.11)

OECD 110CIPAC MT170CIPAC MT187

Requirements: for CIPAC MT187 / OECD 110, 85% of the granules must be within the nominal size range.

CIPAC MT 170 is required for watersolublewater soluble granules and powders.CIPAC MT 187 / OECD 110 is required for water insoluble granules and powders and fibres.

Required for CIPAC MT187 / OECD 110.

Note:It should be noted that some of the criteria for acceptance of technical characteristics of the formulation given in results and in remarks/justification columns are outcomes from expert meetings and can be found in EFSA documents.

4. Analytical methodsAnalytical methods required for product authorizationauthorisation are methods used for post-registration purposes, like monitoring of residues and product specifications. These methods should be specific for their purpose, and they should generally use commonly available equipment and non-hazardous chemicals.

General requirements on analytical methods are included in the TNsG** and the addendum to the TNsG on analytical methods*).*).Generally, the guidance documents SANCO3030/99 and SANCO/825/00 rev. 8.1 can be used. Validation of analytical methods does not have to be performed and reported underto GLP.

In particular cases when a specific analytical method cancan not be developed, a common moiety approach or titration method may be acceptable.

Applicants as well as CA’s should keep be aware that in mind that whencase an evaluation of equivalence of the active substance is required, the analytical methods used for analysis of the active substance will also require evaluation.

4.1 Analytical methods for formulation analysisActive ingredientFor formulation analysis, the analytical method must be suitable to accurately determine the active ingredient content at the specified content of the active ingredient. The TNsG on data requirements specifically states that in the case of a preparation containing more than one active substance, a method capable of determining each, in the presence of the other, should be provided. If a combined method is not submitted, the technical reasons must be stated.Generally, linearity, specificity, accuracy and repeatability should be addressed.Where available the active content can be determined in the formulation using a CIPAC method. When a CIPAC method has been validated for the active in the same formulation

32

Author, 01/03/-1,

? what is this a reference to? NL: * refers to references and internet links provided in appendix VII

Author, 01/03/-1,

? what is this a reference to? NL: * refers to references and internet links provided in appendix VII

Author, 01/03/-1,

Perhaps there could be an explanation of the influence of EFSA on decisions for data requirements for biocidal products. NL: we find this beyond the scope of the EvalMan. Text not amended


type then full validation data are not required. In such cases only specificity data (see below) are required.

Linearity must be displayed at a relevant concentration, overlapping the specified content of the active ingredient in the formulation. Moreover, the calibration curve plot must be provided, including information on the slope and intercept, and the correlation coefficient (r). In general, r may not be below 0.99. The calibration curve must consist of a minimum of 5 concentrations, or 3 concentrations, measured in duplicate. If no linear correlation exists, but for instance, a quadratic fit is more appropriate, this should be well substantiated.

Specificity may be addressed by providing a blank chromatogram of the formulation without active ingredient, a chromatogram of the formulation including active ingredient and a standard, clearly showing that there are no interfering peaks.. There must also be a retention time match of the sample and standard for the specificity to be considered as addressed. Where more than one active substance is present, the data must clearly demonstrate the method is capable of determining each active in the presence of the other(s).

Accuracy should be determined at a relevant concentration. At least 2 recovery determinations should be made on representative samples containing a known quantity of the active. Samples should ideally be laboratory-prepared co-formulant mixes to which a known quantity of the active is added. Where it is not possible to prepare a sample matrix without the presence of the active, or where there are difficulties in replicating the sample to be analysed (for example with pellet formulations), the standard addition method may be used.

Repeatability (Method precision) may be addressed by the repeat analysis of the same sample at least 5 times. The RSD should comply with the modified Horwitz equation.

Substances of concernFor substances of concern, the same requirements are applicable as for the active ingredient with the additional requirement to confirm the identity of the substance of concern. If the method used to determine the substance of concern is not regarded as highly specific then confirmation of the result using a fully validated confirmatory method is required.

4.2 Analytical methods for post-authorisation residue analysis

Generally, analytical methods for the residue analysis of the active substance are described in the CA-Report.

The applicant has to show that they have accessexploitation rights to the studies on analytical methods studies contained in the CA-Report. This regards studies concerning the active substance as well as studies concerning toxicologically and/or ecotoxicologically relevant components, where already available. These The studies have to be submitted together with the application. If the CA-Report contains declared data gaps regarding residue analytical methods, they shouldhave to be filled by the applicant during the product authorisation.

The data requirements regarding analytical methods for the determination of toxicologically and/or ecotoxicologically relevant components of biocidal products (i.e. non-active substances and/or residues thereof) result from section IV of aAnnex IIB of the dDirective

33

Author, 01/03/-1,

What does this mean? NL: text amended

Author, 01/03/-1,

Will the methods be supplied directly to the MS from the manufacturer of the formulant? What if they don’t want to provide a new analytical method that can cost €40,000? Would a formulator have the opportunity to re-formulate with a new formulant? Is this a requirement under REACH? Can the same information be used? NL: We will extend this section in version 2 of the EvalMan so other MS can provide their opinion on this.


98/8/EC. General requirements on the analytical methods that have to be submitted are explicated in the “Additional Guidance on TNsG on Data requirements*”.*” The For the decision about the toxicological and ecotoxicological relevance, the classification of the non-active substance is the key criterion for determining the ecotoxicological and toxicological relevance of that substance. Generally, analytical methods for by-products of the biocidal product classified as toxic or very toxic or dangerous for the environment must be analysed for monitoring purposes if human and/exposure or environmental exposure cannot be excluded.

The submitted analytical methods should be able to detect all relevant compounds of the residue of the product, including . This can imply the non-active substances and/or degradation products thereof.

The required sensitivity of the analytical methods for substances in the residue analysis are deriveddefinition result from the relevant NO(A)EC for the non-active substances in the relevant environmental compartment (i.e. soil and surface water), respectively. If NO(A)EC values were established for different sensitive species or under different conditions, the effect level of the most sensitive species is used.

If the composition or the intended use of the applied biocidal product differs from the formulation evaluated during the process of inclusion in Annex I of the directive 98/8/EC, it must be verified thatchecked if justifications for non-submission of data for residue analytical methods were provided in the CA-Report and thatwhether these justifications are still valid. Where appropriate, the justifications musthave to be adjusted or the missing data have to be submitted together with the application for product authorisation.

If additional analytical methods are required, generally, methods for confirmation of positive results (Confirmatory Methods) have to be provided, as welltoo. If new methods for food and feeding stuffs are required, the results of verifications of the suitability of the analytical methods in an independent laboratory (Independent Laboratory Validations) shouldhave to be provided, too.

34

Author, 01/03/-1,

Under what circumstances might these be required. NL: We will extend this section in version 2 of the EvalMan so other MS can provide their opinion on this.


5. EfficacyAs it is one aim of the BPD to ensure that biocidal products are effective against target organisms without posing unacceptable risks, an assessment must be carried out to determine if the product’s efficacy is sufficient to warrant authorisation. The following chapter outlines the conditions and evaluation criteria used in this process. It describes which information is necessary to assess product efficacy, as well as and unacceptable effects such as the, including development of resistance in target organisms, unnecessary suffering in target vertebrates and any other unacceptable effects..

Only a general overview is given. More specific information on the evaluation of the efficacy of the different product groups is given in separate chapters of the TNsG on Product Evaluation.

5.1 General introductionEfficacy evaluation includes assessment of the following aspects:- intended use (label claim)- efficacy- the occurrence of unacceptable effects on the target organisms, including unacceptable

resistance or cross resistance, or unnecessary suffering and pain in vertebrates and any other unacceptable effects .

The assessment of efficacy and unacceptable effects has been elaborated in the following documents: Biocidal Products Directive 98/8/EC* Article 5 and 8, Annex VI: paragraphs 48-52 and 90-

93 (see Appendix 2 of this chapter) TNsG on product evaluation*(Chapter 6, 7 and 8), including the recently revised chapter

6.2 on resistance (May 2009)* and Addendum TNsG on product evaluation: Revised appendix chapter 7 concerning the efficacy of rodenticides (PT14)*

TNsG on Annex I inclusion*, including the recently revised chapter 10 on resistance (May 2009)*

TNsG on data requirements* (Chapter 2 B)

In appendix B of this chapter (below) the main issues concerning efficacy and unacceptable effects as laid down in the common principals are listed. The relevant guidance for the assessment of products for product authorisation is laid down in the TNsG on product evaluation*.

5.2 Intended useThe applicant must provide sufficient information to clearly specify the field of use for of the product. This information is of importance for both the risk assessment and the efficacy assessment, since it determines for whichclarifies for what uses the product should be assessed. Although the label claim in general provides some information, this is most of the time this is not sufficient.

Note: A “summary of the product characteristics” is included in the product assessment report (PAR, see Appendix VI of this manual).

5.3 EfficacyEfficacy can be defined as the ability of a product to fulfill its fulfil the label claims for it, i.e. is the product effective against the claimed target organisms when used in accordance with the

35

Author, 01/03/-1,

It is not just related to the target organism but also it is related to the label claim as well e.g. kill, control etc. NL: agreed, that is what the rest of this sentence is about (fulfil label claim, conditions specified). No revision needed.

Author, 01/03/-1,

Such as? NL:Revised, see 5.3.4.


conditions specified on the proposed label or with other conditions of authorisation. Next to these label data information should be provided on aspects that influence the efficacy (e.g. resistance) and unacceptable effects (e.g. unnecessary suffering of vertebrates). It should be emphasised that efficacy Although often underestimated, assessment of efficacy is as important as risk assessment. If a product does not function appropriately,give the required result the user may increase the dose or use the product in an unauthorisedunauthorizsed way, resultingwhich might result in a hazard for human health or environment. Thus efficacy data are fundamental to establish the benefits of biocidal products.

5.3.1 Data requirementsFor efficacy, only product information is required. Information but no information concerning the active substance itself should not be submitted. Since for the most part . As in general only a minimal evaluation of efficacy takes place at the Annex I inclusion stage, this evaluation is seldom sufficient for product authorisation by member states. Only if the product assessed in the CAR is the same product and a full efficacy evaluation was done, the evaluation in the CAR can be used for the national authorisation. When only basic efficacy of the product was established in the CAR, additional data have to be provided. For all other products a full set of efficacy data has to be provided.In all cases the CAR may only be used if the applicant has access to the CAR (notifier or LOA).

Studies must be provided which demonstrate that the product, when used in accordance with the label, is sufficiently effective. An untreated control should be included in all tests. The efficacy of the product must, as a minimum, be similar to those resulting from suitable reference products, where such products exist, or to other means of control. Where no reference products exist, which is normally the case, the biocidal product must give a defined level of protection or control in the areas of proposed use. Dose- response data have to be provided, including dose rates lower than the recommended rate, in order to assess if the recommended dose is necessary to achieve the desired effect and is not excessive.

More specific information on data requirements for the evaluation of the efficacy of products belonging to specific product groups is given in chapter 7 of the TNsG on Product Evaluation. In the appendices to this chapter per PT group requirements are specified (e.g. standard methods, efficacy tests, etc.) for each product type (PT) group. For some PTsPT’s no appendix with specified requirements is available. In those cases the general information from of chapter 7 should be used as guidance.

The information in most of the appendices to chapter 7 is rather concise. Therefore, recently a revision of these appendices are currently under revisionis has started. The revised chapters will give more detailed guidance on data requirements and evaluation criteria. Appendix A of this chapter (below) specifies the current status of the reviewreviewing of the appendices to chapter 7.

36

Author, 01/03/-1,

How is this issue linked to products which are inherantly not as effective as others (perhaps because they are natural)? How is this considered in the assessment of products? NL: data requirements and pass criteria are set to make sure that only sufficiently efficacious products will come on the market. No revision needed here because this only focuses on the importance of efficacy.

Author, 01/03/-1,

Who underestimates its relevance? People in industry certainly don’t underestimate the importance of efficacy. NL: This impression of underestimation of efficacy is given during active substance evaluation for Annex 1, where efficacy only plays a minor role. Ctgb is very happy that industry doesn’t underestimate the importance of efficacy. No revision needed.


5.3.2 Norms and criteriaTo establish the meaning of ‘sufficiently effective’ the TNsG on Product Evaluation give guidance concerning norms and criteria for efficacy assessment. For most PTsPT’s the guidance is not very specific, however, in the recent revisions of the appendices to chapter 7 (PT14, 18, 19) norms and criteria are specified. For some other PTsPT’s (PT2, 5, 8, 21) these appendices are currently under revision. The This revised versions will include, where possible, specific specifications of norms and criteria.

It is also possible to compare the product to a reference product. In that case, the choice of reference product is essential. For most types of products no standard reference product is available.

If the criteria are not met in the provided studies the applicationit can be rejected (no decided to reject the authorisation granted), of the product or one or moreto reject part of the intended uses can be rejected (partial authorisation).of the product. In the latter case, a new label claim should be made, which is compatible with the provided data must be written. For instance, the intended use can be reduced, concentration of the product can be adapted, etc..

5.3.3 Resistance and other aspects that influence the efficacyThe applicant should provide information on aspects that can influence the efficacy of the product. Resistance of the target organism is one of the main issues that should always be addressed in this section. Information should be provided on occurrence of resistance and the risk of development of resistance. Chapter 6.2 of the TNsG on Product Evaluation provides general information on resistance. If athe risk of the development of resistance is identified, the applicant should provide a resistance management strategy. This management strategy can be specified on the label.

Other aspects that may influence the efficacy include temperature, pH, combined use with other products (e.g. cleaning products, other biocides), equipment to be used, etc.. For these aspects in general the limits or restrictions can be specified on the label.

5.3.4 Unacceptable effectsArticle 5(1)(b) of the Biocidal Products Directive (98/8/EC) requires that products authorised for use against vertebrate target organisms will not cause them "unnecessary" suffering and pain. This is often called "humanenessHumaneness". This is a term which is difficult to define, but it infers the degree of pain, distress and discomfort of the target organism. This is only of importance for PTs in which vertebrates are the target organism, namely PT 14: rodenticides, PT15: avicides and PT23: products for the control of other vertebrates, in which vertebrates are the target organisms.

Data should be submitted that show that the biocidal product does not cause unnecessary suffering in its effect on target vertebrates, including. This should include an evaluation of the mechanism by which the effect is obtained and the observed effects on the behaviour and health of the target vertebrates. Where; where the intended effect is to kill the target vertebrate, the time between introduction of the biocide and necessary to obtain the death of the target vertebrate, and the conditions under which death occurs, will shall be evaluated.

Chapter 6.3 of the TNsG on product evaluation* provides general information on humaneness.

37


Further practical information on how humaneness can be evaluated is available in:

Sharp, T and Saunders, G (2008). A model for assessing the relative humaneness of pest animal control methods. Australian Government Department of Agriculture, Fisheries and Forestry, Canberra, ACT*

The following references provide a comprehensive humaneness evaluation of all rodenticides covered by the actual European Biocides Review Program:

PSD (Pesticides Safety Directorate), Department for Environment, Food and Rural Affairs 1997. Assessment of humaneness of vertebrate control agents. (Food and environment protection act, 1985, part III, control of pesticides regulations 1986, Evaluation of fully approved or provisionally approved products, Issue 171; York YO1 7PX)

Mason G. and Littin KE. 2003. The humaneness of rodent pest control. Animal welfare 12: 1-37.

Information on any other unacceptable effects, such as wood preservatives negatively affecting wood fastenings and fittings, disinfectants causing destruction of instruments or installations, etc., should be provided when applying for authorisation. When necessary this information should also be mentioned on the label.

38


Appendix A (chapter 5): Status of efficacy guidance for specific product typesPT Reference to available

guidance (link to revised guidance is given)

Remarks

For all PTs: Information on resistance is provided in chapter 6.2 of the TNsG on Product Evaluation*.

Recently revised, however, specific information per PT groupgroups is still lacking.Endorsed May 2009

For all PTs: Information on humaneness is provided in chapter 6.3 of the TNsG on Product Evaluation.

For all PTs: The data requirements for efficacy tests are discussed in Appendices to chapter 7 of the TNsG on Product Evaluation.

Very concise, need revision

1: human hygiene biocidal products2: private area and public health area disinfectants and other biocidal products

Guidance currently under revision, a new version will be available in 2013.by the end of 2011.

3: veterinary hygiene biocidal products4: food and feed area disinfectants5: drinking water disinfectants Guidance will be revised in

2013.2011.6: in can preservatives Guidance currently under

revision, a new version will be available in 2013

7: film preservatives8: wood preservatives Guidance currently under

revision9: fiberfibre, leather, rubber and polymerised materials10: masonry preservatives11: preservatives for liquid cooling and processing systems12: slimicides13: metalworking-fluid preservatives14: rodenticides Addendum TNsG on product

evaluation: Revised appendix chapter 7 concerning the efficacy of rodenticides (PT14)*

Already revised. Endorsed February 2009

15: avicides16: molluscicides17: piscicides

39

Author, 01/03/-1,

When? NL: date added

Author, 01/03/-1,

Is this and subsequent documents available now as we are in the middle of 2012? NL: revised

Author, 01/03/-1,

When will this happen? Perhaps some indication of the timeline for this work in the document will benefit the reader. NL: we would like to know that too but it depends on who is willing to do the revision. So far only the documents mentioned below are revised. The rest will be up to ECHA to coordinate this in the future.


18: insecticides, acaricides and products to control other arthropods

Guidance is revised. Endorsed December 2012., accepted by TM and CA and released for consultation till April 15 2011.

19: repellents and attractants Guidance on invertebrates is revised, accepted by TM and CA and released for consultation till April 15 2011.

20: preservatives for food and feedstocks21: antifouling products Guidance currently under

revision22: embalming and taxidermist fluids23: control of other vertebrates

40

Author, 01/03/-1,

What has happened to this document and the one below since early 2011? NL: In CA meeting December 2012 for endorsement. Text is revised.


Appendix B (chapter 5): Paragraphs of the Common Principles (Annex VI of 98/8/EC) relevant for efficacy evaluation and decision making.

EvaluationUnacceptable effects48. Data shall be submitted to and evaluated by the Member State to assess whether the

biocidal product does not cause unnecessary suffering in its effect on target vertebrates. This shall include an evaluation of the mechanism by which the effect is obtained and the observed effects on the behaviour and health of the target vertebrates; where the intended effect is to kill the target vertebrate the time necessary to obtain the death of the target vertebrate and the conditions under which death occurs shall be evaluated.

49. The Member State shall, where relevant, evaluate the possibility of the development of resistance to an active substance in the biocidal product by the target organism.

50. If there are indications that any other unacceptable effects may occur the Member State shall evaluate the possibility of such effects occurring. An example of such an unacceptable effect would be an adverse reaction to fastenings and fittings used in wood following the application of a wood preservative.

Efficacy 51. Data shall be submitted and evaluated to ascertain if the efficacy claims of the biocidal

product can be substantiated. Data submitted by the applicant or held by the Member State must be able to demonstrate the efficacy of the biocidal product against the target organism when used normally in accordance with the conditions of authorisation.

52. Testing should be carried out according to Community guidelines if these are available and applicable. Where appropriate, other methods can be used as shown in the list below. If relevant acceptable field data exist, these can be used. - ISO, CEN or other international standard method - national standard method - industry standard method (accepted by Member State) - individual producer standard method (accepted by Member State) - data from the actual development of the biocidal product (accepted by Member State).

Decision making Unacceptable effects 90. If the development of resistance to the active substance in the biocidal product is likely

the Member State shall take steps to minimise the consequences of this resistance. This may involve modification of the conditions of authorisation or even refusal of any authorisation.

91. An authorisation for a biocidal product intended to control vertebrates shall not be given unless: — death is synchronous with the extinction of consciousness, or, — death occurs immediately, or, — vital functions are reduced gradually without signs of obvious suffering. For repellent products, the intended effect shall be obtained without unnecessary suffering and pain for the target vertebrate.

Efficacy92. Member States shall not authorise a biocidal product which does not possess acceptable

efficacy when used in accordance with the conditions specified on the proposed label or with other conditions of authorisation.

93. The level, consistency and duration of protection, control or other intended effects must, as a minimum, be similar to those resulting from suitable reference products, where such

41


products exist, or to other means of control. Where no reference products exist, the biocidal product must give a defined level of protection or control in the areas of proposed use. Conclusions as to the performance of the biocidal product must be valid for all areas of proposed use and for all areas in the Member State except where the proposed label prescribes that the biocidal product is intended for use in specific circumstances. Member States shall evaluate dose response data generated in trials (which must include an untreated control) involving dose rates lower than the recommended rate, in order to assess if the recommended dose is the minimum necessary to achieve the desired effect.

42


6. Human health assessmentThis chapter describes the methodology for estimation of health risk resulting from primary and secondary exposure for the authorisation of biocidal products based on the assessment of active substances, included in Annex I of Directive 98/8 (e.g. TNsG on Annex I Inclusion Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation *), and further information on the product itself.

For products containing Annex I included substances, the testing criteria are laid down in Biocidal Products Directive 98/8/EC*.The dossier of the biocidal product must meet the requirements laid down in Annex IIA, IIB, IIIA and IIIB of this directive. Annex IIA describes the common core data set for active substances, while annex IIB describes the common core data set for biocidal products. Annex IIIA describes the additional data set for active substances, while annex IIIB describes the additional data set for biocidal products. Further explanations are given in the TNsG on data requirements*. The TNsG on Dossier Preparation provides a form (the Form for check for ‘completeness and quality of data’ compiled in Doc.Further explanations are given in the TNsG on data requirements*. The TNsG on Dossier Preparation provides a form (the Form for check for completeness and quality of data compiled in Doc. III-B; in Appendix 4.3) that may be useful for evaluating the completeness of data. It should be noted that for those substances included in Annex I, inclusion the data requirements are only met for products with the product related to the intended use defended in the CAR.

The process of human health risk assessment is depicted in Figure 1. For risk characterisation, the information from effect assessment and from exposure assessment has to be combined, andwhere exposure assessment is an iterative process (tiered approach). The implementation of risk management measures (RMMs) is an integral part of exposure assessment.

43

Author, 01/03/-1,

Again it might be useful to explain more clearly what this means in practice. NL: amended.


Figure 1 : The process of human health risk assessment for the evaluation of a biocidal product.

Testing is based on the assumptionstarting point that primary and secondary exposure are sufficiently safe for humans on the basis of a risk assessment. The risk assessment will be carried out with the Margin Of Exposure (MOE) approach and/or the systemic and/or local Acceptable Exposure Level (AEL) approach, and/or the Acceptable Daily Intake (ADI) approach, and/or the Acute Reference Dose (ARfD) approach, depending on the envisaged use and therefore typeform of exposure.

The MOE represents a direct comparison of exposure and toxicity. The “overall assessment factor” depends on the safety factors used. For the MOE approach, however, this is usually 100, based on a factor 10 for intraspecies and a factor 10 for interspecies. The systemic AEL approach is based on an internal (absorbed) dose available for systemic distribution and is expressed as internal level (mg/kg bw/day). The local AEL approach is based on external values such as concentration or percentage, ppm, mg/cm2 or mg/m3. air, depending on the route of exposure (see the document Risk characterisation of local effects, 2010). The ADI approach is based on an external dose expressed as external level (mg/kg bw/day). There will be no cause for concern (risk) if the estimated exposure is lower than the derived limit values. Where appropriate, the DNEL (Derived No Effect Level) approach may also be used (e.g. where AELs have not been derived, such as for many substances of concern). The DNEL is the level of exposure to the substance above which humans should not be exposed. There will be no cause for concern (risk) if the estimated exposure is lower than the DNEL. The In the TNsG on Annex I inclusion chapter 4.1 Quantitative Risk Assessment suggests that, the DNEL approach (based on the allometric scaling method) is mentioned to be used in borderline cases, especially if there is a need to harmonise with

44

Author, 01/03/-1,

Unclear to me whether this means. Can the DNEL approach could be used to refine AEL set for an active substance. Further information should be provided. NL: amended

Author, 01/03/-1,

Perhaps put in full the first time. NL: amended.

Author, 01/03/-1,

The applicant also carries out a risk assessment for the product. Is this no longer required? NL: The risk assessment performed by the applicant is a data requirement and therefore still required.


decisions made in other regulatory fora (e.g. REACH) or as a refinement step in the risk characterisation for biocides.

Experience shows that as regards the choice of an AEL or MOE approach, the AEL approach can best be used. The MOE approach is a dated approach and not very useful for route-to-route extrapolation.

6.1 Combination toxicityCombination toxicity should be determined for a biocidal product containing at least two active substances or one active substance with at least one substance of concern, as well as for combinations of biocides. For biocides containing several active substances and/or substances of concern, the acute toxicity of the product can be estimated based on toxicological studies with the biocidal product or the calculation rules using the classification of all ingredients (= part of data requirements product) and the justified application of Directive 1999/45/EC and CLP-Regulation (EC) No 1272/2008 (see chapter 9 Classification, Labelling and Packaging). A risk assessment must, however, also be carried out for repeated exposure to a combination of two or more active substances and/or substances of concern.

A repeated dose study with the product or preparation with several the different active substances is not part of the data requirements. In the Common Principles, Annex VI of the Biocidal Products Directive 98/8/EC* and the TNsG on product evaluation* however, attention is paid to this aspect. Combined exposure to active substances and/or substances of concern may possibly lead to a different toxicological profile than the profile derived for the individual active substances and/or substances of concern because they may influence each others’each other’s effect. Factors such as toxicological profile (critical effect, mode of action), metabolism of the active substances and/or substances of concern and whether the active substances and/or substances of concern cause enzyme induction shall be taken into account in the evaluation. The effect of two or more active substances and/or substances of concern may be independent, additive, synergistic or antagonistic. Both synergistic as well as antagonistic effects could have an influence on the risk assessment, particularly in cases where exposure takes place at or near the level at which undesirable effects of the individual active substances and/or substances of concern can be expected (in comparison with the AEL/ADI/ARfD). A proposal on combination toxicology (mixture toxicity),, already made available by France and commented by the other MSs will be discussed at theone of the next TM meetings in 20122011. Once accepted it will be incorporated in this manual.

6.2 Exposure assessmentThe use of biocides may result in human exposure. Such exposure may occur via different routes: oral, dermal and respiratory. The fundamental concept underlying the approach for human exposure assessment is the need to establish the full range of human exposure situations that could occur from the use of a biocidal product and to consider all relevant routes of exposure scenarios. The exposure assessment process therefore requires determination of the patterns of use.

Pattern of use (based on TNsG on human exposure (2007)*)

The pattern of use information is used to develop exposure scenarios, which are thenevaluated to derive quantitative exposure estimates. The essential pattern of use information required for deriving exposure scenarios is in its most general format shown below and include information on:

Product Package details (volume/material/closure/bulk delivery/weight of the product).

45

Author, 01/03/-1,

Now 2012, has this happened? What was the outcome? Has the Euroepan level discussions been taken into account? NL: amended

Author, 01/03/-1,

How is the combined risk assessment for all exposures done when considering combination toxicity? Does this mean that more products will fail the risk assessment process? NL: Combination toxicity can be seen as mixture toxicity of multi-substance biocidal product as described by FR discussed at TMIII2012. This will be included in a next version of the evaluation manual after endorsement.

Author, 01/03/-1,

What experience shows that? On what grounds is this statement made? NL: Experience based on route to route extrapolation.


Formulation details (active substance and formulants) Product concentration, relative density formulation (basis) in kg/l, recommended dry layer

thickness in µm and spreading rate in m2/l Physical state (liquid/solid/in-situ generation/particle size/aerosol/volatility/ vapour

pressure, block/granules/spray) Intended use concentration (dilution mixing/loading) Method of application (equipment (pressures), automatic, industrial) Location ofWhere the product usewill be used (location accessibility /system treated) Product userBy whom the product will be used (primary exposure: non-professional user,

professional user, specialised professional user (e.g. pest control operator))

Tasks Tasks application and pre- and post applicationpost-application (primary exposure, see

explanation below) Non-user exposureWho else may be exposed (secondary exposure, see explanation

below) Routes of exposure (route: dermal/inhalation/oral) Volume/area treated “Time frame” (timing seasonality/acute/medium or long-term exposure/events per day) Duration of tasks (min/day) Quantity used per task Risk mitigation measures including technical measures (e.g. ventilation, specially

designed products), organisational measures or PPE

Information on the pattern of use can be gathered through surveys or generic data fromsimilarfrom similar products. Specific information on patterns of use for many biocidal product types islimited. Thus, and therefore applicants wishingwilling to place biocidal products on the market will need to conduct research into patterns of use if actual or surrogate data are not available. A pattern of use database for all different biocidal product types is available in section 3.5 in of the TNsG on human exposure (2007)*. Nevertheless, for product authorisation, a clear overview of pattern of use data requirements is necessary. Use scenarios with respect to pattern of use for deriving scenario data per product type and within one product type are derived from this is needed for product authorisation. The information. The on the pattern of use information for aof one particular biocidal product should be presented in the summary of biocidal product characteristics (SPC) for of that biocidal product.

Information on the use of products by consumers is not widely available. The development of the consumer exposure model, ConsExpo, with detailed ‘use patterns’ and provision of default values for these use patterns (in factsheets), has partly helped to fill this gap,.

When accurate scenery data are scenaryscenery data is absent, then the mentioned defaults for frequency and duration of exposure should serve as a starting point for exposure assessment. The frequency and duration of a task are major determinants influencing the level of exposure. The frequency of task is variable and is critical in deciding whether the exposure is (semi)chronic or acute for risk characterisation purposes. Frequency of exposure should be expressed as events per day (with precision as to how many days per year the user of biocides is exposed). Duration of exposure should be expressed as minutes or hours per day.

46

Author, 01/03/-1,

What does this mean? NL: accurate date based on real practise.

Author, 01/03/-1,

What is the relevance of ConsExpo to biocidal products? It is not used routinely and does not cover many of the PTs. Further explanation on the relevance of ConsExpo to the assessment of consumer biocides should be provided. NL: . This will be included in a next version of the evaluation manual after endorsement.

Author, 01/03/-1,

This sentence is not clear. Perhaps it could be re-worded. NL: amended


The pattern of use is not universal and thus likely to show considerable variability betweenwithinMember States (e.g. different user groups; professional user vs. amateur user/consumer).Also, variability in pattern of use across the EU may be based on, amongst others:

- regional differences- climatic differences

A distinction is made between primary exposure and secondary exposure: Primary exposure is the exposure of the professional and non-professional

operator/worker. Secondary exposure is exposure not covered by primary exposure scenario, i.e. and

which relates to exposure of people who are present during a certain activity or are present at a place where a biocide has been applied or where materials are used which have been treated with biocides, (including food that may containpossibly contains residues..(An of biocides) (an important characteristic of secondary exposure is that itsuch exposure could occur without the exposed person being aware of, or in control ofover the exposure).

Primary exposure is experienced by professionals and non-professionals (consumers) who use/apply a biocidal product. and is related to the task(s). The overall exposure scenario will consist of a series of tasks that can be allocated to three distinct phases of use:

1. Mixing & loading; Including 2. Include the tasks involved in delivery and handling of bulk ready-for-use and concentrate products, dilution of concentrates and/or the introduction of product to the application apparatus/system.

3. Application: Involving 4. Involves all uses of biocidal products, including application by hand, by hand-held tool, by dipping, by spraying, handling treated articles, and in machining. This phase of use can lead to the exposure of people (other than operator) who are present during the product application (secondary exposure).

5. Post-application: Including 6. Includes exposure through separately cleaning and maintaining process equipment and tools. Secondary exposure is also included in the post-application phase.

The contribution of to each route of exposure to the overall exposure scenario may vary considerably between these phases with any given active substance, given that mixing and loading can result inreflect exposure to a concentrate, application to a dilute product, post-application to vapour or dried residue, and removal to waste material (e.g. removing and disposing of a preserved coating).

In practice, exposure data often comes from relates to full-shift sampling and therefore includes all three phases of use. However, it is nonetheless important to ensure that each phase of use has been accounted for in the exposure assessment.

Since the production, formulation and removal stages for biocides use areis basically not fundamentally different from those of general and industrial chemicals, these aspects have not been covered. A guidance document relating to these aspects was endorsed at the 22nd CA meeting (see §4.2.3 Manual of Technical Agreements*).

Humans can be exposed to biocides by use at the place of work or homeprivate, and

47

Author, 01/03/-1,

Many Member States are adding new categories of user during the evaluation e.g. specialised professional. How is this considered in the risk assessment process? NL: in case MSs do not agree with each other or have different policies (such as different user groups for rodenticides) the notification procedure could be used.


indirectly via the environment. Exposure estimation for the identified possible exposure scenarios is based on information regarding the use, where accidents or misuse are not taken into account. Foreseeable misuse (i.e. reasonably expected use not quite in agreement with legal instruction for use), however, does have has to be taken into account.

Human exposure assessment will always be performed even if there is no specific and agreed methodology available for exposure assessment. If this is the case (e.g. for groundwater metabolites or micro-organisms), a proposal on how to perform an exposure assessment should be presented proposed for discussion in different expert groups. It is also possible to check with the Biocides Technical Meeting whether a methodology has previously been proposed by another Member State, but not yet discussed or agreed upon.

Dietary exposure assessmentDirective 98/8/EC requires that a risk assessment be performed for products containing biocidal active substances including the quantification of residues in food and feed. Biocidal products are divided into 23 product types (PTs), some of which are used in areas or on objects where food or feed are produced, stored and/or processed. In this way, or through direct treatment, biocidal active substances can be carried over into food or feed. In addition, through the use of biocides in animal husbandry, livestock can be exposed, leading to residues in the food products obtained from livestock. Based on assessments performed in the course of EU-wide biocidal active substance evaluations, five basic groups of intended uses have been identified throughby way of which livestock animals can be exposed to biocidal active substances:

1. treatment of animal housing (mainly PT 3, 18, 19 and 21)2. treatment of feedstuff and drinking water or of storage facilities (mainly PT 4, 5, 12

and 20)3. treatment of materials that livestock animals may come in contact with (mainly PT

8)4. direct treatment of livestock animals (mainly PT 3, 18 and 19)5. treatment of aquaculture (mainly PT3 and PT21)

For each of these groups, possible methods for exposure estimation will be discussed in the final DRAWG (Dietary Risk Assessment Working Group) Draft Proposal Guidance on estimating livestock exposure to biocidal active substances (available on Circa).

The following PTs are likely to lead to an exposure of livestock animals:

PT3 veterinary hygiene biocidal products PT4 food and feed area disinfectants PT5 drinking water disinfectantsPT6 in-can preservatives (e.g. for inks and adhesives used in packaging of feedstuffs) PT7 film preservatives (e.g. migration to feedstuffs from plastic packaging or plastic coated paper)PT8 wood preservativesPT9 fibre, leather, rubber and polymerised materials preservatives (migration to feedstuffs

from paper, textile or polymerised packaging material)T11 preservatives for liquid cooling and processing systems (migration to feedstuffs from

preservatives used in process water or dosing systems for additives for paper/cardboard industry or process water in feed industry)

PT12 slimicides (used on wood/paper pulp for use as packaging of feedstuffs)PT18 insecticides, acaricides etc.PT19 repellantsrepellents and attractants

48

Author, 01/03/-1,

This is different to what is earlier in the document. NL: not clear what is meant by the comment. Text has not been amended. To be discussed at TM before amendment is to be made

Author, 01/03/-1,

Discussions should included all relevant stakeholders. NL: CEFIC will be present in the technical meeting.

Author, 01/03/-1,

We still conclude that misuse scenarios are outside the methodology of quantitative risk assessment as it is not possible to set reasonable worst case scenario parameters. NL: We do not agree with the comments. Text has not been amended


PT20 preservatives for food and feedstockPT21 antifouling products

For these PTs in particular, the possibility of livestock exposure must be considered and be addressed, either by an exposure assessment or a waiver. Other PTs are unlikely to lead to livestock exposure, but this should nonetheless has to be considered on a case-by-case basis.

Concerning all dietary exposure assessment, the evaluation manual is mainly focused mainly on livestock exposure assessment. Currently, the only available draft proposal guidance is indeed related to livestock exposure assessment to biocidal active substance. However, as previously mentioned, in the first sentences other food or feed products can also be contaminated after biocidal product treatment and this point could be further elaboratedmore developed in the evaluation manual, even whileif guidance documents are still in preparation. The DRAWG has been mandated to work first on the livestock exposure assessment and is now working on estimating residues in foods exposed to biocidal active substances. When biocides are applied directly on animals or in their surroundings surrounding the animal health and welfare has to be considered. A risk assessment for of animals is may be necessaryneeded (this can be relevant for PT 3 and PT 18). This is not always done in the CAR but left to the product authorizationauthorisation level (see § 1.10 Manual of Technical Agreements*).

6.2.1 Sources of information for exposure calculationsThe TNsG on human exposure elaborate the general principles for drawing up exposure estimates. Whether the new TNsG or the previous version should be used is described in the HEEG opinion “Harmonising the use of new and old version of the TNsG on human exposure (included hyperlinks to the different versions) endorsed in TM I 2008 and TM IV 08 and agreed at the 32nd CA meeting, February 2009 (see §4.2.9.6 of Manual of Technical Agreements*).

Where monitoring data under field conditions (i.e. (representative) conditions of use) are lacking, exposure is first estimated by means of models. Initially, exposure is estimated with generic exposure models. If required, more specific models or approaches are used. Besides generic exposure models, the TNsG on Human Exposure also describes more specific models or approaches (mathematical). Computer exposure models based on digital databasescomputerised database of exposure data are described in the TNsG on human exposure. For many uses of different product groups, however, suitable models are lacking or an EU-wide agreement regardingabout a suitable model has not yet been reached.

Pending further research or an EU agreement, an exposure estimate is drawn up for these uses in the different Member States, based on expert judgement, and, where appropriate, on the basis of literature data, or monitoring data and/or other information from of the applicant.

As a general rule, averaging of exposures will not be attempted unless there is sufficient justification (agreement TMIII 2007, see §4.2.1Manual of Technical Agreements*). It should be noted that in ConsExpoConsexpo the chronic exposure is defined as yearly average dose, which would not accurately describe a situation where exposure occurs infrequentlyseldom or sporadically (agreement TM IV 2009, see §4.2.1Manual of Technical Agreements*).

Initially, exposure is estimated for the unprotected operator/worker in normal working clothes. In a later phase of the evaluation, where necessary, the effect of protective measures is

49

Author, 01/03/-1,

Format is different to the rest of the document. NL: amended


taken into account. However, if wearing personal protection equipment would be the only way to restrict exposure for the non-professional user, the product will normally not be authorised (Annex VI Common Principles for evaluation of biocides dossiers, Decision making, Effects on humans 73, Biocides Directive 98/8/EC) (see §6.4.1 of this chapter).

The Human Exposure Expert Group (HEEG) was established in TMV 2007. The group consists of experts nominated by MS CAs, and works mainly by e-consultation and e-mail discussions. It addressesdiscusses issues that arise during discussions of CARs, as well as issues on methodology and the needneeds for update of guidance document updates.documents. The expert group does not make decisions, but produces opinions and proposals which are brought to the TM for endorsement. Members of the HEEG are appointed by the MS CAs and can inform the Commission of a new member by sending an e-mail to [email protected]. The list of current members and the coordinator is available on CIRCA: http://circa.europa.eu/ (Library/Human Health Related Issues/Human Exposure Expert Group/List of Members*).

For several situations additional HEEG opinions* or opinions from other sources on primary exposure situations are available (see also chapter 4 Manual of Technical Agreements*), a.o.:

For models to be used in the exposure assessment for operators during the loading of products into vessels or systems in industrial scale the HEEG opinion endorsed in TM I 2008 is available (HEEG opinion on mixing and loading model 7 alternatives*).

For the use of ConsExpo to assess professional exposure the HEEG opinion endorsed in TM II 2008 is available (HEEG opinion on the use of CONSEXPO for the exposure assessment for professional users*).

PT6: For paints containing in-can preservatives the application of the paint (containing biocide) will be assessed as primary exposure (agreed at TM II 2007 Manual of Technical Agreements*). Exposure during production of an intermediate product was agreed to be considered equivalent to manufacture/formulation (agreed at TM II 2008 see §4.2.4 Manual of Technical Agreements*).

PT8: A wood density of 0.4 g/cm3 will be used as a worst case scenario (agreed at TMI III 2008, see §4.2.5 Manual of Technical Agreements*).

PT8: Defaults and appropriate models to assess human exposure for dipping processes (PT 8) are described in the HEEG opinion (agreed at TM III 2009) (PT08 (wood preservatives): HEEG opinion on defaults and appropriate models to assess human exposure for dipping processes*).

PT13: Specific guidance for the exposure assessment of metalworking fluids is available in the HEEG opinion endorsed in TM III 2008 (see for specific hyperlink §4.2.6 Manual of Technical Agreements*)

PT14: The source for the values to be used for anticoagulant rodenticides for the daily number of manipulations is the company survey document provided by CEFIC. This document is available on Circa: (see Manual of Technical Agreements*). AAn HEEG opinion is in development in which the number of manipulations are

50

Author, 01/03/-1,

Is this necessary for inclusion here? NL: not really. Will be deleted


harmonised for the assessment of rodenticides. As this HEEG opinion is based on data that are protected a Member State can only carry out the assessment using this data if a letter of access has been received from the applicant.

PT21: For Antifouling the Antifouling painting model – Amendment of TNsG on Human exposure to biocidal products is available. This is a HEEG Opinion agreed at TM II 08 (Corrigendum TNsG on human exposure (2007): PT21 (Antifoulings)*).

There is no limit to the number of possible secondary exposure scenarios. The relevant forms of secondary exposure per application are therefore considered on a case-by-case basis. The TNsG on human exposure* contains various examples of exposure estimates for secondary exposure.

The specific models, approaches (mathematical) and agreements have been elaborated in the TNsG on human exposure. For several situations additional HEEG opinions or opinions from other sources on secondary exposure situations are available (see Manual of Technical Agreements*) a.o.:

For PT 2, 3 and 4 the HEEG opinion on the assessment of secondary exposure from a treated surface has been endorsed in TM I 2009 (PT02, 03, 04: HEEG opinion on choice of secondary exposure parameters*).

PT14: The exposure assessment takes into account the possibility of children handling dead rodents is considered unrealistic where oral baits have been used. This was the conclusion of the anti-coagulant expert meeting of May 18th 2006 (TM II 2006, see §4.2.7 Manual of Technical Agreements*).

PT14: The TM III 2008 discussed “mouthing of poison bait” and the exposure scenario is described in the Manual of Technical Agreements*(see §4.2.7). The term “transient mouthing” is not recommended any more. Instead, the scenario should be called “Mouthing of poison bait - an exceptional scenario”. This scenario concerns the situation where an infant manages to access a bait block, despite the preventive measures taken, and then licks the block, or ingests a piece of the block. Exposure is thus acute and is expected to occur only exceptionally. In this scenario, licking of the hands can be disregarded as this would be a marginal addition to the mouthing exposure.

Dietary exposure Currently, no validated models exist to estimate the magnitude of residues in food resulting from the use of biocidal products. Upon request of the Biocides Technical Meeting, the working group DRAWG (Dietary Risk Assessment Working Group) was formed in May of 2009 in order to develop such guidance (available on circa). The DRAWG will focus its efforts on the external exposure1 assessment of livestock animals. The subsequent internal exposure assessment of livestock animals will be dealt with by a joint working group composed of experts from the veterinary medicines and the biocides field (CVMP-BTM (Committee for Medicinal Products for Veterinary Use - Biocides Technical Meeting) Working Group).

1 “External exposure” refers to the amount of substance that (i) falls on the livestock animal’s body surface but is not adjusted for factors such as dermal absorption;(ii) enters the nose, mouth and throat and is available for ingestion, but is not adjusted for factors such as oral absorption or breakdown in the digestive system of the livestock animal;(iii) which enters the livestock animal’s lungs via the nose or mouth, but is not adjusted for factors such as absorption via the livestock animal’s inhalatory system.

51

Author, 01/03/-1,

DRAWG was discussed earlier therefore do you need to explain all this here? NL: amended

Author, 01/03/-1,

? NL: amongst others


The DRAWG has collected from all EU member states livestock external exposure estimates performed as part of EU-wide biocidal active substance evaluations from all EU member states. These estimates were evaluated in order to compile available tools, identify gaps and define external exposure scenarios. The results of these evaluations are the basis of the step-wise approach. In the step-wise approach, exposure estimates are performed successively in different tiers. If a pre-defined threshold of concern (trigger = 0.004 mg a.s./kg bw/d) is exceeded, exposure estimation moves to the next tier. If the trigger is not exceeded, no significant residues are expected in food of animal origin and dietary risk assessment is stopped unless the substance is exceptionally toxic, see below. Methodological tools for assessment Step 1 (initial external exposure estimation) and principles for assessment Step 2 (refined external exposure estimation) are explained in the guidance document “DRAWG Draft Proposal Guidance on estimating livestock exposure to biocidal active substances”. Assessment Steps 1 and 2 are limited to estimating external exposure, i.e. factors such as absorption and elimination are not taken into consideration at this stage. A document detailing how to proceed beyond external exposure estimation is currently under development by the CVMP-BTM Working Group (see also §6.4.1 of this chapter).

In a second project DRAWG is currently developing guidance for biocidal residue assessment of directly exposed foods.

Specific guidance documents for the evaluation of food and feedingstuff studies are currently not available for biocides. As similar studies are being evaluated within the regulatory frameworks of veterinary drugs and pesticides, guidance documents from these fields should be consulted if applicable:

o http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/ general_content_000384.jsp&murl=menus/regulations/regulations.jsp&mid=WC0b01ac058002dd37#ResiduesWithdrawalperiods

o http://ec.europa.eu/food/plant/protection/resources/ publications_en.htm#council

o http://www.oecd.org/document/ 41/0,3746,en_2649_34383_42409449_1_1_1_1,00.html

6.3 Effect assessmentThe use of biocides may result in human exposure. It is therefore important that the intrinsic human toxicological properties of each requested active substance and product need to be evaluated and established. According to Annex IIA and IIIA of Directive 98/8/EC information has to be available about the toxic effects and kinetics of aan active substance, mainly based on the results of experimental toxicological research carried out with different test animal species. Besides toxicity data on the active substance, study data on transformation products, as well as on substances of concern, e.g. formulants and impurities (guidance in development) detected in e.g. soil, plants or water , may also be required if human exposure to such transformation products occurs, and is if not already covered/addressed by available toxicokinetic/metabolism data. According to Annex II B and IIIB of Directive 98/8/EC information has to be submitted covering the following toxicological endpoints of the product: acute oral toxicity, acute dermal toxicity, acute inhalation toxicity, skin and eye irritation, skin sensitisation, and information on dermal absorption.

Effect assessment productInformation on toxicological endpoints according to Annex II B and IIIB of the Directive 98/8/EC might be submitted as:

52

Author, 01/03/-1,

Should this chapter not be before the exposure assessment within this document? Realistically the exposure assessment can’t be started until the effects assessment has been completed. NL: The risk assessment cannot be started before the effect- and exposure assessment. The exposure assessment is important for the effect assessment, because it will be very useful to know more about the relevant exposure routes to ask information/ studies or statements regarding toxicity studies (e.g. if there is no exposure by inhalation no inhalation studies are necessary).

Author, 01/03/-1,

In general this section appears to be well written and offer some clarity. NL: thank you

http://www.oecd.org/document/41/0,3746,en_2649_34383_42409449_1_1_1_1,00.html


http://ec.europa.eu/food/plant/protection/resources/publications_en.htm#council

http://ec.europa.eu/food/plant/protection/resources/publications_en.htm#council

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000384.jsp&murl=menus/regulations/regulations.jsp&mid=WC0b01ac058002dd37#ResiduesWithdrawalperiods




Acute toxicity tests with the biocidal product (applied if adverse health effects of the active substance might be increased by other components of the biocidal product, e.g. due to an elevated dermal absorption owing to a change in lipophilicity or if additive or synergistic effects are likely to occur between some ingredients).

Justification for non-submission of toxicological studies with the biocidal product (as technically not possible to perform, limited/negligible exposure and toxicity, no increased adverse health effects (see first bullet) or read-across).

Waiving based on classification by calculation rules based on the justified application of Directive 1999/45/EC and CLP-Regulation (EC) No 1272/2008 (see chapter 9 Classification, Labelling and Packaging). If, according to the applicant information obtained by the calculation method with regard to acute, oral, dermal and inhalatory toxicity, and skin and eye irritation and sensitisation capacity of the formulation obtained by the calculation method is sufficient, the applicant should submit a toxicologically-based justification.

Unlike for active substances and substances of concern, no experimental studies on toxicological endpoints related to repeated dose toxicity, carcinogenicity, mutagenicity, reproductive toxicity (CMR-properties) or neuro- and immunotoxicity are required for the biocidal product itself.

Toxicological data on acute toxicity, irritation and sensitisation must be sufficient for hazard identification to facilitate proper classification and labelling of the biocidal product according to Directives 67/548/EEC and 1999/45/EC (will be replaced by the CLP-Regulation (EC) No 1272/2008) as regards to toxicological properties. Furthermore, these data (as local irritative irritant or corrosive effects) must be used in risk characterisation to demonstrate that the biocidal product has no unacceptable effects on animal or and human health for all intended uses. Based on hazard identification and risk assessment, specific labelling, use restrictions and risk mitigation measures, might be indicated. (see sentence for more clarification, from the document on risk characterisation of local effects in the absence of systemic effects*:“A qualitative RC is performed assuming that the effects leading to classification will also occur in repeated exposure and at lower concentrations/area doses, and the effects will be managed by means of CLP, RMMs and PPE.”

If toxicological data on sensitisation is submitted, the MSs prefers, in accordance with EU requirements, a local lymph node assay (LLNA test) according to OECD guideline 429 or a Guinea Pig Maximisation Test (OECD 406). If a (modified) Buehler test (OECD 406) is performed, a scientific justification must be submitted to explain why this study was chosenis preferred over the other tests. For studies with the biocidal product, a (modified) Buehler test is not simply rejected. The results of the sensitisation study with the active substance and the presence of formulants with sensitising properties are always taken into account (see further appendix A (chapter 6)).

Reduction of test animal use and suffering currently receives much attention. The MSs prefer newly developed studies (if not already covered/addressed by available studies) that are in line with such a regime (see effect assessment active substance for more details). Existing studies carried out some years ago providing they are scientifically valid will of course be accepted.

Dermal absorptionPrimary and secondary exposure may occur via the dermal route. The expected external dermal exposure is calculated by means of models. For calculation of the systemic exposure it is important to know the extent to which the skin absorbs an active substance and/or substances of concern in the biocidal product after exposure to a relevant level. These

53

Author, 01/03/-1,

This statement seems to be contradictory to the purpose of reducing animal testing. Perhaps further explanation could be added here to explain the position of MSs on animal testing and why they would prefer new animal studies to be carried out instead of considering existing studies carried out some years ago providing they are scientifically valid. NL: amended for clarification

Author, 01/03/-1,

Please further clarification on this point and on whether this means that with future risk assessments we need to consider exposure of e.g. pets? NL: see chapter II.e.2.

Author, 01/03/-1,

This is a new point to be considered in the risk assessment. How will these local effects be considered in the risk assessment process if not already considered by the systemic effects? NL: A comprehensible guidance document has to be developed (the last one was not useful and deleted based on TM decision).


dermal absorption data are used to convert the external exposure into systemic exposure. Subsequently, in the risk evaluation the systemic exposure to active substances and/or substances of concern is compared with the respective systemic AEL.Worst-case defaultdDefault values, i.e. 100 % (diluted formulations) or 10 % (concentrate formulations) depending on physico-chemical properties, may be applied for a first worst-case exposure estimate. Dermal absorption testing is only needed in cases where an unacceptable risk was identified in the first tier. In cases, where relevant dermal absorption studies are available, these data can be used in the first tier.Generally it is not possible to reliably estimate the dermal absorption of from a biocidal product without specific studies using that biocidal product. A dermal absorption study of a representative product is not required for Annex I inclusion purposes (information on the dermal absorption is required, but often a, study is not performed and the absorption percentage of the active substance is used for the risk characterisation).Information Although, information on dermal absorption might be extracted from the CAR-Report for Annex I inclusion of the active substance. It is, however, crucial that the nature of the solvent, the type of formulation and the concentration of the active substance (also compared to the conditions of use, such as mixing&loading, application and post-application)) are carefully considered. In some cases It should especially be recognized that a small change in concentration in some cases can have a major influence on the dermal absorption. The extent of dermal absorption is also affected by various factors such as formulants and exposure level (area dose) and is not an intrinsic property of the active substance. The dermal absorption studies described above must be carried out with dose levels that correspond with the primary and secondary exposure expected for applicator and re-entrant.It is important to consider that the worst case (i.e. the highest percentage of dermal absorption) is often represented by a diluted formulation, rather than by the concentrated formulation.The assessment of dermal absorption of the product will be performed at the product authorisation stage, usually utilising with studies with on products rather than the active substance (see §4.1.1 Manual of Technical Agreements*, agreement TMI 2007). Enhanced dermal absorption due to simultaneous application of a product other than the biocidal product in question should also be considered at product authorisation. If information of such interactions is available, it has been included in the CAR under Elements to be taken into account by MSs when authorising products (see §4.1.1 Manual of Technical Agreements*, agreement TMI 2009).

The ‘Guidance document on dermal absorption’ should be followed for dermal absorption (see for specific hyperlink §4.1.1 Manual of Technical Agreements*, agreement TM III 2006). The startingStarting point is a default value of 100% dermal absorption unless a default value of 10% can be used on the basis of physico-chemical properties. If necessary (if dermal exposure is an important exposure route and if the risk evaluation shows that the limit value set on the basis of health considerations is exceeded) an in vitro and/or in vivo dermal absorption study should be carried out to refine the risk evaluation.

Both situations (no suitable versus suitable data) are elucidated below.

If no suitable (animal) experimental data are available, physico-chemical data cangivecan give an indication of the extent of skin penetration. The following applies: at a molecular weight > 500 g/mol and a Log Pow <-1 or >4, a default value of 10% dermal absorption is used; in all other cases 100% is assumed as a worst case. This choice shouldwill be justified in the decision making. If suitable toxicokinetic data via the oral route are available, it can also be assumed that dermal absorption, in the absence of animal experimental data with the relevant route, will not be higher than oral absorption.

54

Author, 01/03/-1,

In use concentrations? NL: yes

Author, 01/03/-1,

This is true but in some cases it doesn’t have an affect and waiving argumenation should always be considered during the evaluation phase. NL: is true. In the text we stated in some cases.

Author, 01/03/-1,

If studies are available why couldn’t they be used in the tier 1 risk assessment? Under what circumstances would it not relevant to do this. NL: The dermal absorption studies can be used in case they are acceptable for the product in question.


In vitro and/or in vivo research with the formulation is required if it is expected that the systemic AEL will be exceeded under application of default values for dermal absorption, and dermal exposure is an important exposure route. In vivo research (usually carried out with the rat) and/or in vitro research (rat versus man), both carried out with a relevant doses, are used for derivation of the dermal absorption for man. In vitro research is carried out with the formulation to study the differences between species (rat/man). The triple pack (combination of in vitro and in vivo rat studies and an in vitro study on viable human skin according to OECD 427 andund 428) is often considered the “gold standard". If no comparison can be made between species because the required research is lacking, the percentage dermal absorption is derived from the in vivo study with the rat. This is in many cases a worst case assumption because the human skin generally forms a better barrier than shavedthe shaven rat skin. For the interpretation of the animal experimental data and the subsequent derivation of dermal absorption we refer to the guidance document (see for specific hyperlink §4.1.1 Manual of Technical Agreements*, agreement TM III 2006). However, in vitro studies on viable human skin according to OECD 428 willshould also be accepted.According to the MSs, unnecessary use of laboratory animals must be avoided. The MSs therefore preferprefers that an in vitro study is performed. The MSs only consider performance of an in vivo study justified if exceeding the AEL is still expected on the basis of the in vitro study.

In TMIII2006 (see §4.1.1 Manual of Technical Agreements*) it there was agreedagreement that there is no valid ‘a general approach’ approach for inclusion or exclusion of the amount of substance retained in the stratum corneum. The cannot be followed. Including all skin levels is the worst-case approach that can be used in the absence of tape stripping data is to include all skin levels. Expert judgment will be needed, taking into account the overall data set, the exposure time, the tape stripping data (if available) and the kinetics of the substance in the receptor fluid. The number of tape strips needed to remove a given fraction of the stratum corneum varies due to a number of variables, and therefore the risk assessment is based on a decision should be made case by case assessment.. It has been suggested that the two first strips would be excluded, and considered as the upper layer of the stratum corneum. This strategy is in line with the EFSA Agreements made in the expert meetings.

In addition to the methodology specifically agreed to by the TM, newer guidance like the Dermal Absorption document of the WHO (Environmental Health Criteria 235, 2006, see the link below), OECD guidance (Draft 22 October 2010: http://www.oecd.org/dataoecd/0/1/46257610.pdf) and REACH guidance should be taken into account.WHO guidance on Dermal Absorption (Environmental Health Criteria 235, 2006) is available at: http://www.who.int/ipcs/publications/ehc/ehc235.pdf (see also Manual of Technical Agreements* for links).

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Author, 01/03/-1,

What does this mean practically for industry? Is a dermal absorption study required for every formulation? MSs should undertand that a dermal absorption study for each product costs 30-60,000€. This requirement could, alone, result in loss of products. NL: Dermal absorption studies are not compulsory as all other studies. Statements or waiving arguments could be used by the applicant.

Author, 01/03/-1,

What happens if MSs take differing views? NL: Could be a discussion at mutual recognition in case it will be a very important issue for product authorisation or not.

http://www.who.int/ipcs/publications/ehc/ehc235.pdf


Use of alternative methodsReduction of test animal use and suffering currently receives much attention. The MSs prefer newly developed studies that are in line with such a regime. However, if , As long as these alternative testshave, however, not yet been included in the applicable OECD and/or EU Directives, a scientificallytoxicologically justified position statement is required along with the submission of if such tests are submitted. Links to OECD testing methods homepage and tracking system for alternative test methods from JRC as well as ICCVAM are:

http://www.oecd.org/department/0,3355,en_2649_34377_1_1_1_1_1,00.html http://tsar.jrc.ec.europa.eu/ http://iccvam.niehs.nih.gov/

Effect assessment active substanceInformation on toxicological endpoints according to Annex IIA and IIIA of the Directive 98/8/EC havehaves to be met. The toxicological endpoints derived from the submitted studiesresearch form the basis of the risk evaluation for human exposure. The product to be authorised and the product to be defended in the CAR could be different biocidal products. Since a human health risk assessment has already been conducted in order to qualify for inclusion in Annex I of 98/8/EC the data requirements for the active substance are already available for the product defended in the CAR, but and there could be some differences in data requirements for the active substance(s) in with the product to be authorised.

In general, the data requirements for the active substance(s) have been elaborated in the TNsG on data requirements*. For several product types addenda are available (see chapter 1 Manual of Technical Agreements*). The basic principle is that the applicant submits all data (toxicological studies) or provides statements/justifications to meet for the data requirements. In certain cases, data requirements may be waived by the non-submission of a study or by read-across or bridging. The applicant must in such cases explicitly justifiy such cases.give justification. More information about waiving is given in the TNsG on data requirements*(§1.4 and corresponding addenda) and the Manual of Technical Agreements*chapter 1.

At the time of submission of the application for product authorisation, the applicant has the obligation to verify thatif the data and the risk assessment submitted for Annex I/IA Inclusion of the active substance arewould also be sufficient for the assessment of all intended uses of the biocidal product(s). Any data requirements laid down in the assessment report as well as in the specific provisions of the Inclusion Directive (in the CAR under Elements to be taken into account by MSs when authorising products) for the relevant active substance shouldneeds to be considered and fulfilled for the national product authorisation.

Further data might be required if the exposure to the active substance resulting from the use(s) of the biocidal product to be authorised is higher or lasts longer than that considered at Annex I Inclusion, if exposure of other sub-populations occurs, or if there are is an additional routes of exposure.

Where justifications for non-submission of studies were submitted for Annex I inclusion, the applicant must has to confirm that the waiving arguments arewould also applicable to be acceptable for all intended uses of the biocidal product to be authorised. This applies in particular if non-submission of data was justified by the assessment of a dummy product or by reasons of a negligible exposure. The specific use conditions at of the intended uses of the product to be authorised should be

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Author, 01/03/-1,

What if an older test is available but it is still valid? What is the justification for undertaking new studies? NL: see A78

http://iccvam.niehs.nih.gov/

http://tsar.jrc.ec.europa.eu/

http://www.oecd.org/department/0,3355,en_2649_34377_1_1_1_1_1,00.html


carefully considered.

According to the TNsG on data requirements* for Active Substances and Biocidal Products “the applicant is responsible to search for data from all sources which he or she may reasonably be expected to have access to”. Generally, this could be achieved by a recent literature search, i.e. not older than one year.

If the applicant surmises supposes that there are reasons for concern for a certain endpoints, in the very-point of a formulant, at least, data for those endpoints must be submitted. for that end-point data are needed. These requirements are further explained in chapter 4.3 of the TNsG on data requirements* for Active Substances and Biocidal Products. Access to these data could be gained by performing a recent literature search, i.e. not older than one year, and searchingto search databases such as for example IUCLID.

Whether the List of end points (LOEP) cancould be used for the specific product authorisation depends on the intended use defended in the CAR as compared to the intended use for the product authorisation. The physical state, the exposure pathway, the exposed group, and the time frame of exposure are important parameters to be taken into account. An indication of studies (based on the TNsG on data requirements*) that could be relevant and/or necessary for product authorisation (and not for Annex I Inclusion) is given below:

Acute inhalation toxicity must be reported where the active substance is:

a volatile substance (vapour pressure > 1 x 10-2 Pa at 20 0C),

a powder containing a significant proportion (e.g. >1% on a weight basis) of particles with particle size mass median aerodynamic diameter(MMAD) < 50 micrometersmicrometres or to be included in preparations which are powders or are to be applied in a manner which generates aerosols, particles or droplets in the inhalable size range (MMAD < 50 micrometersmicrometres).

A percutaneous repeated dose study is required, where the potential dermal exposure is significant and route-to-route extrapolation is not possible. However, a percutaneous study may also be necessary where it is clearjustified that the dermal exposure route is more appropriate or, when specific effects of concern are different from the effects seen in the studies utilizing in other exposure routes.

For volatile substances (vapour pressure >1x 10-2 Pa) or in cases where the potential inhalation exposure is significant, an inhalation repeated dose study is required instead of the oral study. In some cases (e.g. aerosols and dusts/particulate matter) studies by the inhalation route mayshould be required in addition to studies utilizingby the oral route.

A combined chronic toxicity/carcinogenicity test is required to derivederivate a long-term AEL/ADI in cases where no chronic limit values were derived for Annex I inclusion.

In general, waiving, read-across and bridging arguments taken into account for Annex I inclusion mayhave to be considered in the national for the intended use for product authorisation, dependent upon the intended use in each case. The applicant must justify the use of the Annex I . It has to be justified that waiving, read-across and/or bridging data for the national could also be used for product authorisation. If the intended use for the product authorization means that theOtherwise the studies for which waiving, read-across orand bridging used in the Annex I inclusion are no longernot valid, those studies must be

57

Author, 01/03/-1,

Also that the applicant has access to the underlying data supporting these endpoints. NL: We agree

Author, 01/03/-1,

Some information in databases is not available to industry due to data protection and access issues. NL: We agree

Author, 01/03/-1,

This is not just relevant to toxicology, why isn’t this in the general section at the beginning. NL: In the next version of the EvalMan, after its endorsement, a general section on this will be included.


any more have to be made available or performed or otherwise made available for the national authorization.

The human health effects assessment comprises the following steps of the risk assessment procedure:

Hazard Identification: the aim of the hazard identification is to identify the effects of concern.

Dose (concentration) – response (effect) assessment: at this step the relevant no observed adverse effect level (NOAEL), shall, where possible, be determined.

Assessment of the relevant thresholds as (local)AEL, ADI and ARfD

The AEL is defined as the maximum amount of a substance to which the human population as a whole can be exposed (intake by food not included) at which no adverse effects on health are expected. Where relevant (According to TNsG on Annex I inclusion, chapter 4.1: Quantitative risk characterisation, “AELs should be established for all relevant time-frames of exposure (acute, medium-term and long-term)”, different AELs can be determined for acute, medium-term (semi-chronic/short) or long-term (chronic) exposure. Both systemic as well as local AELs can be relevant. The ADI (acceptable daily intake) is defined as the estimated amount of active substance, expressed in mg per kg body weight per day; the amount to which man a human can life-long be exposed daily without adverse health risk. The ARfD (Acute Reference Dose) is defined as the estimated amount of active substance in food or drinking water, expressed in mg per kg body weight per day; to which a human can be exposedthe amount man can be exposed during a single meal or singlea day without adverse health risk for the consumer. ADI and ARfD are external values (systemic AELs are internal values). The values are compared to external values based on dietary intake calculations.

The choice of the NOAEL as starting point for the (local)AEL and MOE derivation or ARfD or ADI derivation depends on the total package of available toxicity studies and the mutual relationships in dose regimes. The most suitable NOAEL on which the (local) AEL, ARfD or ADI is based should be selected on a case-by-case basis, for which expert judgement is required.

Besides duration and frequency of exposure, the choice of the most relevant study can also be determined by the excretion rate of the active substance and its metabolites, and by the degree to which and rate at which the effects that may be caused by exposure to a substance are reversible.The most relevant studies are selected from the dossier on the basis of these considerations. This The selection must be justified in the decision making.The study with the most relevant NOAEL, obtained with the most relevant test animal, is selected. This isdoes not necessarily always have to be the lowest NOAEL found in the most sensitive test animal. Instructions for the evaluation of toxicity studies are given in several EU documents . Studies are evaluated by using criteria therein, and this . This evaluation leads to a toxicologically based endpoint for each study and for each sub-aspect to a toxicologically based endpoint, and finally to the toxicological profile of a substance (often by using assessment factors). Various EU documents that are relevant for derivation of a toxicological profile of a substance are given below:.

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Author, 01/03/-1,

This information is in the document earlier. Is it necessary to repeat again? NL: amended


TGD: Part I* (General introduction on risk assessment for human health)

TNsG on Annex I inclusion*, chapter 4.1 Quantitative Risk Characterisation (see specific hyperlink in Manual of Technical Agreements*) and Working document on risk characterisation of local effects in the absence of systemic effects*

TNsG on product evaluation*

Specific effects as dental fluorosis or methaemoglobinemia in Manual of Technical Agreements*,

The normal procedure is to use the threshold as AEL, ADI and ARfD already set in the CAR. However, Although in principle whether similar NOAELs for AEL and MOE derivation could be used for the risk assessment for product authorisation as for the risk assessment for the intended use in the CAR depends on the differences in the exposure scenarios based on different patterns ofon use mean that this is not always the case. Additional limit values could be necessary. For example additional limit values could be necessary if no chronic limit values were derived for Annex I inclusion (see effect assessment active substance). Thus,So in exceptional cases new thresholds have to be derived.

Similarly,Also whether the samesimilar assessment factors can be used for the risk assessment for product authorisation as for the risk assessment for the intended use in the CAR depends on whether there are the differences in the respective risk indices. In cases where the risk index will be > 1, refinement of the risk characterisation could be necessary by allometric scaling could be necessary. Ergo in this case other. Other assessment factors (not 10x10) could be used by allometric scaling.

AIn principle, a limit approach cannot be applied and no AEL, or ADI or ARfD can be derived for substances of mutagenicity category 1 and 2, and substances of carcinogenicity category 1 and 2 (see 67/548/EEC for the classification). Deviation from this is only possible if there is convincing evidence for the existence of a limit value for this effect. This is not possible, as the BPD Article 5 (2) clearly indicates that CMR substances cannot be authorised for marketing to the general public or for use by the general public (taking into account the concentration limits) (agreement TMIII 2007).

Any available suitable human data are taken into consideration and may be submitted used to support test animal data. These data may originate from humans exposed during production or application of pesticides or from volunteer studies conducted under ethical criteria (Helsinki Convention 1971), e.g. forinto dermal absorption. However, quality criteria are have to be applied to human data, just as they are for as for the animal data. Poor quality studies on humans should not be used for the risk assessment. When there are no In case human studies data are not available, newhowever, it is not desirable to conduct human studies should NOT be conducted.

6.4 Risk characterisationDirective 98/8/EC requires a risk assessment of biocides before these can be authorised for the European market. Human risk assessment entails testing of the burdening considered acceptable from a health point of view against the estimated or measured exposure.

According to the Directive of the European Parliament and the Council of 16 February 1998 concerning the placement of biocides placing on the market of biocides (98/8/EC) at the time

59


of authorisation it should be ensured that they are sufficiently effective investigated when biocidal products are being authorised, to make sure that, when properly used appropriately and for the purpose intended purpose, and that they , they are sufficiently effective and have, in the light of current scientific and technical knowledge, no unacceptable effects effect on human health, based on currently available knowledge (preamble or recital or clause 8). An unacceptable effect is in principle determined by the risk index. Where the risk index > 1 or the MOE is insufficiently high, an unacceptable effect may exist. Any; exposure then exceeds the acceptable limit value based on the relevant toxicological properties of the substance.

Article 5. 1 (b) (iii) stipulates that Member States only authorise a biocide if this product

(iii) has no unacceptable effects itself or as a result of its residues, on human or animal health, directly or indirectly (e.g. through drinking, food or feed, indoor air or consequences in the place of work) or on surface water and groundwater,”

Article 5. 2 stipulates that “A biocidal product classified according to Article 20(1) as toxic, very toxic or as a category 1 or 2 carcinogen, or as a category 1 or 2 mutagen or classified as toxic for reproduction category 1 or 2, shall not be authorised for marketing to, or use by the general public.”

Starting points for evaluation and decision making as regards the effects on humans are presented in the Common Principles (Annex VI to 98/8/EC). The Manual of Technical Agreements* includes usefulluseful information focussed on methodological decisions with respect to risk assessment from discussions on evaluations of active substances during the technicalTechnical meeting, focussing on methodological decisions with respect to risk assessment..

6.4.1 Tiered approach

The risk characterisation is often based on a tiered approach as described below. In addition,. Although in some cases also a reverse reference scenario will be helpfullhelpful.

Risk assessment refinement based on AEL approachThe tiered approach of the risk characterisation is described in Ch 4.1.TNsG on Annex I inclusion (4.1.10 see specific hyperlink in §4.3 Manual of Technical Agreements*). In this chapter several refinement situations, such as allometric scaling, new dermal absorption data, route specific mitigation measures (as PPE) are described, with no evident preference for one refinement method are described. The exposure assessment refinement is described in the TNsG on human exposure*. A so-called tiered exposure estimation (TNsG Human Exposure) is applied in the risk assessment, where it is common to conduct the first exposure estimation by means of model calculations based on realistic “worst case” assumptions and the use of default values. If this risk assessment based on these “worst case” assumptions results in “no risk”, the risk assessment for the human population in question can be completed and a further refinement of the exposure estimate is not required. Where the initial estimate leads to a potential risk, the exposure estimate must be refined..The exposure estimate must on the other hand be refined where the outcome leads to a risk of a biocide. This refinement will then be based on expert judgement while using additional data and/or reasonable arguments. This tiered approach is a logical risk assessment step process which optimally utilizes the available information in orderwill lead to reducea risk assessment with optimal use of the available information and to a reduction of unnecessary requirements (such as regards human exposure data or studies). The three tiers of the tiered exposure estimation in the risk

60


assessment are described below.

Tier 1 ScreeningThe screening step in the exposure estimation must be kept simple. The startingStarting point is a worst case exposure based on the highest value in an exposure study, or an indicative value based on a generic model, or a worst- case value based on a mathematical model. Tier 1 estimates must be based on realistic worst-case time budget information (such as frequency and duration of use). Exposure-reducing measures, such as personal protection equipment aredo not need to be taken into account. Where available, however, data on dermal absorption, however, are used to determine systemic exposure.

A refined exposure estimate is required if this exposure estimate leads to an unacceptable risk.

Tier 2 Realistic exposure estimateThis step in the exposure estimation process is more complex and requires more specific data and/or reasonable arguments for drawing up a refined exposure estimate. The exposure studies/models are used in the same manner as in tier 1, however specific. Specific data regarding frequency and duration of application, dermal absorption and the effects of personal protection measures are used to adjust the exposure estimate. The However, the limited use of personal protection equipment by consumers must be taken into account. The possibilities of exposure-reducing measures are discussed in the TNsG on Human Exposure (Part 2.2.3). Surrogate exposure values with PPE are available in most models. Potential hand exposure can be calculated from actual measured exposure data (see agreement TM I 2008 in §4.2.9.2 Manual of Technical Agreements*). Default values for PPE can be used in other cases. At the TMI 2010 an HEEG proposal forwas agreed on default protection factors for protective clothing and gloves was agreed upon (see §4.2.9.9 specific hyperlink in Manual of Technical Agreements*).

This step takes into accountFor secondary exposure it is investigated whether or not protective measures can be prescripted.prescribed. In principle, if there is no safe use for the non-professional user without PPE the product cannot be authorised. The proper use of suitable protective clothing for non-professional use is the personal responsibility of the non-professional operator. The Common Principles distinguish between exposure of non-professional users and professional users (primary exposure): It); it is directly stated that if, apart from protection by normal (work) clothing for non-professional users wearing PPE would be the only way to restrict exposure, the product should not normally be authorised for non-professional use. In effect this . This means that, for non-professional uses, as indicated in the TNsG on Human Exposure (2002)* (Part 2.2.3), the effect of PPE in the risk assessment is not taken into account in the risk assessment.

It is clear therefore thatFor product authorisation the tiered approach discourageshas an evident purpose to diminish the prescribed use of PPE in refining the risk assessment, since a non-by professional use cannot be authorized if PPE is necessary.users. Therefore, MSs prefer to first use the allometric extrapolation to refine the risk assessment, then request before asking new dermal absorption data for further refinement. PPE will be included used as a last resort (i.e. only if no other further refinement is possible). Available. To diminish the use of PPE also available exposure data based on actual use canuse in practice could be used (as in tier 3) to lower the need to use PPE in this refinement step.

A further refined exposure estimate is required if this exposure estimate leads to an

61

Author, 01/03/-1,

Repetition from earlier NL: considered necessary for clarity

http://tcsweb3.jrc.it/documents/Biocides/TECHNICAL_NOTES_FOR_GUIDANCE/TNsG_ON_HUMAN_EXPOSURE/TNsG%20-Human-Exposure-2007.pdf


unacceptable risk.

Tier 3 Exposure studies under representative field conditionsThe most detailed level of risk estimation requires human exposure data or studies with the actual product or with a surrogate. The exposure studies must be carried out under representative field conditions, where appropriate with biological monitoring or using external dosimeter dosimeters for monitoring where respectively appropriate. When. Where no monitoring is included in the exposure study, this study only leads to a refined exposure estimate if the setup of the exposure study yields more representative exposure values than a generic/mathematical model. Exposure studies must be carried out in compliance with the OECD guidelines (Organisation for Economic Co-operation and Development). Biological monitoring must be carried out in compliance with the Helsinki Declaration (Helsinki Convention1971).

Where the exposure would still exceed the AEL, the product cannot be authorised.

For several specific situations influencing the exposure assessment and/or the risk assessment agreements are available (see §4.4 Manual of Technical Agreements*).

Paper RISK MITIGATION MEASURES FOR ANTICOAGULANTS USED AS RODENTICIDES (ENV B.3/PC D(2007) - 21/03/2007) discussed at CA-March 07-Doc.6.3 final revised after 25th CA meeting.

Application by spraying is allowed for non-professionals if exposure assessment and risk characterisation reveal no risk for the non-professionals. PPE required for safe use by non-professionals will not be allowed. (TM II 2007).

Risk assessment refinement based on ADI/ARfD approachThe adapted version of chapter 4.1 of the TNsG on Annex I Inclusion (4.1.9, see hyperlink in §4.3 Manual of Technical Agreements*) described the dietary risk assessment approach. A draft Guideline on Risk characterisation and Assessment of Maximum Residue Limits (MRL) for Biocides) has been developed

European legislation specifies that biocidal products containing active substances that, as a result of their use, may lead to residues in food, shall only be authorised if these residues do not have unacceptable effects on human health and that, where appropriate, an ADI and MRL should be established. The legislation further states that the European Medicines Agency is the body responsible for performing MRL evaluations for active substances used in biocidal products for use in animal husbandry (regulation 470/2009).

Where it is likely considered that residues of biocidal products used in animal husbandry might have the potential to lead to consumer health concerns a consumer safety evaluation must be undertaken with, where appropriate, the derivation of maximum residue limits (MRLs). National Competent Authorities use a step-wise procedure to determine whether an MRL assessment is required for a biocidal substance used in animal husbandry. The procedure uses a threshold concept for external exposure of food producing animals to identify those substances for which an MRL evaluation is needed and allows refinement of the external exposure estimate based on relevant data. If the estimated external exposure of a food producing animal to the active substance and/or its toxic degradation products and/or any substance of concern contained in the biocidal product exceeds the trigger value (of 4 µg/kg bw), this is interpreted as indicating a possible consumer risk from of residues and triggers a request for a formal MRL procedure. If, on the other hand, the external exposure is below the trigger value then, in most cases, there will be no need for an MRL evaluation. However, all

62


hazard endpoints need to be carefully considered in making this decision, and if the substance presents a particular concern, then the trigger value of 4 μg/kg bw/day for external exposure of the animal is not considered sufficiently protective and consequently an MRL evaluation would still need to be undertaken. Substances considered to induce non-threshold toxicity effects (either directly or indirectly via metabolites) such as genotoxicity canshould not be used in biocidal products for use in animal husbandry.In those cases where it is determined that an MRL evaluation is required, the responsibility for undertaking the MRL evaluation falls to the European Medicines Agency’s Committee for Medicinal Products for Veterinary Use (CVMP). The CVMP also uses a stepwise procedure in its evaluation. A final ADI or equivalent health based reference value covering all relevant endpoints is required for this evaluation, which compares the estimated worst case consumer exposure to the ADI. Where appropriate data are available it may be possible to use these to refine the initial estimate of consumer exposure. If the estimated exposure is below the ADI then the CVMP will conclude that there is no need to establish specific MRLs for the substance. If, on the other hand, consumer exposure may exceed the ADI, then residue data are needed and specific MRL values willmay be established. Whether MRL values are necessary for enforcement depends on the outcome of discussions in the DRAWG and CVMP (and ultimately the decision on this subject in the CA-meeting). This paragraph will be adapted accordingly, if necessary. The stepwise approach aims to minimise the number of cases in which a full set of residue data will be required. The amountlevel of data required will mainly depend on the type and quantity of the potential residues, and their relation to the established exposure limit (i.e., ADI).

For biocides with uses that lead to exposure of foods (of plant and animal origin), guidance on exposure assessment is currently being developed by the DRAWG. The relevant body for MRL setting is likely to be EFSA. The principles for MRL setting should be similar to those outlined above, and the approaches will probablyapproach should have much in common. Guidance will be made available either in separate documents or by extension of the documents on biocides used in animal husbandry.

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Author, 01/03/-1,

How much? What type? MRL information – how is data protection handled? How is it relvant to other member states? NL: will be described in a next version of the evaluation manual based on new DRAWG documents.

Author, 01/03/-1,

There are a lot of words here but very little useful inforamtion. Could it be made shorter? NL: amended


6.4.2 Risk reduction measuresThe applicant is responsible for implementing risk mitigation measures (RMM). Therefore, the RMM are not included in the evaluation manual. Germany will make a list of safety instruction phrases and will check how this list relates to CLP (see chapter 9). A harmonised approach to acceptable RMM especially for private users as well as professional users will be prepared by UK and DE.

Measures (to be adapted after agreement between UK and DE.) proposed by the applicant must: Measures* proposed by the applicant have to 1. beprefer technical and/or organisational measures. PPE should not be a permanent

measure (Dir. 98/24/EC), and should not be applied by non-professional users,2. include ventilation rate and the way to achieve it if “sufficient ventilation” or similar is

requested. 3. name the standards to be applied for PPE as well as a. the type of protective coverall (type 1 - 6 according EN 13034, 13982-1, 14605 or

934)b. the material, thickness and level of protective gloves, c. type of respiratory equipment (e.g. mask and filter or self containedself-contained

breathing apparatus according EN 529) 4. be included on the label (according art.20 (3) j BPD), 5. be included in the Safety Data Sheet, chapter 8 (according art.31 of Reach

Regulation No. 1907/2006), 6. include a hint on a relatedan according Control Guidance Sheet incl. source (e.g.

http://www.oehc.uchc.edu/news/Control_Guidance_Factsheets.pdf and http://www.coshh-essentials.org.uk/assets/live/CETB.pdf)” if existent (if so: vernacular version).

* be adapted after agreement between UK and DE..

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Author, 01/03/-1,

What is the link between this sentence and the following? The wording does not seem quite correct. NL: the measures have to be based on the agreements summarised.

Author, 01/03/-1,

When available? NL: still under development by MS


Appendix A (chapter 6):

If toxicological data on sensitisation is submitted, the MSs prefers, in accordance with EU requirements, a local lymph node assay (LLNA test) according to OECD guideline 429 or a Guinea Pig Maximisation Test (OECD 406). If a (modified) Buehler test (OECD 406) is performed, a scientific justification must be submitted to explain why this study is preferred over the other tests. For studies with the biocidal product, a (modified) Buehler test is not simply rejected. The results of the sensitisation study with the active substance and the presence of formulants with sensitising properties are always taken into account. AFor clarification, a number of situations clarifying the type of toxicological data on sensitisation that is needed/used in risk assessment are described:

Where the maximisation study with the active substance is negative and the formulation contains no formulants with sensitising properties, the MSs will accept a well performed (modified) Buehler test.

Where the maximisation study with the active substance is negative but the formulation contains formulants with sensitising properties, the MSs will use mathematical methods based on Directive 1999/45/EC and CLP-Regulation (EC) No 1272/2008 (see chapter 9 Classification, Labelling and Packaging) to decide on labelling, instead of accepting a negative results from a (modified) Buehler test with the biocidal product. If available, the outcome of the calculation can be overruled by the results of an LLNA or maximisation study with the biocidal product.

Where the maximisation study with the active substance is positive, the MSs will use the calculation rules to decide on labelling based on Directive 1999/45/EC and CLP-Regulation (EC) No 1272/2008 (see chapter 9 Classification, Labelling and Packaging) , instead of accepting a negative results from a (modified) Buehler test with the biocidal product. If available, the outcome of the calculation can be overruled by the results of an LLNA or maximisation study with the biocidal product.

Where a (modified) Buehler test with the formulation is clearly positive, such a study is in principle acceptable and performance of an LLNA or maximisation study is not required. However, section 3.4.3.3.2. in Guidance on the Application of the CLP criteria should be considered.

Reduction of test animal use and suffering currently receives much attention. The MSs prefer newly developed studies that are in line with such a regime (see effect assessment active substance for more details).

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Author, 01/03/-1,

Needed in the Appendix when in the main body of the text? NL: amended

Author, 01/03/-1,

Is this needed again as it is written in the text. NL: amended

Author, 01/03/-1,

Should the appendicies not be linked into the main body of the text? NL: amended


Appendix B (chapter 6):

Examples regarding data requirements for specific product typesThe following chapter gives examples ofexemplifies data requirements for specific product types and will be updated continuously. For the time being, it covers PT 08 (wood preservatives) and PT 14 (rodenticides) as these are the first product types to be authorised on a national level.

B.1 Data requirements for wood preservatives The general data requirements mentioned above are in general sufficient for wood preservatives.

It is expected that read-across will be of special importance for this product type. As regards the toxicological assessment, Readread-across might be considered in the following cases:

Lowering of the concentration of active substances.

Changes in concentrationsConcentrations of formulants may be changed, as long as they do not reach a certain limit, which would require an additional classification and labelling or which would lead to an increased risk due to synergistic effects.

o The concentration limits laid down in Art. 6 (4) of Directive 1999/45/EC for re-assessment of human health risk may be applied until further notice.

Replacements of pigmentsA pigment may be replaced so that several colour versions of a wood preservative can be authorised. The applicant has to submit the precise composition of each colour version.

Data on primary exposure towards wood preservatives can be found in the TNsG on Human Exposure (2002 and 2008). Moreover, CA reports often contain exposure estimates, which might also be applicable to other wood preservatives.

Data on secondary exposure towards wood preservatives can be found in former versions of the TNsG on Human Exposure, if the current version does not contain respective information.

Wood preservatives intended for non-professional use are normally liquid ready-to-use preparations, which are applied via painting.

Typical examples for relevant secondary exposure scenarios for professionals and the general public might be related to:

Inhalation exposure after sanding of treated wood (adults)

Dermal contact with treated surfaces in indoor and outdoor environments

Oral uptake subsequently to dermal exposure (toddlers)

Oral uptake due to suck of treated wood pieces (toddlers)

Inhalation exposure subsequentsubsequently to indoor use, e.g. treatment of window-frames

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Further information can be found in the documents “Potential and actual hand exposure*” and “Dipping cycles*” prepared by the Human Exposure Expert Group (HEEG) and endorsed by the 32nd Competent Authority Meeting and Spraying method of wood preservatives for amateur users, endorsed by the European Commission.

For wood preservatives intended for fumigation, an appropriate exposure estimate shall be submitted for the general public shall be submitted. This estimation should demonstrate the safety outside a certain exclusion area and at re-entering of treated buildings afternext to fumigation.

A list of relevant human exposure scenarios used in PT 8 has been prepared by the European Commission. It includes scenarios, which have been used in Competent Authority Reports already submitted for Annex I inclusion.

B.2 Data requirements for rodenticidesThe general data requirements mentioned above are in general sufficient for rodenticides.

This also applies also to waiving concepts. Many rodenticides haveare biocidal products with a simple composition, for which, also for animal welfare reasons, experimental data are not considered necessary.

Data on primary and secondary exposure towards rodenticides can be found in Annex IV of the TNsG on Human Exposure (2008). Moreover, CA reports often contain exposure estimates, which might also be applicable to other rodenticides.

The primary exposure depends on bait (e.g., waxblockwax block, pellet, bait box), the number of manipulation (agreed by TM III/10, see HEEG opinion*), application area (e.g. indoor, outdoor) and pest (e.g. rat, mouse), which need to be considered in the specific exposure estimations. Moreover, exposure estimations should also take into accountcomprise the disposal of remaining baits after use.

Secondary exposure scenarios include the disposal of killed rodents and children’s (unintended) oral uptake of baits.

For rodenticides intended for fumigation, an appropriate exposure estimate shall be submitted for the general public, including bystanders and residents, shall be submitted. This estimation should demonstrate the safety outside a certain exclusion area and at re-entering of treated buildings followingnext to fumigation.

A list of relevant human exposure scenarios used in PT 14 has been prepared by the European Commission. It includes scenarios, which have been used in Competent Authority Reports already submitted for Annex I inclusion.

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Author, 01/03/-1,

Data access and protection issues. NL: see A37


7. Environmental assessmentThis chapter describes the methodology for estimating environmental risk resulting from direct and indirect exposure to biocidal products, for the authorisation of biocidal products based on active substances included in Annex I. The environmental risk assessment includes both the active substance(s) and the substances of concern (see for definition section II.c.2).. A substance of concern is any substance which is not an active substance, but has an intrinsically harmful effect on people, animals or the environment and which is present in a biocidal product in sufficient amounts or which a biocidal product gives rise to such an effect (Article 2, paragraph 1, under Directive 98/8/EC). Currently there is a discussion within the PA&MRFG over what data is required for product authorisation for substances of concern at the PA&MRFG (see start of discussion, the minutes of the meeting in December 2010). We will await the outcome of that the discussion to implement substances of concern into the environmental assessment chapter.

The TNsG on data requirements* states that metabolites formed >10% of the active substance in any environmental compartment, should be identified and their behaviour and (eco)toxicity should be assessed. These major metabolites should be evaluated in the same way as an active substance. In general the data requirements for metabolites are similar to those for its parent substance. Of course, certain data requirements can be waived for the metabolite, just as one they can for an active substance. In additionHowever, risks posed by metabolites canmay sometimes be addressed by conservative default assumptions instead of actual testing, thereby avoidingto avoid unnecessary animal testing. Legislation (Biocides Directive)The BPD stipulates that no authorisation is granted for a biocide if the metabolites pose a risk for non-target species in an aquatic, marine or estuarine environment (water and sediment), or in a terrestrial environment unless it is scientifically demonstrated that there is no unacceptable effect under relevant field conditions. Furthermore, concentrations of metabolites should not exceed the permissible limits for surface water and groundwater extracted for drinking water.

Specific guidance for certain types of chemicals and mixturesSome chemical groups have specific additional guidance. Elaboration on these guidance documents is beyond the scope of this evaluation manual but links are provided:

1. If the chemical is rapidly degrading please use Guidance on effect assessment of rapidly degrading substances*.

2. Ifif the chemical is difficult to test due to its physico-chemical properties, which implies (amongst others) hydrophobic substances, extra guidance is given in OECD aquatic toxicity and difficult substances and mixtures*.

3. Forfor mixtures, use OECD aquatic toxicity and difficult substances and mixtures*.4. Guidance developed within the context of Directive 91/414/EEC i.e.:

General guidance for ecotoxicity: a. Guidance Document on Aquatic Ecotoxicology under Council Directive

91/414/EEC*- b. Guidance Document on Terrestrial Ecotoxicology Under Council Directive

91/414/EEC* - Groundwater modelling guidance documents:

FOCUS groundwater scenarios in the EU review of active substances* Generic guidance for FOCUS groundwater scenarios*

Assessment of degradation studies Guidance Document on Estimating Persistence and Degradation Kinetics from

Environmental Fate Studies on Pesticides in EU Registration*Risk assessment

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Author, 01/03/-1,

How is difficult defined in this context? NL: specification added to the text

Author, 01/03/-1,

Repetition – outlined earlier. NL: definition has been deleted

Author, 01/03/-1,

The PEC is calculated using the TGD and the ESDs. To have some information in this section, but not all, is confusing and could cause the assessment to be done incorrectly. Therefore, we propose that either all information is added into this section on how to calculate the PEC or none of it is added and there is a link only to the relevant sections of the TGD and ESDs. NL: we do not agree with the comment. We propose that this is discussed and implemented in version 2 of the EvalMan after version 1 has been endorsed.


European Guidance Document on Risk Assessment for Birds and Mammals*– working document

EPPO Standards - Environmental risk assessment scheme for plant protectionproductsprotection products*

5. Guidance on the data requirements and risk assessment of substances of concern is given in the TNsG on data requirements*.

A Manual of Technical Agreements (MOTA) for environmental issues has beenis currently developed by the European Commission for environmental issues. This MOTA contains agreements for biocidal substances established at European Technical Meetings (TMs) and should be taken into account when evaluating biocidal substances and products.

To additionally aid the risk assessor, the program EUSES has been developed. EUSES is a decision-support tool which enables the user to calculate the risk for the environment using various data inputs. The TGD as well as finalised emission scenario documents for biocides are included in EUSES 2.1. EUSES* can be downloaded from the ex-ECB website.

7.1 Mixture toxicity(this section is under discussion and, will be revised when an agreement has been reached at the TM -, a concept for the evaluation of mixtures will be developed by the member states)

IntroductionIn the TNsG on product evaluation* the following is stated: ‘’…The BPD requires that the risks from products are assessed. For products consisting of an active substance with a simple diluent, the assessment of the active substance is sufficient to cover the risks from the product. Guidance on the assessment of active substance and other constituents can be found in the TNsG on Annex I inclusion and the Technical Guidance Document on risk assessment [EC 2002]. A different approach is needed for products containing two or more active substances or when the product is a complex formulation (cf. Annex VI Par. 15 and 53 of the Directive). A formulation can also change the properties of the active substance in the environment (fate and behaviour, effects).”

An interaction between multiplethe active substances might result in additive, synergistic or antagonistic effects that would remain unaccounted for if the active substances were only assessed separately. The same situation arises if the product contains a diluent enhancing the bioavailability of the active substance. It could then be argued that it is necessary to test the ecological effects of products towards ecosystems whenever it is apparent that there is an interaction between the components of the product. In However, in general, however, an additive approach is taken unless available information suggests otherwise.

Upon release into the environment though, the individual components will typicallyusually have very different transport and transformation behaviour. The integrity of the initial composition of the product will not be maintained. IThusThereby the interaction between the constituents can be disrupted, as well. Even before reaching the environment, the composition of the product can be changed. For example, after application of a wood preservative product, some ingredients will interact with the wood while others may e.g. evaporate. If the treated wood is used in contact with water, the leaching rate out of the wood will be specific to each of the components…’’

An acute toxicity test with a product can lead to variable results because the quantity and the quality of the formulants can vary and the formulation may alter the availability of the active substances. For the acute risk assessment, the combination toxicity on the basis of the tests

69


with the product is compared with the combination toxicity based on studies with the separate active substances. The lowest combination toxicity value or PNEC exceeding the trigger valuetoxicity research with the separate active substances. The lowest combination toxicity value or PNEC exceedance (see below) is then used in the risk assessment.

Ratios between active substances can change in the environment due to differences in sorption and degradation rate, and this plays a role in assessing the chronic risk. This means that the concentration of the product in the environment (the PEC) cannot be accurately predicted because the separate active substances may behave differently after application. For chronic risk assessment it is therefore preferred to determine the toxicity of the combination product on the basis of toxicity research with the separate active substances.

Although there is limited data on the effects of mixtures of active substances in biocidal products have only been studied to a very limited extent and toxicological endpoints have not been studied for all relevant species, it is generally accepted that active substances in a product together contribute to the toxicity of that product. Also, in case of partial addition, the extent of combination toxicity does not deviate strongly from concentration addition. In view of these considerations the evaluation of the toxicity data of combination products is based on concentration addition.

The following applies for determination of the combination toxicity:1. Wherewhere one application is concerned, determination of the acute combination

toxicity is based on the ratio of the substances in the product.;2. Wherewhere several applications are concerned, determination of the acute

combination toxicity is based on the ratio of the substances on the basis of the calculations of the concentrations after the last application.;

3. Chronicchronic toxicity is always based on the ratio of the substances, calculated using their concentrations over a certain period.

In general, mixture toxicity will be assessed in a cumulative risk assessment: the risk for the each active substance will be summed to estimate the risk of the product. The formula presented below describes this concept of risk addition (also known as concentration addition) . In short, the following formula is used to evaluate combination toxicity of a biocide with more than one active substance in water, sediment and soil:

Where:

A, B, C … are the individual active substances

The formula presented above can also be applied to the combination toxicity of active substances with major metabolites.

For some active substances, it is appropriate to perform a combination toxicity assessment of the toxicity of both the parent and its major metabolite(s). This is appropriate when 1) the metabolite is persistent in the environment, 2) parent and its major metabolite(s) will be present in the environmental compartment at the same time and 3) if the PEC/PNEC ratio for both parent and metabolite are close to 1. For example, the biocide thiamethoxam and its metabolite clothianidin might be appropriate to assess for combination toxicity as they are both neonicotinoids, clothianidin is persistent in the environment and their toxicity is similar.

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7.2 Exposure assessment Emission routesVarious phases in the life cycle of a product may cause emissions and environmental exposure. Emissions from active substance production and product formulation are considered less significant thancompared to emissions from the application phase, in- service and waste phases of the product, and these phases are not part of Directive 98/8/EC. For the application, in- service and waste phases, the emission routes should be identified and be assessed. The exposure assessment and the risk assessment shall cover the proposed normal use of the biocidal product together with a realistic worst-case scenario (normal use is covered by realistic worst-case scenario). Therefore the product label should be assessed on clarity regarding its use description, as this is vital for choosing the right emission scenario. For example, for an insecticide it should be clear if a product is used indoors and/or outdoors. Determination of the relevance of the emission routes and quantification of emissions of a product are based on emission scenarios that have been drawn up for various product types (see the ex-ECB web site for emission scenario documents).

Production

Application phase

Waste phase

Exposure pathwaysSewage Treatment Plant (STP)The STP is exposed by indoor application of a product, both in public and private areas, as well as by outdoor applications, e.g. rodenticides or noise barriers. For example, after cleaning of an indoor surface on which the disinfectant or insecticide was previously sprayed the cleaning water may contain still-active productFor example, the indoor use of area disinfectants or insecticides, by which the latter is due to cleaning of the surface where the insecticide was sprayed upon.

The emission of the product to the STP exposes consequentially exposes the following environmental compartments, as shown/discussed below: STP → marine or fresh water → sediment

→ Air (→ soil or surface water, this pathway is not assessed)→ soil → groundwater

(e.g. land application of sewage sludge)

WaterWater can be directly exposed if water is directly in contact with a product or treated article, for example, outdoor spray applications against insects or antifouling agents on ships. Furthermore, it can also be exposed by receiving contaminated effluent from an STP.

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Formulation

In-service phase


The exposure to water consequentially exposes the following environmental compartments: Water → sediment

SoilSoil can be exposed inthrough multiple ways:. Firstly, it can receive direct emission of the active substance while the product is in service. For example, a wooden pole treated with wood preservative placed in soil or outdoor spray applications that settle unto soil. Secondly, soil can be exposed indirectly by the application of contaminated sludge or manure (from treated animal housings) to arable land and grassland.

The exposure to soil consequentially exposes the following environmental compartmentsSoil → groundwater (→ water → sediment)

→ water → sedimentAirAir is exposed if a product contains volatile active substances. Furthermore, it can also be exposed if direct air emission of a product occurs. Obvious to the air of a product. These are for examples are aerosols or sprays, but air exposuresthey also include vented steam containing biocidal preservatives from cooling system (PT 11).

The exposure to air consequentially exposes the following environmental compartmentsAir → Soil (through deposition)

→ Water (e.g. spray drift of insecticide) → sediment

Birds and mammalsThere are two main routes of exposure to birds and mammals:; primary and secondary exposure. Primary exposure is the assessment when birds and/or mammals are directly in contact with the product or if they are exposed directly to the active substance in the environmental compartments. These include, amongst others, rodenticides.

Secondary exposure is entails the exposure to the active substance through the natural food web where the food of birds or mammals have been contaminated with the active substances or metabolites. In general, secondary exposure is assessed if 1) the substance has a high bioaccumulation potential and 2) the toxicity of the active substances to birds is high. For most organics, a cut off value of log Kow of 3 is used to indicate the bioaccumulation potential. However, this cut off value of log Kow is based on a QSAR and not all organic substances are suitable for this QSAR, see therefore it is important to check the TGD: Part II* for details on bioaccumulation potential of substances.

The amount of animal testing, especially on vertebrates, shall be minimised. This means that all unnecessary testing of substances and preparations must be avoided, and existingthe data should be shared between applicants.

ESD scenario documentsThe relevant emission scenario documents are listed under each of the grouped Product Types

1. Disinfectants and general biocidal products (PT 1-5)For disinfectants the following ESD documents are available:PT01-06: Workshop on environmental risk assessment for PT01 to PT06 (2008)*PT01-06: Cover note to workshop on environmental risk assessment for PT01 to PT06 (2008)*PT01: ESD for human hygiene biocidal products*PT02: ESD for private area and public health area disinfectants*

72


ESD for PT1-23 of van der Poel and Bakker (2001)*

ESDs currently being finalised (hyperlinks are not yet available):PT02: ESD for private area and public health area disinfectants and other disinfectants –

supplement (EC, 2010)PT03: Veterinary hygiene biocidal products – supplement (EC, 2010)PT04: Disinfectants used in food and feed areas –supplement (EC, 2010)

2. Preservatives (PT 6-13)For preservatives the following ESD documents are available:PT06: ESD for in-can preservatives*PT06: ESD for biocidal products for paper coating and finishing*PT07: ESD for biocidal products used as film preservatives*PT07: ESD for biocidal products for paper coating and finishing*PT08: ESD for wood preservatives Part 1*PT08: ESD for wood preservatives Part 2*PT08: ESD for wood preservatives Part 3*PT08: ESD for wood preservatives Part 4*PT08: Report of leaching workshop (2005)*PT08: Groundwater exposure assessment – Factors to consider*PT08: Groundwater exposure assessment – Soil studies applicability*PT08: OECD guidance on the estimation of emissions from wood preservative-treated wood to the environment*PT09: ESD for biocidal products for paper coating and finishing*PT09: ESD for preservatives in the leather industry*PT09: ESD for preservatives in rubber and polymerised materials*PT09: ESD for preservatives in the textile processing industry*PT10: ESD for masonry preservatives*PT11:ESD for preservatives in liquid cooling systems*PT12: ESD for slimicides*PT13: ESD for metalworking fluid preservatives*ESD for PT1-23 of van der Poel and Bakker (2001)*

3. Pest control (PT 14-19)For pest control, the following ESD documents are available:PT14: ESD for rodenticides*PT14: Addendum TGD: PNECoral derivation for primary and secondary poisoning for rodenticides*PT15: ESD for avicides*PT18: ESD for insecticides for stables and manure storage systems*PT18: Report of workshop on PT18 (2007)*PT18: ESD for insecticides for household and professional uses*PT18: ESD for preservatives in the textile processing industry*ESD for PT1-23 of van der Poel and Bakker (2001)*

4. Other biocidal products (PT 20-23)PT21: ESD for antifoulings*PT21: Leaching workshop antifoulings (2006)*PT21: MAMPEC 2.0 user manual *PT21: MAMPEC 2.0 technical background document*2

PT22: ESD for biocidal products for taxidermy and embalming processes* 2 Please note that the Mampec 2.5 manual and technical background document can be found in the MAMPEC 2.5 program itself

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ESD for PT1-23 of van der Poel and Bakker (2001)*

7.2.1 Exposure calculationsIn this section a summary is given per environmental compartment on exposure calculations based on the emission scenario documents given in the previous section, the TNsG on data requirements* and the Technical Guidance document (TGD: Part II*). In general, PECs are product specific, but the CAR of the active substances can be used for supportive information. Guidance on whether a certain compartment is relevant can be found in section 7.2.

7.2.1.1 Aquatic compartment (water and sediment)This section describes the exposure assessment of surface water, which is used for risk assessment for organisms that depend on surface water (aquatic organisms, birds and mammals). It describes how emission can be calculated using models and from monitoring data. The concentration in surface water depends, on direct emissions to surface water, indirect emissions to surface water from sewage treatment plant (STP) effluent and the potential application of surplus activated sludge or manure on land and from active substance leaching from treated materials, which reaches the water via drainage pipes. Therefore, there is a relationship with the following sections: 7.2.1.2 Sewage treatment plant (exposure assessment), 7.3.1 Aquatic compartment (water and sediment - effect assessment) and 7.3.2 Sewage treatment plant (effect assessment).

The assessment of fate and behaviour in water has been elaborated in the following documents: TGD: Part II* - chapter 2, section 6.2, Appendix VIII and XI; TNsG on data requirements* – Ch.2, Part B, Section 7; Ch. 3, Part B, Section 7.

The most important substance-related parameters for model estimation of the PEC are:

standard data requirements DT50 for photolysis rate in water at 20 C (days); DT50 for hydrolysis rate in water at 12 C (days); DT50 for biodegradation rate in STP at 12 C (days) from screening biodegradation test or

simulation STP test. Koc, Kow or Kp for sediment (L/kg); Saturated vapour pressure (Pa); Solubility in water (mg/L); Molar mass (g/mol).Including the identification of relevant metabolites formed in more than 10% of the applied active substance.

Additional exposure related data (depending on emission route or PEC/PNEC ratio >1 derived from the preliminary risk assessment).

DT50 for degradation rate in water at 12 C (days); DT50 for degradation rate in sediment at 12 C (days);DT50 for degradation rate in whole water/sediment studies, for the case separate DT50 representing degradation are not available for the water and the sediment compartments, respectively Kp for suspended matter (L/kg).

Studies to derive substance-related parameters are generally performed at 20 °C. However, the commonly used programs (EUSES, MathCad, etc.) for exposure estimation are linked to

74


the average EU outdoor temperature of 12 °C. For some programs it becomes necessary to recalculate the experimental-obtained values from 20 °C to 12 °C.

Simulation tests • Simulation tests for water areis require=d if direct emission to surface water occurs.• Simulation tests can be carried out: - as a first step where the screening stage biodegradation tests are skipped. This can be

the case for biocides that are toxic to the inoculums. - if a substance is “not ready” or “not inherently” biodegradable and further refinement of

degradation rate and route is required.,

Estimation of exposure concentrations in surface water and sedimentExposure concentrations in water are estimated with EUSES (based on TGD: Part II*) and/or emission scenario documents (ESDs) with selection of the emission routes and estimation of the emission amounts (i.e., directly or indirectly via an STP) to surface water. For biocides with an emission to water, calculation of a PEClocalwater is based on a standard environment during an emission episode, taking into account dilution, sorption and - if relevant - sedimentation, volatilisation and degradation (section 2.3.8.3).

The PEC estimation follows a tiered approach in several steps, where depending on the results of the first step -if appropriate- more accurate calculations using additional data may be are carried out in the subsequent steps, on the basis of additional data.

Surface water Step 1 uses basic data for phototransformation, hydrolysis and biodegradation, where

depending on the removal in the STP and distribution over the compartments, possible relevant metabolites formed in more than 10% of the applied active substance are identified and a PECwater is calculated.

Step 2. If direct emission to surface water is expected, data of simulation studies in STP or surface water can be taken into account for the PECwater calculations.

In case of relevant emission to surface water, the behaviour of the active substances should be investigated in a water or water/sediment study. Depending on the partitioning characteristics of the substance a water-sediment simulation test is definitely required if the Kp value is > 2,000.

SedimentThe concentration in bulk sediment can be derived from the corresponding water body concentration, assuming a thermodynamic partitioning equilibrium.

PEClocalsed = (K susp-water / RHO susp) * PEClocalwater *1000

PEClocalwater concentration in surface water during emission episode in mg.l-1Ksusp-water suspended matter-water partitioning coefficient in m3.m-3

RHOsusp bulk density of suspended matter in kg.m-3 PEClocalsed predicted environmental concentration in sediment in mg.kg-1

See for more information TGD: Part II*, chapter 2.3.8.4.

Measured dataMeasured concentrations or monitoring data, e.g. concentrations in waste water or in the environment can be used in risk assessment (see for more guidance, TNsG on data requirements* (Chapter 2, 7.1)). If appropriate, suitable measured data can be used to adjust calculated PEC values (TGD: Part II*, Sections 2.2.1 and 2.5). The availability of suitable

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Author, 01/03/-1,

Why no mention of refinement possibilities? Again, only having some of the information in this document can (and will) cause confusion. NL: we do not understand the comment. Koc, or PECwater can be refined but this is the standard equation to calculate the PECsediment. The section ‘Use of calculated PEC or measured PEC for risk assessment’ explains how measured data can be used as a refinement if the quality is sufficient. We therefore do not agree with the comment and have not changed the text.

Author, 01/03/-1,

Not always relevant e.g. rural hygiene situations NL: please see our response to the previous comment

Author, 01/03/-1,

As outlined eaarlier this is not applicable in all situations and therefore could cause confusion. NL: the previous section is addressing the identification of exposure pathways to the environment to assess which environmental compartments are exposed. We find it self – explanatory that if there is no emission to a certain environmental compartment that you do not need to perform a risk assessment for that compartment.


measured data does not, however, not mean that PEC calculations are not required.The TGD: Part II* describes the procedure for evaluation of measured data in chapter 2.3.1 and a summary is given in appendix ENV-1 of this manual.

Selection and assessment of measured data Available data should be assessed for on quality and for its relevance for the risk assessment. Full details on the assessment and selection of data can be found in section 2.2.1 of the TGD: Part II*

Use of calculated PEC or measured PEC for risk assessmentWhere PEC values from measured as well as calculated data are available, these are compared. A critical evaluation should be carried out in case the measured and calculated values are not of the same order of magnitude (TGD: Part II*, section 2.5)

The following cases are possible: Calculated PEC ≈ PEC based on measured values

The result indicates that the most important emission sources have been taken into account. The most reliable value is used in the risk assessment.

Calculated PEC > PEC based on measured valuesIndicates that possibly relevant removal processes have not been taken into account in the calculated PEC or that the used model is not suitable for simulation of the actual situation. The measured values, however, can also be unreliable or only representative of background values of the PEC.

In case the measured PEC has been derived from a sufficient number of representative samples, this value can replace the calculated PEC value. If it can, however, not be demonstrated that the scenario is a an unrealistic worst-case, however, the calculated PEC is preferred.

Calculated PEC < PEC based on measured valuesThis may be caused by certain emission sources not being taken into account in the calculation of the PEC, or by the use of unsuitableused models. Degradation not being suitable. But degradation of the substances may also be overestimated. Alternatives are leakage, recent changes in of use patterns, or the fact that emission reducing measures are not yet visible in the samples. Other causes may be cross-border influx, the; presence of other sources,; the substance is a metabolite of a different substance,; delayed remobilisation from a source in different environmental compartments, and that; there are other uses of the active substance that are not covered by the present evaluation or that are beyond the scope of the Biocides Directive.

If the measured values meet the procedure of critical statistical and geographical evaluation, these data are considered as very reliable and they then replace the calculated PEC.

7.2.1.2 Sewage treatment plantThis section describes the exposure assessment of microorganisms in a STP. The concentration in the STP depends on factors such as direct emissions to the sewage system or indirect emissions via surfaces to the sewage system. The PEC is calculated in accordance with the TGD: Part II* and the ESDs.

Standard data requirements DT50 for biodegradation rate in STP at 12 C (days) from screening biodegradation test

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Additional data requirements DT50 for biodegradation rate in STP at 12 C (days) by simulation STP test.

Where screening tests for the active substance are available, the test results should fulfill specific criteria in order to assign a degradation rate constant for STP modelling, see Chapter 3 of the TGD: Part II* 2.3.6.4 and Appendix II, pp. 278 -283.

A test on inherent biodegradability according to OECD 302 A (SCAS test) will not be considered for the environmental risk assessment as according to TGD, part II (2003), a rate constant of 0 h-1 will be assigned to a substance, irrespective whether it passes this test or not.

Simulation tests Simulation tests can be carried out: - as a first step, where the screening stage biodegradation tests are skipped. This can be

the case for biocides that are toxic to the inoculums.- if a substance is “not ready” or “not inherently” biodegradable, and further refinement of

degradation rate and route is required.,

There is a relationship betweenwith the sections 7.2.1.1 Aquatic compartment (water and sediment – exposure assessment), 7.3.1 Aquatic compartment (water and sediment-effect assessment) and 7.3.2 Sewage treatment plant (effect assessment).Section 7.2.1.1. Aquatic compartment (water and sediment) also covers the use of monitoring data for exposure assessment of microorganisms in a STP.

7.2.1.3 Marine compartment (water and sediment)This section describes the exposure assessment of organisms in marine waters. Two representative examples that lead to exposure to the marine compartment are presented in this section (for PT12 and 21). However, there are more PTs for which marine exposures can be relevant, e.g. PT8. The concentration in marine waters depends on factors such as direct contact with the biocidal product and direct emissions of effluent fromof sewage systems. The PEC is calculated in accordance with the TGD: Part II* and the ESDs.

Slimicides – PT12Slimicides (PT12) are used in oil extraction processes. The main emission to marine waters is due to the discharge of drilling muds,formuds, for which an ESD was developed as part of the CHARM (Chemical Hazard Assessment and Risk Management) model. This scenario is available in EUSES 2.1. The CHARM model calculates the discharged amount and the resultant concentration of a specific chemical in the receiving marine water and in the sediment. The model is based on default parameters for standard North Sea oil and gas platforms based on information provided by national authorities on conditions at existing platforms. Since the standard platforms are meant to represent the ‘realistic worst case’ situation, the 95 percentile values on these existing North Sea platforms were chosen. The model requires input of a number of parameters for the specific chemical in question. Various parts of the model have been validated in experimental programmes. The CHARM model is to be applied for operational discharges of chemicals in the process of drilling, completion and production under ‘realistic worst case’ conditions. In the ESD, only the slimicide containing water-based drilling mud (WBM) is considered. Within CHARM the offshore environment is divided into two compartments: marine water and sediment. This is done in

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order to acknowledge the fact that a chemical present in the environment will partition between the water and organic matrix in the sediment. Consequently, two PEC values are calculated: PECwater and PECsediment.

Antifouling products – PT21For antifouling products, leaching from ship hulls, fish nets or buoys (PT21) during the in service phase of the product is the main emission model for to marine waters (, see the ESD document PT21: ESD for antifouling* products). Leaching models are available for the estimation of environmental concentrations (e.g. MAMPEC (Marine Antifoulant Model to Predict Environmental Concentrations) for ship hulls. The leaching rate for the active ingredient from the ship hull is an important input parameter for these model calculations. The leaching rate for the active ingredient from the ship hull is an important input parameter for these model calculations, and can be determined in three ways:• Laboratory studies: Standardised ASTM and ISO methods (rotating cylinder methods)

are known to considerably overestimate the leaching rate. • Field tests (such as US Navy Dome Method): These tests are expected to give

reliable and realistic leaching rate measurements. However, these data are very expensive to generate and of limited statistical value due to the small number of data points and low reproducibility.

• Calculations methods (such as the CEPE mass-balance method): The concept of calculation has been developed in order to compensate for the gross overestimation of rates derived by laboratory methods and the excessive cost of undertaking field tests. For the evaluation of active substances under the Biocidal Products Directive the CEPE mass-balance method and the ISO-method (which is a further development of the CEPE method) are used for estimation of the leaching rate. At product authorizationauthorisation stage, the MS has the possibility to ask for additional data if considered necessary.

MAMPEC is a generic model which can be used for the calculation of the PEC for antifouling products in the marine environment. The program is available on CD-ROM or can be downloaded from the website http://delftsoftware.wldelft.nl, www.cepe.org or www.antifoulingpaint.com. The most recent version of MAMPEC is 3.0 (released June 2011).

On the website of the IHCP (formerly European Chemical Bureau) (http://ecb.jrc.it/biocides) and Deltares (developer of MAMPEC, http://www.deltares.nl/en/software/1039844/mampec) a short user manual and a technical report on MAMPEC can be found. The freshwater marina scenario is also available in EUSES 2.1. EUSES 2.1 and its manual can be downloaded from the IHCP site*. Input parameters for MAMPEC are still discussed on EU level. Workshops, TM meetings and e-consultations should be carefully monitored for the latest changes.

Current list of updates, available online:Workshop report PT21 in Ispra, 2006*TM –II 2010 Sediment risk assessment for antifouling products

Other discussions still ongoing includeare:1. the suitability of the methodologies for leaching rate assessment (ASTM, CEPE model

and dome measures, see Workshop report PT21 in Ispra, 2006 and e-consultations); 2. the use of correction factors in marinas and harbours for organic antifouling substances.

These can also be found in the Workshop report PT21 in Ispra, 2006* and the TM discussions on PT21 substances (for example, tralopyril);).

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http://www.antifoulingpaint.com/


3. degradation and hydrolysis settings in MAMPEC (see MOTA and the e-consultation UK CA February 2011);).

4. cumulative risk assessment in harbours and marinas, see e-consultation UK September 2011;

5. risk mitigation measures during application, maintenance and waste phase, see e-consultation UK May 2011.

7.2.1.4 Soil compartment (including groundwater for drinking water production) This section describes the exposure assessment forof soil and the exposure to groundwater. The resulting PEC is an important parameter in the risk assessment for soil organisms. The PEC is calculated according to the ESDs and the TGD: Part II*.

Standard data requirements for fate and behaviourThe following data are required for an initial assessment of persistence:

1. Hydrolysis as function of pH and identification of metabolites; 2. Phototransformation in soil and identification of metabolites; 3. Ready biodegradability;4. Adsorption/desorption screening test

Product-type-specific and additional dataAdditional tests are required if there is a risk for groundwater or if other refinement of the initial risk assessment is required. In addition, additional tests are required for a number of product types. In general, the additional data requirements for certain product types relate to the direct emission to soil that was identified for certain types of uses.These additional tests can in full be found in TNsG on data requirements*, but generally these are:

1. Aerobic degradation in soil, initial studies; 2. Rate The rate and route of degradation, including the identification of the processes

involved and identification of any metabolites and degradation products in at least three soil types under appropriate conditions;

3. Adsorption/Desorption Batch Equilibrium Test on soils and;4. Simulation tests to assess environmental degradation rates or inherent

biodegradability test.

Although Core-data testing for inherent biodegradability may in general not be appropriate, since these tests are accepted, they do not provide adequate information for risk assessment purposes. Therefore, therefore, simulation tests are preferred over inherent biodegradability testsinstead (TNsG on data requirements*).

Product data are only required if there are indications that the composition or the method of application of the product affect degradation and transformation or mobility and adsorption properties of the active substance in such a way that the conclusions of the risk assessment will be change considerably altered. For example, after application of a wood preservative product, some ingredients will interact with the wood while others may evaporate. If the treated wood is used in contact with water, the leaching rate out of the wood will be specific to each of the components. The relative concentration of each component in the leachate from the wood will be very different from its relative concentration in the initially applied product. Moreover, artefacts from ingredients of a biocidal product and constituents of the wood (e.g. phenolic resins) may be formed during treatment (e.g. pressure and elevated temperature during impregnation of timber). In particular, when complex interaction between the ingredients of a biocidal product and the treated material and/or the environmental matrix

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is likely, it will be very difficulthardly possible to predict the ecotoxicological potential of an aqueous leachate, even from tests on the finishedthorough product.

Direct emissionDirect emission to soil only occurs only for a few PTs, not taking into account accidental spills. Application of sewage sludge or manure on agricultural land is considered indirect, as the manure and sludge act as intermediate compartments and are therefore described in the next section: Indirect, indirect exposure.

Direct emissions to soil occur by the use of a biocide outdoors, including,which include among others, wood preservatives and insecticides. As the calculations of PECsoil for direct emission to soil are quite specific per PT, direct links are given to the PTs.

PleansePlease note that the actual ESD for PT3, veterinary hygiene biocidal products (TM I 2011, ENV item 5a, CA-May11-Doc.6.2c) defines no direct emission to soil in the scenario for disinfection of vehicles used for animal transport. The main emission pathway is emission to waste water, but also emission to air can be considered.

PT01-06: Workshop on environmental risk assessment for PT01 to PT06 (2008)*PT01-06: Cover note to workshop on environmental risk assessment for PT01 to PT06 (2008)*PT06, outdoor use of products including in-can preservativesPT8, outdoor use of Wood preservatives:PT08: ESD for wood preservatives Part 1*PT08: ESD for wood preservatives Part 2*PT08: ESD for wood preservatives Part 3*PT08: ESD for wood preservatives Part 4*PT08: Report of leaching workshop (2005)*PT08: Groundwater exposure assessment - Factors to consider*PT08: Groundwater exposure assessment - Soil studies applicability*PT08: OECD guidance on the estimation of emissions from wood preservative-treated wood to the environment*

PT10, masonry preservativesPT10: ESD for masonry preservatives*

PT11, deposition from atmosphere from liquid cooling systemsPT11:ESD for preservatives in liquid cooling systems*PT14, application in and around buildings, open areas and waste dumps

PT18, outdoor use of insecticides:PT18: ESD for insecticides for stables and manure storage systems*PT18: Report of workshop on PT18 (2007)*PT18: ESD for insecticides for household and professional uses*

Indirect emission 1: manure application to land Several types of biocides have applications in animal housings whereby the manure can beget contaminated bywith the product. The manure will be spread or injected on land thereby exposing the soil organisms to the active substance.

Soil concentrations of the active substance can be calculated based on maximal annual manure applications to soil. The manure application to land has an annual limit due to nitrogen and phosphate application limits to soil. Nitrogen and phosphate limits exist for

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grassland and arable land, and vary byper country. These limits can be found per country in Table 5.9, in PT18: ESD for insecticides for stables and manure storage systems*.

Based on the concentration of active substance in manure, annual application limits and incorporation depths, a PIEC is derived. TheThese equations used to derive the PIEC can be found in PT18: ESD for insecticides for stables and manure storage systems*.

One important aspect in PIEC calculations from manure application to land is the degradation of active substance in manure during storage. In general, degradation data for of the active substance in soil can notcannot be used as a substitute for degradation rates in manure. Currently no guideline for simulating biodegradation of biocides in manure is available. A guideline on degradation in manure has been adopted in March 2011 for veterinary medicinal products in manure.” Please update the link as we did in the previous sentence. *. In case degradation rates in manure would be necessary for the environmental risk assessment, a preliminary testing strategy presented during the Workshop on Emission Scenario Documents for PT18 in December 2007* could be used. Degradation times taken into account should be carefully assessed, as manure storage periods can be quite different for different between animal housings, different farming systems and countries. For full details, see PT18: ESD for insecticides for stables and manure storage systems* and veterinary medicinal products in manure*.

Indirect emissions - otherGuidance for calculating PEClocal in soil is given for the following exposure routes in the TGD: Part II*, section 2.3.8.5:

1. application of sewage sludge in agriculture;2. dry and wet deposition from the atmosphere.

The TGD (part II, section 2.3.8.5) gives detailed guidance on how the PEC local soil is calculated as a function of sewage sludge application rate (kg per hectare and year), and other details such as frequency of the sludge application. Atmospheric deposition is assumed to be a continuous flux throughout the year, and thus by which the deposition flux is averaged over a year.

GroundwaterExposure to groundwater is assessed for the risk estimation for organisms that depend on soil (soil organisms) and for evaluation of the quality of groundwater used for the production of drinking water.

Groundwater concentrations are calculated based on calculated soil pore water concentrations of the active substance, which will reach groundwater. In general, the PEC groundwater is set to be equal to the soil pore water concentration. The equation for deriving the concentration in the pore water, based on the Equilibrium partitioning method, is:

PECsoil, porewater = (PECsoil * RHOsoil )/ (Ksoil-water * 1000)

Explanation of symbolsPECsoi predicted environmental conc. in soil in (mg.kg-1) Ksoil-water soil-water partitioning coefficient (m3.m-3) RHOsoil bulk density of wet soil, 1700 (kg.m-3) PECsoil, porewater predicted environmental conc. in porewater (mg.l-1)

In However, in the first tier, PECgroundwater is calculated based on soil pore water concentrations (see formula above), however,) and in a second tier as refinement theoptions PECgroundwater

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could be calculated using available groundwater models or by using measured data, such as ,, for example lysimeter studies or monitoring data. Groundwater models available are PEARL or PELMO. PEARL is preferred over PELMO to assess leaching of the active substance to groundwater (TM III 2010 decision). These models can take degradation of the active substance in soil into account. A full description of these models can be found here: FOCUS groundwater scenarios in the EU review of active substances* or Generic guidance for FOCUS groundwater scenarios*

Lysimeter studies and monitoring data will have to be assessed on a case by case. For lysimeter studies, some technical guidance can be found here: OECD GUIDANCE LYSIMETER STUDIES*

MonitoringFor monitoring data it should be assessed if the data is representative for quality/reliability, and to determine if the data is representative of the environmental compartment which include:

1. Reliability of the measured data. This is also determined by the number of samples, distance between the sampling points, and sampling frequency. Important information also includes information on the sampling depths, hydrological factors (for example the age of the groundwater – it can take decades or centuries for water to penetrate down to the deeper groundwater basins) and landscape conditions (for example possible exposure from sewage sludge applications on agricultural soil).

2. Whether the sampling location is representative of the local or regional scenario. It should be investigated whether sporadic measurements are concerned or whether the substance is measured at the same location over a certain period.

See the aquatic compartment section for more guidance on monitoring data, section 7.2.1.1 Aquatic compartment (water and sediment) or TGD: Part II*, chapter 2.2.1.

7.2.1.5 AirThe exposure of the compartment air is not elaborated in this manual. The degradation rate of a substance in air can be calculated with the formulas from section 2.3.6.3 Photochemical reactions in the atmosphere of the TGD: Part II or EPIWIN suite 3.05 and assuming an OH-radicals concentration of 0.5 x106 [molec.cm-3] and 24 hour.

7.2.1.6 Birds and mammals (primary and secondary exposure)This section describes the exposure assessment for of birds and mammals and is based on the TGD: Part II* and European Guidance Document on Risk Assessment for Birds and Mammals*. This section has a relationship with the human toxicology part of this manual concerning fate and behaviour in environmental compartments, the exposure of water and soil compartments and aquatic and terrestrial ecotoxicology and PBT (bioaccumulation). The amount of animal testing, especially on vertebrates, shall be minimised. This means that all unnecessary testing of substances and preparations must be avoided, and the data should be shared between applicants.

Where appropriate, tests must be conducted in accordance with the provisions laid downin Council Directive 86/609/EEC* of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regardingthe protection of animals used for experimental and other scientific purposes.

Primary exposure is the assessment is conducted when birds or mammals are expected to be directly in contact with the product or if they are exposed directly exposed to the active substance in the environment. Applications al compartments. Direct contact is often related to applications with treated granules, powder or products with a bait are most commonly

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expected to involve primary exposure.Secondary exposure assessment is conducted whenentails the exposure to the active substance is through the natural food web, i.e., where the food of birds or mammals hashave been contaminated with the active substances or metabolites. An example of secondary exposure is the exposure of a black bird by eating an earthworm that has high internal concentrations of the active substance due to soil that is contaminated soilwith the biocidal product.

Determination of the relevance of the emission routes and quantification of emissions are based on emission scenarios drawn up for various product types in emissions scenario documents (see the ex-ECB web site). PT14: ESD for rodenticides* and the addendum for PT14* is in particular relevant and OECD ESD No. 18 for Insecticides*. Some further scenarios have been developed in CARs for PT18 for applications of granules and the feeding of birds and mammals on dead insects (killed by the insecticide).

Exposure via primary poisoningThe risk for primary poisoning of a non-target organism feeding on the biocidal product as a food item, is calculated as the ratio between the concentration in their food (PECoral) and the no-effect-concentration for oral intake (PNECoral). Two Tiers are considered: Tier 1, where the PECoral is the concentration of the active substance in the food (bait)

[mg/kg food]; and Tier 2 for 5 days exposure, considering excretion, where the PECPEC oral is the expected

concentration of the active substance in the non-target animal after 5 days exposure [mg/kg bw], considering excretion.]. A default excretion factor of 0.3 (for birds and mammals) should be used ifin case no specific data are available. As a worst case, the parameters AV*, PT and PD are all 1.

In the first tier it is assumed that the animal in question consumes nothing but the biocide (until an upper limit of 600 g) in one daily meal and therefore this is used as a default value.

As a second tier evaluation, the following more detailed exposure assessment can be done. Basically, the estimated daily uptake of a compound (ETE) is given by the following equation:

ETE = (FIR / BW) * C * AV * PT * PD (mg.kg-1 bw/d) Variable/parameter Symbol Unit Default Input:Food intake rate of indicator species (fresh weight) FIR g.d-1 Body weight BW g Concentration of active compound in fresh diet (bait) C* mg.kg-1 Avoidance factor (1 = no avoidance, 0 = complete avoidance) AV - 1 Fraction of diet obtained in treated area value between 0 and 1) PT - 1 Fraction of food type in diet (number between 0 and 1; one type or more types) PD - 1

Output:Estimated daily uptake of a compound ETE mg.kg.-1d-1

In the calculations of uptake of active substance of a rodenticide, in this first step worst- case scenario, AV, PT and PD are all set to 1. If no other information is available this will also be

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considered as a realistic worst case. However, realisticRealistic worst case values of AV = 0.9, PT = 0.8 and PD = 1 might be used instead, as a refinementsecond step, based on e.g. recommendations of the EPPO Rodent Control Panel on acceptable avoidance factors for rodenticides.

Food intake is dependantdepending on the metabolic rates of the species, the nature of their food, weather conditions and, time of year, and the appropriate rates should be taken from PT14: ESD for rodenticides*.

The expected concentration of active substance in the animal after metabolism and otherelimination is calculated as follows:

EC = ETE * (1 - El) Variable/parameter Symbol Unit DefaultInput:Estimated daily uptake of a compound ETE mg.kg-1d-1 Fraction of daily uptake eliminated (number between 0 and 1) El -

Output:Expected concentration of active substance in the animal EC mg.kg-1

The general formula for calculation of ECn for animals that eats the same daily amounts is then: n-1 ECn = ∑ ETE * (1-EL)n

n=1The predicted environmental concentration of an active substance in food of a rodent-eating predator is calculated as follows:

PECoral, predator = (ECN + ETE) * Frodent Variable/parameter Symbol Unit DefaultInput:Expected concentration of active substance in the rodent on day "n" before the last meal ECN mg.kg-1 Number of days the rodent is eating rodenticideuntil caught by the predator N - 5 Estimated uptake of active substance by rodenton day "n" (i.e. intake of rodenticide in the lastmeal, no elimination) ETE mg.kg-1 Fraction of poisoned rodents in predator's diet Frodent -- short-term exposure 1- long-term exposure 0.5Output:Predicted environmental concentration of anactive substance in food of a predator per day PECoral, predator mg.kg-1 Exposure via granules

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In a number of CARs for of biocidal products applied as granules, methods on exposure were taken from the European Guidance Document on Risk Assessment for Birds and Mammals*.This document specifically refers to the EPPO risk assessment scheme* when granules have to be assessed. In general, the EPPO methods will be followed here. However, in some cases the default values for focal species in the EPPO scheme differ from those in the Guidance Document, and input values from the latter are used here. In line with the assessment of rodenticides (PNECoral derivation for the primary and secondary poisoning assessment of anti-coagulant rodenticides – addendum to the TGD*), the assessment of primary poisoning, is based on a qualitative and quantitative assessment.

Assessment of secondary poisoning via feeding on contaminated target-species For the risk assessment for secondary poisoning, the long-term PEC/PNEC values of the respective substances should be compared. As a worst case, PEC/PNEC ratios of the smallest bird and the smallest mammal should be compared for secondary poisoning. Tier 1 for a long-term exposure:. The PECoral is the concentration in the rodent

immediately after a last meal on day 5 [mg/kg food]; PD = 1 and Frodent = 0.5 (non-target animals consume 50 % of their daily intake on poisoned rodents). For comparison calculations with PD = 0.5 and PD = 0.2 could also be included.

Tier 2 for a long-term exposure:. The PECoral is the concentration in non-target animals after a single day of exposure [mg/kg bw]; PD = 1 and Frodent = 0.5.

Assessment of secondary poisoning via the aquatic food chain

Effects assessments for bioaccumulation In general, secondary exposure is assessed if 1) the substance has a high bioaccumulation potential and 2) the toxicity of the active substances to birds is high. For most organics, a cut off value of log Kow of 3 is used to indicate the bioaccumulation potential. However, this cut off value of log Kow is based on a QSAR and not all organic substances are suitable for this QSAR, see therefore the TGD: Part II* for details on bioaccumulation potential of substances.

Calculation of BCF from log KowIf measured BCF values are not available, the BCF for fish can be predicted from therelationship between Kow and BCF: log Kow of 2-6: log BCFfish = 0.85 * log Kow – 0.70 log Kow >6: log BCFfish = - 0.20 * log Kow2 + 2.74 * log Kow – 4.72

Explanation of symbols Kow octanol-water partition coefficient [-]BCFfish bioconcentration factor for fish on wet weight basis [l.kg wet fish]

Bioaccumulation is assessed using the bioconcentration factor (BCF). The BCF is the quotient of the concentration of the accumulated substance in the organism and the concentration of the substance in water or the surrounding medium. For aquatic species, the OECD TG 305 test for the testing of fish species* should be used or a test protocol similar to this (guideline is under revision). There are also OECD test guidelines available for the testing of bioaccumulation in sediment-dwelling benthic oligochaetes: OECD 315, Bioaccumulation in Sediment-dwelling Benthic Oligochaetes*.

Calculation of a predicted environmental concentration in food (PEC)

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A schematic view of the assessment scheme for the exposure route from water to fish- eating predator is given in the Figure below.

Water ---------------->

---------------->

FishPECoral,predator

fromBCF & BMF

-----------------> Fish-eatingpredator

↓Aquatic

organism

The risk to the fish-eating predators (mammals and/or birds) is calculated as the ratio between the concentration in their food (PECoral, predator) and the no-effect-concentration for oral intake (PNECoral). The concentration in fish is a result of uptake from the aqueous phase and intake of contaminated food (aquatic organisms). Thus, PECoral, predator is calculated from the bioconcentration factor (BCF) and a biomagnification factor (BMF).

The BMF is defined as the relative concentration in a predatory animal compared to theconcentration in its prey (BMF = Cpredator/Cprey). The concentrations used to derive and report BMF values should, where possible, be lipid normalised.

The concentration of contaminant in food (fish) of fish-eating predators (PECoralpredator) iscalculated from the PEC for surface water, the measured or estimated BCF for fish and thebiomagnification factor (BMF):PECoral, predator = PECwater * BCFfish * BMF

In case there is emission to marine waters next to the assessment of predators also an assessment of top-predators is required in addition to the assessment for primary predators:

PECoral, toppredator = PECwater * BCFfish * BMF1 * BMF2 ( Seal)

Explanation of symbols PECoralpredator Predicted Environmental Concentration in food [mg.kg-1]PECoral toppredator Predicted Environmental Concentration in food of top predator [mg.kg-1]PECwater Predicted Environmental Concentration in water [mg.l-1]BCFfish bioconcentration factor for fish on wet weight basis [l.kg wet fish-

1]BMF = BMF1 biomagnification factor in fish [-] BMF2 biomagnification in the predator [-]

PECwater = 50% local water, 50% regional waterPECwater, toppredator = 10% local, 90% regional

Default BMF values for organic substances are based on the log Kow or BCF in fish and can be found in the TGD: Part II*, table 21, chapter 3.8.3.4. 21, chapter

Assessment of secondary poisoning via the terrestrial food chain

Calculation of a predicted environmental concentration in food (PEC)The exposure of the predators may be affected by the amount of substance that is present in the soil. The PECoral,predator is calculated as:

PECoral, predator = Cearthworm

Where Cearthworm is the total concentration of the substance in the worm as a result of

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bioaccumulation in worm tissues and the adsorption of the substance to the soil present in the gut.

Cearthworm = (BCFearthworm * Cporewater* Wearthworm + Csoil * Wgut) / (Wearthworm + Wgut)

Explanation of symbols:PECoral,predator Predicted Environmental Concentration in food [mg.kg-1 wet earthworm]BCFearthworm bioconcentration factor for earthworms on wet weight basis

[L.kg-1 wet earthworm]Cearthworm concentration in earthworm on wet weight basis [mg.kg-1wet earthworm]Cporewater concentration in porewater [mg.L-1]Csoil concentration in soil [mg.kgwwt

-1]Wearthworm weight of earthworm tissue [kgwwt tissue]Wgut weight of gut contents [kgwwt]

Wgut = Wearthworm * Fgut * CONVsoil

Where:

CONVsoil = RHOsoil / (Fsolid * RHOsolid)

Explanation of symbols CONVsoil conversion factor for soil concentration wet-dry weight soil [kgwwt.kgdwt

-1]Fsolid volume fraction of solids in soil [m3.m-3] = 0.6Fgut fraction of gut loading in worm [kgdwt.kgwwt

-1] = 0.1RHOsoil bulk density of wet soil [kgwwt.m-3] = 1,700RHOsolid density of solid phase [kgdwt.m-3] = 2,500

The concentration in a full worm can be written as:

Cearthworm = ( BCFearthworm * Cporewater + Csoil * Fgut * CONVsoil) /(1 + Fgut * CONVsoil )

An OECD guideline is available for the assessment of bioaccumulation in terrestrial oligochaetes: OECD 317*. When measured data on bioconcentration in worms is available the BCF factors can be inserted in the above equation. For most substances, however, these data will not be available and BCF will have to be estimated. The main route of uptake into earthworms will be soil pore water. Bioconcentration can be modelled according to the following equation as described by Jager (1998):

BCFearthworm = (0.84 + 0.012 Kow) / RHOearthworm

Where for RHOearthworm a default value of 1 (kgwwt.L-1) can be used.

7.3 Effect assessment The derivation of the predicted no effect concentration (PNEC) is generally in general based on dose (concentration) – response (effect) assessment studies. Before the PNEC is derived, the data should be carefully assessed for on completeness and quality/adequacy. Guidance will be provided in at the relevant sections but for general guidance on the quality assessment of data, see TGD: Part II*.

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If no additional toxicity data is required and no extra data is supplied on top of the data set provided in the LoEP of the CAR of the active substance, then the PNEC for that compartment stated in the CAR of the active substance can be used and no separate PNEC needs to be derived. If, however, additional data havehas been submitted, then the PNEC mayshould be revised considering the new information. Guidance on PNEC derivation is also given in the following sections.

It is expected that the dossier submitted for the product will containhold the same toxicity data as the LoEP of the CAR of its active substances. Therefore, for eachevery environmental compartment the datait should be checked to determineverified if additional data are required based on the proposed use or product specific properties . Guidance onThe guidance whether additional data are required for the products is given in the following sections hereafter.

Where appropriate, the additional toxicity tests must be conducted in accordance with the provisions laid down in Council Directive 86/609/EEC* of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes.

7.3.1 Aquatic compartment (water and sediment)This section describes the derivation of an exposure limit for aquatic organisms, and is directly related to. This section has a relationship with section 7.2.1.1 Aquatic compartment (water and sediment), where the estimated or measured concentrations in surface water are determined.

If the dossier does not contain substance or product-specific toxicity data additional to the CAR, then the PNEC for water and sediment organisms can be taken from the CAR.

7.3.1.1 Relevant toxicity data for PNEC derivationRevision of this section is awaiting TM text proposal decisionThe data requirements for the active substance and the product for evaluation of the risk to aquatic organisms are laid down in the TNsG on data requirements* corresponding with the Biocidal Products Directive 98/8/EC*.The data requirements are divided into standard data requirements (core data) that apply for each product group and product-type-specific data that should be submitted for different product groups.

Additionally, data must be submitted in case a risk is identified on the basis of the available information.

Data requirements for the active substanceStandard data requirements

Acute toxicity to aquatic and sediment organisms Studies should be carried out according to standardised methods with representatives of at least three trophic levels, i.e.: i.e. primary producers (algae), primary consumers (crustaceans) and secondary consumers (fish). These are the standard test organisms and are required for the active substance.

These studies are described in the TNsG on data requirements*.

There are no standard data requirements for sediment organisms.

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Product type specific and additional data for the active substanceProduct type specific data for aquatic organisms are required if the submitted data on the active substance give insufficient information or if there are indications of risks fromto be ascribed to specific properties of the product. Furthermore, the type of use (including use concentrations, dosages and frequencies) proposed by the applicant may trigger additional data requirements if it deviatesdeviating from the type of use assessed in the EU CAR as part of the Annex I inclusion may trigger additional studies.

Chronic toxicity studies aquatic organisms Chronic toxicity data for the active substance are mandatory for a number of product groups, see TNsG on data requirements*..* In addition, chronic toxicity data must be submitted in the following cases (see TGD: Part II* 3.3.1.1):- chronic (prolonged) exposure;- if substances show no toxicity in short term test but have a log Kow > 3 and/or BCF > 100

and the PEC > 1/100th of the water solubility;- PEC/PNEC > 1 based on acute data. In the TGD: Part II* Chapter 6.3 Refinement Of PNEC: Strategy For Further Testing, the following additional guidance is given: Where L(E)C50 > 100 mg/L, chronic studies are not required; this does not apply for substances with a water solubility < 1 mg/L.

Chronic toxicity studies must be carried out with crustaceans and fish species. Different types of chronic studies can be carried out for fish and which test is most suitable is decided on a case-by-case basis. These studies are described in the TNsG on data requirements*.

Other toxicity data aquatic organismsOther toxicity studies for aquatic organisms are described in the TNsG on data requirements*.

Microcosm or mesocosm studySubmission of microcosm or mesocosm studies is an option for refinement of the risk assessment. These type of studies can be submitted if the calculated concentration in surface water or sediment exceeds the PNEC.

In the EU biocides framework, it has not yet been specifiedindicated which guidelines on the conduct and evaluation of a microcosm or mesocosm study must be followed. An EU workshop will be held on mesocosm and microcosm assessment, but for the time being the Technical guidance for deriving environmental quality standards (February 2010) may be used for the assessment of data from a microcosm or mesocosm study.

Sediment organismsThere are no product-type-specific data requirements for sediment organisms.

7.3.1.2 PNEC derivation

Freshwater organismsThe PNEC can be determined as follows:- at least 10 NOECs of 8 taxonomic groups , then a statistical extrapolation techniques can

be used. If only acute toxicity data on sediment organisms are available, see TGD: Part II*, Chapter 3.3.1.2 forgives more information; about

- if less data is available, the risk is determined on the basis of these toxicity data by applying an assessment factor of 1000, as well as on the basis of the equilibrium

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partitioning method. The lowest PNEC is used to estimate the risk.

Derivation of PNEC using the assessment factor approachA PNEC is established by applying an assessment factor to the lowest determined effect concentration from data submitted on about the toxicity to aquatic organisms (LC50, EC50, NOEC).The assessment factors for freshwater organisms) vary from 1-1000, depending on the amount of chronic, acute and mesocosm data available, and can be found in TGD: Part II* 3.3.1.1.

If the PEC/PNEC > 1, additional toxicity studies can be submitted for refinement of the PNEC derivation. Further test options are presented in the Appendix 1: Decision Table For Additional Aquatic Toxicity Testing in the TNsG on data requirements*.

Derivation of PNEC using statistical extrapolation techniques (SSD method)Species typically vary widely usually show a wide variation in sensitivity to biocides. This variation can be described by a sensitivity curve. In the scientific literature this approach is referred to as the ‘Species Sensitivity Distribution’ (SSD) method. An SSD is a statistical distribution, based on a collection of toxicity data fromon different species, visualised by a cumulative distribution curve (see Figure 1). The toxicity data in SSDs are in general ‘single species lab tests’.

0.0

0.2

0.4

0.6

0.8

1.0

0.0 1.0 2.0 3.0 4.010log Toxicity Data

Pote

ntia

lly A

ffect

ed F

ract

ion

Figure 1: Example of a cumulative SSD curve. The X axis represents the concentration of the relevant toxicity endpoint (e.g., NOECs or EC50s) of the different species; the Y axis represents the potentially affected fraction.

SSD curves can be used to calculate the concentration at which a certain fraction of the collection of species is affected.

The TGD: Part II*, Chapter 3.3.1.2 gives more information about:- input of the data;- which taxonomic groups are required in eachany case required;- minimum number of available data (at least 10 NOECs fromof 8 taxonomic groups);- procedure for dealing with several data for one species;- ‘fitting’ to a correct distribution.

The PNEC is calculated as follows:

PNEC = 5%SSD(50%c.i.) / AF

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N.B.: 5%SSD(50%c.i.) is the median estimate of the 5th percentile of the SSD. A visualisation of the calculation of the HC5 from a cumulative SSD curve and the corresponding 95% confidence intervals. An assessment factor of 1-5 is applied to the HC5. The TGD: Part II* indicates which points need to be taken into account when establishing the assessment factor (AF). A number of other recommendations are made, as well.

Figure 2: Visualisation of the calculation of the HC5 from a cumulative SSD curve and the corresponding 95% confidence intervals.

Derivation of PNEC using microcosm or mesocosm studiesSubmission of a microcosm or mesocosm study is an option for a further refinement of the risk assessment. These type of studies can be submitted if the calculated concentration in surface water exceeds the PNEC. In the EU biocides framework, it has not yet been specifiedindicated which guidelines on the conduct and evaluation of a microcosm or mesocosm study must be followed. An EU workshop will be held on mesocosm and microcosm assessment, but for the time being the Technical guidance for deriving environmental quality standards (February 2010) can be used for the assessment of data from a microcosm or mesocosm study.

Results from mesocosm tests conducted with Plant Protection Products can also be useful in risk assessments for aquatic toxicity in biocides. At TM level it has been agreed upon that it is possible to use a PPP mesocosm study to lower the AF for a laboratory NOEC, if the study provides a reduced uncertainty as to whether the laboratory species was the most sensitive species. The use of mesocosm data should always be assessed on a case-by-case basis. The case-by-case assessment should include an assessment of the quality of the study, the use of formulated products and possible effects of the different exposure patterns. The exposure patterns for biocides are often a continuous exposure and therefore the potential for recovery is disregarded for biocide risk assessment.in biocides. Only NOEC-values will be used in biocide risk assessments.

Sediment organismsThe PNEC can be determined as follows:- If no toxicity data on sediment organisms are available, the equilibrium partitioning method

and the toxicity data fromon aquatic organisms are used to identify whether a potential risk for sediment organisms exists.

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Lower limit

Median value


- If only acute toxicity data on sediment organisms are available, the risk is determined on the basis of these toxicity data by applying an assessment factor of 1000 as well as on the basis of the equilibrium partitioning method. The lowest PNEC is used to estimate the risk.

- If chronic toxicity data on sediment organisms are available, these form the basis for calculating a PNEC by applying assessment factors.

Derivation of PNEC using the equilibrium partitioning methodThe TGD: Part II* outlinesmentions a number of assumptions and remarks regarding the equilibrium partitioning method which should be taken into account before using this method.

PNECsed according to the equilibrium partitioning is derived using the following equation:

PNECsed = (Ksusp-water / RHOsusp) x (PNECwater x 1000)

Explanation of symbolsPNECwater Predicted No Effect Concentration in water [mg.L-1]RHOsusp bulk density of wet suspended matter [kg.m-3]Ksusp warterwater partition coefficient suspended matter water [m3.m-3]PNECsed Predicted No Effect Concentration in sediment [mg.kg-1]

Ksusp-water = Fwatersusp + Fsolidsusp x (Kpsusp / 1000) x RHOsolid

Kpsusp = Focsusp x Koc

RHOsusp = 1,150 [kg (ww) / m3]RHOsolid = 2,500 [kgsolid / msolid]Fwater-susp = 0.9 [mwater3 / msusp3]Fsolidsusp = 0.1 [msolid3 / msusp3] Focsusp = 0.1 [kgoc / kgsolid]

PNECsed is calculated on wet weight basis. Recalculation to dry weight can be derived from PNECsed, dw = 4.6 x PNECsed, wwt

If log Kow > 5 or the substance strongly adsorbs or binds to sediment by other mechanisms (covalent binding, surface activity, ionic binding), an additional assessment factor of 10 should be applied on the PEC/PNEC ratio. This additional assessment factor accounts for the possible oral uptake via sediment and the potential for biomagnification of the active substance for biomagnification.

Derivation of Determination PNEC by applying an assessment factor to chronic EC 10 and NOEC valuesThe PNEC is derived by applying an assessment factor to the lowest available NOEC or /EC10 obtained from chronic tests. The assessment factors for sediment organisms are given in chapter 3.5.4 in the TGD: Part II* 3.5.4. for chronic endpoints. If only acute toxicity data on sediment organisms are available, the risk is determined on the basis of adding a factor 1000 to the lowest toxicity value, as well as on via the basis of the equilibrium partitioning method. The lowest resulting PNEC is used to estimate the risk.

7.3.2 Sewage treatment plantIf the dossier does not require additional substance or product- type specific toxicity data beyond that which is found inadditional to the CAR, then the PNEC for STP can be taken from the CAR.

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7.3.2.1 Relevant toxicity data for PNEC derivationThe data requirements for the active substance and the product for evaluation of the risk to microorganisms in an STP are laid down in the TNsG on data requirements*: Chapter 2, section 7; Chapter 2, Part B, section 7, corresponding with the Biocidal Products Directive 98/8/EC*.

These data requirements are divided into standard data requirements (core data) that apply for each product type, with the . The different product types are elaborated in separatethe relevant chapters. Additional data must also be submitted whenin case a higher tier evaluation must be carried out.

MetabolitesCurrently, there is no guidance on the risk of metabolites foron microorganisms in an STP, as legislation and guidance documents are not clear regarding the definition of relevant metabolites when it comes to STPs. The fate and risk assessment of metabolites should thereforecurrently be performeddone using national guidance.

7.3.2.2 PNEC derivationDerivation of PNECSTP using the assessment factor approachThe data submitted about the toxicity to microorganisms in an STP (ECx, NOEC) are used to establish a PNEC by application of aan assessment factor. The assessment factors are given in chapter 3.4 in the TGD: Part II*.

For hydrophobic substances, two approaches for PNEC derivation are applied in case the test results of the different inhibition tests regarding the observed NOEC are higher than the water solubility of the tested substance. The first approach is that the assessment factor is applied to the observed concentration of the NOEC above solubility. The second approach is that the maximum solubility is used as PNECSTP (see Technical Meeting I and II 2006). At present both approaches are still accepted.

7.3.3 Marine compartment (water and sediment)If the dossier does not require substance or product- type specific toxicity data additional to the CAR, then the PNEC can be taken from the CAR.

7.3.3.1 Relevant toxicity data for PNEC derivationBesides the requirements laid down for freshwater species (see section 7.3.1), this the additional dataset should be submitted if direct emission to marine waters is to be expected (TNsG on data requirements, page 47):

An additional acute toxicity to fish for a marine species. An additional acute toxicity to invertebrates for a marine species. An additional acute toxicity to algae for a marine species.

Pooling of endpoints from freshwater and marine water studies An important part of theany evaluation of aquatic data involvesmust involve an assessment of the usefulness of the main body of freshwater ecotoxicity data in predicting effects in the marine environment. Therefore the use of pooled marine and fresh water toxicity data is recommended unless toxicity data from marine studies are significantly lower than freshwater, and vice versa. In general, if the difference is greatermore than a factor 10 the data cannot be pooled. In addition, the mode of action of the substance under evaluation shouldhas to be considered.

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7.3.3.2 PNEC derivationIf marine and freshwater toxicity data are similar, PNEC values should be derived from the most sensitive endpoint regardless of the medium.’ Additionally, at TMI08 it was concluded that ‘for the derivation of a PNEC for freshwater or saltwater the available toxicity data for freshwater and saltwater organisms can be pooled’. It should be noted that in CARs, a PNEC for marine waters is only addressed if emission of the active substance to marine water is to be expected.

Derivation of PNEC using the assessment factor approachA PNEC is established by applying an assessment factor to the lowest determined effect concentration from data submitted about the toxicity to marine organisms (LC50, EC50, NOEC).

The assessment factors for saltwater organisms vary from 10-10000 (TGD: Part II* chapter 4.3.1.3). The assessment factors for saltwater organisms are higher because there is a larger variety of in organisms and thus potentially larger variations in sensitivity betweenamong saltwater species. Sediment organismsThe PNEC can be determined as follows:- If no toxicity data on sediment organisms are available, the equilibrium partitioning method

and the toxicity data on aquatic organisms are used to identify whether a potential risk for sediment organisms exists.

- If only acute toxicity data on sediment organisms are available, the risk is determined on the basis of these toxicity data by applying an assessment factor of 1000, as well as on the basis of the equilibrium partitioning method. The lowest PNEC is used to estimate the risk.

- If chronic toxicity data on sediment organisms are available, these form the basis for calculating a PNEC by applying assessment factors.

PNECsed according to the equilibrium partitioning is derived using the following equation:

PNECsed = (Ksusp-water / RHOsusp) x (PNECwater x 1000)

The assessment factors for marine sediment organisms are given in chapter 4.3.2.4 in the TGD: Part II* and are applied to the lowest LC50, /NOEC or /EC10 value. A distinction is made between short-term and long-term sediment toxicity tests for the application of assessment factors.

7.3.4 Soil compartmentIf the dossier does not require substance or product type specific toxicity data additional to the CAR, then the PNEC for terrestrial organisms can be taken from the CAR.

7.3.4.1 Relevant toxicity data for PNEC derivationThe following toxicity data are required if the risk assessment for the terrestrial compartment (, based on the equilibrium partitioning method) indicates a concern for the terrestrial compartment, or if there is long term exposure (Chapter 2.5, TNsG on data requirements*).

Data requirements for the active substance(s)

Standard data requirementsFor most biocide uses of biocides, there are no standard data requirements for soil organisms (including bees and non-target arthropods). The TNsG on data requirements,

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however, indicates that for substances with direct release to soil it is necessary to perform initial terrestrial tests with earthworms, plants and soil microbes.microbial activity. Examples includeare substances to be used as soil or solid waste disinfectants (PT2), substances with releases into manure storage facilities (e.g. PT3 and 18 related uses), wood preservatives with high releases to soil (PT8, Hazard Class (HC)3 and HC4a), substances for remedial treatment as well as spray application in general (PT10) or spray drift from open cooling towers (PT11), substances forFor inland use of drilling and oil recovery preservatives (PT12), substances with outdoor use, of products like molluscicides (PT16), insecticides (PT18), attractants and repellents (PT19), rodenticides (PT 14) and products for the control of other vertebrates (PT23), including gassing, fogging or fumigation applications.;Tests with bees and other beneficial arthropods are necessary only for Product type 18: Insecticides, acaricides and products to control other arthropods and Product type 19: Repellents and attractants.

Product - type specific and additional data As a first tier, the equilibrium partitioning method is used to derivewhich derives a PNEC based on aquatic toxicity data (see section 7.3.1 Aquatic compartment (water and sediment) for details on the method). If PEC/PNEC > 1 then tests with soil organisms are required, including: . Furthermore, product-type-specific and additional data can be required for a number of product types. These studies are described in the TNsG on data requirements* w. It is necessary to perform all 3 tests to allow a derivation of a more realistic PNEC for the terrestrial compartment than the PNEC based on the equilibrium partitioning method (TGD: Part II*).

1. Inhibition of microbial activity

2. Acute toxicity to earthworms or other soil non-target macro-organisms

3. Acute toxicity to plants

Results from all 3 tests are necessary in order to derive of a PNEC for the terrestrial compartment that is more realistic than the PNEC based on the equilibrium partitioning method (TGD: Part II*). Furthermore, product-type specific and additional data can be required for a number of product types. These studies are described in the TNsG on data requirements*.

Additional dataLong-term terrestrial tests are required if the risk assessment for the terrestrial compartment, based on the results from the acute test data toxicity tests still indicates a concern for the terrestrial compartment. Data on honeybees and other beneficial arthropods should be provided if the in case of specific mode of action would indicatewhich could expect that these species are more sensitive than earthworms, plants or micro-organisms. The NOEC from the study on the inhibition of microbial activity can be used as an additional long-term endpoint. Other tests may include one or more of the followingresult:

4. Reproduction study with earthworms or other soil non-target macro-organismsE.g. a test according to ISO standard 11268 (part 2, ISO 1998) or 16387, or a Collembola reproduction test according to the draft ISO standard 11267 (ISO, 1996), an). Or to OECD standards OECD 222: Earthworm reproduction test; OECD 226: predatory mite Hypoaspis reproduction test, or an OECD 232: Collembolan reproduction test.

5. Long-term test with terrestrial plants (e.g. ISO 22030)., a test protocol for inhibition of the

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6. Acute toxicity to honeybees and other beneficial arthropods, for example predators.

Field data or data from a model ecosystem studySubmission of field data or data from a model ecosystem study is a possible option for a further refined risk assessment. Such a study can be submitted if the calculated concentration in the soil exceeds the PNEC. Currently, the EU framework Biocides hasholds no guidelines for the execution of field studies or how to assess data from a model ecosystem. The Guidance Document on Terrestrial Ecotoxicology in the context of Directive 91/414/EEC* may be followed for elaboration on of the execution of field tests or a model ecosystem study. A workshop and guidance document are is currently under development for biocides and this document should be used when the final version is availablefinished.

Standardisation of toxicity data Soil toxicity data should be converted to a standard soil before they are used to derive PNECs. This standard soil has an organic-matter content of 3.4% (Fomsoil = 0.034). For non-ionic organic compositions it is assumed that the bioavailability is only determined by the organic matter. NOEC and L(E)C50(standard) are adjusted according to the following formula.

NOEC or L(E)C50(standard) = NOEC or L(E)C50(exp) x (Fom soil(standard) / Fomsoil(exp))

Explanation of symbolsNOEC or NOEC or L(E)C50 in experiment [mg.kg-1]L(E)C50exp

Fomsoil(standard) fraction organic matter in standard soil [kg.kg-1] Fomsoil(exp) fraction organic matter in experimental soil [kg.kg-1]NOEC or NOEC or L(E)C50 in standard soil [mg.kg-1]L(E)C50standard

It should be noted that this recommended normalisation is only appropriate when it can be assumed that the binding behaviour of a non-ionic organic substance in question is predominantly driven by its logKow or Koc, and that organisms are exposed predominantly via pore water. Organic matter standardisation is not relevant for substances with low sorption characteristics.

7.3.4.2 PNEC derivationThree situations can be distinguished for deriving a PNECsoil:1. Whenwhen no toxicity data are available for soil organisms, the equilibrium partitioning

method is applied to identify a potential risk to soil organisms. This method is regarded as a “screening approach” and is explained in Section 3.6.2.1 of the TGD part II* (see also Section 3.5.2 of the TGD part II for sediment).);

2. Whenwhen toxicity data are available for a producer, a consumer and/or a decomposer the PNECsoil is calculated using assessment factors as presented in Section 3.6.2.2.;

3. Whenwhen only one test result with soil dwelling organisms is available the risk assessment is performed both on the basis of this result using assessment factors and on the basis of the equilibrium partition method. From both PECsoil/PNECsoil ratios the highest one is chosen for the risk characterisation.

Equilibrium partitioning methodAssumptionsThere are assumptions which should be met before one can use the equilibrium partitioning method which can be found in TGD: Part II*. Derivation of a PNECsoil according to the equilibrium partitioning method proceeds as follows:

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PNECsoil = (Ksoil-water / RHOsoil) x (PNECwater x 1000)

Explanation of symbolsPNECwater Predicted No Effect Concentration in water [mg.l-1]RHOsoil bulk density of wet soil [kg.m-3]Ksoil-water partition coefficient soil water [m3.m-3]PNECsoil Predicted No Effect Concentration in soil [mg.kg-1]

Ksoil-water = Fair, soil x Kair-water + Fwater,soil + Fsolid, soil x (Kpsoil / 1000) x RHOsolid

Kpsoil = Focsoil x Koc

RHOsoil = 1,700 [kgsoil (ww) / m3]RHOsolid = 2,500 [kgsolid / msolid

3]Fwater, soil = 0.2 [m3

water / msoil3]

Fsolid, soil = 0.6 [m3solid / msoil

3] Fair, soil = 0.2 [m3

air / msoil3]

Focsoil = 0.1 [kgoc / kgsolid]

PNECsoil derived with the equilibrium portioning method is calculated on wet weight basis. Recalculation to dry weight can be derived from PNECsoil, dw = 1.13 x PNECsoil, ww. If log Kow > 5 or the substance strongly adsorbs or binds to soil by other mechanisms (covalent binding, surface activity, ionic binding), an additional assessment factor of 10 on the PEC/PNEC ratio should be applied to the PEC/PNEC ratio. This additional assessment factor accounts for the biomagnification potential of the chemical in soil organisms.

Assessment factorsA PNEC is established by applying an assessment factor to the lowest determined effect concentration from data submitted onabout the toxicity to soil organisms (LC50, EC50, or NOEC). The assessment factors are given in chapter 3.6.2.2. in the TGD: Part II*If PEC/PNEC > 1, the TNsG on data requirements* indicates that additional toxicity studies can be submitted to refine the PNEC derivation.

Species sensitivity distributionThe TGD: Part II* contains a brief introduction about the SSD method for soil organisms. In general, the SSD method for soil organisms corresponds with the SSD method for aquatic organisms (see section 7.3.1.2 Aquatic compartment (water and sediment)). The same minimal requirements for the SSD methodology are used: 10 species from 8 taxonomic groups. In soil, also 95% of the species are protected and thus a hazard concentration at which 5% of the species is at risk (HC5) is calculated. An additional assessment factor of 1-5 could be added on top of the HC5.

Field data or model ecosystem studiesSubmission of field data or data from a model ecosystem study is an option for further refinement of the risk assessment. These type of studies should be submitted if the calculated concentration in the soil exceeds the PNEC. It has not yet been indicated in the EU framework Biocides how field studies or model ecosystem data must be evaluated. The assessment factor to be applied on these type of toxicity data will be decided on a case by case.

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7.3.5 Birds and mammals

7.3.5.1 Relevant toxicity data for PNEC derivation

Standard data requirementsThere are no standard data requirements for birds laid down in the TNsG on data requirements* and the Biocidal Products Directive 98/8/EC*. For mammals, data are submitted for the aspect human toxicology and these can be used to derive a risk limit for mammals in the environment. The amount of animal testing, especially on vertebrates, shall be minimised. This means that all unnecessary testing of substances and preparations must be avoided, and the data should be shared between applicants.

Product - type specific and additional data Product- type specific and additional data are required for a number of product types. These studies are described in the TNsG on data requirements*.

Higher tier studiesSubmission of a higher tier study may be required in the context of a refinement of the risk assessment. This needs to be provided if the PEC/PNEC ratio exceeds the PNEC. The EU framework biocides does not indicate which higher tier studies may be submitted and how these must be carried out.

Data requirements for the specific product Product- type specific data are described in the TNsG on data requirements*. Besides studies that must also be provided for the active substance (7.5.3.1.1, 7.5.3.1.2 and 7.5.3.1.3), in some situations the following data must be provided as additional data. Product-specific data are required if the submitted data on the active substance provide insufficient information or if there are indications of risks to be ascribed to specific properties of the finished product.

For mammals, data on reproduction toxicity are provided for the aspect human toxicology.

Studies for further refinement of the risk assessmentSubmission of a higher tier study is possible in the context of the refinement of a risk assessment. This needs to be provided if the PEC/PNEC exceeds the PNEC. For the possibilities of a higher tier study we refer to the European Guidance Document on Risk Assessment for Birds and Mammals*.

7.3.5.2 PNEC derivationThis section is a summary of the TGD: Part II*, section 3.8.3.5. When deriving PNECoral for anti-coagulants, attention must be paid to the supplement to the TGD , “PNECoral derivation for the primary and secondary poisoning assessment of anti-coagulant rodenticides*.

Calculation of the predicted no-effect concentration (PNECoral)NOECbird = NOAELbird * CONVbird

NOECmammal, food chr = NOAELmammal, oral chr * CONVmammal

Explanation of symbols NOECbird NOEC for birds (kg.kg–1 food)NOECmammal, food chr NOEC for mammals (kg.kg–1 food)NOAELbird NOAEL for birds (kg.kg–1 food)NOAELmammal, oral chr NOAEL for mammals (kg.kg–1 food)

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CONVbird conversion factor from NOAEL to NOEC (kg bw.d.kg–1food) CONVmammal conversion factor from NOAEL to NOEC (kg bw.d.kg–1food)

Conversion factors from NOAEL to NOEC can be found in TGD: Part II*, Table 22, section 3.8.3.5

The PNECoral is ultimately derived from the toxicity data (food basis), applying an assessment factor using the following equation:

PNECoral = TOXoral / AForal

Explanation of symbols PNECoral PNEC for secondary poisoning of birds and mammals [kg.kg-1 food]AForal assessment factor applied in extrapolation of PNEC [-] TOXoral either LC50 bird, NOECbird or NOECmammal, food, chr [kg.kg-1 food]

Assessment can be found in TGD: Part II*, Table 23, section 3.8.3.5

For more additional information about the assessment of secondary poisoning via the aquatic food chain, see the TGD: Part II*, Chapter 3.8.3.6.

7.3.6 PBT/vPvB assessment PBT substances are those substances that are persistent, bioaccumulative and toxic, while vPvB substances are characterised by a particular high persistency in combination with a high tendency to bio-accumulate, but not necessarily proven toxicity. PBT substances will have been flagged at EU level.Inlevel. In general, the PBT/vPvB assessment is based on the single components of the product..

It should be checked in the CAR which methodology was used to establish the PBT/vPvB assessment. Currently, data received for biocidal products according to the legal guidelines for authorisation of biocidal products, data received for biocidal products should will be assessed for PBT/vPvB using REACH Annex XIII guidance.. However, many CARs will have a PBT/vPvB assessment based on (older) TGD requirements. Therefore the CAR mustIt should therefore be checked as to which method was used forin the PBT assessment.CAR. On product authorisation level, REACH Annex XIII* guidance should be followed for the PBT/vPvB assessment.

If an active substance, a metabolite or a substance of concern contained in the product have been flagged as PBT or vPvB substance, then this has consequences for the product assessment.. For PBT substances a “safe” concentration in the environment cannot be established with sufficient reliability. The PBT assessment is particularly developed to take into account the unacceptablyunacceptable high uncertainty in predicting reliable exposure and/or effect concentrations, hampering quantitative risk assessment. According to TNsG on Annex I inclusion (2002) substances which fulfil PBT or vPvB criteria shall not be included in Annex I unless releases to the environment can be effectively prevented. However, there may be cases, in which PBT/vPvB substances are listed in Annex I due to the absence ofno available alternatives for the same product type (e.g. rodenticides). Thus, there is a the possibility, that products couldwill contain PBT/vPvB substances. If the product contains PBT and vPvB substances, this has consequences for the product assessment. To prevent releases to environmental compartments, establishment of the most appropriate and effective risk mitigation measures is necessary.

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If the PBT of vPvB Therefore if the substances are identified, then the following step is an evaluation of the sources, major emissions and pathways to the freshwater or marine environment and soil to sufficiently establish the most appropriate and effective measures to reduce the releases to the environmental compartments. The urgency and stringency of possible measures may, however, be dependent on the potential forof the substance to be transported to the open sea. This can be assessed qualitatively by considering the use pattern, volumes and emissions, or by using measured data. Open applications and wide dispersive uses of the substance, are regarded particularly relevant as well as non-minimised direct discharges from production, formulation and industrial use, are regarded as particularly relevant. See also TGD TGD: Part II*.

The sections below will provide guidance on PBT/ vPvB assessments from REACH Annex XIII* if product data on degradation, toxicity and bioconcentrations are substantially different than the LoEP of its active substance(s).

The PBT assessment of biocides follows the PBT assessment as it is stated in REACH Annex XIII*, as decidedwhich was a decision made during the CA meeting of December 2009. Experience with PBT/vPvB substances has shown that they can give rise to specific concerns that may arise due to their potential to accumulate in parts of the environment and 1) that the effects of such accumulation are unpredictable in the long-term; 2) such accumulation is practically difficult to reverse as cessation of emission will not necessarily result in a reduction in chemical concentration in the environment. Furthermore, PBT or vPvB substances may have the potential to contaminate remote and pristine environments areas that should be protected from further contamination due to their by hazardous substances resulting from human activity because the intrinsic value of pristine environments should be protected.

The criteria for the identification of PBT and vPvB substances are summarised in the table below. For more information about the PBT and vPvB criteria see REACH Annex XIII*. The detailed analysis of the Persistence, Bioaccumulation and Toxicity should be assembledbrought together into a clear conclusion on whether the product includes an ingredient that should be treated as a PBT/vPvB substance.

Property PBT-criteria vPvB-criteriaPersistence The assessment of the persistency in the environment shall be based on available half-life data collected under the adequate conditions, which shall be described by the registrant.

- T1/2 > 60 days in marine water, or- T1/2 > 40 days in fresh- or

estuarine water, or- T1/2 > 180 days in marine

sediment, or- T1/2 > 120 days in fresh- or

estuarine sediment, or- T1/2 > 120 days in soil.

- T1/2 > 60 days in marine, fresh- or estuarine water, or

- T1/2 > 180 days in marine, fresh- or estuarine sediment, or

- T1/2 > 180 days in soil.

Bioaccumulation The assessment of bioaccumulation shall be based on measured data on bioconcentration in aquatic species. Data from freshwater as well as marine water species can be used.

BCF > 2000 L/kg BCF > 5000 L/kg

Toxicity - NOEC (long-term) < 0.01 mg/L for marine or freshwater organisms, or

-

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- substance is classified as carcinogenic (category 1 or 2), mutagenic (category 1 or 2), or toxic for reproduction (category 1, 2 or 3), or

- there is other evidence of chronic toxicity, as identified by the classifications: T, R48, or Xn, R48 according to Directive 67/548/EEC

7.3.7 Endocrine disruptionIn the TGD: Part II* section 3 effects assessment – 3.1 introduction is indicated:

Knowledge on endocrine disrupting effects of some substances is presently under development. When substantial evidence on such effects is available, this should be taken into account on a case-by-case basis in the derivation of the PNEC for each compartment of relevance. Existing knowledge does not allow a more standardised approach for risk assessment of such substances.

Additionally in the TGD: Part II* section 4.3.1.3 PNEC derivation for the marine environment as part of the proposed assessment factors it is indicated that: When substantiated evidence exists that the substances may be disrupting the endocrine system of mammals, birds, aquatic or other wildlife species, it should be considered whether the assessment factor would also be sufficient to protect against effects caused by such a mode of action, or whether an increase of the factor would be appropriate. At present no guidance is available on how to take into account endocrine disruption in the PNEC derivation. On OECD-level a “Guidance document on the Assessment of Endocrine Disrupting Substances*” is under development. Furthermore within the revision of Directive 91/414/EEC concerning the placing of plant protection products on the market the issue of endocrine disruption was introduced as an approval criterion as well. With entry into force of the new Regulation 1007/2009/EC in June 2011, specific criteria for the determination of endocrine disrupting properties have to be developed within the next 4 years. Since this is a living document, new guidance on this subject willshould be added at a later point in time but as soon as new guidance/information is available. Extra attention to possible ecological risks is, however, required if such a product is applied outdoors, or if, due to the use and substance characteristics, large emissions to the environment are expected.

7.4 Risk characterisation

This section contains a lot ofmuch text. The text and structure could be replaced by decision trees in the future throughby input of MSs.

7.4.1 Tiered approachThe risk to environmental compartment follows in general a tiered approach. The first tier is a general conservative evaluation of the behaviour and toxicity of the substance in the environment. It is in general based on model data regarding exposure, laboratory toxicology studies and for example, the equilibrium partitioning for certain PNEC derivations.

If the trigger values of the first tier of the evaluation are not met, the applicant is offered the opportunity to submit additional data for conducting a refined risk evaluation (higher tier). In general this includes additional chronic studies (aquatic and soil) and/or more realistic

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exposure data. Alternatively, the applicant can choose for risk reduction measures, but the applicant must prove that these measures are effective and thus reduce the risk(s).

7.4.1.1 Aquatic compartment (water and sediment)Refinement of the risk assessmentIf the PEC>PNEC, the specific use of the product in question is considered as non-permissible unless a further refinement of the risk assessment shows that there are no unacceptable direct or indirect effects on aquatic organisms under relevant field conditions.

For a further refinement of the risk assessment, data must be submitted which either refine the predicted concentration in surface water or refine the effect concentration under field conditions; here, (semi) field experiments (such as mesocosm studies) are possible, where a more realistic exposure is simulated, or laboratory studies with additional species.

In the EU biocides framework, it has not yet been indicated which guidelines on the conduct and evaluation of a microcosm or mesocosm study must be followed. An EU workshop will be held on mesocosm and microcosm assessment, but for the time being the Technical guidance for deriving environmental quality standards (February 2010) can be used for the assessment of data from a microcosm or mesocosm study. If the refined risk assessment shows that PEC / PNEC ≤ 1, the criteria are met.

If PEC / PNEC > 1 in the refined risk assessment, the criteria are not met and the use in question of the product can notcannot be allowed on the market unless risk reduction measures can be implemented. The applicant should provide evidence that the proposed mitigation measures / restrictions are realistic and will result in an acceptable risk.

Sediment organismsA To avoid extensive testing of chemicals a log Koc or log Kow of < 3 indicates that a sediment effects assessment is not necessary and the. The criteria for toxicity sediment organisms are met. Also if the PEC/PNEC <1 (or if 10 x PEC / PNEC < 1 for log Kow > 5) using the equilibrium partitioning, the criteria for toxicity sediment organisms are met.

Refinement of the risk assessmentIf a PEC/PNEC ratio is >1, the use in question is considered as non-permissible unless a refinement of the risk assessment shows that there are no unacceptable direct or indirect effects on sediment organisms under relevant field conditions.

If the ratio (PEC / PNEC) is greater than 1, study 7.4.3.5.1 (Total sediment tests with sediment organisms (using spiked sediment)) should be carried out.

If a microcosm or mesocosm study data is used and the PEC / PNEC < 1, the criteria for toxicity sediment organisms are met.

If PEC / PNEC > 1 using data from microcosm or mesocosm studies, the criteria are not met and the use in question of the product can notcannot be allowed on the market UNLESS risk reduction measures can be implemented. The applicant should provide evidence that the proposed mitigation measures / restrictions are realistic and will result in an acceptable risk.

7.4.1.2 Sewage treatment plantThe risk assessment for microorganisms in an STP has been elaborated in the following

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documents: Technical Guidance Document (TGD): Part II*, Part 2, Chapter 3.4.

The risk assessment for microorganisms in an STP is carried out by comparing the PNEC with the PEC. In line with the TGD: Part II*,* approval of a certain use of the product is obtained if the PEC / PNEC ≤ 1, thus meeting the criteria for toxicity to microorganisms in the STP the uses in question for the product can be approved.are met. This applies for the active substance, relevant metabolites and other components of the product:

If PEC ≤ PNEC microorganisms then the criteria for toxicity microorganisms in an STP are met.

If the active substance, metabolites or other components of the product do not meet the trigger values above, the criteria for toxicity microorganisms in an STP are not met. The use in question of the product can notcannot be allowed on the market UNLESS risk reduction measures can be implemented. The applicant should provide evidence that the proposed mitigation measures/restrictions are realistic and will result in an acceptable risk.

7.4.1.3 Marine compartment (water and sediment)Section 7.4.1.1 Aquatic compartment (water and sediment) covers both freshwater and marine compartment for determination of the exposure.

7.4.1.4 Soil compartment (including groundwater for drinking water production) The risk assessment for the soil organisms is carried out by comparing the PNEC with the PEC. In line with the TGD: Part II*,* approval of a certain use of the product is obtained if the PEC / PNEC ≤ 1, meetingand thus the criteria for toxicity to soil organisms, the use in question can be approved. is met. This applies for both the active substance and relevant metabolites.

When the PNEC is based on toxicity data fromon soil organisms or the equilibrium partitioning method is used to identify whether a potential risk for soil organisms exists and the PEC/PNEC ratio is < 1 (or if 10 x PEC / PNEC ≤ 1 for log Kow > 5 with the equilibrium partitioning method), then the criteria for toxicity to soil organisms are met.

Refinement of the risk assessmentIf PEC/PNEC >1, the use in question is considered as non-permissible unless a refined risk assessment shows that there are no unacceptable direct or indirect effects on soil organisms under relevant field conditions.

For a refinement of the risk assessment, data must be submitted which supportgive cause for adjustment of the calculated concentration in soil and/or for adjustment of the effect concentration under field conditions. To that end; here, field studies or model ecosystems, where a more realistic exposure is mimicked, or laboratory studies with additional species that are representative of soil, are possible options.

If the refined risk assessment shows that PEC / PNEC ≤ 1, the criteria for toxicity to soil organisms are met.

If the refined risk assessment shows that PEC / PNEC > 1, the criteria are not met and the use in question of the product can notcannot be allowed on the market UNLESS risk reduction measures can be implemented. The applicant should provide evidence that the proposed mitigation measures / restrictions are realistic and will result in an acceptable risk.

The refined risk assessment for bees or non-target species is based on expert judgement

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on a case- by- case basis.

Groundwater criteria evaluation summaryThe Biocidal Products Directive 98/8/EC* statesimplies that for biocides the trigger value for pesticides in groundwater is applied. The concentration in groundwater should therefore be <0.1 μg/L for active substance and relevant metabolites. The total concentration should be <0.5 µg/L. In addition, the trigger value applies for each separate biocide.

A decision tree is given below:.

Leaching to groundwater

7.2.3.1Adsorption / desorption Screening test in 5 soil types for

a.s. and 3 soil types for metabolites > 10% applied a.s.(full scale)

7.2.3.2Field study

(e.g. Monolith lysimeter study)

no

yes

no

yes

Is it ruled out that the activesubstance reaches the soil?

No further researchrequiredyes Permissible

yes

Initial PEC soil based on DT50, Koc/KpESD's and calculation models

PEC/PNEC > 1? orleaching to groundwater?

Koc/Kp

no

PEC groundwater based on DT50, Koc/KpESD's, calculation models or

leaching modelsPEC groundwater > 0.1 ug/l ?

Permissible

PermissiblePEC groundwater > 0.1 ug/l

Not permissible

no PermissibleDirect emission of the activesubstance to the soil?

1

23

4

5

6

6

yes

no

Leaching to groundwater

7.2.3.1Adsorption / desorption Screening test in 5 soil types for

a.s. and 3 soil types for metabolites > 10% applied a.s.(full scale)

7.2.3.2Field study

(e.g. Monolith lysimeter study)

no

yes

no

yes

Is it ruled out that the activesubstance reaches the soil?

No further researchrequiredyes Permissible

yes

Initial PEC soil based on DT50, Koc/KpESD's and calculation models

PEC/PNEC > 1? orleaching to groundwater?

Koc/Kp

no

PEC groundwater based on DT50, Koc/KpESD's, calculation models or

leaching modelsPEC groundwater > 0.1 ug/l ?

Permissible

PermissiblePEC groundwater > 0.1 ug/l

Not permissible

no PermissibleDirect emission of the activesubstance to the soil?

1

23

4

5

6

6

yes

no

7.4.1.5 AirThe distribution of volatile biocides via the air will be evaluated in accordance with the TGD: Part II*. This document states ‘It is evident that the quantitative characterisation of risk by comparison of the PECair to PNECair is not possible at the moment: only a qualitative assessment for air is feasible.’ For most, if not all, chemicals this holds true and therefore only the qualitative methodology is summarised here, based on the TGD: Part II* and TNsG on data requirements*. If however, there is toxicity data available then the TGD: Part II* must

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be followed to assess the risk to biota.

Standard data requirements Phototransformation in air (estimation method) [Ann. IIIA, VII.5] An estimation of this parameter is necessary for the risk assessment. Although for some chemicals direct photolysis may be an important breakdown process, the most effective elimination process in the troposphere for most substances is as a result ofresults from reactions with photochemical generated species such aslike OH radicals, ozone and nitrate radicals. In a first approach, the specific first order degradation rate constant of a substance with OH-radicals can be estimated viaby (Q)SAR methods. Further details can be found in TGD: Part II*.

Further data requirement s – product specific There are no product-type-specific data for behaviour in air. The additional studies as described in the TNsG on data requirements* are presented below.

Fate and Behaviour in Air If the product is a fumigant or its active substance has a large potential to cause risk to the atmospheric environment, its degradation behaviour has to be determined experimentally (e.g. according to the methods described in OECD, 1992). For the most important processes, the rate constants should first be estimated theoretically and then, after considering the relative importance of the various processes, confirmed experimentally. For experimental estimation the data must be submitted for a purified active substance of stated specification.

• The identification of transformation products which at any sampling time account for more than 10% of the active substance added is required unless the half-life of the transformation product is less than 3 hours.

• The data submitted should be representative of for atmospheric conditions (light intensities, spectral distribution, etc.).

• Procedures for assessing the environmental fate and ecotoxicity of pesticides. Ed. M. Lynch. Society of Environmental Toxicology and Chemistry, SETAC - Europe, Brussels. March 1995. ISBN 90-5607-002-9.

Abiotic effectsThe evaluation of an atmospheric risk is mainly based on abiotic effects. The following abiotic effects of a chemical on the atmosphere have to be considered according to the TGD:• global warming;• ozone depletion in the stratosphere;• ozone formation in the troposphere;• acidification.

Additional effects to be taken into account from the TNsG on data requirements*: Degradation ofDegrading air quality (visibility, effects on human health, bad smell, effects

on plants); Long range transport.

If the physico-chemical characteristics of a chemical indicategives an indication that one or several of these effects may occur, expert knowledge should be employed.consulted. A first quantitative approach is described in De Leeuw (1993)*.

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Global warmingThe impact of a substance on global warming depends on its IR absorption characteristics and its atmospheric lifetime. A potential greenhouse gas shows absorption bands in the so-called atmospheric window (800-1,200 nm).

Stratospheric ozoneA substance may have an effect on stratospheric ozone if;• the atmospheric lifetime is long enough to allow for transport to the stratosphere, and;• it contains one or more Cl, Br or F atoms.

In general, ozone depletion potential values approach zero for molecules with atmosphericlifetimes less than one year.

Tropospheric ozoneThe generation of tropospheric ozone depends on a number of factors:• the reactivity of the substance and the degradation pathway;• the meteorological conditions (. The highest ozone concentrations are expected at hightemperatures, high levels of solar radiation and low wind speeds.);• the concentration of other air pollutants (i.e. the. The concentration of nitrogen oxides has to exceedseveral ppb).

Highly reactive compounds (e.g. xylene, olefins or aldehydes) contribute significantly to theozone peak values. Species with a low reactivity (e.g. CO, methane) are important for ozoneformation in the troposphere and therefore for the long-term ozone concentrations.However, all studies have shownshowed significant variability in the tropospheric ozone building potential values assigned to each organic component. It must therefore has to be concluded that at present there is no procedure available to effectively estimate the effect on tropospheric ozone if only the basic characteristics of a substance are known.

AcidificationDuring the oxidation of substances containing Cl, F, N or S constituents, acidifying components (e.g. HCl, HF, NO2 and HNO3, SO2 and H2SO4) may be formed. After deposition, these oxidation products will lead to acidification of the receiving soil or surface water.

DecisionsDecisions on approval are taken in accordance with the Common Principles of the Biocides Directive. The biocide is evaluated against the trigger values for the risk of the behaviour in air, as indicated in the Biocides Directive, as follows.

The following applies for the biocide and relevant transformation products:

If no unacceptable effects on air quality are expected then the criteria are met.

If the possibility of unacceptable effects on air quality is expected and if it is not scientifically demonstrated that no unacceptable effect occurs under relevant field conditions, the.

The criteria are not met.

When determining unacceptable effects, the additional criteria given in the TNsG on product evaluation* should be taken into account.

7.4.1.6 Birds and mammals (primary and secondary exposure)The risk assessment and comparison for acute toxicity for birds and mammals has been elaborated in the following documents:

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TGD: Part II* - Chapter 3.8 and 4.3.3, PT14: Addendum TGD: PNECoral derivation for primary and secondary poisoning for rodenticides* of anti-coagulant rodenticides and TNsG on data requirements*.

Risk assessment for birds and mammals follows a tiered approach. The first tier is based on a general realistic worst case evaluation of behaviour and toxicity of the active substance in the environment. If the trigger values in the first tier of the evaluation are not met, the applicant is given the opportunity to submit additional data for its product on the basis of which a refined evaluation is carried out (higher tier).

The assessment of birds and mammals includes both a qualitative assessment and a quantitative risk assessment. Reason for these separate approaches is that at present the TGD: Part II* does not give guidance on how to derive a PNEC for short term exposure.

Exposure via granules In a number of CARs with biocidal products applied as granules, risk assessment methods were taken from the European Guidance Document on Risk Assessment for Birds and Mammals*. This document specifically refers to the EPPO risk assessment scheme* when granules have to be assessed. In general, the EPPO methods should be followed. However, in some cases the default values for focal species in the EPPO scheme differ from those in the Guidance Document, and input values from the latter should be used.

Qualitative assessment:The qualitative assessment is carried out for both primary poisoning and secondary poisoning. It is intended to give a first indication of the acute toxicity of the substance but is notnever conclusive enough to allow a product on the market. Furthermore this approach is NOT meant for comparative assessment. Except for the conclusion that a substance is acutely toxic (yes or no), no further conclusions can be drawn from this approach.

Primary poisoning via the intake of the biocidal productThe acute toxicity to birds and mammals of a substance is estimated by comparing the estimated concentration in the environment -, the PEC with the acute LD50 for the short term situation [mg/kg bw]. No ratio is determined. Two Tiers are considered: Tier 1, where the PECoral is the concentration of the active substance in the food (bait)

[mg/kg food]. As a Tier 2 for 1 days exposure with and without excretion, where the PECoral is the

expected concentration of the active substance in the non-target animal after 1 day exposure (single meal) [mg/kg bw], taking excretion into account.]. A default excretion factor of 0.3 (for birds and mammals) should be used in case no data is available. For a first step worst case, the parameter avoidance factor (AV), Fraction of diet in the treated area (PT) and Fraction of food type in diet (PD) are all 1. For a more realistic worst case AV = 0.9, PT = 0.8 and PD = 1.

Conclusion: if PEC > LD50 then the substance is acutely toxic.

Secondary poisoning via the contaminated target speciesThe In a first tier is a qualitative approach for the acute situation to compare the possible single uptake (with Frodent = 1) with a LD50 of the active substance (mg/kg bw).

Tier 1:, where the PECoral is the concentration in the rodent immediately after a last meal on day 5 [mg/kg food]. For a short-term exposure PD is 1 (rodents have fed entirely on rodenticide) and Frodent = 1 (non-target animals consume 100 % of their daily intake on

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poisoned rodents). For comparison calculations with PD = 0.5 and PD = 0.2 could also be included.

Conclusion: if PEC > LD50 then the substance is acutely toxic.

Quantitative risk assessment:The quantitative risk assessment for birds and mammals follows two routes:- exposure via primary poisoning (direct intake of the product);- exposure via secondary poisoning (consumption of food items contaminated with the

product).

The risk to birds and mammals is estimated by dividing the estimated concentration in the environment, the PEC, by the PNEC for the long-term situation. The PEC is calculated by using the Emission Scenario Documents and additional guidance, TGDs TGD and the “addendum relevant to biocides to the TGD on risk assessment” from 2006.Furthermore, PNECoral is derived on the basis of the data submitted on the toxicity to birds and mammals (LC50, LD50, NOEC) by the application of an assessment factor.

If the PEC< PNEC than the criteria is met.

If the PEC>PNEC than a second tier study should be submitted or risk reduction measures should be implemented.

A comparison ofThe difference between Tier 1 and Tier 2 is showngiven in the following table:

• • Primary poisoning • Secondary poisoning• Tier 1 • Risk is quantified as the ratio between the

concentration in the food for the non-target organism (PECoral) and the predicted no-effect-concentration for oral intake for the non-target organism (PNECoral)

• Risk is quantified as the ratio between the concentration in the rodent immediately after a last meal on day 5 (EC5) and the predicted no-effectconcentration for oral intake for the predator (PNECoral)

• Tier 2 • Tier 2 Risk is quantified as the ratio between the estimated daily intake of a compound (ETE) and the predicted no-effect-concentration for oral intake for the non-target organism (PNECoral).

• For the long-term exposure the• estimated concentration of the active

substance in the animal can be calculated and compared with the NOAEL

• Risk is quantified as the ratio between the estimated concentration in predatory mammals or birds and noobserved-

• adverse-effect-levels (NOAEL) for the organism

•

Refined risk assessmentSubmission of a higher tier study is possible in the context of a further refined risk assessment. The methodology to evaluate a field study can be found in PT14: ESD for rodenticides*.

7.4.2 Risk reduction measuresIf an unacceptable risk has been identified, it can be mitigated or reduced by risk reduction measures. The applicant and the Ref-MS can suggest certain risk reduction measures. However, the applicant must, provide evidence that the proposed risk reduction measures / restrictions are realistic and will result in an acceptable risk. Some risk reduction measures

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are specific for an environmental compartment while others are specific for a PT.

For the inclusion of active substances on Annex I, only a limited number of risk reduction measures have been accepted during TM meetings. However, many a lot of risk reduction measures are used at national level. Therefore, a workshop on risk reduction measures was held by DE in February 2011. We await the outcome of this workshop to finalise this section.

Measures to be adoptedThese measures include (see Biocidal Products Directive 98/8/EC*, pagpage 46):8.1 Recommended methods and precautions concerning handling, storage, transport and

use8.2. Re-entry periods, necessary waiting periods or other precautions to protect humans

and animals8.3. Emergency measures in case of an accident8.4. Procedures for destruction or decontamination of the biocidal product and its

packaging

In Chapter 2, part B of the TNsG on data requirements* (p. 65) this is further specified.

A well documented MSDS should cover a large part of the requirements regarding handling, use, storage, transport and fire. In some cases, the product label should include further instructions if required, based on the risk assessment.

It should be noted that waste disposal and other elements may depend on local regulations in the various Member States. Furthermore, the label and a Material Safety Data Sheet should be made available in the language(s) of the Member State where authorizationauthorisation is granted.

A harmonised approach is needed with regard to acceptable risk mitigation measures, when biocidal products are to be used by private users. UK will draft a paper on this item, directed at human exposure, not that of environment (listed in appendix III, future work).

Relevant documents:Risk mitigation measures for anticoagulants used as rodenticides*

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Appendix – ENV 1: Quality assessment of dataAll studies performed after the entry into force of the Biocidal Products Directive (BPD) must comply with the relevant EU test methods* and/or OECD Test Guidelines*.

For studies performed before 1998 which do not conform to these principles, a case-by-case decision on their acceptability (“expert judgement”) is required. In order forFor such a decision to be made, the applicant must submit the complete test report and with all data relevant to the interpretation of the study. Data quality assessment should also comply with the rules set out in the TGD: Part II*, chapter 3.2 for effect assessment.

Only secondary studies are available for certain substances. The documentation of these studies is usually considerably less rigorouspoorer than documentation in the form of test reports. As a rule, the following criteria must be satisfied if secondary studies are to be accepted for evaluation purposes:

- Performance in accordance with or closely based on national and international guidelines; and

- For the ecotoxicological effect tests, for example, the documentation of the data and methods must include the following points:a. Test method (apparatus, dosage, exposure time, physico-chemical test

conditions – pH, conductivity, temperature etc.)b. Specification of test substance, incl. purityc. Test organism and number of individuals tested, data on feedingd. Test parameters and their definitionse. Analysis (especially for poorly soluble / non-stable substances)f. Effect concentrations (ECx/NOEC/LOEC) incl. statistical data.

This documentation is to be adapted appropriately for other tests or studies. For example, the concentration, origin and adaptation of the inoculum must be specified in the case of biodegradability studies, or the characteristics of the soils used must be stated in the case of adsorption/ desorption studies.

If there are a large number of studies for an endpoint which yield concurring results although none of the studies taken on its own satisfies the above criteria, the end-point may under certain circumstances be covered by a “weight of evidence” approach under certain circumstances. This is described in more detail in “Guidance on Information Requirements and Chemical Safety Assessment” chapter 4* and chapter 5* (and on the previous REACH websites). This approach may, if appropriate, be supported by (Q)SAR estimates in the case of studies of ecotoxicity and abiotic degradability.

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Classification, Labelling and PackagingBiocidal products need to be classified for their physical, health and environmental hazards.

The system for classification and labelling in the EU consists of the Dangerous Substance Directive (DSD, 67/548/EEC) and the Dangerous Preparations Directive (DPD, 1999/45/EC*). Regulation (EC) No1272/2008* on the classification, labelling and packaging of substances and mixtures (hereafter referred to as CLP-Regulation) implementsis implementing the provisions of the Globally Harmonised System (GHS) within the EU, without lowering the protection of human health and environment, compared to the C&L system in DSD and DPD. The CLP-Regulation will replace DSD and DPD finally from 1 June 2015. UntilTill then, the timetables (taken from the Guidance on the application of Regulation (EC) 1272/2008*) are as follows:

From 1 December 2010 to 1 June 2015:Substances shall be classified, labelled and packaged in accordance with CLP-Regulation, but also classified in accordance with DSD in order to allow these classifications to be used in the classifications of mixtures. Classifications in accordance with both systems shall beincluded in the MSDS.

Mixtures shall be classified, labelled and packaged in accordance with DPD. They mayalso be classified, labelled and packaged in accordance with CLP-Regulation. In that case they shall not be labelled and packaged according to DPD. When a mixture is classified, labelled and packaged according to CLP-Regulation the classification information according to both systems shall be provided in the MSDS.

From 1 June 2015:Both substances and mixtures shall be classified, labelled and packaged in accordancewith CLP-regulation. DSD and DPD are repealed from 1 June 2015 .

However, substances classified, labelled and packaged in accordance with DSD and alreadyplaced on the market (“on the shelves”) before 1 December 2010, and mixtures classified,labelled and packaged in accordance with DPD and already placed on the market (“on theshelves”) before 1 June 2015, do not have to be relabelled and repackaged in accordance with CLP-Regulation until 1 December 2012 and 1 June 2017, respectively.

Harmonised classification and labelling formerly listed on Annex I to DSD can be found in table 3.1 of Annex VI to CLP-Regulation (translated into CLP classification/labelling) and in table 3.2 of Annex VI (according to the DSD criteria).

The CLP-Regulation will be regularly adapted to the technical progress. Recently, the CLP Regulation was amended by Regulation (EU) No 286/2011 (2nd ATP (Adaption to Technical Progress) which entered into force on 19 April 2011. The new rules apply to substances from 1 December 2012 and to mixtures from 1 June 2015, but can be voluntarily applied before those dates. Transitional provisions are foreseen for substances/ mixtures already placed on the market. The Guidance on the application of Regulation (EC) 1272/2008* provides a detailed guidance on the application of CLP criteria for physical, health and environmental hazards.This Guidance on the application of CLP Regulation with regard to the 2nd ATP is currently

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under revision.

The majority of the physical hazards of the biocidal product should be determined through testing of the product itself (see chapter 1-4). For health or environmental hazards, information on the product itself can be used, but the classification of the product can also be determined based on the classification of the active ingredient(s) and formulant(s) and their concentration in the product. CLP-Regulation also allows bridging principles to be used to classify a mixture.

The label of biocidal products has to include the additional details according to article 20(3) of the Biocidal Product Directive 98/8/EC. For this purpose DE provided a list with formulation proposals. MSs were invited to send their instruction phrases to DE. After the list is completed with the other MSs’ proposals, a check will be made how this list relates to CLP-Regulation (project by DE, listed in appendix III, future work).

The principle in selection of S-phrases is described in Annex VI to DSD. Some guidance on the selection of precautionary statements is included in Guidance on the application of Regulation (EC) 1272/2008*. As no guidance is yet developed at UN level, this must be considered as draft recommendations.

PackagingA detailed description of packaging in which the biocidal product will be marketed is required. Information should comprise of the following:- packaging size and dimensions;- the content of biocidal product;- packaging material (e.g. HDPE, PP, epoxy phenolic coating, etc.). If packaging consists

of multiple layers or is co-extruded, the various materials should be specified as well;.- if relevant to the risk-assessment, size of openings and/or photos of packaging.

A shelf-life study should be conducted in the proposed commercial packaging. However, if packaging is not identical, the shelf-life study conducted should bemay represent a worst-case scenario.

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8. Appendices

I Record ofTrack record changes to this Manual (including date of change)

• Version • Content • Date• 0.1 • Efficacy, Human RA,

Environmental RA, CLP• 29-10-2010

• 0.1 • Phys-chem • 13-5-2011• 1.0 (draft final for PA-

MRFG)• Efficacy, Human RA,

Environmental RA, CLP, Phys-chem

• July 2011

• 1.0 (draft final for COM) • • October 2011• 1.0 (draft final for CA) • Efficacy, Human RA,

Environmental RA, CLP, Phys-chem

• November 2011

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II Guidance towhich in the future should be included in future the TNsGs

Efficacy

Guidance missing:Specific guidance on PT 7,9, 11, 12, 16, 17, 19, 22 and 23 is missing. Appendices to chapter 7 should be made for these PT’s, similar to those of the other PT’s.

Guidance to be revised:Appendices to chapter 7 are rather concise. These should be revised for PT 1 to 6, 8, 10, 13 and 15. The appendices for PT 2, 5, 8, 18/19 and 21 are currently under revision. PT 14 is recently revised.

Environment

Guidance missing: Guidance on the use of mesocosms (applicablilityapplicability, reliability, assessment

factors) is missing. Endocrine disruption guidance for environmental risk assessment.

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III Future work

General

Harmonised template for PAR

Human Toxicology HarmonisedHarmonized approach in risk mitigation measures for private users (will

be drafted by UK and discussed with DE) HarmonisedHarmonized approach in risk mitigation measures for professional users

(will be drafted by UK and discussed with DE) Harmonising standard safety instruction phrases according to article 20 (3) of the

Biocidal Product Directive 98/8/EC – will be drafted by Germany Guidance on combination toxicity. The first version is available. MSs commented on

this version for TMI2011. France will adapt the version. HarmonisedHarmonized approach for evaluating micro-organisms Guidance to estimate residues in foods exposed to biocidal active substances

(DRAWG)

Environment: Describe tonnage and consumption based approach (section 7.2) Guidance on harmonised assessment of frame formulations (including efficacy, phys-

chem. and analytical methods, toxicology and ecotoxicology)

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IV List of standard terms and abbreviations

Stand. term / Abbreviation

Explanation

A ampere

ACh acetylcholine

AChE acetylcholinesterase

ADI acceptable daily intake

ADME absorption distribution metabolism and excretion

ADP adenosine diphosphate

AE acid equivalent

AF assessment factor

AFID alkali flame-ionisation detector or detection

A/G albumin/globulin ratio

ai active ingredient

ALD50 approximate median lethal dose, 50%

ALT alanine aminotransferase (SGPT)

Ann. Annex

AOEL acceptable operator exposure level

AMD automatic multiple development

ANOVA analysis of variance

AP alkaline phosphatase

approx approximate

ARC anticipated residue contribution

ARfD acute reference dose

as active substance

AST aspartate aminotransferase (SGOT)

ASV air saturation value

ATP adenosine triphosphate

BAF bioaccumulation factor


Explanation

BCF bioconcentration factor

bfa body fluid assay

BOD biological oxygen demand

bp boiling point

BPD Biocidal Products Directive

BSAF biota-sediment accumulation factor

BSE bovine spongiform encephalopathy

BSP bromosulfophthalein

Bt Bacillus thuringiensis

Bti Bacillus thuringiensis var. israelensis

Btk Bacillus thuringiensis var. kurstaki

Btt Bacillus thuringiensis var. tenebrionis

BUN blood urea nitrogen

bw body weight

c centi- (x 10 –2 )

°C degrees Celsius (centigrade)

CA controlled atmosphere

CAD computer aided design

CADDY computer aided dossier and data supply (an electronic dossier interchange and archiving format)

CAR Competent Authority Report

cd candela

CDA controlled drop(let) application

cDNA complementary DANN

CEC cation exchange capacity

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Explanation

cf confer, compare to

CFU colony forming units

CHARM Chemical Hazard Assessment and Risk Management

ChE cholinesterase

CI confidence interval

CL confidence limits

cm centimetre

CNS central nervous system

COD chemical oxygen demand

CPK creatinine phosphatase

cv coefficient of variation

Cv ceiling value

d day(s)

DES diethylstilboestrol

DIS draft international standard (ISO)

DMSO dimethylsulfoxide

DNA deoxyribonucleic acid

dna designated national authority

DO dissolved oxygen

DOC dissolved organic carbon

dpi days post inoculation

DRP detailed review paper (OECD)

DT50(lab) period required for 50 percent dissipation (under laboratory conditions) (define method of estimation)

DT90(field) period required for 90 percent dissipation (under field conditions) (define method of estimation)

dw dry weight

DWQG drinking water quality

guidelines decadic molar extinction

coefficient

EC50 median effective concentration

ECD electron capture detector

ED50 median effective dose

EDI estimated daily intake

EINECS European inventory of existing commercial substances

ELINCS European list of notified chemical substances

ELISA enzyme linked immunosorbent assay

e-mail electronic mail

EMDI estimated maximum daily intake

EN European norm

EPMA electron probe micro-analysis

ERL extraneous residue limit

ESD emission scenario document

ESPE46/51 evaluation system for pesticides

EUSES European Union system for the evaluation of substances

F field

F0 parental generation

F1 filial generation, first

F2 filial generation, second

FBS full base set

FELS fish early-life stage

FIA fluorescence immuno-assay

FID flame ionisation detector

Fmol fractional equivalent of the metabolite´s molecular

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weight compared to the active substance

FOB functional observation battery

foc organic carbon factor (compartment dependent)

fp freezing point

FPD flame photometric detector

FPLC fast protein liquid chromatography

g gram(s)

GAP good agricultural practice

GC gas chromatography

GC-EC gas chromatography with electron capture detector

GC-FID gas chromatography with flame ionisation detector

GC-MS gas chromatography-mass spectrometry

GC-MSD gas chromatography with mass-selective detection

GEP good experimental practice

GFP good field practice

GGT gamma glutamyl transferase

GI gastro-intestinal

GIT gastro-intestinal tract

GL guideline level

GLC gas liquid chromatography

GLP good laboratory practice

GM geometric mean

GMO genetically modified organism

GMM genetically modified micro-organism

GPC gel-permeation chromatography

GPS global positioning system

GSH glutathione

GV granulosevirus

118


h hour(s)

H Henry’s Law constant (calculated as a unitless value)

ha hectare(s)

Hb haemoglobin

HC5 concentration which will be harmless to at least 95 % of the species present with a given level of confidence (usually 95 %)

HCG human chorionic gonadotropin

Hct haematocrit

HDPE High Density Polyethylene

HDT highest dose tested

hL hectolitre

HEED high energy electron diffraction

HID helium ionisation detector

HPAEC high performance anion exchange chromatography

HPLC high pressure liquid chromatography or high performance liquid chromatography

HPLC-MS high pressure liquid chromatography - mass spectrometry

HPPLC high pressure planar liquid chromatography

HPTLC high performance thin layer chromatography

HRGC high resolution gas chromatography

HS Shannon-Weaver index

Ht haematocrit

HUSS human and use safety standard

I indoor

I50 inhibitory dose, 50%

IC50 median immobilisation concentration or median

119


inhibitory concentration 1

ICM integrated crop management

ID ionisation detector

IEDI international estimated daily intake

IGR insect growth regulator

im intramuscular

inh inhalation

INT 2-p-iodophenyl-3-p-nitrophenyl-5-phenyltetrazoliumchloride testing method

ip intraperitoneal

IPM integrated pest management

IR infrared

ISBN international standard book number

ISSN international standard serial number

IUCLID International Uniform Chemical Information Database

iv intravenous

IVF in vitro fertilisation

k (in combination)

kilo

k rate constant for biodegradation

K Kelvin

Ka acid dissociation constant

Kb base dissociation constant

Kads adsorption constant

Kdes apparent desorption coefficient

kg kilogram

KH Henry´s Law constant (in atmosphere per cubic metre per mole)

Koc organic carbon adsorption

coefficient

Kom organic matter adsorption coefficient

Kow octanol-water partition coefficient

Kp solid-water partition coefficient

kPa kilopascal(s)

l, L litre

LAN local area network

LASER light amplification by stimulated emission of radiation

LBC loosely bound capacity

LC liquid chromatography

LC-MS liquid chromatography- mass spectrometry

LC50 lethal concentration, median

LCA life cycle analysis

LC-MS-MS liquid chromatography with tandem mass spectrometry

LD50 lethal dose, median; dosis letalis media

LDH lactate dehydrogenase

ln natural logarithm

LOAEC lowest observable adverse effect concentration

LOAEL lowest observable adverse effect level

LOD limit of detection

LOEC lowest observable effect concentration

LOEL lowest observable effect level

log logarithm to the base 10

LOQ limit of quantification (determination)

LPLC low pressure liquid chromatography

LSC liquid scintillation counting

120


or counter

LSD least squared denominator multiple range test

LSS liquid scintillation spectrometry

LT lethal threshold

m metre

M molar

µm micrometre (micron)

MAC maximum allowable concentration

MAK maximum allowable concentration

MAMPEC Marine Antifoulant Model to Predict Environmental Concentrations

MC moisture content

MCH mean corpuscular haemoglobin

MCHC mean corpuscular haemoglobin concentration

MCV mean corpuscular volume

MDL method detection limit

MFO mixed function oxidase

µg microgram

mg milligram

MHC moisture holding capacity

MIC minimum inhibitory concentration

min minute(s)

MKC minimum killing concentration

mL millilitre

MLT median lethal time

MLD minimum lethal dose

mm millimetre

MMAD mass median aerodynamic diameter

mo month(s)

MOE margin of exposure

mol mole(s)

MOS margin of safety

mp melting point

MRE maximum residue expected

MRL maximum residue level or limit

mRNA messenger ribonucleic acid

MS mass spectrometry

MSDS material safety data sheet

MTD maximum tolerated dose

MT material test

MW molecular weight

n.a. not applicable

n- normal (defining isomeric configuration)

n number of observations

NAEL no adverse effect level

nd not detected

NEDI national estimated daily intake

NEL no effect level

NERL no effect residue level

ng nanogram

nm nanometre

NMR nuclear magnetic resonance

no, n° number

NOAEC no observed adverse effect concentration

NOAEL no observed adverse effect level

NOEC no observed effect concentration

NOED no observed effect dose

NOEL no observed effect level

NOIS notice of intent to suspend

NPD nitrogen-phosphorus detector or detection

NPV nuclear polyhedrosis virus

121


NR not reported

NTE neurotoxic target esterase

OC organic carbon content

OCR optical character recognition

ODP ozone-depleting potential

ODS ozone-depleting substances

OEL occupational exposure limit

OH hydroxide

OJ Official Journal

OM organic matter content

Pa pascal

PAD pulsed amperometric detection

PAR product assessment report

2-PAM 2-pralidoxime

PBT Persistence, bioaccumulation, toxicity

pc paper chromatography

PC personal computer

PCV haematocrit (packed corpuscular volume)

PEC predicted environmental concentration

PECA predicted environmental concentration in air

PECS predicted environmental concentration in soil

PECSW predicted environmental concentration in surface water

PECGW predicted environmental concentration in ground water

PED plasma-emissions-detector

pH pH-value

PHED pesticide handler’s exposure data

PIC prior informed consent

pic phage inhibitory capacity

PIEC Predicted Initial Effect Concentration

PIXE proton induced X-ray emission

pKa negative logarithm (to the base 10) of the acid dissociation constant

pKb negative logarithm (to the base 10) of the base dissociation constant

PNEC predicted no effect concentration (compartment to be added as subscript)

po by mouth

POP persistent organic pollutants

PP Polypropylene

ppb parts per billion (10 -9 )

PPE personal protective equipment

ppm parts per million (10 -6 )

PPP plant protection product

ppq parts per quadrillion (10 -

24 )

ppt parts per trillion (10 -12 )

PSP phenolsulfophthalein

PrT prothrombin time

PRL practical residue limit

PT product type

PT(CEN) project team CEN

PTDI provisional tolerable daily intake

PTT partial thromboplastin time

QA quality assurance

QAU quality assurance unit

(Q)SAR quantitative structure-activity relationship

r correlation coefficient

r 2 coefficient of determination

122


RA risk assessment

RBC red blood cell

REACH Registration, Evaluation and Authorisation of CHemicals

REI restricted entry interval

RENI Registry Nomenclature Information System

Rf retardation factor

RfD reference dose

RH relative humidity

RL50 median residual lifetime

RNA ribonucleic acid

RP reversed phase

rpm revolutions per minute

rRNA ribosomal ribonucleic acid

RRT relative retention time

RSD relative standard deviation

s second

S solubility

SAC strong adsorption capacity

SAP serum alkaline phosphatase

SAR structure/activity relationship

SBLC shallow bed liquid chromatography

sc subcutaneous

sce sister chromatid exchange

SCAS semi-continous activated sludge

SCTER smallest chronic toxicity exposure ratio (TER)

SD standard deviation

se standard error

SEM standard error of the mean

SEP standard evaluation procedure

SF safety factor

123


SFC supercritical fluid chromatography

SFE supercritical fluid extraction

SIMS secondary ion mass spectroscopy

S/L short term to long term ratio

SMEs small and medium sized enterprises

SOP standard operating procedures

sp species (only after a generic name)

SPC summary of product characteristics

SPE solid phase extraction

SPF specific pathogen free

spp subspecies

SSD - sulphur specific detector (physico-chemical detection method),

- species sensitivity distribution (statistical distribution of toxicity data for different species)

SSMS spark source mass spectrometry

STEL short term exposure limit

STER smallest toxicity exposure ratio (TER)

STMR supervised trials median residue

STP sewage treatment plant

t tonne(s) (metric ton)

t½ half-life (define method of estimation)

T3 tri-iodothyroxine

T4 thyroxine

T25 tumorigenic dose that causes tumours in 25 % of the test animals

TADI temporary acceptable daily intake

TBC tightly bound capacity

TCD thermal conductivity detector

TG technical guideline, technical group

TGD Technical guidance document

TID thermionic detector, alkali flame detector

TDR time domain reflectrometry

TER toxicity exposure ratio

TERI toxicity exposure ratio for initial exposure

TERST toxicity exposure ratio following repeated exposure

TERLT toxicity exposure ratio following chronic exposure

tert tertiary (in a chemical name)

TEP typical end-use product

TGGE temperature gradient gel electrophoresis

TIFF tag image file format

TLC thin layer chromatography

Tlm median tolerance limit

TLV threshold limit value

TMDI theoretical maximum daily intake

TMRC theoretical maximum residue contribution

TMRL temporary maximum residue limit

TNsG technical notes for guidance

TOC total organic carbon

Tremcard transport emergency card

tRNA transfer ribonucleic acid

TSH thyroid stimulating hormone (thyrotropin)

TTC 2,3,5-triphenylterazoliumchloride

124


testing method

TWA time weighted average

UDS unscheduled DNA synthesis

UF uncertainty factor (safety factor)

ULV ultra low volume

UR unit risk

UV ultraviolet

UVC unknown or variable composition, complex reaction products

UVCB undefined or variable composition, complex reaction products in biological material

v/v volume ratio (volume per volume)

vis visible

WBC white blood cell

wk weekwt weight

w/v weight per volume

ww wet weight

w/w weight per weight

XRFA X-ray fluorescence analysis

yr year

< less than less than or equal to

> greater than greater than or equal to

Abbreviations of Organisations and Publications

Abbreviation ExplanationASTM American Society for

Testing and Materials

BA Biological Abstracts (Philadelphia)

BART Beneficial Arthropod Registration Testing Group

BBA German Federal Agency of Agriculture and Forestry

CA(S) Chemical Abstracts (System)

CAB Centre for Agriculture and Biosciences International

CAC Codex Alimentarius Commission

CAS Chemical Abstracts Service

CCFAC Codex Committee on Food Additives and Contaminants

CCGP Codex Committee on General Principles

Abbreviation ExplanationCCPR Codex Committee on

Pesticide Residues

CCRVDF Codex Committee on Residues of Veterinary Drugs in Food

CE Council of Europe

CEC Commission of the European Communities

CEFIC European Chemical Industry Council

CEN European Committee for Normalisation

CEPE European Committee for Paints and Inks

CIPAC Collaborative International Pesticides Analytical Council Ltd

CMA Chemicals Manufacturers Association

COREPER Comite des Representants Permanents

COST European Co-operation in the field of Scientific and

125


Abbreviation ExplanationTechnical Research

DG Directorate General

DIN German Institute for Standardisation

EC European Commission

ECB European Chemicals Bureau

ECCO European Commission Co-ordination

ECDIN Environmental Chemicals Data and Information Network of the European Communities

ECDIS European Environmental Chemicals Data and Information System

ECE Economic Commission for Europe

ECETOC European Chemical Industry Ecology and Toxicology Centre

EDEXIM European Database on Export and Import of Dangerous Chemicals

EEC European Economic Community

EHC Environmental Health Criteria

EINECS European Inventory of Existing Commercial Chemical Substances

ELINCS European List of New Chemical Substances

EMIC Environmental Mutagens Information Centre

EPA Environmental Protection Agency

EPAS European Producers of Antimicrobial Substances

EPFP European Producers of Formulated Preservatives

EPO European Patent Office

EPPO European and

Mediterranean Plant Protection Organization

ESCORT European Standard Characteristics of Beneficials Regulatory Testing

EU European Union

EUPHIDS European Pesticide Hazard Information and Decision Support System

EUROPOEM European Predictive Operator Exposure Model

EWMP European Wood Preservation Manufacturers

FAO Food and Agriculture Organization of the UN

FOCUS Forum for the Co-ordination of Pesticide Fate Models and their Use

FRAC Fungicide Resistance Action Committee

GATT General Agreement on Tariffs and Trade

GAW Global Atmosphere Watch

GIFAP Groupement International des Associations Nationales de Fabricants de Produits Agrochimiques (now known as GCPF)

GCOS Global Climate Observing System

GCPF Global Crop Protection Federation (formerly known as GIFAP)

GEDD Global Environmental Data Directory

GEMS Global Environmental Monitoring System

GRIN Germplasm Resources Information Network

IARC International Agency for Research on Cancer

IATS International Academy of Toxicological Science

126


ICBP International Council for Bird Preservation

ICCA International Council of Chemical Associations

ICES International Council for the Exploration of the Seas

ILO International Labour Organization

IMO International Maritime Organisation

IOBC International Organization for Biological Control of Noxious Animals and Plants

IPCS International Programme on Chemical Safety

IRAC Insecticide Resistance Action Committee

ISCO International Soil Conservation Organization

ISO International Organization for Standardisation

IUPAC International Union of Pure and Applied Chemistry

JECFA FAO/WHO

Joint Expert Committee on Food Additives

JFCMP Joint FAO/WHO Food and Animal Feed Contamination Monitoring Programme

JMP Joint Meeting on Pesticides (WHO/FAO)

JMPR Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues (Joint Meeting on Pesticide Residues)

MITI Ministry of International Trade and Industry, Japan

NATO North Atlantic Treaty Organization

NAFTA North American Free Trade Agreement

127


NCI National Cancer Institute (USA)

NCTR National Center for Toxicological Research (USA)

NGO non-governmental organisation

NTP National Toxicology Program (USA)

OECD Organization for Economic Co-operation and Development

OLIS On-line Information Service of OECD

OPPTS Office of Prevention, Pesticides and Toxic Substances (US EPA)

OSPAR Oslo Paris Convention (Convention for the Protection of the Marine Environment of the North-East Atlantic)

PAN Pesticide Action Network

Ref-MS Reference Member State

RIVM Netherlands National Institute of Public Health and Environmental Protection

RMS Rapporteur Member State

RNN Re-registration Notification Network

RTECS Registry of Toxic Effects of Chemical Substances (USA)

SETAC Society of Environmental Toxicology and Chemistry

SI Système International d'Unitès

SITC Standard International Trade Classification

TOXLINE Toxicology Information On-line

UBA German Environmental Protection Agency

UN United Nations

128


UNEP United Nations Environment Programme

WFP World Food Programme

WHO World Health Organization

WPRS West Palearctic Regional Section

WTO World Trade Organization

WWF World Wildlife Fund

129

V Overview of product types

Biocidal product-types* and their descriptions as referred to in Article 2(1)(a) of the Biocidal Product Directive 98/8/EC. These product-types exclude products where they are covered by the Directives mentioned in Article 1(2) of Directive 98/8/EC. For for the purposes of these Directives and their subsequent modifications. PT23 will be adapted within the Regulation. It will be PT20, and. PT20 will probably included in other Regulation, as well.

MAIN GROUP 1: Disinfectants and general biocidal productsThese product types exclude cleaning products that are not intended to have a biocidal effect, including washing liquids, powders and similar products.

Product-type 1: Human hygiene biocidal productsProducts in this group are biocidal products used for human hygiene purposes.

Product-type 2: Private area and public health area disinfectants and other biocidal productsProducts used for the disinfection of air, surfaces, materials, equipment and furniture which are not used for direct food or feed contact in private, public and industrial areas, including hospitals, as well as products used as algaecides. Usage areas include, inter alia, swimming pools, aquariums, bathing and other waters; air-conditioning systems; walls and floors in health and other institutions; chemical toilets, waste water, hospital waste, soil or other substrates (in playgrounds).

Product-type 3: Veterinary hygiene biocidal productsProducts in this group are biocidal products used for veterinary hygiene purposes including products used in areas in which animals are housed, kept or transported.

Product-type 4: Food and feed area disinfectantsProducts used for the disinfection of equipment, containers, consumption utensils, surfaces or pipework associated with the production, transport, storage or consumption of food, feed or drink (including drinking water) for humans and animals.

Product-type 5: Drinking water disinfectantsProducts used for the disinfection of drinking water (for both humans and animals).

MAIN GROUP 2: PreservativesProduct-type 6: In-can preservativesProducts used for the preservation of manufactured products, other than foodstuffs or feedingstuffs, in containers by the control of microbial deterioration to ensure their shelf life.

Product-type 7: Film preservativesProducts used for the preservation of films or coatings by the control of microbial deterioration in order to protect the initial properties of the surface of materials or objects such as paints, plastics, sealants, wall adhesives, binders, papers, art works.

Product-type 8: Wood preservativesProducts used for the preservation of wood, from and including the saw-mill stage, or wood products by the control of wood-destroying or wood-disfiguring organisms. This product type includes both preventive and curative products.

Product-type 9: Fibre, leather, rubber and polymerised materials preservativesProducts used for the preservation of fibrous or polymerised materials, such as leather, rubber or paper or textile products and rubber by the control of microbiological deterioration.

Product-type 10: Masonry preservativesProducts used for preservation and remedial treatment of masonry or other construction materials other than wood by the control of microbiological and algal attack.

Product-type 11: Preservatives for liquid-cooling and processing systemsProducts used for the preservation of water or other liquids used in cooling and processing systems by the control of harmful organisms such as microbes, algae and mussels.Products used for the preservation of drinking water are not included in this product type.

Product-type 12: SlimicidesProducts used for the prevention or control of slime growth on materials, equipment and structures, used in industrial processes, e.g. on wood and paper pulp, porous sand strata in oil extraction.

Product-type 13: Metalworking-fluid preservativesProducts used for the preservation of metalworking fluids by the control of microbial deterioration.

MAIN GROUP 3: Pest controlProduct-type 14: RodenticidesProducts used for the control of mice, rats or other rodents.

Product-type 15: AvicidesProducts used for the control of birds.

Product-type 16: MolluscicidesProducts used for the control of molluscs.

Product-type 17: PiscicidesProducts used for the control of fish; these products exclude products for the treatment of fish diseases.

Product-type 18: Insecticides, acaricides and products to control other arthropodsProducts used for the control of arthropods (e.g. insects, arachnids and crustaceans).

Product-type 19: Repellents and attractantsProducts used to control harmful organisms (invertebrates such as fleas, vertebrates such as birds), by repelling or attracting, including those that are used for human or veterinary hygiene either directly or indirectly.

MAIN GROUP 4: Other biocidal products

Product-type 20: Preservatives for food or feed stocksProducts used for the preservation of food or feed stocks by the control of harmful organisms.

Product-type 21: Antifouling productsProducts used to control the growth and settlement of fouling organisms (microbes and

higher forms of plant or animal species) on vessels, aquaculture equipment or other structures used in water.Product-type 22: Embalming and taxidermist fluidsProducts used for the disinfection and preservation of human or animal corpses, or parts thereof.

Product-type 23: Control of other vertebratesProducts used for the control of vermin.

VI Format PAR with SPC

The current version of the agreed EU format is used in this 1.0 version of the Evaluation Manual. Itevaluation manual is used by severaldifferent MSs (see below). However, a

A new « harmonised version» version based on experience will be included in the a next version of the Evaluation Manualevaluation manual.

VII Frequently used internet links in the evaluation manualMost of the links can be found on the websiteThe site of the European Commission for the Environment: were most of the links can be found is: http://ec.europa.eu/environment/biocides/index.htmhttp://ec.europa.eu/environment/biocides/index.htm

Biocidal Products Directive 98/8/EC http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31998L0008:EN:NOT

Biocidal products typeshttp://ec.europa.eu/environment/biocides)

TNsG on data requirements http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_DATA_REQUIREMENTS/TNsG-Data-Requirements.pdf

Technical notes of guidancehttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/guidance-documents

FAO manual http://www.fao.org/agriculture/crops/core-themes/theme/pests/pm/jmps/manual/en/

Addendum to the TNsG on analytical methods http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_DATA_REQUIREMENTS/Addendum-TNsG-Data_Requirements_Analytical_Methods.pdf

TNsG on product evaluationhttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_PRODUCT_EVALUATION/TNsG-Product-Evaluation.pdf

Recently revised chapter 6.2 on resistance (May 2009)http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_PRODUCT_EVALUATION/TNsG_Product_Evaluation_Annex_I_Inclusion_Chapter_Resistance.pdf

Addendum TNsG on product evaluation: Revised appendix chapter 7 concerning the efficacy of rodenticides (PT14)http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_PRODUCT_EVALUATION/Revised_Appendix_Chapter_7_PT14_2009.pdf

TNsG on Annex I inclusionhttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ANNEX_I_INCLUSION/TNsG-Annex-I-Inclusion.pdf

TNsG on Annex I Inclusion Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation http://ihcp.jrc.ec.europa.eu/our_activities/public-health/risk_assessment_of_Biocides/doc/TNsG/TNsG_ANNEX_I_INCLUSION/Revision_TNsG_Annex_I_Inclusion_Chapter_4.1_2009.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ANNEX_I_INCLUSION/TNsG-Annex-I-Inclusion.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ANNEX_I_INCLUSION/TNsG-Annex-I-Inclusion.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_PRODUCT_EVALUATION/Revised_Appendix_Chapter_7_PT14_2009.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_PRODUCT_EVALUATION/Revised_Appendix_Chapter_7_PT14_2009.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_PRODUCT_EVALUATION/TNsG_Product_Evaluation_Annex_I_Inclusion_Chapter_Resistance.pdf



http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_PRODUCT_EVALUATION/TNsG-Product-Evaluation.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_PRODUCT_EVALUATION/TNsG-Product-Evaluation.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_DATA_REQUIREMENTS/Addendum-TNsG-Data_Requirements_Analytical_Methods.pdf



http://www.fao.org/agriculture/crops/core-themes/theme/pests/pm/jmps/manual/en/

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/guidance-documents


http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_DATA_REQUIREMENTS/TNsG-Data-Requirements.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_DATA_REQUIREMENTS/TNsG-Data-Requirements.pdf

http://ec.europa.eu/environment/biocides

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31998L0008:EN:NOT

http://ec.europa.eu/environment/biocides/index.htm

Recently revised chapter 10 on resistance (May 2009)http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ANNEX_I_INCLUSION/TNsG_Product_Evaluation_Annex_I_Inclusion_Chapter_Resistance.pdf

Sharp, T and Saunders, G (2008). A model for assessing the relative humaneness of pest animal control methods. Australian Government Department of Agriculture, Fisheries and Forestry, Canberra, ACT. http://www.daff.gov.au/animal-plant-health/welfare/aaws/humaneness_of_pest_animal_control_methodsappendixhttp://www.daff.gov.au/animal-plant-health/welfare/aaws/humaneness_of_pest_animal_control_methods/appendix_assessment_of_humaneness_worksheet

TNsG on human exposure (2007)http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/TNsG%20-Human-Exposure-2007.pdf

Manual of Technical Agreementshttp://circa.europa.eu/Members/irc/env/ber/library?l=/meeting_documents/technical_agreements&vm=detailed&sb=Title

HEEGHeeg opinionshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS

TNsG on human exposure all versionshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/guidance-documents

http://circa.europa.eu/(Library/Human Health Related Issues/Human Exposure Expert Group/List of Members).http://circa.europa.eu/Members/irc/env/ber/library?l=/health_related_issues/exposure_expert&vm=detailed&sb=Title

HEEG opinion on mixing and loading model 7 alternativeshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202008_Mixing%20Loading%20model%207%20alternatives.pdf/view

HEEG opinion on the use of CONSEXPO for the exposure assessment for professional usershttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202008_Use%20ConsExpo%20Prof%20Use.pdf/view

PT08 (wood preservatives): HEEG opinion on defaults and appropriate models to assess human exposure for dipping processeshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202009_Dipping%20cycles%20PT%208.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202009_Dipping%20cycles%20PT%208.pdf/view



http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202008_Use%20ConsExpo%20Prof%20Use.pdf/view



http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202008_Mixing%20Loading%20model%207%20alternatives.pdf/view



http://circa.europa.eu/Members/irc/env/ber/library?l=/health_related_issues/exposure_expert&vm=detailed&sb=Title

http://circa.europa.eu/Members/irc/env/ber/library?l=/health_related_issues/exposure_expert&vm=detailed&sb=Title



http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS

http://circa.europa.eu/Members/irc/env/ber/library?l=/meeting_documents/technical_agreements&vm=detailed&sb=Title

http://circa.europa.eu/Members/irc/env/ber/library?l=/meeting_documents/technical_agreements&vm=detailed&sb=Title

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/TNsG%20-Human-Exposure-2007.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/TNsG%20-Human-Exposure-2007.pdf

http://www.daff.gov.au/animal-plant-health/welfare/aaws/humaneness_of_pest_animal_control_methods/appendix_assessment_of_humaneness_worksheet



http://www.daff.gov.au/animal-plant-health/welfare/aaws/humaneness_of_pest_animal_control_methods

http://www.daff.gov.au/animal-plant-health/welfare/aaws/humaneness_of_pest_animal_control_methods

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ANNEX_I_INCLUSION/TNsG_Product_Evaluation_Annex_I_Inclusion_Chapter_Resistance.pdf



PT13 exposure metalworking fluidshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202008_Exposure%20metalworking%20fluids%20PT%2013.pdf/view

Number of manipulations in the assessment of rodenticideshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG_2010%20Harmonising%20the%20number%20of%20manipulations%20in%20the%20assessment%20of%20rodenticides.pdf/view

Corrigendum TNsG on human exposure (2007): PT21 (Antifoulings)http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG_2008_Antifouling_painting_model_TNsG_correction.pdf/view

PT02, 03, 04: HEEG opinion on choice of secondary exposure parametershttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202009_Choice%20parameters%20PT%202%203%204.pdf/view

Potential and actual handexposurehttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202008_Potential%20and%20Actual%20Hand%20Exposure.pdf/view

Working document on risk characterisation of local effects in the absence of systemic effectshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/Guidance_Risk_Characterization_Local_Effects_Working_Document_2010.pdf

TGD part 1 http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/tgd/technical-guidance-document-tgd

Guidance on effect assessment of rapidly degrading substanceshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/Guidance_rapidly_degrading_substances_TWA_2009.pdf

OECD aquatic toxicity and difficult substances and mixtureshttp://www.oecd.org/officialdocuments/displaydocumentpdf/?cote=ENV/JM/MONO(2000)6&doclanguage=en

Guidance Document on Aquatic Ecotoxicology under Council Directive 91/414/EEChttp://focus.jrc.ec.europa.eu/gw/docs/FOCUS_GW_Report_Main.pdf

Guidance Document on Terrestrial Ecotoxicology Under Council Directive 91/414/EEChttp://www.pesticides.gov.uk/psd_pdfs/registration_guides/data_reqs_handbook/Supporting/Terrestrial-Ecotox-rev2_final.pdf

FOCUS groundwater scenarios in the EU review of active substanceshttp://focus.jrc.ec.europa.eu/gw/docs/FOCUS_GW_Report_Main.pdf

http://focus.jrc.ec.europa.eu/gw/docs/FOCUS_GW_Report_Main.pdf

http://www.pesticides.gov.uk/psd_pdfs/registration_guides/data_reqs_handbook/Supporting/Terrestrial-Ecotox-rev2_final.pdf

http://www.pesticides.gov.uk/psd_pdfs/registration_guides/data_reqs_handbook/Supporting/Terrestrial-Ecotox-rev2_final.pdf

http://focus.jrc.ec.europa.eu/gw/docs/FOCUS_GW_Report_Main.pdf%20

http://www.oecd.org/officialdocuments/displaydocumentpdf/?cote=ENV/JM/MONO(2000)6&doclanguage=en


http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/Guidance_rapidly_degrading_substances_TWA_2009.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/Guidance_rapidly_degrading_substances_TWA_2009.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/tgd/technical-guidance-document-tgd


http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/Guidance_Risk_Characterization_Local_Effects_Working_Document_2010.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/Guidance_Risk_Characterization_Local_Effects_Working_Document_2010.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202008_Potential%20and%20Actual%20Hand%20Exposure.pdf/view



http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202009_Choice%20parameters%20PT%202%203%204.pdf/view



http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG_2008_Antifouling_painting_model_TNsG_correction.pdf/view



http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG_2010%20Harmonising%20the%20number%20of%20manipulations%20in%20the%20assessment%20of%20rodenticides.pdf/view



http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/TNsG_ON_HUMAN_EXPOSURE/HEEG_OPINIONS/HEEG%202008_Exposure%20metalworking%20fluids%20PT%2013.pdf/view



Generic guidance for FOCUS groundwater scenarioshttp://focus.jrc.ec.europa.eu/gw/docs/Generic_guidance_for_FOCUS_groundwater_scenarios1.1.pdf

Guidance Document on Estimating Persistence and Degradation Kinetics from Environmental Fate Studies on Pesticides in EU Registrationhttp://focus.jrc.ec.europa.eu/dk/docs/finalreportFOCDegKin04June06linked.pdf

European Guidance Document on Risk Assessment for Birds and Mammalshttp://ec.europa.eu/food/plant/protection/evaluation/guidance/wrkdoc19_en.pdf

EPPO Standards - Environmental risk assessment scheme for plant protection productshttp://archives.eppo.org/EPPOStandards/PP3_ERA/pp3-11(2).pdf

EUSEShttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/euses

TGD part 2 http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/tgd/technical-guidance-document-tgd

PT01-06: Workshop on environmental risk assessment for PT01 to PT06 (2008)http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/WS_ENV_RA_PT_2008/PT1-6_Workshop_Environmental_Risk_Assessment_2008.pdf/view

PT01-06: Cover note to workshop on environmental risk assessment for PT01 to PT06 (2008)http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/WS_ENV_RA_PT_2008/PT1-6_Cover_Note_Workshop_Environment_Risk_Assessment_2008.pdf/view

PT01: ESD for human hygiene biocidal productshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_1_Human_Hygiene.pdf/view

PT02: ESD for private area and public health area disinfectantshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_2_Private_area_and_public_health_area_disinfectants.pdf/view

ESD for PT1-23 of van der Poel and Bakker (2001)http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ADD_INFO/ESDs_RIVM_2001_ESD_PT1-PT23.pdf/view

PT06: ESD for in-can preservativeshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_06/PT_6_In-Can_preservatives.pdf/view

PT06: ESD for biocidal products for paper coating and finishinghttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_06/PT_6_PT_7_PT_9_Paper_coating_and_finishing.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_06/PT_6_PT_7_PT_9_Paper_coating_and_finishing.pdf/view


http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_06/PT_6_In-Can_preservatives.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_06/PT_6_In-Can_preservatives.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_2_Private_area_and_public_health_area_disinfectants.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_2_Private_area_and_public_health_area_disinfectants.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_1_Human_Hygiene.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_1_Human_Hygiene.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/WS_ENV_RA_PT_2008/PT1-6_Cover_Note_Workshop_Environment_Risk_Assessment_2008.pdf/view



http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/WS_ENV_RA_PT_2008/PT1-6_Workshop_Environmental_Risk_Assessment_2008.pdf/view





http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/euses

http://archives.eppo.org/EPPOStandards/PP3_ERA/pp3-11(2).pdf

http://ec.europa.eu/food/plant/protection/evaluation/guidance/wrkdoc19_en.pdf

http://focus.jrc.ec.europa.eu/dk/docs/finalreportFOCDegKin04June06linked.pdf

http://focus.jrc.ec.europa.eu/gw/docs/Generic_guidance_for_FOCUS_groundwater_scenarios1.1.pdf

http://focus.jrc.ec.europa.eu/gw/docs/Generic_guidance_for_FOCUS_groundwater_scenarios1.1.pdf

PT07: ESD for biocidal products used as film preservativeshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_07/PT_7_Film_preservatives.pdf/view


PT08: ESD for wood preservatives Part 1http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_08/PT_8_Wood_preservatives_1.pdf/view




PT08: Report of leaching workshop (2005)http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_08/PT_8_Leaching_Workshop_2005.pdf/view

PT08: Groundwater exposure assessment – Factors to considerhttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_08/PT_8_Leaching_Workshop_2005.pdf/view

PT08: Groundwater exposure assessment – Soil studies applicabilityhttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/Guidance_degradation_sorption_groundwater_assessment.pdf

PT08: OECD guidance on the estimation of emissions from wood preservative-treated wood to the environmenthttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_08/OECD_Guidance_Emission_Estimation_Treated_Wood_2009.pdf/view


PT09: ESD for preservatives in the leather industryhttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_09/PT_9_Leather_industry.pdf/view

PT09: ESD for preservatives in rubber and polymerised materials

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_09/PT_9_Leather_industry.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_09/PT_9_Leather_industry.pdf/view



http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_08/OECD_Guidance_Emission_Estimation_Treated_Wood_2009.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_08/OECD_Guidance_Emission_Estimation_Treated_Wood_2009.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/Guidance_degradation_sorption_groundwater_assessment.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/TNsG/Guidance_degradation_sorption_groundwater_assessment.pdf

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_08/PT_8_Leaching_Workshop_2005.pdf/view




http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_08/PT_8_Wood_preservatives_4.pdf/view










http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_07/PT_7_Film_preservatives.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_07/PT_7_Film_preservatives.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_09/PT_9_Rubber_Polymerised_Materials_preservatives.pdf/view

PT09: ESD for preservatives in the textile processing industryhttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_09/PT_9_PT_18_Textile_processing_industry.pdf/view

PT10: ESD for masonry preservativeshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_10_Masonry_preservatives.pdf/view

PT11:ESD for preservatives in liquid cooling systemshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_11_Preservatives_for_liquid-cooling_and_processing_systems.pdf/view

PT12: ESD for slimicideshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_12_Slimicides.pdf/view

PT13: ESD for metalworking fluid preservativeshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_13_Metalworking_fluid.pdf/view

PT14: ESD for rodenticideshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_14/PT_14_Rodenticides.pdf/view

PT14: Addendum TGD: PNECoral derivation for primary and secondary poisoning for rodenticideshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_14/Addendum-TGD-PNEC_Derivation_Rodenticides.pdf/view

PT15: ESD for avicideshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_15_Avicides.pdf/view

PT18: ESD for insecticides for stables and manure storage systemshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_18/PT_18_Insecticides_for_stables_and_manure.pdf/view

PT18: Report of workshop on PT18 (2007)http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_18/PT18_Workshop_Environmental_Risk_Assessment_2007.pdf/view

PT18: ESD for insecticides for household and professional useshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_18/OECD_ESD_PT18_Household_Professional_Uses.pdf/view

PT18: ESD for preservatives in the textile processing industryhttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_18/PT_9_PT_18_Textile_processing_industry.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_18/PT_9_PT_18_Textile_processing_industry.pdf/view


http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_18/OECD_ESD_PT18_Household_Professional_Uses.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_18/OECD_ESD_PT18_Household_Professional_Uses.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_18/PT18_Workshop_Environmental_Risk_Assessment_2007.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_18/PT18_Workshop_Environmental_Risk_Assessment_2007.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_18/PT_18_Insecticides_for_stables_and_manure.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_18/PT_18_Insecticides_for_stables_and_manure.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_15_Avicides.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_15_Avicides.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_14/Addendum-TGD-PNEC_Derivation_Rodenticides.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_14/Addendum-TGD-PNEC_Derivation_Rodenticides.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_14/PT_14_Rodenticides.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_14/PT_14_Rodenticides.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_13_Metalworking_fluid.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_13_Metalworking_fluid.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_12_Slimicides.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_12_Slimicides.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_11_Preservatives_for_liquid-cooling_and_processing_systems.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_11_Preservatives_for_liquid-cooling_and_processing_systems.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_10_Masonry_preservatives.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_10_Masonry_preservatives.pdf/view





PT21: ESD for antifoulingshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_21/PT_21_antifouling_products.pdf/view

PT21: Leaching workshop antifoulings (2006)http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_21/PT_21_Leaching_Workshop.pdf/view

PT21: MAMPEC 2.0 user manualhttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_21/DOCUMENTATION_MAMPEC_2.0

PT21: MAMPEC 2.0 technical background documenthttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_21/DOCUMENTATION_MAMPEC_2.0

PT22: ESD for biocidal products for taxidermy and embalming processeshttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_22_Embalming_and_taxidermist_fluids.pdf/view

veterinary medicinal products in manurehttp://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/03/WC500104495.pdf

OECD GUIDANCE LYSIMETER STUDIEShttp://www.oecd.org/officialdocuments/displaydocumentpdf/?cote=ENV/JM/MONO(2000)8&doclanguage=en

European Guidance Document on Risk Assessment for Birds and Mammals http://ec.europa.eu/food/plant/protection/evaluation/guidance/wrkdoc19_en.pdf

Council Directive 86/609/EEChttp://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31986L0609:EN:NOT

OECD TG 305 test for the testing of fish species, flow through fish testhttp://www.oecd-ilibrary.org/environment/test-no-305-bioconcentration-flow-through-fish-test_9789264070462-en

OECD 315, Bioaccumulation in Sediment-dwelling Benthic Oligochaeteshttp://www.oecd-ilibrary.org/environment/test-no-315-bioaccumulation-in-sediment-dwelling-benthic-oligochaetes_9789264067516-en

OECD 317, bioaccumulation in terrestrial oligochaeteshttp://www.oecd-ilibrary.org/environment/test-no-317-bioaccumulation-in-terrestrial-oligochaetes_9789264090934-en

Council Directive 86/609/EEChttp://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31986L0609:EN:NOT

REACH Annex XIIIhttp://guidance.echa.europa.eu/docs/guidance_document/information_requirements_r11_en.pdf?vers=20_08_08Chapter 4

http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_r11_en.pdf?vers=20_08_08



http://www.oecd-ilibrary.org/environment/test-no-317-bioaccumulation-in-terrestrial-oligochaetes_9789264090934-en

http://www.oecd-ilibrary.org/environment/test-no-317-bioaccumulation-in-terrestrial-oligochaetes_9789264090934-en

http://www.oecd-ilibrary.org/environment/test-no-315-bioaccumulation-in-sediment-dwelling-benthic-oligochaetes_9789264067516-en

http://www.oecd-ilibrary.org/environment/test-no-315-bioaccumulation-in-sediment-dwelling-benthic-oligochaetes_9789264067516-en

http://www.oecd-ilibrary.org/environment/test-no-305-bioconcentration-flow-through-fish-test_9789264070462-en

http://www.oecd-ilibrary.org/environment/test-no-305-bioconcentration-flow-through-fish-test_9789264070462-en


http://ec.europa.eu/food/plant/protection/evaluation/guidance/wrkdoc19_en.pdf



http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_22_Embalming_and_taxidermist_fluids.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_22_Embalming_and_taxidermist_fluids.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_21/DOCUMENTATION_MAMPEC_2.0




http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_21/PT_21_Leaching_Workshop.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_21/PT_21_Leaching_Workshop.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_21/PT_21_antifouling_products.pdf/view

http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/doc/ESD/ESD_PT/PT_21/PT_21_antifouling_products.pdf/view

http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_r4_en.pdf?vers=20_08_08chapter 5http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_r5_en.pdf?vers=16_12_10

Guidance document on the Assessment of Endocrine Disrupting Substances http://www.oecd.org/dataoecd/63/8/46436593.pdf

De leeuw 1993http://www.sciencedirect.com/science/article/pii/004565359390226U

Risk mitigation measures for anticoagulants used as rodenticideshttp://ec.europa.eu/environment/biocides/pdf/anticoagulants.pdf

Guidance documents on the implementation of Directive 98/8/EChttp://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_assessment_of_Biocides/guidance-documents

OECD Test Guidelineshttp://www.oecd.org/document/22/0,3343,en_2649_34377_1916054_1_1_1_1,00.html

1999/45/EChttp://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1999:200:0001:0068:EN:PDF

1272/2008/EChttp://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:353:0001:1355:EN:PDF

Guidance on the application of Regulation (EC) 1272/2008http://guidance.echa.europa.eu/docs/guidance_document/clp_en.pdf

http://guidance.echa.europa.eu/docs/guidance_document/clp_en.pdf

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:353:0001:1355:EN:PDF

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1999:200:0001:0068:EN:PDF




http://ec.europa.eu/environment/biocides/pdf/anticoagulants.pdf

http://www.sciencedirect.com/science/article/pii/004565359390226U

http://www.oecd.org/dataoecd/63/8/46436593.pdf



