APP203638 Science memo - EPA

SCIENCE MEMO

APP203638 – Custodia®

FEBRUARY/ 2020

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Science memo for application to import or manufacture Custodia® for release (APP203638)

FEBRUARY 2020

Executive Summary

The applicant, Adama New Zealand Limited, submitted an application to the Environmental Protection

Authority (EPA) on 1 June 2018 to seek approval for Custodia®, a fungicide containing 200 g/L tebuconazole

and 120 g/L azoxystrobin in a suspension concentrate formulation, for control of foliar diseases of forage

beet crops. It was given Application Number APP203638 and was formally received on 26 June 2019 as a

Category B application.

Both tebuconazole and azoxystrobin are approved individually in New Zealand on a wide range of crops

(except sugar beet and fodder beet) at rates higher than those of Custodia® (up to 375 g/ha for

tebuconazole and up to 620 g azoxystrobin/ha), with different application methods (including aerial

application). The crops on which both active ingredients are currently used are listed below:

Azoxystrobin: barley, field tomato, grape, maize, onion, pea, potato, rye grass seed crop, sweetcorn, turf,

wheat.

Tebuconazole: wheat, barley, oats, ryegrass seed crop, pea, onion, summer fruit, pasture, grape.

However, they have never been approved as a combination in New Zealand previously.

Mammalian toxicity studies with Custodia® indicate that the substance is of low acute toxicity and should be

classified 6.1D for acute oral toxicity. The substance is not irritating to the skin or eyes, and is not a contact

sensitiser. Based on mixture rules, Custodia® should be classified 6.8B and 6.9B (oral). Based on test data

for the formulation, Custodia® should also be classified 6.1D and 9.1B but does not require classification as

being toxic to terrestrial vertebrates or invertebrates.

It is considered that there is potential for significant exposure to people and the environment during the use

phase of the lifecycle of Custodia®. As such, quantitative risk assessments have been undertaken to

understand the likely exposures to the substance under the use conditions proposed by the applicant, using

the endpoint data available and the standard risk assessment methodologies used by the EPA.

It is considered that the risks to human health from the proposed use of Custodia® are acceptable with the

use of appropriate and full Personal Protective Equipment (PPE). No REIs are required to protect crop

worker re-entry. No buffer zone is required to protect bystanders.

It is considered that the risks to the environment from the proposed use of Custodia® are acceptable with

the proposed controls.

A set of controls have been proposed for Custodia®, and are detailed under section 6.

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Table of Contents

APP203638 – Custodia® ....................................................................................................................... 1

Executive Summary .............................................................................................................................. 2

1. Introduction/Background ........................................................................................................... 7

2. Hazardous properties ................................................................................................................. 9

Hazard classification of Custodia® ............................................................................................... 9

3. Risk assessment context ........................................................................................................... 9

4. Human health risk assessment................................................................................................ 10

5. Environmental risk assessment .............................................................................................. 10

6. Proposed controls ..................................................................................................................... 12

Additional and varied controls ..................................................................................................... 12

Application rate ............................................................................................................................ 12

Application method ...................................................................................................................... 12

Buffer zones ................................................................................................................................ 12

Additional label statements ......................................................................................................... 12

Appendix A: Identity of the active ingredient, use pattern and mode of action ........................... 14

Identity of the active ingredient and metabolites ......................................................................... 14

Regulatory status ........................................................................................................................ 14

Impurities and or restrictions on purity or composition ................................................................ 15

Use pattern and mode of action .................................................................................................. 15

Use pattern ........................................................................................................................ 15

Mode of action ................................................................................................................... 15

Table 5: List of intended uses for Custodia® ................................................................... 16

Appendix B: Physico-chemical properties of Custodia® ................................................................ 18

Appendix C: Mammalian toxicology .................................................................................................. 19

Executive summaries and list of endpoints for Custodia® .......................................................... 19

Appendix D: Environmental fate ........................................................................................................ 21

Residues relevant to the environment ......................................................................................... 21

Azoxystrobin ...................................................................................................................... 21

Tebuconazole .................................................................................................................... 21

Degradation and fate of azoxystrobin and tebuconazole in aquatic environments..................... 21

Degradation and fate of azoxystrobin and tebuconazole in soil.................................................. 23

General conclusion about environmental fate ............................................................................. 25

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Azoxystrobin ...................................................................................................................... 25

Tebuconazole .................................................................................................................... 25

Appendix E: Ecotoxicity ..................................................................................................................... 26

List of endpoints .......................................................................................................................... 26

Aquatic toxicity ............................................................................................................................ 26

General conclusion about aquatic toxicity......................................................................... 31

Soil toxicity................................................................................................................................... 32

General conclusion about soil toxicity ............................................................................... 36

Terrestrial vertebrate toxicity ....................................................................................................... 36

General conclusion about ecotoxicity to terrestrial vertebrates ........................................ 38

Ecotoxicity to bees and other terrestrial invertebrates ................................................................ 38

General conclusion about ecotoxicity to bees and terrestrial invertebrate toxicity ........... 40

Appendix F: Hazard classification of Custodia® ............................................................................. 41

Appendix G: Human health risk assessment ................................................................................... 43

Quantitative risk assessment ...................................................................................................... 43

Input values for the human health risk assessment .................................................................... 43

Operator exposure assessment .................................................................................................. 45

Re-entry worker exposure assessment ....................................................................................... 46

Quantitative bystander risk assessment ..................................................................................... 46

Groundwater contamination risk assessment ............................................................................. 47

Conclusions of the human health risk assessment ..................................................................... 48

Appendix H: Environmental risk assessment .................................................................................. 49

Evaluation of toxicity of the mixture ............................................................................................. 49

Aquatic risk assessment .............................................................................................................. 52

Calculation of expected environmental concentrations .................................................... 52

Output from the GENEEC2 model .................................................................................... 54

Azoxystrobin ................................................................................................................................ 54

Tebuconazole .............................................................................................................................. 55

Calculated risk quotients ................................................................................................... 57

Refinement of the aquatic risk assessment ...................................................................... 59

Spray drift .................................................................................................................................... 59

Input variables used for the aerial AGDISP v8.15 modelling ...................................................... 61

Aerial buffer zones ...................................................................................................................... 63

Overall conclusion ....................................................................................................................... 63

Runoff .......................................................................................................................................... 66

Conclusions of the aquatic risk assessment ..................................................................... 66

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Use restrictions ............................................................................................................................ 66

Buffer zones ................................................................................................................................ 67

Groundwater risk assessment ..................................................................................................... 67

Conclusions of the groundwater risk assessment ............................................................ 67

Sediment risk assessment .......................................................................................................... 68

Conclusions of the sediment risk assessment .................................................................. 68

Terrestrial risk assessment ......................................................................................................... 68

Soil macro-organisms ....................................................................................................... 68

Soil micro-organisms ......................................................................................................... 70

Conclusions of the soil organism risk assessment ........................................................... 70

Non-target plant risk assessment ................................................................................................ 70

Conclusion for non-target plant risk assessment .............................................................. 71

Bird risk assessment ................................................................................................................... 72

Screening assessment ...................................................................................................... 72

Calculation of TERs ..................................................................................................................... 73

Conclusions of the bird screening risk assessment .................................................................... 74

Tier 1 assessment ............................................................................................................. 74

Conclusion for bird risk assessment (Tier 1) ............................................................................... 75

Refinement ........................................................................................................................ 75

Scenario 1 ................................................................................................................................... 75

Secondary poisoning ......................................................................................................... 76

Conclusions for bird risk assessment ............................................................................... 76

Pollinator risk assessment ........................................................................................................... 76

Conclusions of the pollinator risk assessment .................................................................. 77

Non-target arthropod risk assessment ........................................................................................ 77

Conclusion for non-target arthropod risk assessments .................................................... 79

Conclusions of the ecological risk assessment ........................................................................... 79

Aquatic environment: ..................................................................................................... 79

Groundwater: ................................................................................................................... 79

Sediment: ......................................................................................................................... 79

Soil organisms: ............................................................................................................... 80

Terrestrial plants: ............................................................................................................ 80

Birds: ................................................................................................................................ 80

Bees and non-target arthropods: .................................................................................. 80

Appendix I: Study summaries ............................................................................................................ 82

Toxicity ........................................................................................................................................ 82

Mammalian toxicology - Robust study summaries for Custodia® .................................... 82

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Ecotoxicity ................................................................................................................................... 90

Aquatic organisms ............................................................................................................. 91

Terrestrial toxicity .............................................................................................................. 99

Non-target plants ............................................................................................................. 103

Soil micro-organisms ....................................................................................................... 105

Birds ................................................................................................................................ 109

Pollinators ....................................................................................................................... 111

Non-target arthropods ..................................................................................................... 113

Appendix J: Standard terms and abbreviations ............................................................................. 127

Appendix K: References ................................................................................................................... 130

Appendix L: Confidential Composition ........................................................................................... 131

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1. Introduction/Background

1.1. This application is to import or manufacture for release Custodia®, a Suspension Concentrate (SC)

containing the active ingredients tebuconazole (200 g/L) and azoxystrobin (120 g/L), plus other

components.

1.2. Custodia® is intended to be used as a fungicide for the control of foliar diseases in forage beet crops.

It is intended to be applied using ground-based and aerial application methods at the maximum

application rate of 0.12 kg/ha azoxystrobin and 0.2 kg/ha tebuconazole.

1.3. Both tebuconazole and azoxystrobin are approved individually in New Zealand on a wide range of

crops (except sugar beet and fodder beet) at rates higher than those of Custodia® (up to 375 g/ha for



Azoxystrobin: barley, field tomato, grape, maize, onion, pea, potato, rye grass seed crop, sweetcorn,

turf, wheat.



1.4. The active ingredient tebuconazole has been approved internationally in Australia, Europe, Japan,

Canada and USA.

1.5. The active ingredient azoxystrobin has been approved internationally in Australia, Europe, Japan,

Canada and USA.

1.6. The substance Custodia® is also registered internationally, for instance in Australia and Europe.

1.7. More details about the use pattern of Custodia® and the regulatory status of tebuconazole and

azoxystrobin can be found in Appendix A.

1.8. It is considered that there is potential for significant exposure to people and the environment during

the use phase of the lifecycle of Custodia®. As such, quantitative risk assessments have been

undertaken to understand the likely exposures to the substance under the use conditions proposed by

the applicant, using the endpoint data available and the standard risk assessment methodologies used

by the EPA.

1.9. Physical and Chemical properties of Custodia® can be found in Appendix B.

1.10. Mammalian toxicological properties Custodia® have been reported in Appendix C.

1.11. Environmental Fate properties of tebuconazole, azoxystrobin and their respective metabolites have

been reported in Appendix D.

1.12. Ecotoxicological properties of Custodia®, azoxystrobin and tebuconazole have been reported in

Appendix E.

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1.13. Hazard properties and classification determination of Custodia® derived from their properties can be

found under section 2 and Appendix F.

1.14. Mammalian toxicological data have subsequently been used to generate human health risk

assessment and this is detailed in Appendix G.

1.15. Environmental Fate, Ecotoxicological and other relevant data have subsequently been used to

generate environmental risk assessment and this is detailed in Appendix H.

1.16. Relevant study summaries can be found in Appendix I.

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2. Hazardous properties

Hazard classification of Custodia®

2.1. The hazard classifications of Custodia® determined by the EPA are 6.1D, 6.8B, 6.9B and 9.1B (Table

1). The hazard classifications of Custodia® were determined based on the information provided by the

applicant (including toxicity and ecotoxicity studies), information on the individual components of

Custodia®, mixture rules and other available information. Table 30 in Appendix F shows the method

used for classification and indicates the main component that contributes to each hazard

classification).

Table 1: Hazard classification of Custodia®

Hazard EPA classification

Acute toxicity (oral) 6.1D

Reproductive/ developmental toxicity 6.8B

Target organ or systemic (routes) 6.9B

Aquatic ecotoxicity 9.1B

2.2. Mammalian toxicity studies with Custodia® indicate that the substance is of low acute toxicity and

should be classified 6.1D for acute oral toxicity. The substance is not irritating to the skin or eyes, and

is not a contact sensitiser. Based on mixture rules, Custodia® should be classified 6.8B and 6.9B

(oral). Based on test data for the formulation, Custodia® should also be classified 6.1D and 9.1B but

does not require classification as being toxic to terrestrial vertebrates or invertebrates.

3. Risk assessment context

3.1. It is considered that there is potential for significant exposure to people and the environment during

the use phase of the lifecycle of Custodia®. As such, quantitative risk assessments have been

undertaken to understand the likely exposures to the substance under the use conditions proposed by

the applicant, using the endpoint data available and the standard risk assessment methodologies used

by the EPA (EPA 2018).

3.2. During the importation, manufacture, transportation, storage and disposal of this substance, it is

estimated that the proposed controls and other legislative requirements will sufficiently mitigate risks to

a negligible level. This assessment takes into account the existing EPA Notices around packaging,

identification and disposal of hazardous substances. In addition, the Land Transport Rule 45001, Civil

Aviation Act 1990, Maritime Transport Act 1994 and New Zealand’s Health and Safety at Work (HSW)

requirements all have provisions for the safe management of hazardous substances.

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4. Human health risk assessment

4.1. The risks from the use of tebuconazole are considered as a proxy for Custodia® on users and

operators of the substance, re-entry workers and bystanders. Full details can be found in Appendix G:

Human health risk assessment.

4.2. Operator Exposure:

Predicted operator exposures to tebuconazole are below the Acceptable Operator Exposure Level

(AOEL), provided full PPE (gloves, hood/visor, coveralls, and heavy boots without a respirator) is worn

during mixing, loading, and application. Therefore operator exposures to Custodia® are not expected

to result in adverse health effects, if adequate PPE is worn.

4.3. Worker Re-Entry:

Risk Quotient resulting from predicted exposures to tebuconazole for workers re-entering and working

in areas where Custodia® has been applied are below the LOC. No re-entry intervals are necessary.

4.4. Bystanders:

Estimated bystander exposure from spray drift after application of Custodia® to the soil around fodder

beet and sugar beet is below the AOEL. No buffer zone is required in protect bystanders.

4.5. Groundwater:

The estimated ground water concentration of 1,2,4-triazole from the application of Custodia® has

been estimated using SciGrow as 0.11 μg/L (see Appendix H). The EPA notes that this value is lower

than the TEL (Drinking Water) derived for 1,2,4-triazole which suggests that ground water

concentrations result in acceptable risks after use of Custodia®.

4.6. Overall human health conclusion:

It is considered that the risks to human health from the proposed use of Custodia® are acceptable

with the use of appropriate and full Personal Protective Equipment (PPE). No REIs are required to

protect crop worker re-entry. No buffer zone is required to protect bystanders..

5. Environmental risk assessment

5.1. The risks to a range of environmental receptors, from the use of azoxystrobin and tebuconazole are

considered as a proxy for the risks from Custodia®. Full details can be found in Appendix H:

Environmental risk assessment.

5.2. Aquatic environment:

Predicted chronic exposures concentrations of azoxystrobin and tebuconazole, applied as the

formulated product Custodia® resulted in calculated Risk Quotients above the Level Of Concern

(LOC) for the aquatic environment (fish, crustacean). To manage these risks, it is proposed to apply

controls to reduce spray-drift into the aquatic environment. Together with prescribed controls,

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additional controls setting a maximum application rate and use restrictions regarding the droplet size

will reduce the risks to below the level of concern. Details are provided in section 6.

5.3. Groundwater:

The EPA considers the environmental risk as below the level of concern for aquatic organisms.

5.4. Sediment:

The risk quotient of tebuconazole for sediment-dwelling organisms was below the level of concern.

Due to a lack of data on the active ingredient azoxystrobin, the risk to sediment-dwelling organisms

resulting from the application of Custodia® cannot be determined. However, azoxystrobin is already

approved in New Zealand at a higher rate (250 g ai/ha) than the proposed rate (120 g ai/ha).

5.5. Soil organisms:

Acute and chronic risk quotient to soil organisms applicable to azoxystrobin and tebuconazole

following the application of Custodia® are below the Level Of Concern (LOC).

For 1,2,4-triazole (metabolite tebuconazole) the chronic risk to threatened earthworms was above the

level of concern. Further evaluation indicated that threatened species are unlikely present in the

application areas of Custodia®, as a result, the risk is considered to be below the level of concern.

5.6. Non-target Plants:

Overall, it is considered that the risks to non-target plants following an application of Custodia® are

likely below the LOC.

5.7. Birds:

TER values for birds calculated for azoxystrobin and tebuconazole, when applied to fodder and sugar

beet as the formulated product Custodia®, are below the level of concern for acute risks, and any

risks are negligible. In the reproductive screening assessments, the TER values indicate a chronic risk

below the level of concern to birds for azoxystrobin but above the level of concern to birds from the

use of tebuconazole in fodder and sugar beet. After refinement, it is considered that it is likely that

threatened species will obtain less than 60% of their food from the treated fields as agricultural areas

are not the natural habitat of threatened bird species. Therefore, the risks from tebuconazole is

considered to be low. Furthermore, both active ingredients are already approved in New Zealand at

higher rates than the proposed rate. The risks from secondary poisoning is considered to be low as

both active ingredients are not considered to be bioaccumulative.

5.8. Pollinators:

The acute risks to pollinators are below the level of concern. Chronic risks could not be evaluated due

to a lack of data. However, both active ingredients are already approved in New Zealand at higher

rates than the proposed rate.

5.9. Non-target Arthropods:

Risks to non-target arthropods are above the level of concern for the in-field situation for parasitic

wasps following an application with Custodia®. For the other tested and assessed non-target

arthropods, the risks are below the level of concern. For the off-field situation, the risks for parasitic

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wasps are below the level of concern using the GENEEC model drift factors (aerial application). Re-

colonization from off-field is expected when the concentration has decreased.

The EPA recommends a label statement to warn end-users on the potential impact on beneficial

insects as risks cannot be fully excluded. Label statement indicating “WARNING” the substance might

not be compatible with Integrated Pest Management (IPM).

5.10. Overall Ecological risk assessment conclusion:

It is considered that the risks to the environment from the proposed use of Custodia® are acceptable

with the proposed controls.

6. Proposed controls

Additional and varied controls

Application rate

6.1. The maximum application rate is 120 g azoxystrobin and 200 g tebuconazole/ha, with a maximum of 2

applications/year and a minimum interval of 14 days.

Application method

6.2. When applied using ground-based or aerial application methods, the nozzle must be set to coarse

droplet quality spray, as defined by the American Society of Agricultural and Biological Engineers

ASABE Standard (S572) or the British Crop Production Council guideline.

Buffer zones

6.3. The following buffer zones have been determined for Custodia® for aerial application:

Table 2: Proposed buffer zones to downwind water body for aerial applications of Custodia®

Application method Aerial

BBCH-stage 12-19 31-39 >40

Bufferzone control (metres) 120 70 30

Additional label statements

6.4. Label statement indicating “WARNING” the substance might not be compatible with Integrated Pest

Management (IPM).

6.5. A label statement indicating: “DO NOT apply when wind speeds are less than 3 km/hr or more than 20

km/hr as measured at the application site”.

6.6. A label statement indicating the buffer zones for aerial applications:

BBCH stage 12-19: A downwind buffer zone of 120 m is required to mitigate the risks

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BBCH stage 31-39: A downwind buffer zone of 70 m is required to mitigate the risks

BBCH stage >49: A downwind buffer zone of 30 m is required to mitigate the risks

6.7. For aerial and ground-based application, use minimum coarse droplets, as defined by the American

Society of Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop

Production Council guideline. This information should be required on the label so that users are aware

of this control.

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Appendix A: Identity of the active ingredient, use pattern and mode of action

Identity of the active ingredient and metabolites

General data on tebuconazole and azoxystrobin are provided in Table 3.

Table 3: Identification of tebuconazole and azoxystrobin

Common name Tebuconazole Azoxystrobin

IUPAC name

(RS)-1-p-chlorophenyl-4,4-dimethyl-

3-(1H-1,2,4-triazol-1-

ylmethyl)pentan-3-ol

methyl (2E)-2-{2-[6-(2-

cyanophenoxy)pyrimidin-4-

yloxy]phenyl}-3-methoxyacrylate

CAS name

α-[2-(4-chlorophenyl)ethyl]-α-(1,1-

dimethylethyl)-1H-1,2,4-triazole-1-

ethanol

methyl (αE)-2-[[6-(2-cyanophenoxy)-

4-pyrimidinyl]oxy]-α-

(methoxymethylene)benzeneacetate

Molecular formula C16H22ClN3O C22H17N3O5

CAS Number 107534-96-3 131860-33-8

Molecular weight 307.82 g/mol 403.39 g/mol

Structural formula

Purity 975 g/kg 965 g/kg

Regulatory status

The regulatory history of azoxystrobin and tebuconazole is summarised in Table 4 below.

Table 4: Active ingredients regulatory status

Active ingredient

name

Regulatory history in

New Zealand

International regulatory history

(Australia, Canada, Europe,

Japan, USA)

Tebuconazole Approved (HSR002879) Approved in Australia, Canada,

Europe, Japan and USA

Azoxystrobin Approved (HSR100142) Approved in Australia, Canada,

Europe, Japan and USA

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Both tebuconazole and azoxystrobin are approved individually in New Zealand on a wide range of crops

(except sugar beet and fodder beet) at rates higher than those of Custodia® (up to 375 g/ha for



Azoxystrobin: barley, field tomato, grape, maize, onion, pea, potato, rye grass seed crop, sweetcorn, turf,

wheat.



Impurities and or restrictions on purity or composition

No relevant impurities have been identified by the Food and Agriculture Organization (FAO) or the Australian

Pesticides and Veterinary Medicines Authority (APVMA) on either active ingredient.

Use pattern and mode of action

Use pattern

Custodia® is intended to be used on sugar beet and fodder beet at rates of 1 L formulated product/ha,

corresponding to 200 g/ha tebuconazole and 120 g/ha azoxystrobin, with two application methods

(broadcast ground-based and aerial application). Full details are given in Table 5.

Mode of action

Tebuconazole belongs to the triazole group of fungicides that inhibit the 14-alpha-demethylase enzyme

which results in a disruption of the permeability of the fungal cell membrane. The accumulation of lanosterol

and other methylated sterols and a decrease in sterols, especially ergosterols, results in decreased fungal

growth and finally death. Tebuconazole does not prevent spore germination and some species of fungi can

still produce infective structures.

Azoxystrobin belongs to the oximino-acetate group of fungicides that has a different mode of action to

tebuconazole. The site of action of this group is in the mitochondrial respiration pathway (Complex III:

cytochrome bc1 and Qo site). This impacts cell respiration. It is an inhibitor of spore germination and mycelial

growth.

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Table 5: List of intended uses for Custodia®

Crop

and/or

situation

(a)

Use

pattern

(b)

Pests or

group of

pests

controlled

(c)

Mixture Application Application rate per treatment Remarks

(l) Type

(d-f)

Conc of ai

(g)

Method

and kind

(h-i)

Growth

stage &

season

(j)

Number

Min max

(k)

Interval

between

applications

– days

(minimum)

kg ai/hL

min max

water

L/ha

min

max

kg ai/ha

max

Fodder

beet

Sugar

beet

F

Cercospora

beticola;

Erisiphe

betae;

Uromyces

beticola;

SC

Azoxystrobin

120g/L

Tebuconazole

200g/L

Ground

based

broadcast

spray

BBCH

12-BBCH

49

Spring-

Autumn

1-2 14 days

Azoxystrobin

Min: 0.03

Max: 0.06

Tebuconazole

Min: 0.050

Max: 0.100

200L

min

400L

max

Azoxystrobin

Min. 0.120

Max: 0.120

Tebuconazole

Min: 0.200

Max: 0.200

Fodder

beet

Sugar

beet

F

Cercospora

beticola;

Erisiphe

betae;

Uromyces

beticola;

SC

Azoxystrobin

120g/L

Tebuconazole

200g/L

Aerial

application

BBCH

12-BBCH

49

Spring-

Autumn

1-2 14 days

Azoxystrobin

Min: 0.1240

Max: 0.240

Tebuconazole

Min: 0.200

Max: 0.400

50L min

100L

max

Azoxystrobin

Min. 0.120

Max: 0.120

Tebuconazole

Min: 0.200

Max: 0.200

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a Where relevant, the use situation should be described (eg fumigation of soil) b Outdoor or field use (F), glasshouse application (G) or indoor application (I). c eg biting and sucking insects, soil borne insects, foliar fungi, weeds d eg wettable powder (WP), emulsifiable concentrate (EC), granule (GR) e CropLife international, 2008. Technical Monograph no 2, 6th edition. Catalogue of pesticide formulation types and international coding system f All abbreviations used must be explained g g/kg or g/l or others h Method, eg high volume spraying, low volume spraying, spreading, dusting, drench, aerial, etc i Kind, eg overall, broadcast, aerial spraying, row, individual plant, between the plant - type of equipment used must be indicated. If spraying include droplet size spectrum j growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell (ISBN 3-8263-3152-4) , including where relevant, information on season at time of application k Indicate the minimum and maximum number of application possible under practical conditions of use l Remarks may include: Extent of use/economic importance/restrictions

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Appendix B: Physico-chemical properties of Custodia®

The physico-chemical properties of Custodia® are listed in Table 6.

Table 6: Physical and chemical properties of Custodia®

Property Value Reference

Colour White Liquid Application form

Odour Characteristic Application form

Physical state Suspension Concentrate Application form

Density 1.085 g/ml Application form

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Appendix C: Mammalian toxicology

Unless otherwise noted, all studies were conducted according to Good Laboratory Practice (GLP) and were

fully compliant with the requirements of the international test guidelines followed.

Executive summaries and list of endpoints for Custodia®

The mammalian toxicology data for Custodia® are summarised in Table 7.

Table 7: Summary of mammalian toxicology data for Custodia®

Endpoint

(Test Guideline)

Klimisch

score Result

HSNO

Classification Reference

Acute oral toxicity

(EC method B.1 and

OECD 423)

1 300 < LD50 ≤ 2000

mg/kg bw 6.1D

Appendix I; Table 62 ;

Report number: 24364

Acute dermal toxicity

(EC method B.3 and

OECD 402)

1 LD50 >2000 mg/kg bw No

Appendix I;

Table 63 ; Report

number: 24365

Acute inhalation toxicity

(EC method B.2 and

OECD 403)

1 LC50 >4.79 mg/L No


Project Number:

2684/0002

Skin irritation/corrosion

(EC method B.4 and

OECD 404)

1

Mean irritation score

(24, 48, and 72 hrs) –

Erythema: 0.1

Oedema: 0.0

No Appendix I; Table 65 ;


Eye irritation/corrosion

(EC method B.5 and

OECD 405)

1

Mean Draize Score

(24, 48, 72 hrs) –

Conjunctiva

-Redness: 0.33

-Chemosis: 0.0

Corneal opacity: 0.0

iritis: 0.0

No Appendix I; Table 66 ;


Contact sensitisation

(EC method B.6 and

OECD 406)

1

Magnusson and

Kligman grading scale:

Grade 1 skin reaction

in induction phases

and grade 0 in

challenge phase

No Appendix I;Table 67 ;


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Dermal absorption studies with tebuconazole are summarised in Table 8.

Table 8: Summary of dermal absorption studies with tebuconazole

Study type Results

Dermal absorption

Applicant has submitted in vitro dermal absorption studies on a number of formulation

types: soluble concentrate (SC), emulsifiable concentrate (EC), WG (water dispersible

granules) and flowable concentrate (FC) in rat and human skin and an in vivo dermal

absorption in rat on an EC formulation conducted using the concentrate and dilutions of

the formulations. The absorption values derived from in vitro human/rat studies were not

markedly different and are judged similar for occupational risk assessments. Average

dose and potentially absorbed dose differences for rat and human skin were calculated.

An in vivo dermal absorption study in rats on an EC formulation was considered to be

represent all tebuconazole formulations, based on the similarity of integrated data from

the in vitro human/rat studies.

Triple pack calculations were based on averaging maximum flux ratios across studies

and then calculating the ratio and using the average absorption values from the in vitro

studies. The most conservative absorption factors from these calculations were 1% for

the concentrate and 13% for the field dilution (OCS 2015). The in vivo dermal absorption

data from a monkey study summarised in EC DAR (EC 2007) further supports the

absorption factors derived from triple pack calculations.

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Appendix D: Environmental fate

Both active ingredients, azoxystrobin and tebuconazole, are already approved in New Zealand and data

were sourced from previous applications and the EPA substance database. Some data for azoxystrobin and

its metabolites were sourced from the European Union (EU) Renewal Assessment Report (RAR) on

azoxystrobin [ European Commission ; (EC 2009)].

Residues relevant to the environment

For both active ingredients in laboratory and field degradation studies in soil and water, major metabolites

(ie, those found at ≥ 10% applied radioactivity (AR) at any sample interval) were identified.

Azoxystrobin

For azoxystrobin, the metabolite, R234886 was considered a major metabolite in soil (laboratory maximum

28.8% and field maximum 67.7%) as well as in surface water (maximum 17.7% of applied radiation). In soil

two more major metabolites were identified namely R401553 and R402173 which were both observed at a

maximum of 17.7% of the applied radiation in the field studies.

The other major metabolite observed in the water was R230310 during the photolysis study (>10% of applied

radiation).

Ecotoxicological information was sourced from the European Union (EU) Renewal Assessment Report

(RAR) on azoxystrobin (EC 2009).

Tebuconazole

For tebuconazole, the metabolite 1,2,4-triazole accounted for up to 32.1% of applied radioactivity in soil

under aerobic conditions. No other information was provided that would indicate that any other soil

metabolites were exceeding 10% of applied radioactivity.

In aqueous systems, 1,2,4-triazole was found at levels up to 14%. Two additional major water metabolites

were identified: HWG 1608-pentanoic acid (maximum 40.2% AR) and HWG 1608-lactone (maximum 21.0%

AR).

Degradation and fate of azoxystrobin and tebuconazole in aquatic

environments

Information on the degradation and fate of azoxystrobin and tebuconazole in the aquatic environment is

summarised in Table 9 and Table 10 respectively. Information on bioaccumulation potential for azoxystrobin

and tebuconazole is listed in Table 11 and Table 12 respectively.

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Table 9: Degradation and fate in aquatic environments of azoxystrobin

Test type Value or conclusion for

azoxystrobin Reference

Ready biodegradation ND, considered to be not

readily biodegradable

EU RAR (EC 2009)

Aqueous photolysis half-life (DT50) 13.9 d

Degradation in aerobic water/sediment (DT50) 180- 234 d (whole system)

Water solubility at 20°C [mg/L] 6.0

Hydrolysis half-life (DT50) Stable at pH 5-9

Table 10: Degradation and fate in aquatic environment of tebuconazole

Test type tebuconazole Reference

Ready biodegradation No EPA substance database

Aqueous photolysis half-life (DT50) 590 d (pH 7, sunlight irradiation

for 30 d)

Degradation in aerobic water/sediment (DT50) 38.7 d (whole system)

Water solubility at 20°C [mg/L] 32

Hydrolysis half-life (DT50) Stable at pH 5, 7, 9.

Table 11: Bioaccumulation potential of azoxystrobin

Test type azoxystrobin Reference

Partition coefficient octanol/water [Log Kow] 2.5 EU RAR (EC 2009)

Fish bioconcentration (whole fish) ND

Table 12: Bioaccumulation potential of tebuconazole

Test type Active ingredient Reference

Partition coefficient octanol/water (Log Kow) 3.7 (pH 7.2, 20oC) EPA substance database

Fish bioconcentration (whole fish) BCF = 78 L/kg

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Degradation and fate of azoxystrobin and tebuconazole in soil

Information on the degradation and fate of azoxystrobin and its relevant metabolites in the soil environment

is summarised in Table 13 and information on the degradation and fate of tebuconazole and its major

metabolite 1,2,4-T triazole is given in Table 14.

Table 13: Degradation and fate of azoxystrobin and its metabolites in soil

Test type azoxystrobin metabolite Reference

Aerobic half-life in soil

(DT50lab)1 56.4, 66.9, 94.1, 72.8, 87,

141.6, 118.4, 153.4 days

80th percentile = 132.32

days

R234886

29.9, 25.5, 56.5, 31.8, 23.7

days

R4015531.4, 1.6, 2.0

daysR4021738.4, 4.2, 9.8

days

EU RAR (EC 2009)

Anaerobic degradation

in soil (DT50lab) 59.8, 49 days

EU RAR (EC 2009)


(DT50field)

186.4, 120.9 and 261.9

(SFO)

80.6, 61.3, 93.7, 121.6, 68,

34.5, 105, 66, 93.7, 73.7

(DOFB slow phase)

EU RAR (EC 2009)

Sorption to soil (Kd /

Koc)2

Kd:

12 sandy clay loam, 6.0

loamy sand, 9.0 loamy sand,

2.1 sand, 12 silty clay loam,

20 clay loam

Koc:

690 sandy clay loam,

357 loamy sand,

304 loamy sand,

724 sand,

739 silty clay loam,

718 clay loam

R234886

Kd: 1.0 loamy sand, 14.2

clay loam, 0.6 loamy sand,

2.3 sand, 9.1 silty clay loam,

1.1 sandy clay loam

Koc: 34 loamy sand, 514

clay loam, 32.4 loamy sand,

772 sand, 564 silty clay

loam, 65 sandy clay loam

R401553

Kd: 3 sandy clay loam, 1.1

loamy sand, 3.6 sandy loam,

17.6 silty clay loam, 2.2 silty

clay loam, 3.6 clay loam

Koc: 172 sandy clay loam,

376 loamy sand, 121 sandy

loam, 808 silty clay loam, 90

silty clay loam, 138 clay loam

R402173

EU RAR (EC 2009)

Page 24 of 131


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Test type azoxystrobin metabolite Reference

Kd: 0.7 sandy clay loam, 0.3

loamy sand, 0.8 sandy loam,

5.5 silty clay loam, 2.4 silty

clay loam, 3.2 clay loam

Koc: 40 sandy clay loam,

101 loamy sand, 27 sandy

loam, 254 silty clay loam,

100 silty clay loam, 124 clay

loam

1: Upper 80% of stated values used for risk assessment

2: Lowest value non-sandy soil used for risk assessment

Table 14: Degradation and fate in soil of tebuconazole and its major soil metabolite 1,2,4-triazole

Test type Reference

Active ingredient Tebuconazole


(DT50lab)1 > 1 year (770 days)

EPA substance database


(DT50field)

57.5 days (upper 80th percentile of 57.5, 28.9, 29.5,

65.3, 25.8 and 48.4 days)


Sorption to soil (Kd / Koc)1

Kd = 16.39; Koc = 910.4

Sandy loam kd = 12.69 koc = 906

Silt kd = 16.39 koc = 910.4

Low-humus sand kd = 7.67 koc = 1023

Sandy loam kd = 15.89 koc = 1249


Metabolite 1,2,4-triazole


(DT50lab) No data available


(DT50field)

92.8 days (upper 80th percentile of slow phase DT50s

of 70.7, 59.8, 25.1 and 126 days).


Sorption to soil (Kd / Koc)1

Koc = 43 (clay loam); Kd = 0.722 L/kg (silty clay loam)

Silty clay, Kd = 0.833 Koc = 120;

Clay loam Kd = 0.748 Koc = 43;

Sand Kd = 0.234 Koc = 2.2;

Silty clay loam Kd = 0.722 Koc = 104;

Sandy loam Kd = 0.719 Koc = 89


1: Lowest non-sand value

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General conclusion about environmental fate

Azoxystrobin

Azoxystrobin is not readily biodegradable in the aquatic environment according to HSNO criteria (DT50 =16

days – 2 months and not readily biodegradable). The photolysis half-life is 13.9 days makes it a relevant

degradation pathway, azoxystrobin does not degrade via hydrolysis.

In aerobic soils laboratory studies, the DT50 ranged from 56.4 to 153.4 days and considered to be persistent

(DT50 80th percentile = 30 days – 6 months). Azoxystrobin has a medium to low mobility in soil according to

McCall classification system (McCall P.J., Laskowski D.A. et al. 1981).

Azoxystrobin has a low potential for bioaccumulation based on the log Kow of 2.5.

Three metabolites were formed in soil environment, R234886 (67.7% after 181 days), R401553 (5% day 9.8

and 5.7% day 31.3, in field 17%) and R402173 (5.4% day 9.8 and 7.6% day 31.3, in field 17%). These

metabolites are less persistent than the parent but all three have a very high to low mobility according to

McCall classification system (McCall P.J., Laskowski D.A. et al. 1981). R234886 is also formed in the aquatic

environment (17.7%) however, no information on the environmental fate of this metabolite in this medium is

available.

Tebuconazole

Tebuconazole is not readily biodegradable in aquatic environment according to HSNO criteria (DT50 16 days

– 2 months). Photolysis (DT50 = 590 days) and hydrolysis (stable) are not considered important degradation

pathways.

In soil, tebuconazole was persistent in laboratory (DT50 = 770 days) studies but not under field conditions

(representative DT50field = 57.5 days). It is expected to exhibit low mobility in soil according to McCall

classification system (McCall P.J., Laskowski D.A. et al. 1981).

It is not considered bioaccumulative in the environment based on the BCF for fish (78 L/kg).

The only soil metabolite considered in this assessment was 1,2,4-triazole, formed up to 32.1% AR. No

information is available for persistence of this metabolite in soil in a controlled environment, however the

metabolite is considered slightly degradable in field studies (DT50 = 92.8 days). The metabolite may be

considered very highly mobile in the soil environment based on standard soil adsorption/desorption data

(Koc = 43 L/kg) according to McCall classification system (McCall P.J., Laskowski D.A. et al. 1981).

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Appendix E: Ecotoxicity

Both active ingredients, azoxystrobin and tebuconazole, are already approved in New Zealand and data

were sourced from previous applications and the EPA substance database. Some data for azoxystrobin and

its metabolites were sourced from the European Union (EU) Renewal Assessment Report (RAR) on

azoxystrobin (EC 2009).

The applicant provided studies with the formulated product, these are summarised in Appendix I. Unless

otherwise noted, all studies were conducted according to GLP and were fully compliant with all requirements

of the standard international test methods used.

List of endpoints

Aquatic toxicity

Table 15 contains the acute and chronic aquatic toxicity test results for the active ingredient azoxystrobin,

Table 16 contains the acute and chronic aquatic test results for the azoxystrobin metabolites,

Table 17 contains the acute and chronic aquatic toxicity test results for the active ingredient tebuconazole,

Table 18 contains the acute and chronic aquatic test results for the tebuconazole metabolites and Table 19

contains the acute and chronic aquatic toxicity test results for the formulated product Custodia®. Values in

bold are those used for the risk assessment. Underlined values are those used to determine the

classification.

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Table 15: Summary of aquatic toxicity data for azoxystrobin

Test species Test type and

duration

Endpoint value

(mg/L) Reference

Fish Acute

Rainbow trout. Oncorhynchus

mykiss

96 hr LC50

0.47 EU RAR (EC 2009)

Common carp, Cyprinus carpio 1.6

Bluegill sunfish, Lepomis

macrochirus 1.1

Fish Chronic

Fathead minnow, Pimephales

promelas

33-d, ELS, Flow-

through, NOEC 0.147

EPA substance

database

Invertebrates Acute

Daphnia magna 48 hr EC50 0.23 EU RAR (EC 2009)

Macrocyclops fuscus 48 hr EC50 0.13 EPA substance

database

Chironomus riparius 48 hr EC50

(spiked water) 0.21

EU RAR (EC 2009)

Chronic

Daphnia magna

21-d

reproduction

NOEC

0.044

EU RAR (EC 2009)

Algae and aquatic macrophytes

Green alga, Selenastrum

capricornutum 72 hr ErC50 0.36

EU RAR (EC 2009)

Duckweed, Lemna gibba 7-d EC50 0.64 EPA substance

database

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Table 16: Summary of aquatic toxicity data for azoxystrobin metabolites


duration

Tebuconazole metabolites

Metabolite Value Reference

Rainbow trout, Oncorhynchus mykiss

96 hr LC50 R234886 >150 mg/L EU RAR (EC

2009)

Daphnia magna 48 hr EC50 R234886 >180

Green alga, Selenastrum capricornutum

72 hr EC50 R234886 47.0

Table 17: Summary of aquatic toxicity data for tebuconazole


duration

Tebuconazole

Reference

Fish Acute

Rainbow trout, Oncorhynchus

mykiss

96 hr LC50

4.4 mg/L

EPA substance

database

Bluegill sunfish, Lepomis

macrochirus 5.7 mg/L

Golden orfe (Leuciscus idus) 8.7 mg/L

Sheepshead minnow

(Cyprinodon variegatus)

5.9 mg/L

>7.82 mg/L

Chronic

Rainbow trout. Oncorhynchus

mykiss

83 d ELS, NOEC 0.012 mg/L

EPA substance

database

21 d, semi static,

NOEC 0.010 mg/L

Fathead minnow, Pimephales

promelas

FSDT1, 122-125 d,

NOEC

NOAEC

0.00625 mg/L;

0.0125 mg/L

Sheepshead minnow

(Cyprinodon variegatus)

36 d ELS, NOEC 0.0219 mg/L

FFLC2, 203 d,

NOEC 0.0436 mg/L

EPA substance

database

Invertebrates Acute

Daphnia magna 48 hr EC50 2.79 mg/L

Page 29 of 131


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duration

Tebuconazole

Reference

Mysid shrimp (Mysidisopsis

bahia) 96 hr LC50 0.46 mg/L

EPA substance

database Eastern oyster (Crassostrea

virginica) 96 hr EC50 3.0 mg/L

Chronic

Daphnia magna

21 d flow through

NOEC 0.12 mg/L

EPA substance

database

21 d semi static

NOEC 0.010 mg/L

Mysid shrimp (Mysidisopsis

bahia)

28 d

NOEC

0.035 mg/L (formulation

FOLICUR)

Chironomus riparius

28 d, spiked water

NOEC emergence 2.33 mg/L

28 d spiked

sediment, NOEC

emergence

40 mg/kg sediment dw


Green alga,

Pseudokirchneriella

subcapitata

72 hr ErC50 2.83 mg/L

EPA substance

database Algae, Desmodesmus

subspicatus 72 hr ErC50 5.30 mg/L

Duckweed, Lemna gibba 14 d ErC50 0.144 mg/L

1) FSDT = Fish Sexual Development Test; 2) FFLC = Fish Full Life Cycle

Page 30 of 131


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Table 18: Summary of aquatic toxicity data for tebuconazole metabolites


duration

Tebuconazole metabolites

Metabolite Value Reference

Rainbow trout,

Oncorhynchus

mykiss

96 hr LC50

HWG 1608-pentanoic acid >10 mg/L EPA substance

database

HWG 1608-lactone >10 mg/L

Daphnia magna 48 hr EC50

1,2,4-Triazole >100 mg/L EPA substance

database

HWG 1608-pentanoic acid >100 mg/L


Green alga,

Pseudokirchneriella

subcapitata

72 hr EC50

1,2,4-Triazole >31 mg/L EPA substance

database

HWG 1608-pentanoic acid >100 mg/L


Chironomus riparius 28 d EC15 HWG 1608-lactone 51.2 mg/L EPA substance

database

Table 19: Summary of aquatic toxicity data for Custodia®


duration

Test substance

Value Reference

Fish Acute

Rainbow trout. Oncorhynchus mykiss

96 hr LC50

5.4 mg formulation/L Appendix I, Table 69 ;

Project 47653230

Zebrafish, Danio rerio 7.8 mg formulation/L Appendix I, Table 68 ;

Project 44748230

Invertebrates Acute

Daphnia magna 48 hr EC50 2.15 mg formulation/L Appendix I, Table 70 ;

project 47652220

Page 31 of 131


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duration

Test substance

Value Reference


Acute

Green alga, Pseudokirchneriella

subcapitata 72 hr ErC50 8.72 mg formulation/L


project 47651210

General conclusion about aquatic toxicity

Both active ingredients are already approved and are classified as 9.1A HSNO classification.

The metabolites for both active ingredients show a much lower toxicity profile compared with the parent

substance and therefore the aquatic risk assessment is considered to cover the metabolites (assuming the

persistence is similar to the parent). As the metabolites formed in soil (R234886, R401553, R402173, 1,2,4-

triazole) show a higher mobility, a groundwater assessment will be performed.

Custodia® triggers a 9.1B HSNO classification (ecotoxic in the aquatic environment) based on the provided

data with the formulation on fish, invertebrates and algae.

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Soil toxicity

Table 20 contains the acute and chronic soil toxicity test results for the active ingredient azoxystrobin and its

metabolites and Table 21 for the active ingredient tebuconazole and its metabolites.

Table 22 contains the acute and chronic soil toxicity test results for the formulated product Custodia®.

Values in bold are those used for the risk assessment.

Underlined values are those used to determine the classification.

Table 20: Summary of soil toxicity data for azoxystrobin and its metabolites

Test species Test type and duration Value Reference

Azoxystrobin

Earthworm, Eisenia

fetida

Acute, 14-d LC50 283 mg/kg dw soil

(EC50= 28.3 mg/kg dry soil)

EU RAR (EC 2009)

Reproduction, ND

Metabolites

Earthworm, Eisenia

fetida

Acute, 14-d LC50 R234886, R401553 and

R402173

> 1000 mg/kg dw soil

EU RAR (EC 2009)

Terrestrial plants

Azoxystrobin

Six dicot and four

monocot crop

species

Vegetative vigour, 21 days

Foliar application to

seedling plants

ND

Seedling emergence, 21

days

Application to soil surface

ER50 > 20 mg/kg dw soil

(equivalent to 15 kg ai/ha

based on 5 cm depth and

density 1.5 g/cm3)

EU RAR (EC 2009)

Soil microbial function

Soil microflora Nitrogen mineralisation, 28

days

No significant effects were

observed on nitrogen and

carbon mineralisation up to 2.5

g ai/ha.

The metabolites, R234886 (up

to 10 mg/kg soil), R401553 (up

to 2.6 mg kg/soil) and R402173

(up to 4.1 mg/kg soil), appear to

EU RAR (EC 2009)

Carbon mineralisation, 28

days

Page 33 of 131


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Test species Test type and duration Value Reference

have no effects on soil

microbial processes

Page 34 of 131


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Table 21: Summary of soil toxicity data for tebuconazole and its major soil metabolite


duration Test substance Result Reference

Soil macro fauna

Earthworm,

Eisenia

foetida

Acute, 14-day LC50 Tebuconazole LC50 = 1381 mg/kg soil dw EPA substance

database 1,2,4-Triazole LC50 >1000 mg/kg soil dw

Reproduction, Tebuconazole NOEC = 10 mg/kg soil dw

1,2,4-Triazole NOEC = 1.0 mg/kg soil dw

Springtail,

Folsomia

candida

Reproduction 28-

day

Tebuconazole NOEC = 250 mg/kg soil dw

1,2,4-Triazole NOEC = 1.8 mg/kg soil dw


Soil

microflora

Nitrogen

mineralisation, 28

days

Tebuconazole <25% effects at 8.23 mg/kg

soil dw

EPA substance

database

Carbon

mineralisation, 28

days

Table 22: Summary of soil toxicity data for Custodia®.


duration Custodia® Reference

Earthworm, Eisenia

fetida

Acute, 14-d LC50 >1000 mg formulation/kg soil Appendix I, Table

72; project

47657021

Reproduction, ND

Springtail, Folsomia

candida

Reproduction 28-d

NOEC

500 mg formulation/ kg soil Appendix I, Table

73; project

47742016

Terrestrial plants

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Six dicot and four

monocot crop species

Vegetative vigour,

21-d NOER

Foliar application

to seedling plants

EC50 >3.375 L formulation/ha (limit test, tested

concentration)

(> 4.88 mg formulation/kg soil, based on 5 cm

depth and 1.5 g/cm3 density)

NOER ND

Appendix I, Table

74 ; project

47650087

Seedling

emergence, 21

days

Application to soil

surface

ND


Soil microflora Nitrogen

mineralisation, 56

days

No long term adverse effects, maximum

tested concentration 18 mg formulation/

kg dw soil (12.5 L formulation/ha)

Appendix I, Table

75 ; project

51941080

Carbon

mineralisation, 28

days

No adverse effects, maximum tested

concentration 18 mg formulation/ kg dw

soil (12.5 L formulation/ha)

Nitrogen

mineralisation, 41

days

No long term adverse effects, maximum

tested concentration 14.4 mg formulation/ kg

dw soil (5 L formulation/ha)

Appendix I, Table

76 ; project

47659080

Carbon

mineralisation, 28

days

No adverse effects, maximum tested

concentration 14.4 mg formulation/ kg dw soil

(5 L formulation/ha)

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General conclusion about soil toxicity

Both active ingredients are already approved. Azoxystrobin triggers 9.2C HSNO classification and

tebuconazole does not trigger the HSNO threshold for toxicity to the soil environment.

The toxicity of Custodia® could not be determined based on the formulation data available. Custodia®

shows some toxicity in the vegetative vigour test (13.1% at >3.375 L formulation/ha), however the

mechanism is unknown and could potentially also effect seedling emergence (exposure via soil). No

information on seedling emergence has been provided, and as effects cannot be excluded the

substance can potentially be toxic to seedlings via exposure through the soil.

The EPA attempted to classify the substance using mixture rules but insuffient information was

available. Given that the classification of multiple components is not known, the EPA could not

determine the classification, therefore it is ND for soil toxicity.

The major soil metabolites of azoxystrobin (R234886, R401553 and R402173) do not indicate toxicity,

these metabolites also degrade faster than the parent. Therefore, the risk assessment for the parent

is considered to cover the risks from the metabolites.

The major soil metabolite of tebuconazole (1,2,4-triazole) has a higher chronic soil toxicity and a

higher DT50 value in soil. Therefore, this metabolite has been included in the risk assessment.

Terrestrial vertebrate toxicity

For effects on terrestrial vertebrates other than birds, refer to the mammalian toxicity section.

Table 23 contains the acute and chronic avian toxicity test results for the active azoxystrobin and

Table 24 for the active ingredient tebuconazole.

Table 25 contains the acute and chronic avian toxicity test Custodia®.

Table 23: Summary of terrestrial vertebrate toxicity data for azoxystrobin

Test species

Test type

and

duration


xBobwhite quail,

Colinus

virginianus

Acute oral

LD50 >2000 mg/kg bw

EU RAR (EC 2009)

8-d dietary

LC50

>5200 mg/feed

(>1179 mg/kg bw/day)

Reproductive

1 generation,

22 weeks

NOEL

1200 mg/kg feed

(117 mg/kg bw/day)

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Test species

Test type

and

duration


Mallard duck,

Anas

platyrhynchos

Acute oral

LD50 >2000 mg/kg bw1

EU RAR (EC 2009)

8-d dietary

LC50

>5200 mg/kg feed

(>1754 mg/kg bw/day)

Reproductive

1 generation,

21 weeks

NOEC

1200 mg/feed

(187 mg/kg bw/day)

1: regurgitation observed and the recommended reduction of the LD50 is 1000 mg/kg bw. However, as no mortality was

observed and the study with the bobwhite quail also has an LD50 of 2000 mg/kg bw the endpoint for risk assessment will be

2000 mg/kg bw.

Table 24: Summary of terrestrial vertebrate toxicity data for tebuconazole

Test species

Test type

and

duration

Test item Reference

Bobwhite quail,

Colinus

virginianus

Acute oral

LD50

1555 mg/kg bw


1988 mg/kg bw

8-day dietary

LC50

>703 mg/kg bw bw/d (>5000 mg/kg

diet)

Reproductive

NOEL = 5.8 mg/kg bw/d (73.5

mg/kg diet)

LOEL = 12.4 mg/kg bw/d (156

mg/kg diet)

Mallard duck

(Anas

platyrhynchos)

8-day dietary

LC50 >4816 mg/kg diet

Reproductive

NOEC reproduction 75.8 mg/kg diet

NOEC reproduction 170 mg/kg

diet (17.7 mg/kg bw/d)

Table 25: Summary of terrestrial vertebrate toxicity data for Custodia®



Japanese quail,

Coturnix japonica Acute oral LD50 >2000 mg ai/kg bw

Appendix I, Table 77 ; project

24366

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8-d dietary LC50 ND

Reproductive 1

generation, 22 weeks

NOEC

ND

General conclusion about ecotoxicity to terrestrial vertebrates

Both active ingredients are already approved. Tebuconazole triggers 9.3C HSNO classification and

azoxystrobin does not trigger the HSNO threshold for toxicity to terrestrial vertebrates based on the

data available.

Custodia® does not trigger the HSNO thresholds for toxicity to the terrestrial vertebrates based on the

data available.

Ecotoxicity to bees and other terrestrial invertebrates

Table 26 contains the toxicity test results for the active ingredient azoxystrobin on non-target

organisms and Table 27 for the active ingredient tebuconazole.

Table 28 contains the toxicity test results for Custodia® on non-target organisms.

Table 26: Summary of terrestrial invertebrate toxicity data for azoxystrobin


duration azoxystrobin Reference

Honeybee, Apis

mellifera

48 hr, Acute

oral, LD50 >25 µg ai/ bee EU RAR (EC 2009)

24 hr Acute

contact LD50 >200 µg ai/ bee

EU RAR (EC 2009)

Parasitic wasp,

Aphidius

rhopalosiphi

48 hr LR50

laboratory glass

plate

>1000 g ai/ha

Predatory mite,

Typhlodromus pyri

48 hr LR50

laboratory glass

plate

>1500 g ai/ha

Page 39 of 131


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Table 27: Summary of bees toxicity data for tebuconazole


duration tebuconazole Reference

Tebuconazole

Honeybee, Apis

mellifera

Acute oral LD50 >83.05 µg/bee


Acute contact LD50 >100 µg/bee

Table 28: Summary of bees toxicity data for Custodia®



Honeybee, Apis

mellifera

Acute oral, 48 hr

LD50

>208.4 μg

formulation/bee Appendix I, Table 78 ;

project 47741035

Acute contact LD50 >200 μg

formulation/bee

Table 29: Summary of terrestrial invertebrate toxicity data for Custodia®



Parasitic wasp,

Aphidius rhopalosiphi

48 hr LR50 Extended

laboratory residues

on barley

605 mL formulation/ha

Appendix I, Table

79 ; project

47744002

48 hr LR50 Extended

laboratory dry

residues on beans

The effects of MCW 710

SC (3.38 L/ha) were

below the trigger value of

50% on mortality and

fecundity.

Appendix I, Table

80 ; project

47654003

Predatory mite,

Typhlodromus pyri

7 d LR50

Extended laboratory

dry residues on

beans

> 3375 mL

formulation/ha

Effects on reproduction

are above 50% for the

dose rates 171, 463 and

3375 mL formulation/ha.

Appendix I, Table

84 ; project

47745062

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7 d LR50

Extended laboratory

fresh and dry

residues on beans

> 3.38 L/ha.

Appendix I, Table

83 ; project

47655060

Field study, grape

vines effect on

population

No unacceptable effects

were observed after 2

applications with MCW

710 SC at a rate of 0.263

and 0.438 L/ha.

Appendix I, Table

85 ; project FCS02

Green lacewing,

Chrysoperla carnea

48 hr LR50

Extended laboratory

dry residues on

beans

>3.375 L formulation/ha

Appendix I, Table

82 ; project

47747047

Ladybird beetle,

Coccinella

septempunctata

20 d LR50

extended laboratory

dry residues on

beans

>3.375 L formulation/ha

Appendix I, Table

81 ; project

47746012

General conclusion about ecotoxicity to bees and terrestrial invertebrate toxicity

Both active ingredients are already approved. Azoxystrobin and tebuconazole do not trigger the

HSNO threshold for toxicity to terrestrial invertebrates.

Custodia® does not trigger the HSNO thresholds for toxicity to the terrestrial invertebrates based on

the data available.

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Appendix F: Hazard classification of Custodia®

The hazard classifications of Custodia® are listed in Table 30.

Table 30: Applicant and EPA classifications of Custodia®1

Hazard Class/Subclass

Mixture

classification

by:

Method of classification

Remarks

Applicant EPA

Mix

ture

data

Read

acro

ss

Mix

ture

ru

les

Class 1 Explosiveness No ND

Class 2, 3 & 4 Flammability No ND

Class 5 Oxidisers/Organic

Peroxides No ND

Subclass 8.1 Metallic

corrosiveness No ND

Subclass 6.1 Acute toxicity

(oral) 6.1E 6.1D

300 < LD50 ≤ 2000

mg/kg bw

Subclass 6.1Acute toxicity

(dermal) No No LD50 >2000 mg/kg bw

Subclass 6.1 Acute toxicity

(inhalation) No No LC50 >4.79 mg/L

Subclass 6.1 Aspiration

hazard No No

Subclass 6.3/8.2 Skin

irritancy/corrosion No No

Subclass 6.4/8.3 Eye

irritancy/corrosion No No

Subclass 6.5A Respiratory

sensitisation No ND

Subclass 6.5B Contact

sensitisation No No

Subclass 6.6 Mutagenicity No ND

1 Use of mixture rules may not adequately take into account interactions between different components in some circumstances and must be considered of lower reliability than substance (formulation) data.

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Hazard Class/Subclass

Mixture

classification

by:

Method of classification

Remarks

Applicant EPA

Mix

ture

data

Read

acro

ss

Mix

ture

ru

les

Subclass 6.7

Carcinogenicity No ND

Subclass 6.8 Reproductive/

developmental toxicity 6.8B 6.8B Tebuconazole

Subclass 6.8 Reproductive/

developmental toxicity (via

lactation)

Subclass 6.9 Target organ

systemic toxicity (oral) 6.9B 6.9B

Tebuconazole ;

azoxystrobin


systemic toxicity (dermal)


systemic toxicity (inhalation)

Subclass 9.1 Aquatic

ecotoxicity 9.1A 9.1B

EC50 Daphnia magna =

2.15 mg formulation/L

Subclass 9.2 Soil ecotoxicity No ND

Subclass 9.3 Terrestrial

vertebrate ecotoxicity No No

Subclass 9.4 Terrestrial

invertebrate ecotoxicity No No

NA: Not Applicable. For instance testing for a specific endpoint may be omitted if it is technically not possible to

conduct the study as a consequence of the properties of the substance: eg very volatile, highly reactive or

unstable substances cannot be used, mixing of the substance with water may cause danger of fire or explosion

or the radio-labelling of the substance required in certain studies may not be possible.

ND: No Data or poor quality data [according to Klimisch criteria (Klimisch, Andreae et al. 1997)]. There is a lack

of data for one or more components.

No: Not classified based on actual relevant data available for the substance or all of its components. The data

are conclusive and indicate the threshold for classification is not triggered.

Mammalian toxicity studies with Custodia® indicate that the substance is of low acute toxicity and

should be classified 6.1D for acute oral toxicity. The substance is not irritating to the skin or eyes, and

is not a contact sensitiser. Based on mixture rules, Custodia® should be classified 6.8B and 6.9B

(oral). Based on test data for the formulation, Custodia® should also be classified 6.1D and 9.1B but

does not require classification as being toxic to terrestrial vertebrates or invertebrates

Page 43 of 131


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Appendix G: Human health risk assessment

Quantitative risk assessment

The operator exposure assessment is based on a modification of the approach used by European

regulators, taking into account New Zealand specific factors. The model is based on the results of

actual measurements carried out in the field and has an established history of providing reliable and

reproducible results.

The re-entry worker exposure assessment is based on a modification of the approach used by

European regulators and the US EPA. The parameters for the modelling are based on empirical data

relating to measurements of dermal exposure of workers from contact with residues on foliage for

various activities and the amount of foliar residues that are dislodgeable.

The bystander exposure assessment is based on a modification of the approaches used by European

regulators and the US-EPA. Spray drift deposition from ground based application is estimated using

the AgDrift model using the curves produced by the Australian Pesticides and Veterinary Medicines

Authority [APVMA, (APVMA 2010)]. The parameters are based on empirical data. Spray drift

deposition from aerial application is estimated using the AGDISP model along with appropriate New

Zealand input parameters.

Full details of the methodology can be found in the EPA risk assessment methodology document

(EPA 2018).

To assess risks the predicted systemic exposures to the active ingredient(s) are compared with an

acceptable operator exposure limit (AOEL) for the active ingredient and a risk quotient (RQ) is

calculated. RQ values greater than one indicate that predicted exposures are greater than the AOEL

and potentially of concern. RQ values below one indicate that predicted exposures are less than the

AOEL and are not expected to result in adverse effects.

Input values for the human health risk assessment

Custodia® is a fungicide containing 200 g/L tebuconazole and 120 g/L azoxystrobin in a suspension

concentrate formulation for control of foliar diseases of forage beet crops. Neither tebuconazole nor

azoxystrobin are approved on sugar beet and fodder beet. In addition, there is no existing approved

substance that contain both active ingredients in combination to date. The EPA decided to

quantitatively assess the risk only for tebuconazole because it has higher application rates (200 g

ai/ha versus 120 g ai/ha), a more conservative AOEL (0.03 mg/kg bw/day versus 0.20 mg/kg bw/day),

and is present at a higher concentration in the substance (200 g/L versus 120 g/L) than azoxystrobin.

Thus, all controls used to support the safe use of tebuconazole will automatically support and protect

against any risk associated with azoxystrobin.

Reference doses for tebuconazole established by internationally reputable regulatory authorities are

summarised in Table 31.

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Table 31: Reference doses established by regulators

Available

international

Reference

doses

Key systemic

effect

NOAEL

mg/kg

bw/d

Uncertaint

y factors

Reference

value (nature

of the value)

mg/kg bw/d

Staff’s

modifications Remarks

ADI-

Tebuconazole –

(EFSA 2014)

Subtle hypertrophy of

adrenal zona

fasciculate cells in all

animals of the 150 ppm

group was observed.

3 100 0.3 None None

ARfD-

Tebuconazole –

(EFSA 2014)

Increased enzyme

activity in livers and

increased post

implantation loss,

increased external

skeletal and visceral

anomalies

10 100 0.1 None None

The relevant toxicity studies that were considered to derive an acceptable operator exposure level

(AOEL) for tebuconazole are summarised in Table 32.

Table 32: Summary of studies relevant for establishing an AOEL

Key systemic effect

NOAEL

(mg/kg

bw/d)

Uncertainty

factors

Absorption

factor

AOEL

mg/kg

bw/d

Justification

Subtle hypertrophy of

adrenal zona fasciculate

cells in all animals of the

150 ppm group was

observed.

3 100 - 0.03

Conservative NOAEL; dogs were

found to be the most sensitive

species in short-term studies

Other input values for the exposure assessment are summarised in Table 33.

The applicant has submitted in vitro dermal absorption studies on a number of formulation types:

soluble concentrate (SC), emulsifiable concentrate (EC), WG (water dispersible granules) and

flowable concentrate (FC) in rat and human skin and an in vivo dermal absorption in rats on an EC

formulation conducted using the concentrate and dilutions of the formulations. The absorption values

derived from in vitro human/rat studies were not markedly different and are judged similar for

occupational risk assessments. Average dose and potentially absorbed dose differences for rat and

human skin were calculated. An in vivo dermal absorption study in rats on an EC formulation was

Page 45 of 131


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considered to be represent all tebuconazole formulations, based on the similarity of integrated data

from the in vitro human/rat studies.

Triple pack calculations were based on averaging maximum flux ratios across studies and then

calculating the ratio and using the average absorption values from the in vitro studies. The most

conservative absorption factors from these calculations were 1% for the concentrate and 13% for the

field dilution (OCS 2015). The in vivo dermal absorption data (13.02%) from a rhesus monkey study

summarised in EC DAR (EC 2007) and EFSA (EFSA 2014) further supports the absorption factors

derived from triple pack calculations.

Table 33: Input values for human exposure modelling

Active

ingredient

Physical

form

Concentration

of each active

(%)

Maximum

application rate

(for each active,

for each

method of

application)

g ai/ha

Dermal absorption

(%)

AOEL

mg/kg

bw/d

Concentrate Spray

Tebuconazole Liquid

(suspension

concentrate)

18.433 200 (for aerial and

ground based

application)

1 13 0.03

Operator exposure assessment

The results of the operator exposure assessment are shown in Table 34.

Table 34: Output of operator mixing, loading and application exposure assessment for

tebuconazole

Exposure Scenario Estimated operator

exposure (mg/kg bw/d)

Risk

Quotient

Boom

No personal protective equipment (PPE)2 during mixing, loading and

application

0.0623 2.08

Gloves only during mixing and loading 0.0577 1.92

Gloves only during application 0.0528 1.76

Full PPE during mixing, loading and application (excluding respirator) 0.0042 0.14

2 ‘Full PPE’ includes: gloves, hood/visor, coveralls, and heavy boots during application and gloves during mixing and loading.

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Full PPE during mixing, loading and application (including FP1, P1 and

similar respirator achieving 75 % inhalation exposure reduction)

0.0040 0.13

Full PPE during mixing, loading and application (including FP2, P2 and

similar respirator achieving 90 % inhalation exposure reduction)

0.0039 0.13

Predicted operator exposures to tebuconazole are below the Acceptable Operator Exposure Level

(AOEL), provided full PPE (gloves, hood/visor, coveralls, and heavy boots without a respirator) is

worn during mixing, loading, and application. Therefore operator exposures to Custodia® are not

expected to result in adverse health effects, if adequate PPE is worn. Risks associated with the

operator during aerial application are believed to be lower than those determined for boom as

exposure to the applicator is qualitatively deemed to be negligible during application. Accordingly, no

PPE is required for the operator during aerial application.

Re-entry worker exposure assessment

The results of the re-entry worker exposure assessment are summarised in Table 35.

Table 35: Output of the re-entry worker exposure assessment for tebuconazole

Active

ingredient Crop/activity

Internal (absorbed)

dose available for

systemic

distribution

(mg/kg bw/8 hours)

AOEL

(mg/kg

bw/d)

Risk Quotient

immediately

after

application

Re-entry

interval

without

gloves

Tebuconazole

Fodder beet and

sugar beet /

scouting,

irrigation

0.02 0.03 0.61 0.0

Risk Quotient resulting from predicted exposures to tebuconazole for workers re-entering and working

in areas where Custodia® has been applied are below the LOC. No re-entry intervals are necessary.

Quantitative bystander risk assessment

It is considered that the main potential source of exposure to the general public for substances of this

type (other than via food residues which will be considered as part of the registration of this substance

under the Agricultural Compounds and Veterinary Medicines (ACVM) Act 1997) is via spray drift. In

terms of bystander exposure, toddlers are regarded as the most sensitive sub-population and are

regarded as having the greatest exposures. For these reasons, the risk of bystander exposure is

assessed in this sub-population. The AOEL calculated for the operator and re-entry worker exposure

assessments has been used for the bystander assessment, as the use of an oral chronic reference

dose (CRfD) is usually likely to be over precautionary.

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The results of the bystander exposure assessment are summarised in Table 36.

Table 36: Output of the bystander exposure assessment for tebuconazole

Exposure Scenario

Estimated exposure of

15 kg toddler exposed

through contact to

surfaces 8 m from an

application area

(µg/kg bw/d)

Risk Quotient

Buffer zone needed

to reduce toddler

exposure to the

AOEL

Boom

High boom, fine droplets 1.30 0.0433 0

High boom, coarse droplets 0.21 0.0069 0

Low boom, fine droplets 0.44 0.0146 0

Low boom, coarse droplets 0.10 0.0035 0

Aerial - agriculture

Swath width 20 m, Med-coarse

droplet size

7.73 0.2576 0

Swath width 20 m, coarse- v.

coarse droplets

6.77 0.2257 0

Swath width 20 m, extremely

coarse droplets

6.05 0.2018 0

Swath width 24 m, v. fine-fine

droplets

10.53 0.3511 0

Swath width 24 m, fine-med.

droplets

12.17 0.4058 0

Swath width 24 m, med.-coarse

droplets

13.01 0.4337 0

Estimated bystander exposure from spray drift after application of Custodia® to the soil around fodder

beet and sugar beet is below the AOEL. No buffer zone is required in protect bystanders.

Groundwater contamination risk assessment

The ecotoxicity assessment (see appendix H; Table 48) has identified that the metabolite 1,2,4-triazole

may occur in ground water after application of the substance. Therefore TEL (Drinking Water) have

been derived which can be used if necessary to assess the significance of ground water concentrations

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if the residues are found in sources used for human consumption. For this, ADI for 1,2,4-triazole

established by the European Food Safety Authority (EFSA 2014) is summarised in Table 37 below.

Table 37: Using an existing ADE, ADI or CRfD for 1,2,4-triazole

Available

international

toxicological

thresholds

NOAEL

(mg/kg

bw/day)

Uncertainty

factors

ADE

(mg/kg

bw/day)

EPA

Modifications Remarks

[ADI]

(EFSA 2014) 20.0 1000 0.02 None

Based on the rat

multigeneration study.

Exposure Thresholds

The EPA has reviewed health based exposure guidance values established by overseas regulators

(Table I-3) to inform the selection of ADE and PDE values for 1,2,4-triazole (Table 38).

Table 38: Metabolite exposure thresholds

Metabolite

Acceptable Daily

Exposure (ADE) – mg/kg

bw/d

Potential Daily

Exposure (PDE) –

mg/kg bw/d

Tolerable Exposure

Limit (TEL)

mg/L (water)

1,2,4-triazole 0.02 PDE (Drinking water) =

0.004

TEL (Drinking Water) =

0.004

TEL (Drinking Water) = [PDE (Drinking Water) x adult body weight]/ 2 L

TEL (Drinking Water) = 0.004 (mg/kg bw/day) x 70 kg/2L/day = 0.14 mg/L

The assumptions involved are that the value applies to an adult human with a body weight of 70 kg and

that an adult who consumes 2 litres of drinking water/day (the standard value used by the Ministry of

Health and the World Health Organization to derive drinking water standards).

The estimated ground water concentration of 1,2,4-triazole from the application of Custodia® has been

estimated using SciGrow as 0.11 μg/L (see Appendix H). The EPA notes that this value is lower than

the TEL (Drinking Water) derived for 1,2,4-triazole which suggests that ground water concentrations

result in acceptable risks after use of Custodia®.

Conclusions of the human health risk assessment

It is considered that the risks to human health from the proposed use of Custodia® are acceptable

with the use of appropriate and full Personal Protective Equipment (PPE). No REIs are required to

protect crop worker re-entry. No buffer zone is required to protect bystanders.

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Appendix H: Environmental risk assessment

Evaluation of toxicity of the mixture

The formulations and tank mixes consist of multiple components which potentially can have effects

deviating from additivity by showing toxicity which is more than additive (synergism) or less than

additive (antagonism). The nature of these mixtures will be evaluated if the formulation consists of

multiple active ingredients or when tank mixes are considered “mandatory” on the label (ie the

formulation should be mixed with a specific other product). To evaluate the toxicity of the components

in the formulation the toxicity is evaluated using the methodology described by EFSA (EFSA 2013).

Evaluation of mixtures is complicated for long-term scenarios, since environmental fate information on

the whole formulation is generally not available.

To enable an assessment regarding the relative toxicity of the formulation the calculated toxicity of the

formulation is determined using the Concentration Addition (CA) model (see equation 1).

𝐸𝐶𝑥𝑓𝑜𝑟𝑚𝑢𝑙𝑎𝑡𝑖𝑜𝑛−𝐶𝐴 = (∑𝑃𝑖

𝐸𝐶𝑥𝑖

𝑛

𝑖=1

)

−1

Equation 1: Determination of calculated toxicity following the concentration addition model

Where:

n: number of components included in evaluation

i: index from 1 – n mixture components

Pi: The ith component as relative fraction of the mixture (sum of Pi should be 1, therefore a final component with very low toxicity, 10,000 mg/L, 10,000 mg/kg, 10,000 mg/ha, 10,000 mg/kg bw is added to the equation)

ECxi: Concentration of component i provoking X% effect.

This calculated toxicity is compared with the toxicity of the formulation measured in the toxicity test to

calculate the Model Deviation Ratio (MDR) which can be found in equation 2.

𝑀𝐷𝑅 = 𝐸𝐶𝑥𝑓𝑜𝑟𝑚𝑢𝑙𝑎𝑡𝑖𝑜𝑛−𝐶𝐴

𝐸𝐶𝑥𝑓𝑜𝑟𝑚𝑢𝑙𝑎𝑡𝑖𝑜𝑛

Equation 2: Calculation of the Model Deviation Ratio (MDR)

ECxi: Concentration of component i provoking X% effect, formulation-CA (see equation X), formulation measured toxicity.

Based on the values of the MDR it can be determined if the formulation shows additive, more than

additive or less than additive toxicity.

MDR 0.2 – 5: Non-additive / Additive: independent toxic effects / one substance contributes to

the effect of one or more of the other substances (concentration addition / partial addition)

MDR >5: More than additive (synergism): enhancement of effects, the combined effect is

greater than the sum of the individual effects

MDR <0.2: Less than additive (antagonism): attenuation of toxic effects

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Table 39: Additivity evaluation

Test Azoxystro

bin

Tebuco-

nazole

Formulation

calculated

Formulation

measured MDR Conclusion

Fish acute

LC50 (mg/L) 0.47 4.4 3.6 5.4 0.7 In agreement

Daphnid

acute

EC50 (mg/L)

0.23 2.79 1.8 2.15 0.85 In agreement

Algae

ErC50 (mg/L) 0.36 2.83 2.7 8.72 0.31 In agreement

Earthworm

acute

LC50 (mg/kg)

283 1381 1681 >1000 <1.68

Inconclusive likely

in agreement. Else

less than additive

Bird acute

LD50 (mg/kg

bw) >2000 1555 4092.5 >2000 >/<2.0

Inconclusive likely

in agreement.

Toxicity low

therefore no

concern

Bee oral

LD50 (µg/bee) >25 >83.05 148.9 >208.4 >/<0.7

Inconclusive likely

in agreement.

Toxicity low

therefore no

concern

Bee dermal

LD50 (µg/bee) >200 >100 405.4 >200 >/<2.0

Inconclusive likely

in agreement.

Toxicity low

therefore no

concern

For active ingredients in formulations that behave in an additive manner it is considered that a risk

assessment based on the test results with “pure” active ingredients will adequately reflect the toxic

effects in the field.

For active ingredients in formulation that behave in a less than additive manner considered that a risk

assessment based on the test results with “pure” active ingredients results in the most conservative

approach potentially overestimating the effects in the environment. However, the antagonistic

interaction only occurs when an organism is exposed to the antagonistic components at the same

time. It is highly likely that these antagonistic components have a different degradation pattern and

thus it is still possible that the components will not behave antagonistically in the environment.

Therefore, the approach to evaluate toxicity using the test results with “pure” active ingredients is

considered justified.

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For active ingredients in formulations that behave in a more than additive manner the risk

assessments based on the test results of “pure” active ingredients are likely to be underestimating the

risks. Co-occurrence of the synergistic components is likely directly after the application and therefore

the potential risk from the formulation should be considered and not just the acute risk from the active

ingredient. Based on the results expert judgement is required to determine which assessment is the

most appropriate one (eg more sensitive species were tested with the active ingredient).

Based on the additivity assessment, it was determined that for the endpoints that are assessed, the

components in the formulation interacted in agreement. Consequently, the acute assessment for the

endpoints will be based on the “pure” active ingredients. For all endpoints, controls managing the

risks from the “pure” active ingredients will manage the risks from the formulation.

For practical application, if a single active ingredient can be shown to contribute ≥90% towards toxicity

and the formulation does not deviate from additivity, the (acute) risk assessment will be performed for

that active constituent only. The relative contribution of each active constituent may be determined

according using the toxic unit concept (Equation 3). This approach can only be taken for the acute

toxicity assessment since during prolonged exposure environmental fate processes are likely

changing the ratio of the components in the formulation.

%𝑟𝑒𝑙𝑎𝑡𝑖𝑣𝑒_𝑒𝑐𝑜𝑡𝑜𝑥𝑖𝑐𝑖𝑡𝑦_𝑐𝑜𝑛𝑡𝑟𝑖𝑏𝑢𝑡𝑖𝑜𝑛 =

𝑝𝑖𝐸𝐶𝑥𝑖

∑𝑝𝑖

𝐸𝐶𝑥𝑖

𝑛𝑖=1

× 100

Equation 3: Determination of contribution of toxicity of the active ingredients

n: number of components included in evaluation

i: index from 1 – n mixture components

Pi: The ith component as relative fraction of the mixture (sum of Pi should be 1, therefore a final component with very low toxicity, 10,000 mg/L, 10,000 mg/kg, 10,000 mg/ha, 10,000 mg/kg bw is added to the equation)

ECxi: Concentration of component i provoking X% effect.

Table 40: Contribution of active ingredients to toxicity of formulation

Test azoxystrobin tebuconazole

Fish acute 85 15

Daphnid acute 88 12

Algae 82 17

Earthworm

acute

66 22

Bird acute 32 68

Bee oral 66 33

Bee dermal 22 75

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Based on the relative contribution of the active ingredients to the toxicity of the formulation, it was

concluded that the risk assessment has to be performed for both active ingredients.

When data on metabolites of the active ingredients indicate that these are less toxic than the parent

for a specific environment , the risk assessment focusses on the active ingredient. When data on

metabolites of the active ingredients indicate that these are more toxic than the parent, an

assessment of this metabolite will be performed as well.

Aquatic risk assessment

The basis for the aquatic risk assessment is a comparison of the Expected Environmental

Concentrations (EEC) with toxicity endpoints to which safety factors have been applied. The EEC is

divided by the toxicity endpoint to calculate a risk quotient (RQ) value. The methodology for the aquatic

risk assessment, including the level of concern (LOC) ascribed to specific RQ values, is described in

detail in the EPA standard risk assessment methodology (EPA 2018).

The major metabolites of tebuconazole (HWG 1608-pentanoic, HWG 1608-lactone, 1,2,4-triazole)

have a lower acute toxicity for aquatic species than the parent tebuconazole. Therefore, the

assessment of the parent covers these metabolites as well.

The major metabolites of azoxystrobin (R401553 and R402173) have a lower acute toxicity for

aquatic species than the parent azoxystrobin. Therefore, the assessment of the parent covers these

metabolites as well.

Calculation of expected environmental concentrations

The parameters used in GENEEC2 modelling are listed in Table 41.

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Table 41: Input parameters for GENEEC2 analysis for the active ingredients

Parameter Azoxystrobin Tebuconazole

Crop(s) Fodder and sugar beet Fodder and sugar beet

Application rate

(kg/ha)

0.12 0.2

Application

frequency

2 2

Application interval

(days)

14 14

Kd 12 16.39

Aerobic soil DT50

(days)

132.32 57.5

Pesticide wetted in? no no

Methods of

application

Ground boom, high boom

Aerial

Ground boom, high boom

Aerial

‘No spray’ zone 0 0

Water solubility

(ppm)

6.0 32

Hydrolysis (DT50 in

days)

stable stable

Aerobic aquatic

DT50 whole system(days)

234 38.7

Aqueous photolysis

DT50 (days)

13.9 590

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Output from the GENEEC2 model

Azoxystrobin

Ground based

RUN No. 2 FOR azoxystrobin ON beet * INPUT VALUES *

--------------------------------------------------------------------------------------------------------------

RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

-------------------------------------------------------------------------------------------------------------

0.107( 0.206) 2 14 12.0 6.0 GRHIFI( 6.6) 0.0 0.0

FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)

--------------------------------------------------------------------

METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

--------------------------------------------------------------------------------------------------------------------------

132.32 2 N/A 13.90- 1723.60 234.00 206.03

GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

---------------------------------------------------------------------------------------------------------------

PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

--------------------------------------------------------------------------------------------------------------

4.84 4.81 4.62 4.23 3.97

Aerial

RUN No. 2 FOR azoxystrobin ON beet * INPUT VALUES *

------------------------------------------------------------------------------------------------------------



-------------------------------------------------------------------------------------------------------------------

0.107( 0.206) 2 14 12.0 6.0 AERL_B( 13.0) 0.0 0.0

Page 55 of 131


FEBRUARY 2020


------------------------------------------------------------------------------------------------------------------------



------------------------------------------------------------------------------------------------------------------------

132.32 2 N/A 13.90- 1723.60 234.00 206.03


---------------------------------------------------------------------------------------------------------------



------------------------------------------------------------------------------------------------------------------

5.36 5.33 5.12 4.70 4.40

Tebuconazole

Ground based

RUN No. 3 FOR tebuconazole ON beet * INPUT VALUES *

------------------------------------------------------------------------------------------------------------------



--------------------------------------------------------------------------------------------------------------

0.178( 0.328) 2 14 16.4 32.0 GRHIFI( 6.6) 0.0 0.0


--------------------------------------------------------------------------------------------------------------------



--------------------------------------------------------------------------------------------------------------------

57.50 2 N/A 590.00-73160.00 38.70 38.68


------------------------------------------------------------------------------------------------------------


Page 56 of 131


FEBRUARY 2020


----------------------------------------------------------------------------------------------------------------

5.96 5.85 5.23 4.11 3.48

Aerial

RUN No. 4 FOR tebuconazole ON beet * INPUT VALUES *

-----------------------------------------------------------------------------------------------------------------



---------------------------------------------------------------------------------------------------------------

0.178( 0.328) 2 14 16.4 32.0 AERL_B( 13.0) 0.0 0.0


---------------------------------------------------------------------------------------------------------------------



---------------------------------------------------------------------------------------------------------------------

57.50 2 N/A 590.00-73160.00 38.70 38.68


---------------------------------------------------------------------------------------------------------------------



----------------------------------------------------------------------------------------------------------------------

6.70 6.59 5.90 4.65 3.93

The maximum Estimated Environmental Concentrations (EEC) for azoxystrobin when used in

Custodia® as estimated by GENEEC2 is 5.36 μg/L for the aerial application.

The maximum Estimated Environmental Concentrations (EEC) for tebuconazole when used in

Custodia® as estimated by GENEEC2 is 6.70 μg/L for the aerial application.

Page 57 of 131


FEBRUARY 2020

Calculated risk quotients

The calculated acute risk quotients for each trophic level considering the above EEC and lowest

relevant toxicity figures are presented in Table 42. The calculated chronic risk quotients are presented

in Table 43.

The aerial application is worst case. Therefore, the assessment focusses on this application first.

When the model indicates that the risks of this application is below LOC, the ground-based

application will not be assessed.

Table 42: Acute risk quotients derived from the GENEEC2 model and toxicity data

Species

Peak EEC

from

GENEEC2

(mg/L)

LC50 or

EC50

(mg/L)

Acute

RQ Conclusion

AERIAL

Azoxystrobin

Fish, Oncorhynchus

mykiss 0.00536 0.47 0.011

Below LOC for threatened/non-

threatened species

Crustacea, Macrocyclops

fuscus 0.00536 0.13 0.041


threatened species

Algae, Selenastrum

capricornutum 0.00536 0.36 0.015 Below LOC

Aquatic plants, Lemna

gibba 0.00536 0.64 0.008


threatened species

Tebuconazole

Rainbow trout.

Oncorhynchus mykiss 0.0067 4.4 0.002


threatened species

Crustacea, Daphnia

magna 0.0067 2.79 0.002


threatened species

Green alga,

Pseudokirchneriella

subcapitata

0.0067 2.83 0.002 Below LOC

Duckweed, Lemna gibba 0.0067 0.144 0.047 Below LOC for threatened/non-

threatened species

Page 58 of 131


FEBRUARY 2020

Table 43: Chronic risk quotients derived from the GENEEC2 model and toxicity data

Species

Relevant EEC

from GENEEC2

(mg /L)*

NOEC

(mg/L)

Chronic

RQ Conclusion

AERIAL

Azoxystrobin

Fish, Pimephales

promelas

(33 d ELS)

0.00512 0.147 0.035


threatened species

Crustacea, Daphnia

magna (21 d) 0.00512 0.044 0.116

Below LOC for non-threatened

species

Above LOC for threatened

species

Tebuconazole

Rainbow trout.

Oncorhynchus mykiss

(83 d ELS)

0.00465 0.012 0.3875


species


species

Crustacea, Daphnia

magna (21 d) 0.00590 0.010 0.59


species


species

GROUND BASED

Azoxystrobin

Fish, Pimephales

promelas

(33 d ELS)

0.00462 0.147 0.03


threatened species

Crustacea, Daphnia

magna (21 d) 0.00462 0.044 0.11


species


species

Tebuconazole

Rainbow trout.

Oncorhynchus mykiss

(83 d ELS)

0.00348 0.012 0.29


species


species

Page 59 of 131


FEBRUARY 2020

Species

Relevant EEC

from GENEEC2

(mg /L)*

NOEC

(mg/L)

Chronic

RQ Conclusion

Crustacea, Daphnia

magna (21 d) 0.00523 0.010 0.52

Above LOC for non-threatened

and threatened species

* EEC selected must be as close as possible to the exposure duration of the study selected for risk assessment purposes.

Refinement of the aquatic risk assessment

RQs resulting from predicted acute exposures are below the LOC for threatened/ non-threatened

species for both active ingredients for aerial application. As exposure for ground based application is

lower than for aerial application, the exposure is below the LOC as well.

The predicted chronic exposures are above LOC for threatened species for both active ingredients

after aerial application. Using ground based application, the chronic exposures are above LOC for

threatened species and for tebuconazole also for non-threatened species. The scenario modelled is a

worst-case, using the maximum application rate at the shortest interval and maximum frequency of

application. Because risks were identified further modelling was performed to consider whether buffer

zones may be able to mitigate risks from spray drift and runoff.

Spray drift

The Agdrift model was used to calculate the required downwind buffer zone to protect the aquatic

environment from adverse effects of the substance due to spray drift using high boom [see Table 44

and relevant spray drift scenarios (APVMA 2010)].

For aerial application the AGDisp® model was used to calculate the deposition curves. The input

parameters are in Table 45.

For the formulation Custodia®, the same spray-drift curve as for the active ingredient was used.

Exact buffer zones are impractical and too precise to be applied in the real world. Therefore, the

buffer zone distance is rounded so it can be visualized and remembered by end-users.

Page 60 of 131


FEBRUARY 2020

Table 44: Input parameters and calculation of spray drift buffer zone for the refined risk

assessment of azoxystrobin and tebuconazole (groundbased application)

Azoxystrobin Tebuconazole

Input parameters Ground based Ground based

Application rate (kg

ai/ha)

0.12 0.2

Number of applications 2 2

Application interval 14 d 14 d

Koc 690 mL/g 910.4 mL/g

DT50 soil 132.32 d 57.5 d

DT50 water 234 d 38.7 d

Toxicity endpoint

(chronic)

0.044 mg/L 0.010 mg/L

Assessment factor 10 10

Buffer zone (m) - model

Using the average time of

21 days to reflect the

used study data:

0

Using the average time of 21 days to reflect the used

study data:

High boom

fine 18 m (BBCH < 09: no interception)

fine 12 m (BBCH 10-19: 20% interception)

fine 2 m (BBCH 31-39: 70% interception)

fine 0 m (BBCH >49: 90% interception)

coarse 2 m (all BBCH stages)

Buffer zone (m) – control

(coarse droplets)

0 Highboom coarse (all BBCH stages):

0 m3

With coarse droplets the model indicates that there is a need for a 2 m buffer zone to protect the

aquatic environment if the product is applied using ground based equipment with coarse droplets.

However, 20 - 90% of the substance is likely to be intercepted (depending on growth stage) and

therefore no downwind buffer zone is required if the substance is applied using a coarse droplet with

a high boom.

3 To simplify the controls and to have consistent controls with aerial spray the staff suggest to limit the dropletsize to coarse.

The applicant has confirmed that this does not impact the use of the product.

Page 61 of 131


FEBRUARY 2020

Input variables used for the aerial AGDISP v8.15 modelling

The input variables for the aerial modelling are presented in Table 45. Aircraft information was

provided by the New Zealand Agricultural Aviation Association (NZAAA). The EPA assumes a flat

surface given the proposed use pattern in fodder and sugar beet. The applicant confirmed that the

proposed crop will not be grown on slopes.

Table 45: Aerial modelling input variables

Aerial Agricultural Fungicide/ Insecticide

Aircraft FW Air Tractor AT-402B

Wing semispan 7.79 m

Rotor radius NA

Weight 4000 kg

Typical speed 60 m/s

Propeller / Rotor

RPM 2000

Propeller radius 1.33 m

Biplane separation 0

Planform area 26.02 m2

Engines 1

Engine vertical 0 m

Engine forward 4.35 m

Engine horizontal 0 m

Wing vertical 0.3622 m

Boom vertical 0.38 m

Boom forward 0.3 m

Release height 3 m

Swath width 24 m

Swath displacement 2 m

Droplet size American Society of Agricultural and Biological Engineers (ASABE) medium and fine

American Society of Agricultural and Biological Engineers (ASABE) coarse

Water rate 50 – 100 L/ha, 50 L is worst case

Spray lines 10 (typical width of a NZ spray block assumed to be 240 m; sensitivity analysis

showed this was not very important for predicting spray drift)

Side slope angle 0 degrees (assume flat terrain)

Page 62 of 131


FEBRUARY 2020

Aerial Agricultural Fungicide/ Insecticide

Canopy height 0 m (assume no canopy)

Active Fraction 0.0024 (azoxystrobin)

0.004 (tebuconazole)

Non volatile fraction 0.0064

Boom length relative

to wingspan 73 %

Number of nozzles 60 (67 used on typical NZ boom but 60 is maximum that can be used in AGDISP)

Wind Speed 3 m/s

Temperature 21°C

Relative Humidity 46 % (obtained from NIWA data)

Surface roughness 0.005 m (lowest value recommended equivalent to grass)

Canopy roughness NA

Canopy displacement NA

Atmospheric stability Overcast

The input parameters for the spreadsheet to calculate the buffer zones are the same as in Table 44

with the exception of the refined endpoint for tebuconazole.

The tebuconazole endpoint applied in the assessment is from the 21 day Daphnia magna study.

There is evidence that under more realistic exposure conditions, toxicity to this organism is reduced

(Kern and Lam, 2005). The change to the chronic tebuconazole endpoint, however, will not change

significantly as results for fish will need to be adopted. There are several longer term fish endpoints

based on early life cycle testing and full fish life cycle testing (see Table 17). An evaluation of these

different studies, with the intention of confirming an appropriate chronic fish endpoint, was provided

(Grau and Breur, 2007), and it was concluded that the overall population relevant No Observed

Adverse Effect Concentration (NOAEC) for chronic risk assessments of fish of 12 µg ai/L is

considered to be justified. The EPA agrees with this conclusion.

That endpoint is from an 83 day early life stage test with rainbow trout. Applying this endpoint and an

83 day exposure period in the EPA’s spreadsheet allows a reduction in chronic buffer zones.

Crop interception has been applied for BBCH 10-19 (20% crop interception) and BBCH 31-30 (70%

crop interception).

Page 63 of 131


FEBRUARY 2020

Aerial buffer zones

BBCH 0 – 09 (No crop interception)

For azoxystrobin, a 134 metre downwind buffer zone is required to mitigate the risks when a fine –

medium droplet size is used. This buffer zone is reduced to 82 metres when a coarse droplet size is

used.

For tebuconazole a 436 metre downwind buffer zone is required to mitigate the risks when a fine –


used.

BBCH 10-19 (20% crop interception)



used.



used.

BBCH 31-39 (70% crop interception)



used.



used.

BBCH >40 (90% crop interception)

No buffer zone is required for azoxystrobin.



used.

Overall conclusion

Table 46 summarizes the calculated downwind buffer zones and proposed controls for all scenarios.

To mitigate the risks to the aquatic environment from ground-based high boom applications, no

buffer zones are required when applied using with coarse droplet size.

To mitigate the risks to the aquatic environment from aerial applications the following downwind

buffer zone controls based on BBCH stage are required:

1. BBCH stage 12-19: A downwind buffer zone of 120 m is required to mitigate the risks

Page 64 of 131


FEBRUARY 2020

2. BBCH stage 31-39: A downwind buffer zone of 70 m is required to mitigate the risks

3. BBCH stage >49: A downwind buffer zone of 30 m is required to mitigate the risks

The substance should only be applied using a coarse droplet.

Page 65 of 131


FEBRUARY 2020

Table 46: Overview of modelled downwind buffer zones and corresponding control (in bold and underlined EPA recommendation for

the controls)

Application

method

Groundbased Aerial

Droplet size Fine-medium Coarse Fine-medium Coarse

BBCH-stage 0-09 10-19 31-39 >40 0-09 10-19 31-39 >40 0-09 10-19 31-39 >40 0-10 09-19 31-39 >40

Bufferzone model 18 12 2 0 2 436 292 112 44 130 116 70 26

Bufferzone

control

20 20 0 0 0 0 0 0 450 300 120 50 130 120 70 30


FEBRUARY 2020

Runoff

The REXTOX model was also used to calculate the required buffer zone to protect the aquatic

environment from adverse effects of the substance due to runoff (see Table 47). A crop interception

value of 20% has been used and no slope.

Table 47: Input parameters and calculation of runoff buffer zone for the refined risk

assessment

Input parameters Azoxystrobin Tebuconazole

Application rate (kg ai/ha) 0.12 0.2

Kd 12 16.39

DT50 soil 132.32 d 57.5 d

Crop interception 20% (BBCH 10-19)

Slope 0.1

Toxicity endpoint 0.044 0.010


Buffer zone (m) – model 0 0

Buffer zone (m) – control 0 0

The model indicates that there is no need for a buffer zone to protect the aquatic environment from

adverse effects of runoff if applied after BBCH 10.

Conclusions of the aquatic risk assessment






will reduce the risks to below the level of concern.

The following controls are proposed to reduce exposures below the level of concern:

Use restrictions

The maximum application rate is 120 g azoxystrobin and 200 g tebuconazole/ha, with a maximum

of 2 applications/year and a minimum interval of 14 days.

Apply with a minimum coarse droplets, as defined by the American Society of Agricultural and

Biological Engineers ASABE Standard (S572) or the British Crop Production Council guideline.

This information (all of the above restrictions) should be required on the label so that users are

aware of this control.


FEBRUARY 2020

Buffer zones

To mitigate risks from spraydrift, when applied using aerial equipment, the substance should not

be applied within (this information should be required on the label so that users are aware of this

control):

o 120 m downwind of any waterbody when applied to crops at BBCH 12-19

o 70 m downwind of any waterbody when applied to crops at BBCH 19-39

o 30 m downwind of any waterbody when applied to crops at BBCH >40

A label statement indicating: “DO NOT apply when wind speeds are less than 3 km/hr or more

than 20 km/hr as measured at the application site”.

Groundwater risk assessment

The predicted concentration of azoxystrobin and tebuconazole and its relevant metabolite 1,2,4-

triazole in groundwater, calculated using the Sci-Grow model, is shown in Table 48. The

concentration is initially compared to the EU limit for the maximum permissible concentration of

pesticide active ingredients and their relevant metabolites of 0.1 µg/L.

Table 48: Input parameters for Sci-Grow analysis and resulting PEC values

Input

parameters Azoxystrobin Tebuconazole

1,2,4-triazole

Application rate

(kg ai/ha) 0.12 0.20

0.0642 (fraction

formation = 0.321)

70% crop

interception: 0.019

Application rate (lb

ai/acre)1 0.107 0.178 0.0573 0.017

Number of

applications 2 2

2

Koc2 690 910.4 43

Aerobic soil DT50

(days) 132.32 57.5 92.8

PECgw (µg/L) 0.0377 0.0251 0.369 0.11

1 The application rate is conversion from kg ai/ha to lb/acre (the units required to be entered into the model) by multiplying it by 0.892

2 Lowest Koc from a non-sandy soil (normalised values for the OC, temp and pH)

Conclusions of the groundwater risk assessment

For azoxystrobin and tebuconazole, the concentration is below the 0.1 µg/L trigger level set by the

European regulators. The concentration of the metabolites will be lower than that of the parent

substance. Therefore, the risks are considered below the level of concern.

However, for the metabolite of tebuconazole, 1,2,4,-triazole, the model indicated that the

concentration in the groundwater might reach concentrations above the trigger level and therefore

risks are potentially above the level of concern. If a crop interception value of 70% is applied the


FEBRUARY 2020

groundwater concentration is just above 0.1 µg/L. However, the predicted concentration is

significantly lower than the aquatic EC50 values for this metabolite (lowest algae > 31 mg/L). The EPA

considers the environmental risk as below the level of concern for aquatic organisms. The risks to

human health are addressed in Appendix G.

Sediment risk assessment

The sediment risk assessment for tebuconazole is performed following the method outlined in the

EPA standard risk assessment methodology (EPA 2018). For the active ingredient azoxystrobin no

data of sediment dwelling organisms are available.

The input parameters used in the risk assessment are summarised in Table 49.

Table 49: Input values and calculations for sediment risk assessment

Input parameters Tebuconazole

Ground based Aerial

PEC local water 0.00596 mg/L 0.0067 mg/L

Koc 910.4 910.4

Toxicity value 40 mg/kg sediment (NOEC) 40 mg/kg sediment (NOEC)


PEC local sediment 0.1839 mg/kg sediment 0.1378 mg/kg sediment

RQ 0.31 0.34

Conclusions of the sediment risk assessment





Terrestrial risk assessment

The terrestrial risk assessment considers the risks to soil organisms, terrestrial plants, birds, bees and

non-target arthropods.

The methodology for the terrestrial risk assessment is described in the EPA standard risk assessment

methodology (EPA 2018).

Soil macro-organisms

The soil organism risk assessment is based on a comparison of the Predicted Environmental

Concentration (PEC) with acute toxicity values for the azoxystrobin. The toxicity value is divided by

the PEC to give a Toxicity Exposure Ratio (TER). The different levels of concern assigned to specific

TER values are listed in the EPA standard risk assessment methodology (EPA 2018).


FEBRUARY 2020

The results of the acute risk assessment for soil organisms are summarised in Table 50.

For the active ingredient azoxystrobin, no chronic data are available, the formulation data have been

used as an alternative. Chronic data of tebuconazole are available. The results of this chronic risk

assessment are summarised in Table 51and this will provide an indication of the risks after an

application with Custodia®.

Table 50: Acute TER values for soil organisms

Species

LC50

(mg/kg

soil)

Drift (%)

PEC

(mg/kg

soil)

TER

acute Conclusion

Azoxystrobin – 120 g/ha – “in-field”

Earthworm 283 NA 0.31 917 Below LOC for threatened/non-

threatened species

Tebuconazole – 200 g/ha – “in-field”

Earthworm 1381 NA 0.49 2807 Below LOC for threatened/non-

threatened species

Table 51: Chronic TER values of tebuconazole for soil organisms

Species

NOEC

(mg/kg

soil)

Drift

factor

PEC

(mg/kg

soil)1

TER chronic Conclusion

Azoxystrobin – 120 g/ha – “in-field”

Springtail 55.31 NA 0.31 179 Below LOC for threatened/non-threatened

species

Tebuconazole – 200 g/ha – “in-field”

Earthworm 10 NA 0.49 20 Below LOC for threatened/non-threatened

species

1,2,4-triazole (tebuconazole metabolite – 64.2 (fraction formation = 0.321) – “in-field”

Earthworm 1.0 NA 0.16 6.15 Below LOC for non-threatened species

Above LOC for threatened species

1,2,4-triazole (tebuconazole metabolite – 64.2 (fraction formation = 0.321) – “off-field”

Earthworm 1.0 NA 0.004 260 Below LOC for threatened/non-threatened

species

1: 11.06% (maximum concentration azoxystrobin) of 500 mg formulation/kg soil (NOEC for Custodia®)


FEBRUARY 2020

The acute toxicity of the metabolites of azoxystrobin and tebuconazole is less than that of the parent.

Therefore, the risks to soil organisms from these metabolites are considered below the LOC as well.

The chronic toxicity of the metabolites of azoxystrobin is less than that of the parent. Therefore, the

risks to soil organisms from these metabolites are considered below the LOC as well. The risks for

tebuconazole are below the LOC. The toxicity of the metabolite 1,2,4-triazole is higher than that of

tebuconazole and in combination with the higher DT50 in soil, the risks are above the LOC for

threatened earthworm species.

There are 179 taxa or earthworms in New Zealand with only one species reported as “at risk –

declining” (Deinodrilus gorgon) and 31 reported as “at risk – naturally uncommon” (Department Of

Conservation (DOC) 2014). Despite a potentially large distribution area for this earthworm species on

the West Coast, the best documented natural habitat is not threatened by agriculture but rather by on-

going and future mining activities on the Stockton and Denniston Plateaus. Furthermore, Deinodrilus

gorgon is reported have a total area of occupancy ≤1000 ha (10 km2) in New Zealand. The other 31

species ranked as “naturally uncommon” are predominantly endemic to New Zealand. These 32

earthworm species are confined to a specific forestry areas or occur within naturally small and widely

scattered populations, where this distribution is not the result of human disturbance.

A recent survey (Kim Y. 2017) sampled earthworms on the South Island including several locations in

the Canterbury region. Samples collected from agricultural land found only native earthworm species

classified as “not threatened” and/or earthworm species exotic to New Zealand. The additional lines of

scientific evidence provided by the Department of Conservation (2014) and Kim Y. et al (2017)

indicate threatened species of earthworms in New Zealand are unlikely to be exposed to Custodia®.

Therefore this risk is considered to be below the level of concern.

Soil micro-organisms

For Custodia®, the provided data indicate that there are no effects on the nitrogen and carbon

transformation at application rates up to 12.5 L formulation/ha (highest concentration tested). The

proposed application rate is lower (1 L formulation/ha) and therefore this risk is considered below the

level of concern.

Conclusions of the soil organism risk assessment

Acute and chronic risk quotient to soil organisms applicable to azoxystrobin and tebuconazole

following the application of Custodia® are below the Level Of Concern (LOC).

For 1,2,4-triazole (metabolite tebuconazole) the chronic risk to threatened earthworms was above the

level of concern. Further evaluation indicated that threatened species are unlikely present in the

application areas of Custodia®, as a result, the risk is considered to be below the level of concern.

Non-target plant risk assessment

The non-target plant risk assessment is based on a comparison of the PEC with toxicity values for the

active ingredient azoxystrobin and the formulated product. Depending on the type of data provided,

for non-threatened plants a TER or an RQ is calculated (a TER is used when an EC50 is available, an


FEBRUARY 2020

RQ is used when an EC25 is available). For threatened non-target plants a RQ is calculated by

comparing the PEC with a NOEC. The different levels of concern assigned to specific TER/RQ values

are listed in the EPA standard risk assessment methodology (EPA 2018)

TER values for non-threatened non-target plants are shown in Table 52. TER values for threatened

non-target plants are shown in Table 53.

Table 52: TER value for non-target plant

Scenarios

Exposure

(g ai/ha) *

drift factor

EC50

(g ai/ha) TER Conclusion

Azoxystrobin- seedling emergence

Fodder and

sugar beet –

ground based

4.86 15000 3089


species

Fodder and

sugar beet –

aerial

26.5 15000 566


species

Custodia® – Vegetative vigour

Fodder and

sugar beet –

ground based

0.040 >3.375 >83


species

Fodder and

sugar beet –

aerial

0.22 >3.375 >15


species

Table 53: TER value for threatened non-target plant

Scenarios

Exposure (L

formulation/ha)

* drift factor

NOEC

(L

formulation/ha)

RQ Conclusion

Custodia® - 1 L product/ha- vegetative vigour

Fodder and

sugar beet 0.040 <3.375 >0.012

Most likely below LOC for

threatened species as the RQ is

far below the threshold and the

proposed rate is considerably

lower (1 L/ha).

Conclusion for non-target plant risk assessment

The risks to non-target plants, for seedling emergence, calculated for azoxystrobin, are below the

level of concern. No information is available of the effects of tebuconazole on seedling emergence.


FEBRUARY 2020

No data on vegetative vigour of the individual active ingredients are available, however, the

information of Custodia® has been used. Risks were considered below the level of concern for non-

threatened plant species.

Insufficient information is available to determine the effects on threatened non-target plants. For

vegetative vigour, data on vegetative vigour with the formulation Custodia® is available. The NOEC

could not be determined as a 13.1% effect on fresh weight was observed on one of the tested

species. Although the NOEC could not be determined, it is considered that the risks are most likely

below LOC as the RQ calculated with the highest value tested, which only showed 13% effect on

fresh weight, is far below the threshold (RQ >0.012 and >0.06) and the proposed rate is considerably

lower (1 L/ha) than the tested rate (3.375 L/ha). Furthermore, crop interception (20-70% for this

product has not been included in the RQ calculation).

Off-target seeds are likely sheltered and interception by other plants is not taken into account and this

will reduce possible drift. However, risks cannot be fully excluded.


likely below the LOC.

Bird risk assessment

The bird risk assessment is based on a comparison of the PEC with toxicity values for the active

ingredients azoxystrobin and tebuconazole. The toxicity value is divided by the PEC to give a Toxicity

Exposure Ratio (TER). The different levels of concern assigned to specific TER values are listed in

the EPA standard risk assessment methodology (EPA 2018).

Screening assessment

Predicted exposure to both active ingredients under the bird acute dietary and reproduction screening

assessments is shown in Table 54.

Table 54: Exposure of birds for acute and reproduction screening assessments

Screening

type1

Indicator

species2

Application

rate

(kg/ha)

Short-

cut

value

(90th%)3

TWA4

MAF

(90th

%)5

No of

applications DDD

Azoxystrobin

Acute Small

omnivorous

bird

0.12 158.8 NA 1.2 2 22.87

Reproduction 0.12 64.8 0.53 1.4 2 5.77

Tebuconazole


FEBRUARY 2020

Acute Small

omnivorous

bird

0.2 158.8 NA 1.2 2 38.11

Reproduction 0.2 64.8 0.53 1.4 2 9.62

1 EFSA (EFSA 2009), Table 5 p27 2 EFSA, (EFSA 2009), Table 6 p28 3 90th %ile short-cut value used for the acute assessment, mean value used for the reproduction assessment. EFSA

(EFSA 2009), Table 6 p28 4 The exposure assessment of the reproduction assessment uses time-weighted average (TWA) exposure estimates

over 1, 2, 3 or 21 days for different phases of the assessment. 1 d = 1.0; 2 days = 0.93; 3 days = 0.9; 21 days = 0.53. EFSA, (EFSA 2009), Table 11 p34.

5 90th %ile MAF value used for the acute assessment, mean value used for the reproduction assessment. EFSA, (EFSA 2009), Table 7 p29

Calculation of TERs

TER calculations for the acute dietary risk assessment are detailed in Table 55 and calculations for

the reproductive risk assessment are shown in Table 56.

Table 55: TER values for acute dietary risk assessment (TWA = 0.53; MAF=1.2)

Crops & BBCH

class

Generic focal

species1

Daily

dietary

dose (DDD)

Toxicity

endpoint value

(mg/kg bw/d)*

TER ratio Conclusion

Azoxystrobin-0.12 kg/ha twice

Fodder and sugar

beet

Small

omnivorous bird

22.87 >2000 >87.5 Below LOC for

threatened/non-

threatened

species

Tebuconazole- 0.2 kg/ha twice

Fodder and sugar

beet

Small

omnivorous bird

38.11 1555 40.8 Below LOC for

threatened/non-

threatened

species

Table 56: TER values for reproductive risk assessment (TWA = 0.53; MAF=1.4).

Crops &

BBCH class

Generic

focal

species1

DDD

Toxicity

endpoint

value

(mg/kg

bw/d)*

TER ratio

Conclusion

Azoxystrobin-0.12 kg/ha twice

Fodder and

sugar beet

Small

omnivorous

bird

5.77 117 20.3 Below LOC for

threatened/non-

threatened species


FEBRUARY 2020

Crops &

BBCH class

Generic

focal

species1

DDD

Toxicity

endpoint

value

(mg/kg

bw/d)*

TER ratio

Conclusion

Tebuconazole-0.2 kg/ha twice

Fodder and

sugar beet

Small

omnivorous

bird

9.62 5.8 0.6 Above LOC for

threatened/non-

threatened species

* Normally the NOAEL has to be converted from units of ppm (mg/kg diet) to mg/kg bw/d. In the first instance a factor of 0.1 is used for such conversion. If specific information is available from the test reports, this is preferable. When reported as ppm in the studies, daily dose (mg/kg/d) = [Concentration in food (mg/kg) * Daily food consumption (g/bird/d)] / body weight (g) (over the entire exposure period).

Conclusions of the bird screening risk assessment

The acute screening risk assessment indicates an acute risk below the level of concern to birds from

azoxystrobin and tebuconazole from the use of Custodia®. In the reproductive screening assessment,

the TER values indicate a chronic risk above the level of concern to birds for tebuconazole. As risks

were above the level of concern, a Tier 1 risk assessment was performed.

Tier 1 assessment

Tier 1 uses the same general approach as the screening assessment but requires more specific

exposure scenarios. More details are provided in the EPA standard risk assessment methodology

(EPA 2018).

For each generic focal species, the Daily Dietary Dose (DDD) is presented in Table 57.

The toxicity figures are the same than those considered in the screening assessment.

The indicator species mentioned in Table 57 (chronic) are not real species but have to be considered

as representative of groups of birds of the same size and same feeding behaviour.

Table 57: TER values for chronic risk assessment – Tier 1 assessment

Crops &

BBCH

class

Focal species

Short-

cut

value2

(90th %)

DDD Toxicity

endpoint

(mg/kg

bw)

TER

ratio Conclusion

Tebuconazole-0.2 kg/ha twice

Fodder and

sugar beet

Small

insectivorous

bird, ground

invertebrates

without

interception

5.9 0.876 5.8 6.6 Above LOC for

threatened species

Below LOC for non-

threatened species


FEBRUARY 2020

Small

insectivorous

bird, ground

invertebrates

with interception

2.8 0.416 5.8 14.0 Below LOC for threatened/

non-threatened species

Small

insectivorous

bird with

interception 50%

ground

arthropods 50%

foliar arthropods

9.7 1.44 5.8 4.0 Above LOC for

threatened/ non-

threatened species

Small

omnivorous bird

10.9 1.62 5.8 3.6 Above LOC for

threatened/ non-

threatened species

Small

granivorous bird

11.4 1.69 5.8 3.4 Above LOC for

threatened/ non-

threatened species

Conclusion for bird risk assessment (Tier 1)

The chronic Tier 1 risk assessment indicates risks above the level of concern to both threatened and

non-threatened birds from the use of Custodia®.

Refinement

Scenario 1

The chronic risk has been triggered by the active ingredient tebuconazole.

The initial assessment was based on the most sensitive species, however, chronic NOEC values of

another species are available. The long term NOEC to mallard duck is 170 mg tebuconazole/kg diet

to mallard duck. Applying the group mean body weights and daily food consumption, a daily dietary

dose of 17.7 mg/kg bw/d is derived. A geometric mean NOEC of 10.1 mg/kg bw/d is derived. Using

this endpoint, the TER ranges from 6.0 to 24.3 (maintaining the TWA = 0.53), which indicate that the

risk to non-threatened birds is below the level of concern. Generally, this type of refinement is only

applied to acute data, however, the NOECs were in the same order of magnitude and therefore it was

considered acceptable to apply this approach in this particular case to chronic data.

Using the geometric mean a risk for threatened birds is identified. Using the DDD of the worst case

situation (1.69) for small granivorous birds and the geometric mean NOEC of 10.1, these birds must

forage circa 40% outside the treated area. It is considered that it is likely that threatened species will

obtain less than 60% of their food from the treated fields as agricultural areas are not the natural

habitat of threatened bird species. Therefore, the risks from tebuconazole is considered low.


FEBRUARY 2020

Secondary poisoning

Given the criteria under the HSNO Act azoxystrobin and tebuconazole are not considered to be

bioaccumulative (BCF < 500). Therefore, no risk assessment via secondary poisoning is performed.

Conclusions for bird risk assessment

TER values for birds calculated for azoxystrobin and tebuconazole, when applied to fodder and sugar

beet as the formulated product Custodia®, are below the level of concern for acute risks, and any

risks are negligible. In the reproductive screening assessments, the TER values indicate a chronic

risk below the level of concern to birds for azoxystrobin but above the level of concern to birds from

the use of tebuconazole in fodder and sugar beet. After refinement, it is considered that it is likely that

threatened species will obtain less than 60% of their food from the treated fields as agricultural areas

are not the natural habitat of threatened bird species. Therefore, the risks from tebuconazole is

considered to be low. Furthermore, both active ingredients are already approved in New Zealand at

higher rates than the proposed rate. The risks from secondary poisoning is considered to be low as

both active ingredients are not considered to be bioaccumulative.

Pollinator risk assessment

The basis for the pollinator risk assessment is a comparison of the environmental exposure

concentration (EEC) with toxicity endpoints to which safety factors have been applied. The EEC is

divided by the toxicity endpoint to calculate a risk quotient (RQ) value. The methodology for the

pollinator risk assessment, including the level of concern (LOC) ascribed to specific RQ values, is

described in detail in the EPA standard risk assessment methodology (EPA 2018). The results of the

bee risk assessment are shown in Table 58.

Table 58: Bee exposure estimates and RQ values

Use scenario

Application rate

(kg ai/product

/ha)

EEC (µg

ai/product

/bee)

Toxicity

endpoint

value (µg

ai/product

/bee)

RQ Conclusion

Acute / Adult bees – contact

Azoxystrobin

Fodder and

sugar beet 0.12

0.288 >200 <0.00144 Below LOC

Tebuconazole

Fodder and

sugar beet

0.2 0.48 >100 <0.0048

Below LOC

Custodia®

Fodder and

sugar beet

11 2.4 >2001 <0.012

Below LOC


FEBRUARY 2020

Acute / Adult bees – oral

Azoxystrobin

Fodder and

sugar beet 0.12

3.43 >25 <0.14 Below LOC

Tebuconazole

Fodder and

sugar beet

0.2 5.72 >83.05 <0.07

Below LOC

Custodia®

Fodder and

sugar beet

11 28.62 >208.41

<0.14 Below LOC

1: units are L/ha

Conclusions of the pollinator risk assessment

The acute risks to pollinators are below the level of concern. Chronic risks could not be evaluated due

to a lack of data. However, both active ingredients are already approved in New Zealand at higher

rates than the proposed rate.

Non-target arthropod risk assessment

The non-target arthropod risk assessment is a comparison of the predicted environmental

concentration (PEC) with toxicity endpoints to which safety factors have been applied. The PEC is

divided by the toxicity endpoint to calculate a hazard quotient (HQ) value. The methodology for the

non-target arthropods risk assessment, including the level of concern (LOC) ascribed to specific HQ

values, is described in detail in the EPA standard risk assessment methodology (EPA 2018).

No data on non-target arthropods of tebuconazole are available. Results of the in-field and off-field

non-target arthropods risk assessment of azoxystrobin are shown in Table 59 and Table 60,

respectively.

Table 59: In-field HQ values for non-target arthropods (TIER I)

Species LR50

(mL/ha)

Application rate

(mL/ha) MAF

Hazard

Quotient Conclusion

Custodia®

Parasitic wasp, Aphidius

rhopalosiphi1 605 1000 1.7 2.8 Above LOC

Predatory mite,

Typhlodromys pyri1 >3375 1000 1.7 <0.504 Below the LOC

1: note this is an extended study which normally is evaluated in Tier II


FEBRUARY 2020

Table 60: Off-field HQ values for non-target arthropods (TIER I)

Species

LR50

(g /ha or mL

/ha)

Application rate

(g /ha or mL /ha) MAF

Hazard

Quotient Conclusion

Custodia®, (drift factor =2.38%, BBA driftcurves for ground based)


rhopalosiphi1 605 1000 1.7 0.07 Below the LOC

Custodia®, (drift factor =13%, aerial GENEEC)


rhopalosiphi1 605 1000 1.7 0.37 Below the LOC

1: note this is an extended study was normally is evaluated in Tier II

Tier I could not be performed according to the ESCORT II guidance (Workshop, Candolfi et al.), the

reason is that only extended laboratory tests were available which normally are evaluated in Tier II.

However, the EPA considers it acceptable as also the impact of fresh residue was evaluated in these

studies.

As effects were observed one additional species were evaluated in Tier II as per ESCORT II

guidance. In the table the study with the Green Lacewing has been added, however, another study

with ladybirds was provided. The endpoint for this study was identical to the endpoint of the Green

Lacewing and outcomes would therefore be identical.

Table 61: In-field HQ values for non-target arthropods (TIER II)

Species LR50

(mL/ha)

Application rate

(mL/ha) MAF

Hazard

Quotient Conclusion


rhopalosiphi1 605 1000 1.7 2.8

Above LOC

(1.4x)

Green Lacewing,

Chrysoperla carnea >3375 1000 1.7 <0.504 Below the LOC

1: already included in TIER I but as this is a TIER II test also included here.

The EPA informed the applicant about the identified risk for parasitic wasps using the most

conservative value available. The EPA requested more information as the results of two studies both

performed with the parasitic wasps are conflicting. One study resulted in an LR50 of 605 mL

formulation/ha (see Appendix I, Table 79 ; project 47744002) while the other indicated that less than

50% of mortality was observed at 3.38 L formulation/ha (see Appendix I, Table 80; project 47654003).

Both studies are performed according to the guideline. No additional information was provided by the

applicant to clarify the difference. Therefore, the EPA has taken the precautionary approach and used

the most conservative data for the assessment which indicated that in-field, the risks for parasitic

wasps are above the level of concern (1.4x).


FEBRUARY 2020

Conclusion for non-target arthropod risk assessments




wasps are below the level of concern using the GENEEC model drift factors (aerial application). Re-

colonization from off-field is expected when the concentration has decreased.


insects as risks cannot be fully excluded. Label statement indicating “WARNING” the substance might

not be compatible with Integrated Pest Management (IPM).

Conclusions of the ecological risk assessment

The EPA assessed the potential risk to be triggered by the use of Custodia® following the instructions

captured in the proposed label and GAP table.

It is considered that the risks to the environment from the proposed use of Custodia® are acceptable

with the proposed controls.

Aquatic environment:

For azoxystrobin and tebuconazole chronic risks were identified. These risks can be managed with

controls.






will reduce the risks to below the level of concern.

Groundwater:

For azoxystrobin and tebuconazole, the concentration is below the 0.1 µg/L trigger level set by the

European regulators. Therefore, the risks are considered below the level of concern. However, there

is a risk for groundwater contamination with 1,2,4-triazole. The predicted concentration is significantly

lower than the aquatic EC50 values for this metabolite (lowest algae > 31 mg/L). Therefore, the EPA

considers the risk as below the LOC for aquatic organisms.

Sediment:





Terrestrial environment


FEBRUARY 2020

Soil organisms:

Acute risk quotient to soil organisms applicable to azoxystrobin following the application of Custodia®

are below the LOC.

Due to a lack of chronic data of azoxystrobin, the chronic risk assessment is performed with the other

active ingredient tebuconazole. The model indicates a chronic risk below the LOC for tebuconazole, a

chronic risk to threatened earthworms was determined for 1,2,4-triazole, however, it is considered

unlikely that threatened earthworms are present at the application site.

Chronic data for springtail of the formulated product Custodia® is available indicating a low toxicity to

soil organisms. Overall, it is considered that the risks to soil organisms (macro and micro-organisms)

following an application of Custodia® are below LOC.

Terrestrial plants:

The risks to non-target plants, for seedling emergence, calculated for azoxystrobin, are below the

LOC. No information is available of the effects of tebuconazole on seedling emergence. No data on

vegetative vigour of the individual active ingredients are available however the information of

Custodia® has been used. Risks were considered below the LOC for non-threatened plant species.

Insufficient information is available to determine the effects on threatened non-target plants. For

vegetative vigour, data on vegetative vigour with the formulation Custodia® is available. The NOEC

could not be determined as a 13.1% effect on fresh weight was observed on one of the tested

species. Although the NOEC could not be determined, it is considered that the risks are most likely

below LOC as the RQ calculated with the highest value tested, which only showed 13% effect on

fresh weight, is far below the threshold (RQ >0.012 and >0.06) and the proposed rate is considerably

lower (1 L/ha) than the tested rate (3.375 L/ha).

Off target seeds are likely sheltered and interception by other plants is not taken into account and this

will reduce possible drift. However, risks cannot be fully excluded.


likely below LOC.

Birds:

No acute risks from the use of Custodia® are identified. Chronic risks are identified and the risk

assessment was refined. Based on these results, it was identified that there is a low risk to threatened

birds. No other risks were identified. Given the criteria under the HSNO Act azoxystrobin and

tebuconazole are not considered to be bioaccumulative (BCF < 500). Therefore, no risk assessment

via secondary poisoning is performed.

Bees and non-target arthropods:

There are no concerns for adult honeybees from acute exposure. Possible chronic effects could not

be assessed due to a lack of data. However, both active ingredients are already approved in New

Zealand at higher rates than the proposed rate.


FEBRUARY 2020




wasps are below the level of concern for both use patterns. Re-colonization from off-field is expected

when the concentration has decreased.

The risks for predatory mites are below the 50% threshold for both fresh and aged residues after an

application with the product at 3.38 L/ha. Further in a field study, focussing on the population of

predatory mites, no unacceptable effects were observed after 2 applications with Custodia® at a rate

of 0.263 and 0.438 L/ha [note: proposed rate is 1 L/ha].


insects as risks cannot be fully excluded (parasitic wasps). Label statement indicating “WARNING”

the substance might not be compatible with Integrated Pest Management (IPM).


FEBRUARY 2020

Appendix I: Study summaries

The manufacturer code name for Custodia® is MCW 710 SC

Toxicity

Mammalian toxicity studies on Custodia® have been reviewed. These studies are used to describe

potential risks to human health. The effects on mammals in these studies are used as proxies for the

impact on humans. Data from the studies have been used for classifying the active ingredient and the

formulated substance and for derivation of appropriate health-based criteria which are used in risk

assessment. The summary of the studies is provided in Table 62 to Table 67.

Mammalian toxicology - Robust study summaries for Custodia®

Acute toxicity [6.1]

Table 62: Acute Oral Toxicity [6.1 (oral)]

Type of study Acute oral toxicity in rats

Flag Key study

Test Substance MCW 710 SC (Azoxystrobin: 120 g/L and Tebuconazole: 193 g/L)

Endpoint Acute lethality (LD50), signs of toxicity

Value 300 < LD50 ≤ 2000 mg/kg bw

Reference

2009. Acute oral toxicity study of MCW 710 SC in rats.

Klimisch Score 1

Amendments/Deviations None of significance

GLP Yes

Test Guideline/s EC method B.1

OECD 423

Species Rat

Strain CD:Crl

No/Sex/Group 9/F

Dose Levels 300 and 2000 mg/kg bw

Exposure Type Oral by gavage

Study Summary

An acute oral toxicity test was conducted in rats to determine the

potential for MCW 710 SC to produce toxicity from single dose.

Set I animals (n=6) received test substance at the dose of 300 mg/kg

bw. No mortality and signs of toxicity were observed.


FEBRUARY 2020

Set II animals (n=3) received test substance at the dose of 2000 mg/kg

bw. Slight to severely reduced motility, slight to severe ataxia, slight to

moderate dyspnoea and slightly to moderately reduced muscle tone was

observed in all animals. Two of three animals revealed lateral position

and died prematurely.

Additional Comments No additional comments

Conclusion The LD50 of MCW 710 SC in CD rats was estimated to be in the range of

300 < LD50 ≤ 2000 mg/kg bw.


FEBRUARY 2020

Table 63: Acute Dermal Toxicity [6.1 (dermal)]

Type of study Acute dermal toxicity in rats

Flag Key study


Endpoint Acute lethality (LD50), signs of toxicity

Value LD50 >2000 mg/kg bw

Reference

2007. Acute dermal toxicity study of MCW 710 SC in rats.

Klimisch Score 1


GLP Yes

Test Guideline/s EC method B.3. (92/69/EEC)

OECD 402

Species Rat

Strain CD / Crl: CD(SD)

No/Sex/Group 5/sex/group

Dose Levels 2000 mg/kg bw

Exposure Type Dermal, on the shaved intact dorsal skin

Study Summary

An acute dermal toxicity study was conducted in rats (5/sex/group).

Animals received MCW 710 SC (undiluted) at dose level of 2000 mg/kg

bw. The test substance was administered for 24 hours on shaved intact

dorsal skin area. The patched were removed without washing skin and

animals were observed for 14 days. At the end of study all animals were

sacrificed and gross necropsy was performed.

All animals survived during the study. There were no signs of toxicity. No

skin reactions at the application site were observed. All animals gained

the expected body weight throughout the whole study period. No

macroscopic findings were observed at necropsy.


Conclusion The acute dermal LD50 of MCW 710 SC in rats was estimated to be

greater than 2000 mg/kg bw for each sex.


FEBRUARY 2020

Table 64: Acute Inhalation Toxicity [6.1 (inhalation)]

Type of study Acute inhalation toxicity in rats

Flag Key study


Endpoint Acute lethality (LC50), signs of toxicity

Value LC50 >4.79 mg/L

Reference

2010. MCW 710 SC: Acute inhalation toxicity (nose only)

study in the rat.

Klimisch Score 1


GLP Yes

Test Guideline/s EC method B.2

OECD 403

Species Rat

Strain HsdRccHan : WIST

No/Sex/Group 5/sex/group

Dose Levels 4.79 mg/L; Mass Mean Aerodynamic Diameter (MMAD): 2.46 µm;

Geometric Standard Deviation (GSD): 2.94

Exposure Type Nose only

Study summary

An acute inhalation toxicity study was conducted on rats (5/sex/group)

which were exposed for 4 hours using nose only exposure system

followed by 14 day observation period. Due to the nature of the test

substance it was considered that a suitable atmosphere would not be

able to be generated from material as supplied. Hence, a formulation

was prepared with sterile water to improve aerosolisation properties of

the material.

No mortality was observed in rats when exposed to a mean achieved

atmosphere concentration of 4.79 mg/L. Increased respiration rate,

hunched posture, pilo-erection and wet fur were noted. However,

animals appeared normal on Day 4 to 8 post-exposure. Reduced body

weight gain or slight body weight. No macroscopic abnormalities were

detected in animals at necropsy.


Conclusion The LC50 was greater than 4.79 mg/L in combined male and female

groups.


FEBRUARY 2020

Table 65: Skin Irritation [6.3/8.2]

Type of study Acute skin irritation in rabbits

Flag Key study


Endpoint Mean Draize Score

Value 0.1 for erythema and 0.0 for oedema at 24, 48 and 72 hours

Reference

2009. Acute dermal irritation/corrosion test (patch test)

of MCW 710 SC in rabbits.

:

Klimisch Score 1


GLP Yes

Test Guideline/s EC method B.4. (2004/73/EC)

OECD 404

Species Rabbit

Strain Himalayan

No/Sex/Group 3 Male

Dose Levels 0.5 mL of undiluted MCW 710 SC

Exposure Type Dermal application onto the shaved, intact dorsal skin (semi-occlusive)

Study Summary

In a skin irritation study, 0.5 mL of undiluted test substance was applied

to dorsal area (about 6 cm2) of the trunk of rabbits (n=3) for 4 hours and

was then covered with a gauze patch. The patch was held in place with

non-irritating tape. After 4 hours, the patch was removed and skin sites

were examined and scored for erythema and oedema formation at 60

minutes, and at 24, 48 and 72 hours.

At 60 minutes, very slight erythema was observed in two animals and

remained only in one animal at 24 hour after patch removal. All animals

exhibited an oedema score of 0 during the observation.


Conclusion The substance was non-irritant.


FEBRUARY 2020

Table 66: Eye Irritation [6.4/8.3]

Type of study Acute eye irritation

Flag Key study


Endpoint Mean Draize Score

Value 0.33 for conjunctival redness and 0.0 for cornea opacity, iris lesion and

chemosis

Reference

2009. Acute eye irritation/corrosion test of MCW 710

SC in rabbits.

Klimisch Score 1


GLP Yes


OECD guideline 405

Species Rabbit

Strain Himalayan

No/Sex/Group 3/male/group

Dose Levels 0.1 mL of MCW 710 SC (undiluted)

Exposure Type Single instillation into the conjunctival sac

Study Summary

An eye irritation study was performed in himalayan rabbits (n=3). 0.1 mL

of undiluted MCW 710 SC of was instilled into right conjunctival sac of

all rabbits. After 24 hours, the eyes were rinsed with 20 mL of sodium

chloride solution. After instillation (day 0), eyes were observed for

irritation reactions and abnormalities in cornea, iris, and conjunctiva. The

left eye of all animals was untreated and served as control.

Cornea opacity, iris lesion and chemosis were not observed in any

animal.

The Mean Draize Score (24, 48, 72 hours) for conjunctival redness was

0.33 and 0.0 for cornea opacity, iris lesion and chemosis.


Conclusion The test substance is not an eye irritant.


FEBRUARY 2020

Table 67: Contact Sensitisation [6.5]

Type of study Sensitisation in the Guinea Pigs

Flag Key study


Endpoint Magnusson and Kligman grading scale (maximisation test)

Value Grade 1 skin reaction in induction phases and grade 0 in challenge

phase

Reference

2009. Examination of MCW 710 SC in the skin

sensitisation test in guinea pigs according to Magnusson And Kligman

(maximisation test)

Klimisch Score 1

Amendments/Deviations None

GLP Yes


OECD 406

Species Guinea Pigs

Strain Hartley strain

No/Sex/Group 15 male

Dose Levels

Stage 1 (induction): 0.5% suspension of MCW 710 SC in aqua ad

iniectabilia

Stage 2 (induction): undiluted MCW 710 SC

Stage 3 (Challenge): 50% suspension of MCW 710 SC in aqua ad

iniectabilia

Exposure Type

Intracutaneous (shoulder region) in stage 1

topical (shoulder region) in stage 2

topical (flank region) in stage 3

Study Summary

Sensitization study with the guinea pig maximization test was performed

with MCW 710 SC which consisted of two group: vehicle control and

main test. Animals in main test received the test substance in three

stages:

Stage 1 (intradermal induction): animals received three pairs of

intradermal injections in the shoulder region a) 0.1 mL of 0.5%

suspension of MCW 710 SC. b) Freund's complete adjuvant and c) test

substance in a 1:1 mixture (v/v) FCA/physiological saline.

Stage 2 (topical induction): After seven days, the shoulder region of the

same animals was shaved again and coated with sodium lauryl sulfate

to induce local irritation before administration of test substance. Topical


FEBRUARY 2020

patch containing 2 mL of undiluted test substance was then

administered for 48 hours exposure time.

Stage 3 (challenge): On day 21, after the topical application the flanks of

same animals were shaved and filter paper containing 2 mL of 50% test

substance in water was applied to the left flank and the right flank was

untreated.

Animals were observed for mortality, body weight, clinical signs and skin

reactions.

In both induction phases after intracutaneous injection and topical

administration of the test substance, skin reaction grade 1 was observed

in all animals at 24, 48 and 72 hours post application. Mortalities were

not observed during the study and the body weight gain of treated

animals was within the range of vehicle control group animals.

Behaviour of the animals remain unchanged.


Conclusion The test substance is not a contact sensitiser.


FEBRUARY 2020

Ecotoxicity

Both active ingredients azoxystrobin and tebuconazole are already approved in New Zealand.

Therefore, no ecotoxicity data for the active ingredients are provided. Endpoints are summarised in

Appendix E and sourced from previous applications and the EPA internal database.

Several studies on the toxicity of Custodia® (code name MCW 710 SC) on environmental receptors

have been provided by the applicant and summarised and reviewed by the EPA. The data from the

studies have been used for classifying Custodia®. Summary of these studies is provided in Table 68

to Table 85.


FEBRUARY 2020

Aquatic organisms

Table 68: Aquatic toxicity: Acute toxicity to zebrafish, formulation, key study

Study type

Acute toxicity to fish

Flag

Key study

Test Substance

MCW-710 SC

Endpoint

96h-LC50

Value


Reference

(2010). Acute toxicity of MCW-710 SC to

zebrafish (Danio rerio) in a 96-hour flow through test.

Klimisch Score

1

Amendments/Deviations

None that impacted the study

GLP

Yes

Test Guideline/s

OECD 203, 1992

Nominal Dose Level

0.0, 0.3, 0.8, 1.7, 3.6 and 8.0 mg formulation/L

Mean measured Dose

Level

0.0, 0.3, 0.8, 1.7, 3.6 and 8.0 mg formulation/L (based on tebuconazole and

azoxystrobin, analytical confirmed nominal)

Analytical measurements

HPLC

Validity criteria met Yes

Study Summary

5 concentrations of the formulation plus a control containing 7 fish each were

tested for a period of 96 hours in a flow-through setting.

Fish were observed after approximately 2, 24, 48, 72 and 96 hours after the

start of exposure to observe lethal and sub lethal effects. Dead fish were

removed at least once daily.

Environmental conditions were within the limits set by the guideline. The

exposure at the start of the test was determined to be nominal and remained

stable during the test (based on tebuconazole and azoxystrobin).


FEBRUARY 2020

In the control and up to 3.6 mg/L all fish survived till the end of the test with

no sub lethal signs. In the highest concentration 4 fish died after 72 hours of

exposure.

The 96h-LC50 was determined to be 7.8 mg/L.

Comments

The fish are slightly outside the range of the new guideline

recommendations (OECD 203, 2019) (1-2 cm). This deviation might have

decrease the sensitivity of the fish to the formulation.

Conclusion

The 96h-LC50 was determined to be 7.8 mg formulation/L


FEBRUARY 2020

Table 69: Aquatic toxicity: Acute toxicity to rainbow trout, formulation, key study

Study type

Acute toxicity to fish

Flag

Key study

Test Substance

MCW-710 SC

Endpoint

96h-LC50

Value


Reference

(2010). Acute toxicity of MCW-710 SC to

rainbow trout (Oncorhynchus mykiss) in a 96-hour flow through test.

Klimisch Score

1



GLP

Yes

Test Guideline/s

OECD 203,1992

Nominal Dose Level


Mean measured Dose

Level

Yes, endpoint is based on nominal of the formulation


HPLC


Study Summary

5 concentrations of the formulation plus a control containing 7 fish each were

tested for a period of 96 hours in a flow-through setting.

Fish were observed after approximately 2, 24, 48, 72 and 96 hours after the

start of exposure to observe lethal and sub lethal effects. Dead fish were

removed at least once daily.


exposure at the start of the test was determined to be nominal. For

azoxystrobin the mean value ranged from 80 to 97% of nominal, the

exception was 3.6 mg/L which had a geometric mean of 58%. The mean

value for tebuconazole ranged from 65 to 125% of nominal. The endpoint is

based on the nominal concentration of the formulation.


FEBRUARY 2020

In the control and up to 3.6 mg/L all fish survived till the end of the test with

no sub lethal signs. In the highest concentration all fish died within 2 hours of

exposure.

The 96h-LC50 was determined to be 5.4 mg/L

Conclusion

The 96h-LC50 was determined to be 5.4 mg formulation/L


FEBRUARY 2020

Table 70: Aquatic toxicity: Acute toxicity to Daphnia magna, formulation, key study

Study type

Acute toxicity to daphnia

Flag

Key study

Test Substance

MCW-710 SC

Endpoint

48h-EC50

Value


Reference

Hoffmann, K. and Wydra V. (2010). Acute toxicity of MCW-710 SC to

Daphnia magna in a static 48-hour immobilisation test. IBACON Project

47652220

Klimisch Score

1



GLP

Yes

Test Guideline/s

OECD 202, 2004

Nominal Dose Level

0.0, 0.08, 0.2, 0.4, 0.8, 1.8 and 4 mg formulation/L

Measured Dose Level

Within nominal, 0.0, 0.08, 0.2, 0.4, 0.8, 1.8 and 4 mg formulation/L

(based on tebuconazole and azoxystrobin, analytical confirmed nominal)


HPLC


Study Summary

6 concentrations of the formulation plus a control containing 20 daphnids

each were tested for a period of 48 hours in a static test.

Immobility was determined after 24 and 48 hours.


exposure at the start of the test was determined to be nominal and

remained stable during the test (based on tebuconazole and

azoxystrobin).

After 48 hours of exposure no immobilisation was observed at 0.08 and

0.4 mg/L. One animal was immobilized in the control and at 0.2 mg/L. At

0.8 mg/L two animals were immobilized. At the two highest

concentrations, 1.8 and 4.0, 5 and 18 daphnids were immobilized

respectively.


FEBRUARY 2020

The 48h-EC50 was determined to be 2.15 mg/L

Conclusion

The 48h-EC50 was determined to be 2.15 mg formulation/L


FEBRUARY 2020

Table 71: Aquatic toxicity: Algal growth inhibition, formulation, key study

Study type

Acute toxicity to algae

Flag

Key study

Test Substance

MCW-710 SC

Endpoint

72h-ErC50

Value

8.72 mg/L

Reference

Hoffmann, K. and Wydra V. (2010). Acute toxicity of MCW-710 SC to

Pseudokirchneriella subcapitata in an algal growth test. IBACON Project

47651210

Klimisch Score

1



GLP

Yes

Test Guideline/s

OECD 201,2006

Nominal Dose Level


Measured Dose Level

Within nominal, 0.0, 0.1, 0.34, 1.1, 3.4 and 10.5 mg formulation/L (based

on tebuconazole and azoxystrobin, analytical confirmed nominal)


HPLC


Study Summary

5 concentrations of the formulation plus a control containing 3 replicates

per treatment level and 6 for the control. Test was run for a period of 72

hours under static conditions.

Cell density was determined after 24, 48 and 72 hours. Growth rate and

yield were determined after 72 hours. Inoculation density was 5000

cells/mL obtained from an exponentially growing culture.


exposure at the start of the test was determined to be nominal and

remained stable during the test (based on tebuconazole and azoxystrobin).

The shape of the algal cells was not obviously affected by the test

substance. The 72h-ErC50 was determined to be 8.72 mg/L and EbC50 was

1.34 mg/L. NOEC was 0.34 mg/L.


FEBRUARY 2020

At 0.1 mg/L the pH deviated more than 1.5 units during the test namely

1.7. This is a minor deviation that unlikely impacts the results

Conclusion

The 72h-ErC50 was determined to be 8.72 mg formulation/L


FEBRUARY 2020

Terrestrial toxicity

Table 72: Soil toxicity: Acute toxicity to earthworm, formulation, key study

Study type

Acute toxicity earthworm

Flag

Key study

Test Substance

MCW-710 SC

Endpoint

LC50

Value

>1000 mg formulation/ kg soil

Reference

Witte B (2009) Acute toxicity (14 days) of MCW-710 SC to the earthworm

Eisenia fetida in artificial soil with 5% peat. Report 47657021

Klimisch Score

1


None that affected the study results

GLP

yes

Test Guideline/s

OECD 207,1984

Nominal Dose Level

62.5, 125, 250, 500 and 1000 mg formulation/ kg soil


NA

Validity criteria met yes

Study Summary

The objective of this study was to investigate the acute toxicity of MCW-

710 SC to the earthworm Eisenia fetida after 7 and 14 days exposure.

Effects on behaviour weight and mortality were evaluated.

The formulation was applied at the rates 62.5, 125, 250, 500 and 1000

mg formulation/ kg soil to artificial soil. Peat content was decreased to

5% to consider the Kow of the active ingredients (>2).

The test was performed in 4 replicates with 10 individuals per replicate.

The pH ranged from 5.6 to 6.2, and maximum WHC was 39%.

After 14 days of exposure no mortality was observed in the control or any

test item concentration. The body weight changes were statistically

significantly different compared to the control at all test concentrations

except at the concentration of 125 mg/kg soil. The significant effect

observed at 62.5 mg/kg soil was considered not biologically relevant as


FEBRUARY 2020

the higher concentration was not significant different. No behavioural

effects were observed in any treatment group.

The LC50 was determined to be higher than 1000 mg formulation/kg soil.

Conclusion LC50>1000 mg formulation/ kg soil


FEBRUARY 2020

Table 73: Soil toxicity: Chronic toxicity to Collembola, formulation, key study

Study type

Reproduction Folsomia candida

Flag

Key study

Test Substance

MCW 170 SC

Endpoint

NOEC

Value

500 mg MCW 170 SC/ kg soil

Reference

Witte B (2009) Effects of MCW 170 SC of the Collembola Folsomia

candida in artificial soil with 5% peat. Project 47742016

Klimisch Score

1


None

GLP

Yes

Test Guideline/s

ISO 11267

Nominal Dose Level

62.5, 125, 250, 500 and 1000 mg formulation/kg soil


NA


Study Summary

Ten juvenile Folsomia candida (5 replicates, 10-12 days old) were

exposed in an artificial soil system with 5% peat content over a period

of 28 days to MCW 170 SC. The test concentrations were 62.5, 125,

250, 500 and 1000 mg formulation/kg soil. A toxic reference

(phenmedipham) was tested in a separate study.

Temperature was 18-21°C and the photoperiod was 16 h light (420-800

lux) and 8 hours dark. pH ranged from 5.5 to 5.7. WHC was 52.8 to

54.4% at the start of the test and 48.8 to 51.2% at the end of the test.

Mortality and reproduction were determined and were used to

determine the endpoints.

The validity criteria were met. Mortality in control ≤ 20% (observed

16%) and number of juvenils per replicate ≥100 (observed 379). and

coefficient of variance of reproduction in the control ≤30% (observed

20.6%).


FEBRUARY 2020

The LC50 mortality value of the toxic reference was 143 mg/ kg soil and

EC50 was 70.9 mg /kg soil.

Mean mortality of the test susbtance was ranged from 16% up to 52%

for the highest test concentration. The LC50 was estimated to be more

than 1000 mg /kg soil.

Mean number of offspring after 28 days ranged from 345 at the lowest

concentration to 196 at the highest concentration. The EC50 for

reproduction was 1010.63 mg / kg soil.

Only at the highest concentration were the differences signficant

compared to the control.

The NOEC was determined to be 500 mg test substance / kg dry

weight soil.

Conclusion

NOEC = 500 mg MCW 170 SC/ kg soil


FEBRUARY 2020

Non-target plants

Table 74: Non-target plant toxicity: Vegetative vigour, formulation, key study

Study type

Limit test: Vegetative vigour

Flag

Key study

Test Substance

MCW 170 SC

Endpoint

NOER

Value

Not determined (< 3.375 L formulation/ha)

Reference

Butzler R., Mollandin G. (2010) Effects of MCW 170 SC on terrestrial (non-

target) plants: vegetative vigour test Project 47650087

Klimisch Score

1

Amendments/Deviatio

ns


GLP

Yes

Test Guideline/s

OECD 227

Nominal Dose Level

3.375 L/ha

Analytical

measurements

HPLC/ UV detection


Study Summary

This study aimed to determine the effects of the test item with respect to

vegetative vigour. The study was performed on ryegrass, onion, cabbage,

soybean, sugar beet and sunflower. The test treatment at a rate of 3.375 L/ha

were sprayed on the 2 to 4 true leaf stage. A minimum of 20 plants per

treatment and species were used.

Endpoints measured were mortality, phytotoxicity, growth stages and

determination of NOER based on fresh weight.

The analytical recovery of both active ingredeints was 118% for azoxystrobin

and 110% of tebuconazole of the nominal value.

No mortality was observed for any species tested. No phytotoxicity was

observed 21 days after application.


FEBRUARY 2020

The plant development was not delayed.

Sugar beet was the only sensitive species regarding fresh weight with a

statistical significant reduction of 13.1%. The other species did not show

significant effects.

The NOER for all species was 3.375 L formulation/ha with the exception of

sugar beet for which the NOER could not be determined (NOER < 3.375 L

formulation/ha).

Conclusion

NOER not determined (<3.375 L formulation/ha)


FEBRUARY 2020

Soil micro-organisms

Table 75: Soil toxicity: Nitrogen and carbon transformation, formulation, key study

Study type

Toxicity soil microflora, nitrogen and carbon transformation

Flag

Key study

Test Substance MCW-710 SC

Exposure

28 d, carbon transformation

56 d, nitrogen transformation

Test species Soil microflora

Endpoint Effects on nitrogen and carbon transformation

Value

Carbon transformation: No adverse effects observed

Nitrogen transformation: no long term adverse effects observed.

Reference

Feil N (2010), Effects of MCW-710 SC on the activity of soil microflora

in the laboratory. Report no 51941080

Klimisch Score 1


GLP yes

Test Guideline/s OECD 216 and 217

Dose Levels

3.6 and 18 mg MCW-710 SC / kg dry soil

(equivalent to 2.5 and 12.5 L formulation/ha)


Study Summary

The aim of the study was to determine the effects of MCW-710 SC to

soil microflora activity (nitrogen and carbon transformation).

Application rates were equivalent to 2.5 and 12.5 L test substance/ha.

The used soil was a mid-loamy sand soil with pH of 6.9, % C 1.17, and

WHC 42.4% enriched with Lucerne meal enriched with Lucerne meal

for nitrogen transformation test and added glucose for the respiration

test. Three replicates were used.

Nitrogen transformation


FEBRUARY 2020

NH4-nitrogen, NO3- and NO2- nitrogen were determined by an ion

chromatograph at different sampling intervals (0, 7, 14 and 28, 41 and

56 days after treatment).

The variation of the control was below 15%, except for day 98 for soil

respiration and day 14 for nitrogen content. In a separate study the

reference substance sodium chloride (16 g/kg soil) had a retarding or

stimulating effect of more than 25% compared to the control at days 28

and 98 after application.

MCW-710 SC caused a temporary inhibition of the nitrate

transformation at both concentrations at day 28 (-29.1% low rate and -

26.6% high rate). At day 56 the inhibition was decreased to -16.5%

(low rate) and -14.1% (high rate).

At day 28 after application, the differences between the soil nitrate

content of MCW-710SC treated soil at both concentrations and the

control were below the 25% trigger value (-17.87% low rate and -

18.23% high rate). After 56 days the differences compared to the

control were -12.65% and -11.81% for the lower and higher

concentrations, respectively.

Mineral nitrogen content: at day 56 the deviation from the control was

-12.37% and 11.89% at the lower and higher concentration,

respectively.

Carbon transformation

At day 7, 14 and 28 after application Co2 production was determined

using the BSB-Sensomat system for 24 hours.

The variation of the control was below 15%

At day 28 the respiration rates of MCW-710SC treated soils differed

from the control by 0.05% and 3.93% at the lower and higher

concentration, respectively.

Conclusion

MCW-710 SC did not cause long term adverse effects on nitrogen and

carbon transformation up to a rate of 18 mg/ kg soil (equivalent to 12.5

L formulation/ha).


FEBRUARY 2020

Table 76: Soil toxicity: Nitrogen and carbon transformation, formulation, key study

Study type

Toxicity soil microflora, nitrogen and carbon transformation

Flag

Key study


Exposure

28 d, carbon transformation

41 d, nitrogen transformation

Test species Soil microflora

Endpoint Effects on nitrogen and carbon transformation

Value

Carbon transformation: No adverse effects observed

Nitrogen transformation: no long term adverse effects observed.

Reference

Feil N (2010), Effects of MCW-710 SC on the activity of soil microflora in

the laboratory. Report no 47659080

Klimisch Score 1


GLP yes

Test Guideline/s OECD 216 and 217

Dose Levels

5.76 and 14.4 mg MCW-710 SC / kg dry soil

(equivalent to 2 and 5 L formulation/ha)


Study Summary

The aim of the study was to determine the effects of MCW-710 SC to soil

microflora activity (nitrogen and carbon transformation).

Application rates were equivalent to 2 and 5 L test substance/ha. The used

soil was a mid-loamy sand soil with pH of 6.9, % C 1.17, and WHC 42.4%

enriched with Lucerne meal for nitrogen transformation test and added

glucose for the respiration test. Three replicates were used.

Nitrogen transformation

NH4-nitrogen, NO3- and NO2- nitrogen were determined by an ion

chromatograph at different sampling intervals (0, 7, 14 and 28, 41 days

after treatment).

The variation of the control was below 15%. In a separate study the

reference substance sodium chloride (16 g/kg soil) had a retarding or


FEBRUARY 2020

stimulating effect of more than 25% compared to the control at days 28

and 98 after application.

Nitrate content: at day 28 the differences compared to control were -

21.31% and -16.41% for the lower and higher concentrations, respectively.

At day 41 the deviation was -21.39% (low rate) and -19.42% (high rate).

Nitrate formation: for the lower test concentration the deviation compared

to control was less than 25% at the 14-28 day interval. At the higher test

concentration the deviation was more than 25% at the 14-28 day interval (-

29.45%) and remained within the trigger level at 28-41 day interval (-

23.33%).

Mineral nitrogen content: for both concentrations the differences were

below the 25% trigger value at 28-41 day interval. At day 41 the deviation

from the control was -20.88 % and -18.73% at the lower and higher

concentration, respectively.

Carbon transformation

Co2 production was determined by the BSB-Sensomat system for 24

hours at different sampling intervals (0, 7, 14 and 28 days after treatment).

The variation of the control was below 15%. In a separate study the

reference substance sodium chloride (16 g/kg soil) showed the required

response.At day 28 after application, the respiration rates of MCW-710SC

treated soils differed from the control by -0.5% and -0.7% at the lower and

higher concentration, respectively.

Conclusion

MCW-710 SC did not cause long term adverse effects on nitrogen and

carbon transformation up to a rate of 14.4 mg/ kg soil (equivalent to 5 L

formulation/ha).


FEBRUARY 2020

Birds

Table 77: Terrestrial toxicity: Acute toxicity to quail, formulation, key study

Study type

Limit acute toxicity test to birds

Flag

Key study

Test Substance MCW 170 SC

Exposure oral

Test species Japanese quail

Endpoint LD50

Value >2000 mg ai/ kg bw

Reference

(2009), Avian acute toxicity study of MCW 170 SC-

Japanese quail – limit test.

Klimisch Score 1

Amendments/Deviations None that impacted the results of the study

GLP yes

Test Guideline/s SETAC and OPPTS 850.2100

Dose Levels 2000 mg ai/ kg bw

Analytical measurements NA

Study Summary

The aim of the study was to determine the acute effects of MCW 170 SC to

Japanese quail (Coturnix coturnix japonica).

Forty day old adult Japanese quails (5 males and 5 females) were orally

dosed by gavage into the birds crop at a limit dose level of 2000 mg

formulation/kg body weight. The control group (5 males and 5 females)

were treated with the vehicle tap water. Observations included

regurgitation, mortality, signs of intoxication and remission and abnormal

behaviour. Body weight was determined within 24 hours of dosing and

weekly after administration. Food consumption was recorded for periods 1-

3 days, 4-7 days, 8-14 days.


FEBRUARY 2020

Under the present test conditions, a single oral administration of 2000 mg

MCW 710 SC/kg b.w. did not reveal any signs of toxicity. No mortality

occurred. Normal body weight development was observed for all animals

during the course of the study.

No signs or abnormalities were noted at necropsy.

LD50 > 2000 mg/kg

Conclusion LD50 > 2000 mg ai/ kg bw


FEBRUARY 2020

Pollinators

Table 78: Terrestrial toxicity: Acute toxicity to honey bees, formulation, key study

Study type

Acute contact and oral toxicity. Limit test

Flag

Key study

Test Substance

MCW 710 SC

Endpoint

LD50

Value

Contact: > 200 μg formulation/bee

Oral: >208.4 µg formulation/ bee

Reference

Sekine T. (2010) Effects of MVW 710 SC (acute contact and oral) on honey

bee Apis mellifera in the laboratory. Project 47741035

Klimisch Score

1



GLP

Yes

Test Guideline/s

OECD 213 and 214

Nominal Dose Level

Contact and oral: 200 µg formulation/ bee

Measured dose level

Oral: 208.4 μg formulation/bee


NA


Study Summary

The aim of this study was to assess the acute contact and oral toxicity of

MCW 710 SC to the honey bee, Apis mellifera, in a laboratory study. The

nominal dose levels for the contact toxicity test was 200 μg formulation/bee

and for the oral test 208.4 μg formulation/bee.

For the contat test MCW 710 SC was applied with tap water with 0.5%

wetting agent. Bees in the control group received tap water with wetting

agent.

MCW 710 SC was diluted with 50 % sugar syrup solution for the oral test.

Bees in the control group received tap water with sugar syrup. A toxic


FEBRUARY 2020

reference (dimethoate) was used. The test solutions were offered to the bees

for 4.5 hours.

In both tests, 5 replicates with 10 bees each were tested. Assessments of

mortality and abnormal behavioural effects were carried out at 4, 24 and 48

hours after start of feeding the test solutions.

Contact test

No mortality was observed in the control and treatment group. No abnormal

behaviour was observed in the control and treatment group. Therefore, the

LD50 is considered to be higher than 200 µg formulation/ bee.

Oral test

No mortality occurred in the control group fed with pure 50% sugar solution

and 2.0% mortality was observed in the treatment group.

No abnormal behaviour was observed in the control and treatment group.

Therefore, the LD50 is considered to be higher than 208.4 µg formulation/

bee.

Conclusion

Contact LD50 > 200 μg formulation/bee

Oral LD50 > 208.4 μg formulation/bee oral


FEBRUARY 2020

Non-target arthropods

Table 79: Terrestrial toxicity: Toxicity to parasitoids, formulation, key study

Study type Beneficial insect toxicity

Flag Key study


Endpoint LR50

Value 605 mL product/ha

Reference

Moll M. (2009) Effects of MCW-710 SC on the parasitoid Aphidius rhopalosiphi

extended laboratory study-Dose response test. Project 47744002

Klimisch Score 1

Amendments/Deviatio

ns


GLP Yes

Test Guideline/s Mead Briggs et al

Nominal Dose Level 144, 317, 697, 1534 and 3375 mL formulation/ha


Study Summary

In a laboratory test parasitoid wasp, Aphidius rhopalosiphi, were exposed to

dried residues of MCW 710 SC for 48 hours. Test product was applied at rates

of 144, 317, 697, 1534 and 3375 mL formulation/ha on barley plants. A water

control and a reference product (dimethoate) were included in the test. Six

replicates of 5 wasps (females) were used for each treatment. Survival and

behaviour were assessed at 2, 24 and 48 hours. Fecundity was assessed after

48 hours from concentrations with >50% corrected survival. Females were

transplanted onto aphid invested plants and were removed after 24 hours. After

11 days mummies were assessed.

In the control no mortality was observed and in the toxic reference 100%.

The mortality in the treatments was 0, 20, 50, 96.7 and 100% at 144, 317, 697,

1534 and 3375 mL formulation/ha respectively. The LR50 was determined to be

605 mL product/ha.

The number of mummies per female was 71.1 in the control. The number of

mummies per female was 61.1, 55.5 and 36.2 at 144, 317 and 697 mL


FEBRUARY 2020

product/ha respectively. Only at 697 mL product/ha the difference compared to

control was significant but the effect on reproduction was just below the trigger

value of 50% (49.2%).

Conclusion LR50 is 605 mL product/ha


FEBRUARY 2020

Table 80: Terrestrial toxicity: Toxicity to parasitoids, formulation, key study


Flag Key study


Endpoint Effects on survival and reproduction

Value

The effects of MCW 710 SC were below the trigger value of 50% on

mortality and fecundity after application with the product at 3.38 L/ha.

Reference

Moll M. (2010) Effects of MCW-710 SC on the parasitoid Aphidius

rhopalosiphi extended laboratory study- aged residue test. Project

47654003

Klimisch Score 1

Amendments/Deviations None that affected the study results

GLP Yes

Test Guideline/s Mead Briggs et al

Nominal Dose Level 3.38 L formulation/ha


Study Summary

In a laboratory test parasitoid wasp, Aphidius rhopalosiphi, were exposed

to freshly dried residues of MCW 710 SC for 48 hours. Test product was

applied at the rate of 3.38 L product/ha on leaves of bean plants. A water

control and a reference product (dimethoate) were included in the test.

Four replicates of 10 wasps (7 females and 3 males) were used for each

treatment. Survival and behaviour were assessed at 2, 24 and 48 hours

and fecundity was assessed after 48 hours. Females were transplanted

onto aphid invested plants and were removed after 24 hours. After 11

days mummies were assessed.

In the control no mortality was observed and in the toxic reference 100%.

The mortality in the treatment was 15% (significant different compared to

control).

The number of mummies per female was 36.8 in the control group and

38.7 in the treatment group.

The effects of MCW 710 SC were below the trigger value of 50%.


FEBRUARY 2020

Conclusion

The effects of MCW 710 SC were below the trigger value of 50% on

mortality and fecundity.


FEBRUARY 2020

Table 81: Terrestrial toxicity: Toxicity to ladybird beetles, formulation, key study


Flag Key study


Endpoint LR50

Value >3375 mL product/ha

Reference

Moll M. (2009) Effects of MCW-710 SC on the ladybird beetle Coccinella

septempunctata extended laboratory study-Dose response test. Project

47746012

Klimisch Score 1


GLP Yes

Test Guideline/s Schmuck et al

Nominal Dose Level 63.5, 171, 463, 1250, 3375 mL formulation/ha


Study Summary

In a laboratory test the ladybird beetle Coccinella septempunctata (4-5

day old larvae), were exposed to dried residues of MCW 710 SC. Test

product was applied at rates of 63.5, 171, 463, 1250, 3375 mL

formulation/ha on bean leaves. A water control and a reference product

(dimethoate) were included in the test. Forty replicates containing one

beetle larva were used for each treatment. Survival and behaviour were

assessed during 20 days. Fecundicy of the survival was assessed for 2

weeks from concentrations with >50% corrected survival.

In the control 10% mortality was observed and in the toxic reference

100%.

The corrected mortality in the treatments was -5.6, -5.6, 0, 2.8 and

16.7% at 63.5, 171, 463, 1250, 3375 mL formulation/ha respectively. The

LR50 was determined to be >3375 mL product/ha.

The number of fertile eggs per female per day was 6.4 in the control. The

number of fertile eggs/female/day was 10.2, 5.3, 7.5, 11.4, 7.4 at 63.5,

171, 463, 1250, 3375 mL product/ha respectively.


FEBRUARY 2020

Conclusion LR50 >3375 mL product/ha


FEBRUARY 2020

Table 82: Terrestrial toxicity: Toxicity to lacewings, formulation, key study


Flag Key study


Endpoint LR50

Value >3375 mL product/ha

Reference

Moll M. (2009) Effects of MCW-710 SC on the lacewing Chrysoperla

carnea extended laboratory study-Dose response test. Project

47747047

Klimisch Score 1


GLP Yes

Test Guideline/s Vogt et al



Study Summary

In a laboratory test the lacewing Chrysoperla carnea larvae (2 days

old), were exposed to dried residues of MCW 710 SC. Test product

was applied at rates of 63.5, 171, 463, 1250, 3375 mL formulation/ha

on bean leaves. A water control and a reference product (dimethoate)

were included in the test. Forty replicates containing one larva were

used for each treatment. Exposure lasted as long as pupae were

transferred to the reproduction units for development of adults

(concentrations with corrected mortality <50%). Mortality (until hatching

of adults) and reproduction were assessed.

In the control 7.5% mortality was observed and in the toxic reference

100%.

The corrected mortality in the treatments was 24.3, 13.5, 8.1, 13.5 and

8.1 at 63.5, 171, 463, 1250, 3375 mL formulation/ha respectively.

Mortality at 63.5 mL/ha was significantly impacted but considered not

biologically relevant as higher concentrations were not significantly

impacted. The LR50 was determined to be >3375 mL product/ha.


FEBRUARY 2020

The number of eggs per female per day was 19.0 in the control. The

number of eggs/female/day was 26.8, 24.7, 19.0, 22.5 and 28.9 at

63.5, 171, 463, 1250, 3375 mL product/ha respectively.

Fertility was 79.7% in the control. Fertility was 60.7, 68.5, 40.9, 58.7

and 48.6% at 63.5, 171, 463, 1250, 3375 mL product/ha respectively.

Mortality was not affected but there was an effect on fertility.

Conclusion LR50 >3375 mL product/ha


FEBRUARY 2020

Table 83: Terrestrial toxicity: Toxicity to predatory mites, formulation, key study


Flag Key study


Endpoint Effects on survival and reproduction

Value

Effects on mortality and reproduction were below the 50% threshold for

both fresh and aged residues after application with the product at 3.38

L/ha.

Reference

Schwarz A. (2010) Effects of MCW-710 SC on the predatory mite

Typhlodromus pyri, extended laboratory study- Aged residue test. Project

47655060

Klimisch Score 1


GLP Yes

Test Guideline/s Blumel et al, Oomen

Nominal Dose Level 3.38 L product/ha

Validity criteria met

In the study with fresh residues the reproduction of the control was below 4

eggs per female. Therefore, the study with aged residues was performed.

The reproduction in the control in this study was conform the guideline.

Study Summary

In a laboratory test the predatory mite Typhlodromus pyri, were exposed to

dried residues (fresh and 7 days aged) of MCW 710 SC. Test product was

applied at a rate of 3.38 L formulation/ha on bean leaves. A water control

and a reference product (dimethoate, not in ages residue test) were

included in the test. Ten replicates containing ten mites were used for each

treatment. Mortality was assessed 7 days after exposure and reproduction

were assessed (as corrected mortality was <50%).

Fresh residue

In the control 13% mortality was observed and in the toxic reference 78.2%

(corrected). The corrected mortality in the treatment was 24.1%.

The number of eggs per female was 2.7 in the control and 5.6 in the

treatment of test item. The validity criteria in the control were not fulfilled.

Aged residue


FEBRUARY 2020

In the control 18% mortality was observed and the corrected mortality in

the treatment was 27%.

The number of eggs per female was 4.2 in the control and 7.2 in the

treatment of test item.

Conclusion

Effects on mortality and reproduction were below the 50% threshold for

aged residues.


FEBRUARY 2020



Flag Key study


Endpoint Effects on mortality and reproduction

Value

Effects on mortality are below 50% threshold.

Effects on reproduction are above 50% for the dose rates 171, 463 and 3375

mL formulation/ha.

Reference

Schwarz A. (2009) Effects of MCW-710 SC on the predatory mite

Typhlodromus pyri, extended laboratory study- Dose response test. Project

47745062

Klimisch Score 1


GLP Yes

Test Guideline/s Blumel et al, Oomen



Study Summary

In a laboratory test the predatory mite Typhlodromus pyri, were exposed to

dried residues of MCW 710 SC. Test product was applied once at rates of

63.5, 171, 463, 1250, 3375 mL formulation/ha on bean leaves. A water

control and a reference product (dimethoate) were included in the test. Six

replicates containing ten mites were used for each treatment. Mortality was

assessed 3 and 7 days after exposure and reproduction were assessed for

test group with <50% corrected mortality.

In the control 6.7% mortality was observed and in the toxic reference 100%.

The mortality in the treatments was 28.3, 40.0, 11.7, 31.7, 36.7% ( corrected

mortality 23.3, 35.7, 5.4, 26.8, 32.1%) at the rates 63.5, 171, 463, 1250, 3375

mL formulation/ha respectively. With the exception of the mortality of 463 mL

formulation/ha, the difference compared to the control was statistically

significant.

The number of eggs per female was 4.9 in the control. In the treatments the

number of eggs per female were 3.5, 2.4, 2.2, 3.5 and 1.4 at the rates 63.5,

171, 463, 1250, 3375 mL formulation/ha respectively (no significant


FEBRUARY 2020

differences). The effect on reproduction was 28.8, 51.2, 54.9, 29.2 and 71.9%

at the rates 63.5, 171, 463, 1250, 3375 mL formulation/ha respectively.

The reproduction for all treatments was below the trigger value of 4

eggs/female and the effects on reproduction are above 50% for the dose rates

171, 463 and 3375 mL formulation/ha.

Conclusion

Effects on mortality are below 50% threshold.

Effects on reproduction are above 50% for the dose rates 171, 463 and 3375

mL formulation/ha.


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Flag Key study


Endpoint Effects on population predatory mites

Value

No unacceptable effects were observed after 2 applications with MCW

710 SC at a rate of 0.263 and 0.438 L/ha.

Reference

Ipach R. (2012) Effects of MCW-710 SC on predatory mites

(Typhlodromus pyri), under typical vine culture conditions after 2

applications (beginning BBCH 55-57); grapevines, Germany 2011

Study number FCS02

Klimisch Score 1


GLP Yes

Test Guideline/s Blumel et al, BBA-Guideline VI, 23-2.3.4

Nominal Dose Level 0.263 and 0.438 L formulation/ha

Validity criteria met NA

Study Summary

The purpose of the field trial was to assess the effect of MCW 710 SC

on the populations of the predatory mite Typhlodromus pyri in

grapevines. The formulation was applied twice at a rate of 0.263 and

0.438 L/ha at growth stage BBCH 55-57 and 69. A water control and a

reference product (deltamethrin) were also applied twice. The

application interval was 14 days. All treatments were conducted in five

replicates with 15 vines each.

The population development of mites was assessed by determining the

number of mites on leaf samples, using a washing method. 25

leaves/plot were taken before the 1st application, 6 days and 28 days

after the 2nd application.

The pre-assessment one day before the 1st application showed that the

mite population was homogenous.

Mean number of predatory mites per 25 leaves are presented in the

table below.

Mean number of mites/25 leaves


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Assessment

timing

control MCW 710 SC reference

Pre assessment 125 135 130

6DAA2 85 73 7

28DAA2 95 88 1

Effects of MCW 710 SC compared to the control according to Abbott is

14% 6DAA2 and 7% 28DAA2. Effects of the reference according to

Abbott is 92 and 99% at 6DAA2 and 28DAA2 respectively. The results

of the reference indicate that the test system is suitable to determine

the effects of the treatments.

Conclusion

No unacceptable effects were observed after 2 applications with MCW

710 SC at a rate of 0.263 and 0.438 L/ha.

[Note that the proposed application rate is 1 L formulation /ha.]


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Appendix J: Standard terms and abbreviations

Abbreviation Definition

ai active ingredient

ADE Acceptable Daily Exposure

ADI Acceptable Daily Intake

AOEL Acceptable Operator Exposure Level

BBA Biologishe Bundersantalt für Land- und Forstwirtschaft

BBCH Biologische Bundesanstalt, Bundessortenamt und CHemische Industrie

BCF BioConcentration Factor

Bw body weight

CAS # Chemical Abstract Service Registry Number

cm centimetres

CoA Certificate of Analysis

CRfD Chronic Reference Dose

DDD Daily Dietary Dose

DT50 Dissipation Time (days) for 50% of the initial residue to be lost

dw dry weight

EbC50 EC50 with respect to a reduction of biomass

EyC50 EC50 with respect to a reduction of yield (y)

EC European Commission

EC25 Effective Concentration at which an observable adverse effect is caused in 25 %

of the test organisms

EC50 Effective Concentration at which an observable adverse effect is caused in 50 %

of the test organisms

EEC Estimated Environmental Concentration

EEL Environmental Exposure Limit

EFSA European Food Safety Authority

ErC50 EC50 with respect to a reduction of growth rate (r)

ER50 Effective Residue concentration to 50% of test organisms

FAO Food and Agriculture Organization

g grams

GAP Good Agricultural Practice


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GENEEC Generic Estimated Environmental Concentration

ha hectare

HQ Hazard Quotient

Kd partition (distribution) coefficient

Koc organic carbon adsorption coefficient

Kow octanol water partition coefficient

Kg Kilogram

L litres

Lb pounds

LC50 Lethal Concentration that causes 50% mortality

LD50 Lethal Dose that causes 50% mortality

LOAEC Lowest Observable Adverse Effect Concentration

LOAEL Lowest Observable Adverse Effect Level

LOC Level Of Concern

LOD Limit Of Detection

LOEC Lowest Observable Effect Concentration

LOEL Lowest Observable Effect Level

LR50 Lethal Rate that causes 50% mortality

M Molar

m3 cubic metre

MAF Multiple Application Factor

μm micrometre (micron)

mg milligram

μg microgram

mol mole(s)

MSDS Material Safety Data Sheet

NAEL No Adverse Effect Level

ng nanogram

NOAEC No Observed Adverse Effect Concentration

NOAEL No Observed Adverse Effect Level

NOEC No Observed Effect Concentration

NOED No Observed Effect Dose


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NOEL No Observed Effect Level

NOER No Observed Effect Rate

OCS Office of Chemical Safety

OECD Organisation for Economic Cooperation and Development

OPPTS Office of Prevention, Pesticides, and Toxic Substances (US Environmental

Protection Agency)

PDE Potential Daily Exposure

PEC Predicted Environmental Concentration

PHI Pre-Harvest Interval

pKa Acid dissociation constant (base 10 logarithmic scale)

PNEC Predicted No Effect Concentration

POW Partition coefficient between n-octanol and water

ppb parts per billion (10-9)

PPE Personal Protective Equipment

ppm parts per million (10-6)

REI Restricted Entry Interval

RPE Respiratory Protective Equipment

RQ Risk Quotient

TER Toxicity Exposure Ratio


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Appendix K: References

APVMA (2010). "Standard spray drift risk assessment scenarios."

Department Of Conservation (DOC) (2014). Conservation status of New Zealand earthworms, 2014.

EC (2007). Draft Assessment Report - Initial risk assessment provided by the rapporteur Member

State Denmark for the existing active substance tebuconazole.

EC (2009). Azoxystrobin - Report and Proposed Decision of The United Kingdom made to the

European Commission under Commission Regulation 737/2007.

EFSA (2009). "Risk Assessment for Birds and Mammals." EFSA Journal 7(12): 1438.

EFSA (2013). "Guidance on tiered risk assessment for plant protection products for aquatic organisms

in edge-of-field surface waters." EFSA Journal 11(7): 3290.

EFSA (2014). "Conclusion on the peer review of the pesticide risk assessment of the active substance

tebuconazole." EFSA Journal 12(1): 3485.

EPA (2018). Risk Assessment Methodology for Hazardous Substances ; Draft for Consultation.

HSNO

Kim Y., D. N., Nowie M., Robinson B., Boyer S. (2017). "Molecular identification and distribution of

native and exotic earthworms in New Zealand human-modified soils." New Zealand Ecological

Society(41(2)).

Klimisch, H. J., M. Andreae and U. Tillmann (1997). "A systematic approach for evaluating the quality

of experimental toxicological and ecotoxicological data." Regul Toxicol Pharmacol 25(1): 1-5.

McCall P.J., Laskowski D.A., Swann R.L. and D. H.J. (1981). Measurement of sorption coefficients of

organic chemicals and their use, in environmental fate analysis. Test Protocols for Environmental

Fate and Movement of Toxicants, Proceedings of AOAC Symposium, AOAC. Washington DC.

OCS (2015). Health Risk Assessment - Technical Report - Custodia Fungicide.

Workshop, E., M. P. Candolfi, S. Europe and C. Commission of the European Guidance document on

regulatory testing and risk assessment procedures for plant protection products with non-target

arthropods : from the ESCORT 2 Workshop (European Standard Characteristics of Non-Target

Arthropod Regulatory Testing) : a joint BART, EPPO/CoE, OECD, and IOBC workshop organised in

conjunction with SETAC Europe and EC : held at Wageningen International Conference Center,

Wageningen, the Netherlands, 21-23 March 2000, Pensacola, FL, Society of Environment Toxicology

and Chemistry.


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Appendix L: Confidential Composition

Documents

APP203638 Science memo - EPA