Adjuvants and Inerts in the USA –How They are Regulated by USEPA

Brasilia, December 9, 2013

Debra Edwards, Ph.D., Consultant

Former Director of EPA Pesticide Programs

1

Legal and Regulatory DefinitionsInert Ingredients

The Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), Section 2(m) defines an inert ingredient as “an ingredient which is not active.”

The Code of Federal Regulations (40 CFR 152.3) further describes an inert ingredient as “any substance . . . other than an active ingredient, which is intentionally included in a pesticide product, . . .”

2

FIFRA Safety StandardInert Ingredients

Registration and reregistration of pesticide products under FIFRA include a determination that each pesticide product formulation will not result in “any unreasonable risk to man or the environment, taking into account the economic, social and environmental costs and benefits of the use . . . “

The entire pesticide product formulation, including inert ingredients, must meet this standard.

3

Tolerances under FFDCA Required forFood Use Inerts

The Federal Food, Drug and Cosmetic Act (FFDCA) requires that inert ingredients in pesticide products used on food and feed crops, agricultural commodities, or livestock must have a tolerance or tolerance exemption in place under the Code of Federal Regulations (CFR), Title 40, Part 180.

4

FFDCA Safety StandardFood-Use Inerts

Determination that “there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposure and all other exposures for which there is reliable information.”

FFDCA defines a “pesticide chemical” to include all active and inert ingredients within the product.

5

Adjuvants

• Adjuvants are broadly defined as any substance separately added to a pesticide product (typically as part of a spray tank mixture) that will improve the performance of the pesticide product.

• EPA treats any tank-mixed substance used on food and feed crops, agricultural commodities, or livestock as part of the pesticide and thus needing an FFDCA food additive regulation or tolerance exemption.

FIFRA 2(u): “The term “pesticide” means any substance or mixture of substances . . . “

6

FDA Regulation of Adjuvants

• FDA officially has the authority to establish direct food additive regulations for “adjuvants for pesticide use dilutions” (21 CFR 172.710) or “adjuvants for pesticide chemicals” (21 CFR 182.99).

• Ten direct food additive regulations for surfactants and related adjuvants for pesticide use dilutions are published in 21 CFR 172.710. The remainder are covered under 21 CFR 182.99.

7

21 CFR 182.99

The vast majority of adjuvant food additive regulations are addressed by FDA under 21 CFR 182.99, which states:

“Adjuvants, identified and used in accordance with 40 CFR 180.910 and 180.920, which are added to pesticide use dilutions by a grower or applicator prior to application to the raw agricultural commodity, are exempt from the requirement of tolerances under section 409 of the FFDCA.”

8

EPA sets tolerance exemptions under 40 CFR 180.910 and 180.920

Thus, though FDA officially has the responsibility for setting food additive regulations for adjuvants that are sold separately from a pesticide product, that responsibility has, in effect, been delegated to EPA.

9

40 CFR Part 180 - Exemptions from the requirement of a tolerance for inert

ingredients, including adjuvants

• 180.910 – Inert ingredients used pre- and post-harvest

• 180.920 – Inert ingredients used pre-harvest

10

40 CFR Part 180 – Other exemptions from the requirement of a tolerance

for active and inert ingredients

• 180.930 – Inert ingredients applied to animals

• 180.940 – Active and inert ingredients for use in food contact surface sanitizing solutions

• 180.950 – Minimal risk active and inert ingredients

• 180.960 - Polymers

11

Limitations on Tolerance Exemptions

Each exemption may have a chemical-specific limitation that affects its approval status.

Example:

3,6-Dimethyl-4-octyn-3,6-diol is approved under 180.920 for use on growing crops; however, it is limited to applications to “soil prior to planting or to plants before the edible parts form” when used as a surfactant or related adjuvants of surfactants.

12

Procedures for Requesting Establishment of a New/Amended

Inert Ingredient Tolerance Exemption

• Request a presubmission call or meeting with the Inert Ingredient Assessment Branch of EPA’s Office of Pesticide Programs

• Prepare and Submit a Petition, which must include a “Notice of Filing,” a Petition Summary, and toxicity and exposure data.

13

Presubmission Meeting

• Informal discussion to determine if the applicant has enough information to proceed with the petition process.

• Applicant provides a brief summary of information regarding the chemical, including use information, limitations, applicable sections of the Code of Federal Regulations, and toxicity and environmental fate data.

• EPA staff then advises the applicant as to additional information that will be needed in the petition.

14

Petition ContentsNotice of Filing

• Summary of the request for an exemption from tolerance for an inert ingredient, including all supporting data.

• Published in the US Federal Register with a public comment period of 30 days.

• Published Notice of Filing states that EPA has not evaluated the application or decided if the data support granting of the tolerance exemption.

15

Petition ContentsSummary of the request

Name, chemical identity and composition

Purpose, including use pattern

Any proposed limitations

Current uses of the chemical and existing tolerances or exemptions

16

Petition ContentsSummary of the Data

• Relevancy of each submitted study

• Study results and conclusions

• Discussion of missing data and justification as to why this information is not needed to grant the tolerance or exemption

• Summarize applicant’s position regarding human health and environmental risks, based on the data and information provided.

17

Petition ContentsData

• Physical/chemical properties

• Toxicity

• Human/animal metabolism

• Exposure

• Environmental fate and effects

• Ecotoxicity

18

Petition ContentsToxicity Data

• Acute (oral, dermal, inhalation, skin and eye irritation, and skin sensitization)

• Chronic/repeat dose • Reproduction/Developmental• Mutagenicity• Carcinogenicity (or Quantitative Structure Activity

Relationship/QSAR modeling)• Neurotoxicity• Endocrine• Immunotoxicity

19

Petition ContentsHuman/Animal Metabolism Data

• Is the chemical absorbed by the body?

• How much of the chemical is excreted and how is it excreted (e.g., urine, feces)?

• Will it bioaccumulate?

• Are the degradates/metabolites of the chemical more toxic than the parent chemical?

20

Petition ContentsExposure Data

• Dietary - intended crops, application rate, % in formulation

• Drinking water (if EPA default modeling indicates a concern) - Surface and Ground Water modeling

• Occupational – Anticipated exposure to workers mixing, loading and applying the inert + post application re-entry workers

• Residential – home use handler and post application exposure - % in formulation

21

Petition ContentsEnvironmental Fate and Ecotoxicity Data

• Biodegradation/Persistence

• Expected “fate” of the chemical

• Aquatic organism toxicity

• Avian organism toxicity

• Invertebrate organism toxicity

22

“EPI Suite” and “ECOSAR”

The publicly available EPI Suite (Estimation Program Interface) model may be used if no environmental fate data are available:

http://www.epa.gov/oppt/exposure/pubs/episuite.htm

The publicly available EPI Suite or ECOSAR (Ecological Structural Activity Relationship) models may be used if no ecotoxicity data are available:

http://www.epa.gov/oppt/newchems/tools/21ecosar.htm

23

Acceptable Sources of Data

• EPA guideline studies: http://www.epa.gov/ocspp/pubs/frs/home/guidelin.htm

• Publically available literature and data, including peer-reviewed assessments and journals

• Modeled data: http://www.epa.gov/pesticides/science/models_db.htm#models

• Analog/surrogate data

24

Unacceptable Sources of Data

• MSDS sheets are only useful if the product contains 100% of the chemical in question and it clearly states this on the MSDS. Also, any studies cited (e.g., toxicity) on the MSDS must be provided.

• Unpublished studies that are submitted without the full study report are not acceptable.

25

EPA Petition Review Process

• 21-day screen of the petition for adequacy/completeness

• 45- to 90-day technical screen to determine if the application and data are accurate and complete

• Full review and risk assessment

• Proposed and Final “Rule” (regulation) published in the Federal Register, to grant the tolerance or tolerance exemption. Proposed Rules generally provide a 90- to 120-day public comment period.

26

EPA Decision Review Time Frames and Fees

• New food use inert = 12 months/$18,900

• Amendment of a currently approved food use inert with new data = 10 months/$5250

• Amendment of a currently approved food use inert without new data = 8 months/$3150

• Adjuvants that are not inert ingredients (i.e., not part of a product formulation) currently have no established time frame for review or any fee schedule.

27

Pesticide Product Registration and Inert Ingredients

• All inert ingredients in a pesticide product must be approved by EPA before the product can be registered.

• Confidential statements of formula (CSFs) are screened to ensure that all inert ingredients are approved for the labeled use of the pesticide formulation.

28

Inert Ingredients in Proprietary Mixtures

• Pesticide products may contain proprietary mixtures of multiple inert ingredients.

• Each component of the mixture must be approved by EPA.

• EPA maintains a confidential master file of proprietary mixtures that contains the complete compositional information (provided to EPA by the manufacturer of the mixture product).

29

Data Protection and Exclusive Use

• Section 408(i) of the FFDCA states that data submitted to support tolerances or tolerance exemptions for inert ingredients are entitled to data compensation and exclusive use data rights.

• Exclusive Use = 10 years from publication of the final tolerance or tolerance exemption rule

• Data compensation = 15 years from the date the data were submitted.

30

EPA Role in Data Protection and Exclusive Use Rights for Inert Ingredient Data

EPA screens pesticide product registration applications to ensure that the applicant has:

1. Made an offer to pay for the use of data,2. Obtained authorization for the use of data,3. Purchased the chemical from the data owner,4. Purchased the chemical from a company that has

made an offer to pay to the data submitter, OR5. Submitted its own data to satisfy the obligation.

The data protection/exclusive use situation for adjuvants not in pesticide products is unclear.

31

For more information on EPA inert ingredient regulation . . .

• Guidance documents and procedural information: http://www.epa.gov/opprd001/inerts

“Inert Finder” - Search engine for approved food and non-food inert ingredients:

http://iaspub.epa.gov/apex/pesticides/f?p=175:1:

• Questions? InertsBranch@epa.gov P.V. Shah, Branch Chief, (703) 308-1846

32