1 / 30

Dietary Risk Assessments Under FIFRA

This presentation covers the statutory framework, antimicrobials, circumstances for EPA dietary risk assessment, determining dietary exposure, and evaluation of risk assessment results. Includes a case study on dipropylene/triethylene glycol.

kirschbaum
Download Presentation

Dietary Risk Assessments Under FIFRA

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Dietary Risk Assessments Under FIFRA Seth Goldberg March 8, 2018

  2. Topics for Today’s Presentation • Statutory Framework • Antimicrobials • Under what circumstances will EPA do a dietary risk assessment? • Determining Dietary Exposure • Evaluation of Risk Assessment Results • Case Study: Dipropylene/Triethylene Glycol

  3. Statutory Framework: FIFRA • Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) is the statute under which EPA regulates pesticides. FIFRA is in the Agriculture Code at 7 U.S.C. § 136a, et seq. • FIFRA defines a pesticide is “any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest.” FIFRA § 2(u)(1).

  4. Statutory Framework: FIFRA • Pests • Defined by EPA to include, “[a]ny fungus, bacterium, virus, prion, or other microorganism, except for those on or in living man or other living animals and those on or in processed food or processed animal feed, beverages, drugs (as defined in FFDCA § 201(g)(1)) and cosmetics (as defined in FFDCA § 201(i)). 40 CFR § 152.5(d). • FIFRA – Generally risk benefit standard for registration under Section 2(bb).

  5. Statutory Framework: FFDCA • Federal Food, Drug, and Cosmetic Act regulates residues of substances in food. Food considered adulterated if it has residues unless they are allowed by regulation. • FFDCA Section 408 authorizes EPA to set standards governing pesticide chemical residues in food. • Tolerances (maximum legally permissible levels for pesticide residues in food). • Exemptions from tolerance (no numeric limit but use conditions). • FFDCA Section 409, administered by FDA, authorizes food additives (substances which result or may reasonably be expected to result in becoming a component of food).

  6. Statutory Framework: FQPA • Food Quality Protection Act of 1996 amended both FIFRA and FFDCA • Key driver was “Delaney Clause,” prohibiting carcinogens in pesticide residues. • FQPA amended FFDCA Section 408 to eliminate “Delaney Clause” and include stricter safety standards (“a reasonable certainty of no harm”). • Required consideration of sensitive subpopulations. • Required reassessment of pesticide tolerances in place when FQPA was signed. • EPA completed reassessment of over 9,000 pesticide tolerances, revoking or modifying almost 4,000 tolerances.

  7. Statutory Framework: FQPA • The definition of “Pesticide Chemical Residue” in section 201q of FFDCA was further amended by the Antimicrobial Reform Technical Corrections Act of 2004. • The definition is quite complex, so determining when residues are subject to EPA and/or FDA jurisdiction is challenging. Privileged and Confidential Attorney Work Product

  8. Antimicrobials: Pesticide Chemical Residue, FFDCA § 201 (q)(2) • Defined as residues in or on raw agricultural commodity or processed food of • A pesticide chemical; or • Any other added substance that is present on or in the commodity or food primarily as a result of the metabolism or other degradation of a pesticide chemical. • Food that contains a “Pesticide Chemical Residue” is deemed to be adulterated unless EPA has issued a tolerance or exemption from food tolerance.

  9. Antimicrobials that may leave residues on food: Joint EPA-FDA Jurisdiction • Different uses of the same antimicrobial pesticide may be subject to • Different statutes or statutory provisions; • Different risk standards: EPA views 408 standard as different from 409 standard; • Different data requirements. • Same antimicrobial use may be subject to review and approval by both FDA and EPA.

  10. Example: Egg Washes • EPA: • Regulated under Section 408 if product is intended to control microbial growth in the rinse water. • FDA: • Regulated under Section 409 if product is intended to limit contamination on the egg. • Joint regulation: • If the product makes both claims.

  11. Under what Circumstances will EPA perform a Dietary Risk Assessment? • Liquids used on hard surfaces. • Regardless of whether or not there is a potable rinse. • Almost all “kitchen” uses. • Now includes the outside of appliance; • Kitchen floors. • Treated materials that may come not contact with food or that are mouthed by an infant/child. • No current, practical approach to demonstrate “that there is no reasonable expectation of residues in/on food”

  12. EPA Guidance Decision in Antimicrobial Use Site Index https://www.epa.gov/sites/production/files/2016-10/documents/158w-usi.pdf • No current, practical approach to demonstrate “that there is no reasonable expectation of residues in/on food.”

  13. Determining Dietary Exposure for a Risk Assessment • Indirect Food Use: E.g., liquid antimicrobials used on non-porous, hard surfaces in Residential Settings • Indirect Dietary Residential Exposure Assessment Model (IDREAM). • Developed to estimate acute and chronic indirect ingestion exposure that can result from use of disinfectants and sanitizers on kitchen surfaces. https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/indirect-dietary-residential-exposure-assessment

  14. Determining Dietary Exposure for a Risk Assessment • Indirect Food Use: E.g., liquid antimicrobials used on non-porous, hard surfaces in Commercial Settings • The Food Contact Sanitizing Solutions Model (FCSSM). • Developed to estimate indirect dietary exposure to components of sanitizing solutions used in commercial settings. https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/food-contact-sanitizing-solutions-model-fcssm

  15. Determining Dietary Exposure for a Risk Assessment • Indirect Food Use: E.g., antimicrobials used as preservatives in food contact surfaces • Dislodgeable surface residue + default transfer coefficients for different surface • SHEDS model for dislodgeable surface residue • OPPTS 875.2100 Foliar Dislodgeable Residue Dissipation Study – guideline may need to be adapted to antimicrobials

  16. Determining Dietary Exposure for a Risk Assessment • Direct Food Use (Fruit and Vegetable Wash for Raw Agricultural Commodities). • Dietary Exposure Evaluation Model (DEEM); • Estimates exposure to pesticides in food in the diets of the US population. https://archive.epa.gov/pesticides/news/web/html/deem-2.html

  17. Determining Toxicity Endpoints for a Risk Assessment • Determination by EPA’s Antimicrobial Division Toxicity Endpoint Selection Committee (ADTC). • Most sensitive endpoint from FIFRA testing. • Chronic endpoints are typically used. • Sensitization also of concern.

  18. Adjustments to the Exposure / Hazard EPA’s Conservative Approach • Uncertainty factors are applied to the endpoint values to determine appropriate reference dose. • 10X for inter-species extrapolation; • 10x for intra-species variability; • 3x for lack of a chronic endpoint; • 3x for lack of a chronic endpoint; Values can range from 3 to 300 (10 x 10 x 3).

  19. Adjustments to the Exposure / Hazard EPA’s Conservative Approach • FQPA safety factor is then applied to the reference dose to meet “reasonable certainty of no harm standard” in FFDCA Section 408 • Special consideration of sensitive subpopulations; • Default value is 10x; • Values can be reduced to 1x if EPA determines the toxicity data set is complete.

  20. EPA assigned Safety/Uncertainty Factor • Alkylbenzene Sulfonates (ABS) Dietary Exposure Scoping Document dated July 20, 2017 (EPA-HQ-OPP-2013-0097-0006). • Uncertainty factor: 100 (10 x 10) • 10x for inter-species extrapolation; • 10x for intra-species variability. • FQPA safety factor. • 1x – for the overall US population or any population subgroup. https://www.regulations.gov/document?D=EPA-HQ-OPP-2013-0097-0006

  21. EPA assigned Safety/Uncertainty Factor • Nuosept 95 (common name: Azadioxabicyclooctane) Revised Dietary Exposure Scoping Document dated April 20, 2017 (EPA-HQ-OPP-2013-0604-0005). • Uncertainty factor: 300 (10 x 10 x 3). • 10x for inter-species extrapolation; • 10x for intra-species variability; • 3x for lack of a chronic endpoint. • FQPA safety factor. • 10x – due to lack of a 2nd developmental toxicity study and a repro study. https://www.regulations.gov/document?D=EPA-HQ-OPP-2013-0604-0005

  22. Evaluation of Risk Assessment Results • Exposure must be less than the hazard plus safety factors • If exposure is greater than hazard, EPA will demand uses must be dropped / modified until exposures fall to acceptable levels.

  23. EPA Dietary Risk Assessments – Expanded Applicability • Under FFDCA Sec. 409, FDA has, since the 1980’s assumed that all residues of concern are removed by a potable water rinse. • Until recently, EPA followed this interpretation and considered those uses to be non-food uses. • Now, EPA asserts these are indirect food uses. • EPA performs dietary risk assessments on all uses that may result in residues on food. • For food in commerce, those newly defined indirect food uses now require a tolerance or exemption.

  24. Case Study: Dipropylene/Triethylene Glycol • A tolerance or tolerance exemption was not previously required for the registered uses of dipropylene glycol and triethylene glycol because the labels required a potable water rinse after application. • EPA’s scientific assumption was that if an antimicrobial pesticide use required a potable water rinse on the label, the use was considered nonfood and no tolerance or tolerance exemption was needed.

  25. Case Study: Dipropylene/Triethylene Glycol • The Agency reviewed data suggesting that a potable water rinse may not be 100% efficient and no longer considers a use as nonfood just because the label requires a potable water rinse. • Therefore, a tolerance or tolerance exemption is required for dipropylene glycol and triethylene glycol to address indirect dietary exposure from surface disinfectant uses. Interim Registration Review Decision Document for Propylene Glycol, Dipropylene Glycol and Triethylene Glycol, Section 3: Tolerances, available at https://www.regulations.gov/document?D=EPA-HQ-OPP-2013-0218-0007.

  26. Case Study: Dipropylene/Triethylene Glycol • Existing tolerance exemptions • Dipropylene glycol when used as a solvent, cosolvent 40 CFR 180.910 (pre-and post-harvest uses only); • Triethylene glycol when used as a deactivator 40 CFR 180.920 (pre-harvest uses only).

  27. Case Study: Dipropylene/Triethylene Glycol • Antimicrobial formulations (food-contact surface sanitizing solutions) need tolerance exemptions under 40 CFR 180.940. • The Agency is proposing to establish a tolerance exemption for both actives after the interim decision is published. • Specified in both the Proposed Interim Registration Review Document (March 2017) and the Interim Registration Review Document (December 2017); • Interim Decision Document released February 27, 2018.

  28. Observations • Recently EPA has expanded the situations in which it performs dietary risk assessments. • Useful to ask whether EPA might view a particular use as having the potential to leave residues on food. • EPA assessments can be very conservative, with up to 3000x safety factors, but advocacy is possible • Where dual approvals needed, consider advocating coordination to minimize transaction costs and inconsistency.

More Related