goldberg2018-03-08-dietary-risk-assessmentppt.ppt

This is about dietary assessment and introduces rules in dietary assessment

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
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4. 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).
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5. 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).
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6. 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).
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7. 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.
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8. 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.
8Privileged and Confidential Attorney Work Product

9. 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.
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10. 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 bothFDA and EPA.
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11. 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.
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12. 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”
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13. EPA Guidance Decision in Antimicrobial Use
Site Index
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No current, practical approach to demonstrate “that there is no
reasonable expectation of residues in/on food.”
https://www.epa.gov/sites/production/files/2016-10/documents/158w-usi.pdf

14. 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
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15. 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
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16. 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
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17. 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
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18. 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.
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19. 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).
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20. 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.
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21. 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
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22. 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 2
nd
developmental toxicity study and a repro
study.
https://www.regulations.gov/document?D=EPA-HQ-OPP-2013-0604-0005
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23. 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.
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24. 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.
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25. 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.
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26. 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.
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27. 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).
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28. 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.
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29. 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.
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