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Health Effects Division Office of Pesticide Programs
Dietary Exposure Assessment at the US EPA: Overview of Residue Chemistry Guidelines and Dietary Exposure Modeling
David Hrdy Health Effects Division Office of Pesticide Programs US Environmental Protection Agency Presentation to AAPCO March 6, 2017
HealthEffectsDivisionOfficeofPes5cidePrograms
Health Effects Division Office of Pesticide Programs
Objectives
1. Provide overview of U.S. EPA’s Office of Pesticide Programs (OPP)
2. OPP’s regulatory role in food safety
3. Describe Residue Chemistry Guideline requirements
4. Describe OPP’s dietary exposure assessment methodology
5. Where to find tolerances.
6. OECD calculator
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Health Effects Division Office of Pesticide Programs
EPA’s Office of Pesticide Programs
• Roughly 700 Staff 4 Risk Assessment Divisions 2 Risk Management Divisions Communications & Stakeholder Engagement Economic and Lab Analysis IT Support
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Antimicrobials
Health Effects
Environmental Fate & Effects
Biopesticides & Pollution Prevention
Biological & Economic Analysis
Registration
Pesticide Re-Evaluation
Field & External Affairs
Information Technology & Resource Management
Office Director
March 6, 2017
Health Effects Division Office of Pesticide Programs
EPA’s Office of Pesticide Programs
• Registers pesticides for agricultural, residential, and public health applications
• Evaluates safety of pesticides by assessing exposure and associated risks
• Establishes legal limits (aka “tolerances”) for residues of pesticides in/on agricultural commodities
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Health Effects Division Office of Pesticide Programs
EPA’s Office of Pesticide Programs:
� Residential Assessments � Information on use practices, activity patterns, and
pesticide concentrations in various residential media are used to produce estimates of exposures in the home
� Occupational Assessments � Information on application rates, activities, contact rates,
and pesticide concentrations are used to assess exposures to mixers/loaders, applicators, and re-entry workers
� Dietary Assessments � Information on pesticide residues in food and water are
combined with consumption information to produce distributions of estimated exposures
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Health Effects Division Office of Pesticide Programs
EPA’s Office of Pesticide Programs • Registers pesticides used on food crops, in and
around the home, for industrial purposes, and for public health protection
• In order to perform this, EPA must: – Establish legal limits (aka “tolerances” or maximum
residue limits) for pesticides on agricultural commodities, which are enforced by FDA via monitoring
– Determines safety of pesticides by assessing dietary and residential/occupational exposures and associated risks
• EPA assessment rely on a review of registrant-submitted studies that follow a series of study guideline requirements
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Health Effects Division Office of Pesticide Programs
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• Excellent publication summarizing OPP’s Risk Asssessments.
https://www.extension.purdue.edu/extmedia/PPP/PPP-48.pdf
Health Effects Division Office of Pesticide Programs
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WHY We Require Data: The Statutes
• Two Statutes:
– The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)
– The Federal Food Drug and Cosmetic Act (FFDCA)
• In 1996, both were amended by: – The Food Quality Protection Act (FQPA)
Health Effects Division Office of Pesticide Programs
Regulatory Framework
Food Quality Protection Act of 1996 • Amended both FIFRA and FFDCA • Major impact on OPP Program Office
– Established more health protective standard – Required OPP to re-evaluate over 10,000 pesticide tolerances
• Required more advanced assessment methods – Aggregate pesticide exposure
Diet + Residential + Water
– Cumulative effects of pesticides with common mode of toxicity Evaluate exposure to multiple OP pesticides, rather than individual compounds
– Special sensitivity of infants and children
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Health Effects Division Office of Pesticide Programs
EPA Sets Tolerances To Ensure Food Safety
• Before allowing the use of a pesticide on food crops, EPA sets a tolerance, or maximum residue limit, which is the amount of pesticide residue allowed to remain in or on each treated food commodity.
– The tolerance is the residue level that triggers enforcement actions. That is, if residues are found (by either FDA, USDA FSIS, TTB, or NOAA) above that level, the commodity will be subject to seizure by the government.
• In setting the tolerance, EPA must make a safety finding that the pesticide can be used with "reasonable certainty of no harm." To make this finding, EPA considers
– the toxicity of the pesticide and its break-down products – how much of the pesticide is applied and how often – how much of the pesticide (i.e., the residue) remains in or on food by the time it is
marketed and prepared
• EPA ensures that the tolerance selected will be safe. The tolerance applies to food imported into this country, as well as to food grown here in the U.S.
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Health Effects Division Office of Pesticide Programs
Tolerance Setting Requires Numerous Scientific Studies
• Pesticide companies, or registrants, must submit a wide variety of scientific studies for review before EPA will set a tolerance. – The data are designed to identify possible harmful
effects the chemical could have on humans (its toxicity), – the amount of the chemical (or breakdown products)
likely to remain in or on food, and – other possible sources of exposures to the pesticide
(e.g., through use in homes or other places).
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Health Effects Division Office of Pesticide Programs
OPP’s Assessment Rely on a Series of Guideline Requirements
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AVAILABLE AT: http://www.epa.gov/ocspp/pdfs/OCSPP-TestGuidelines_MasterList.pdf
Health Effects Division Office of Pesticide Programs
Residue Chemistry Guidelines
• OPPTS Harmonized 860 Series Guidelines [http://www.epa.gov/ocspp/pubs/frs/publications/Test_Guidelines/series860.htm ]
• 1000 – Background • 1100 – Chemical Identity • 1200 – Directions for Use • 1300 – Nature of the Residue in Plants
and Livestock • 1340 – Residue Analytical Method • 1360 – Multiresidue Method • 1380 – Storage Stability Data • 1400 – Water, Fish, and Irrigated Crops • 1460 – Food Handling
• 1480 – Meat, Milk, Poultry, and Eggs • 1500 – Crop Field Trials • 1520 – Processed Food and Feed • 1550 – Proposed Tolerances • 1560 – Reasonable Grounds • 1650 – Submittal of Standards • 1850 – Confined Accumulation in
Rotational Crops • 1900 – Field Accumulation in
Rotational Crops
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Health Effects Division Office of Pesticide Programs
Nature of the Residue in Plants and Livestock
• “What’s there?” & “What happens to the chemical?” – metabolism
• Radiolabel studies – Plants: 3 dissimilar crops – Livestock: goats & chickens
• Method validation
GDLN 860.1300
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Health Effects Division Office of Pesticide Programs
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Crop Field Trials • Determine maximum pesticide residues that can be
expected in foods and feeds. – Conducted in the field – Maximum application rate – Shortest pre-harvest interval
• How Are Crop Field Trial Magnitude of Residue Studies Used? – To quantify the maximum levels of residues of concern identified in
plant metabolism studies – To set tolerances (aka Maximum Residue Limits) in crops – To estimate and refine dietary exposure for risk assessment
purposes
GDLN 860.1500
Health Effects Division Office of Pesticide Programs
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Meat, Milk, Poultry, and Eggs • Conducted with cows,
chickens, and pigs Interested in:
– Primary Residues • Direct treatment of livestock
or premises – Secondary Residues
• Residue in livestock from feed
• How Are Livestock Magnitude of Residue Studies Used? – To quantify the maximum levels of residues of concern identified in
livestock metabolism studies – To set tolerances in meat, fat, meat byproducts, eggs, and milk – To estimate and refine dietary exposure for risk assessment
purposes GDLN 860.1480 March 6, 2017
Health Effects Division Office of Pesticide Programs
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Residue Analytical Method • Enforcement
– Accurate – Specific – Universal – Repeatable
GDLN 860.1340
Health Effects Division Office of Pesticide Programs
Storage Stability
• Support FT/residue studies – Determine if samples change during storage – Provide information for adjusting residue values for
losses, if necessary
860.1380
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Health Effects Division Office of Pesticide Programs
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Processed Food and Feed • Determine whether or not residue levels change
with processing.
860.1520
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Health Effects Division Office of Pesticide Programs
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Processed Food and Feed • (b) Purpose. Processing studies are required to determine
whether residues in raw commodities may be expected to degrade or concentrate during food processing.
860.1520
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Health Effects Division Office of Pesticide Programs
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Processed Food and Feed • However, if residues do not concentrate in processed
commodities, the tolerance for the raw agricultural commodity (RAC) itself applies to all processed food or feed derived from it.
860.1520
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Health Effects Division Office of Pesticide Programs
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Fitting the Pieces Together
Conducting a Dietary Exposure Assessment …
Health Effects Division Office of Pesticide Programs
Tolerance Setting Requires Numerous Scientific Studies…
• And all of this information -- and then some -- is used in EPA's risk assessment process. – The risk assessment includes consideration of the
amounts and types of food people eat and how widely the pesticide is used (that is, how much of the crop is actually treated with the pesticide), as well as chemistry, toxicity, and exposure information.
– EPA also uses data from USDA on what foods people eat and the quantity they eat, collected through the Pesticide Data Program.
– Through these evaluations, EPA is ensuring the overall safety of proposed pesticide uses, as required by FQPA.
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Health Effects Division Office of Pesticide Programs
Dietary Exposure Assessment Approach • Combine food consumption data and residue
concentrations to develop distribution of dietary exposures
• Assessments range from simple to complex, but
based on same general exposure algorithm • Tiering process used to refine exposure estimates to
reflect more realistic assumptions
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= All Residue Values
All Consumption Values
Range of Dietary Exposures
March 6, 2017
consumed s)commoditie food(or foods unique ofnumber n here w
) Residue ConversionUnit nConsumptio( ExposureDietary n
1i food) ai/kg (mgifood) gm food/1000 kg (1bwt) food/kg (gm
ibwt) ai/kg (mg
=
∑=
××=
X
Health Effects Division Office of Pesticide Programs
Dietary Risk Assessment Models • Exposure assessment models based on
nationally-representative monitoring surveys
Key data surveys and databases: – NHANES/”What We Eat in America” (2003-2008)
Nationally representative food consumption survey
– U.S. EPA’s Food Commodity Intake Database (FCID)
Nationally representative food commodity consumption database
– USDA’s Pesticide Data Program (PDP) and/or Field Trial Data -PDP is Nationally representative commodity residue sampling program -Field Trials represent “high-end” concentrations used to establish tolerances/MRLs
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Health Effects Division Office of Pesticide Programs
JIFSANWebsiteUpdatewww.fcid.foodrisk.org
• JIFSAN FCID Website has updated their data from 2003-2008 to 2005-2010.
• The 2005-2010 data provides improved water consumption data for our risk assessments in OPP.
• The 2005-2010 consumption data are more recent. • Next consumption update would not occur for at
least another 2 years.
Health Effects Division Office of Pesticide Programs
Dietary Risk Assessment Models
Food Consumption (NHANES/WWEIA)
Food Recipe Database http://fcid.foodrisk.org/recipes/
Raw Ingredient Consumption
(FCID) http://
fcid.foodrisk.org/dbc/
Ingredient Pesticide Residue
(PDP or FT)
+=
Dietary Exposure
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RiskAcceptableLevelaPAD,cPAD,etc.
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Health Effects Division Office of Pesticide Programs
Exposure Assessment Software and Modeling
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• OPP uses a number of software models to perform its risk assessments:
• All models incorporate food commodity
consumption data • http://www.epa.gov/opp00001/science/deem • http://thelifelinegroup.org/lifeline/index.php • http://www.ilsi.org/researchfoundation/pages/cares.aspx • http://www.epa.gov/heasd/products/sheds_multimedia/sheds_mm.html
DEEM-FCID/Calendex
SHEDS-Multimedia
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Health Effects Division Office of Pesticide Programs
• The modeling tools rely on probabilistic techniques (Monte-Carlo) to evaluate exposure
• Techniques are routinely applied by OPP for virtually all of its pesticide risk assessments
• More accurate estimates of entire range of exposures and their associated probabilities
• Allow the Agency to characterize and quantify the variability in dietary exposure across various subgroups of interest
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Exposure Assessment Software and Modeling
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Health Effects Division Office of Pesticide Programs
Tolerances, eCFR, and www.globalmrl.com
• Non-standard tolerance look-up methods can be resource & knowledge intensive. – “Non-standard” = anything other than by pesticide active
ingredient – eCFR reference
• http://www.ecfr.gov/cgi-bin/text-idx?SID=b3890dda26481ee899bee522362cdaa8&c=ecfr&tpl=/ecfrbrowse/Title40/40cfrv25_02.tpl
• We have been working closely with a firm that supports the web program ( 5 yr. EPA/USDA grant) – https://www.globalmrl.com/db#query – We are working to have other options provided on the web
for downloading such as an Excel spreadsheet with all the chemicals and MRLs. Many folks are more inclined to find information through the spreadsheet.
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Health Effects Division Office of Pesticide Programs
https://www.globalmrl.com/
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Health Effects Division Office of Pesticide Programs
OECD MRL Calculator OECD-wide method to estimate MRLs
____________________
Health Effects Division Office of Pesticide Programs
OECD MRL Calculator
• OECD Workgroup formed in 2008 with the goal of harmonizing the calculation of MRLs across the OECD
– Practical implementation of sound statistical methods
– Simple to use – Clear and unambiguous MRL proposal – Harmonize EU and NAFTA procedures to extent
possible
• Working Group on Pesticides approved draft OECD MRL calculator in 2010
• Links to OECD User Guide, White paper, and draft calculator available at
http://www.epa.gov/pesticide-tolerances/oecd-maximum-residue-limit-calculator
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Health Effects Division Office of Pesticide Programs
OECD MRL Calculator
• EPA and PMRA use OECD MRL calculator as standard practice EPA Exceptions: – If Codex MRL exists, law requires EPA to harmonize with
Codex, if feasible/practical as per OECD MRL calculator result
• Section 408(b)(4) of Federal Food, Drug, and Cosmetic Act (FFDCA)
• Otherwise, reviewers need to describe reasons for non-harmonized tolerance
– Harmonization with key trading partners (e.g., Canada) – Specific peculiarities/oddities in field trial data
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Health Effects Division Office of Pesticide Programs
OECD MRL Calculator
• Field trial issues may result in non-harmonized OECD Calculator results among different reviewers
• For example, how to handle: – replicate samples or non-independent field trials – LOD or LOQ values – specific peculiarities/oddities in field trial data or
conditions – Outliers
• EPA and PMRA working to develop common practices with respect to use of the OECD calculator
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Health Effects Division Office of Pesticide Programs
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Summary • EPA’s Office of Pesticide Programs is responsible for
establishing the safety of pesticides, registering their use, and establishing tolerances/MRL’s.
• OPP has published a number of Guidelines to guide pesticide registrants in meeting OPP registration requirements.
• OPP Sets Tolerances to ensure the food supply is safe using a plethora of guideline studies to support their findings.
• Depending upon the commodity, FDA, FSIS, TTB, or NOAA enforce these tolerances.
• EPA’s Office of Pesticide Programs makes extensive uses probabilistic (Monte-Carlo) techniques to evaluate dietary exposure and ensure the safety of the food supply. – these techniques make extensive use of both food consumption and
pesticide residue data that are publically available on the internet
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Health Effects Division Office of Pesticide Programs March 6, 2017 37
Health Effects Division Office of Pesticide Programs
Questions?
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Health Effects Division Office of Pesticide Programs
Contactinforma5on:DavidHrdy
ChemistryandExposureBranchHealthEffectsDivision
OfficeofPes5cideProgramsPhone:703-305-6990
Email:[email protected]
Health Effects Division Office of Pesticide Programs
Additional References Discussed in Presentation
Pesticides and Human Health Risk Assessment: Policies, Processes, and Procedures. Purdue University
Cooperative Extension Service Publication No. PPP-48. available at:
https://mdc.itap.purdue.edu/item.asp?item_number=PPP-48#.VaAM_a5VhBc
PDP Data Program background. Available at : http://www.ams.usda.gov/pdp
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