Cumulative Risk Assessment of Pesticides Under the Food Quality Protection Act FQPA: An Overview

1. Cumulative Risk Assessment of Pesticides Under the Food Quality Protection Act (FQPA): An Overview Mary A. Fox, PhD, MPH AAAS Risk Policy Fellow, USDA Mid-Atlantic Cumulative Risk Workshop May 28-29, 2003

2. Outline FQPA language on cumulative assessment How US EPA interpreted that language Review cumulative assessment of organophosphate pesticides Ongoing activities Selected references Start with FQPA language and definitions Talk about what EPA had to do to implement their charge Review the first cumulative assessment of pesticides � emphasize dietary (what I�ve been working on at USDA) Discuss ongoing activities and issues of concernStart with FQPA language and definitions Talk about what EPA had to do to implement their charge Review the first cumulative assessment of pesticides � emphasize dietary (what I�ve been working on at USDA) Discuss ongoing activities and issues of concern

3. FQPA* Section 408 (b) 2 (C): Exposure of Infants and Children The [US EPA] Administrator shall assess the risk of the pesticide chemical residue based on Information about consumption patterns Information concerning special susceptibility Information concerning the cumulative effects of such residues that have a common mechanism of toxicity Ensure that these is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue I�ve pulled this from a section specific to infants and children. Similar language appears in a section applying to the general population. This part of the law outlines what must be considered when reviewing a pesticide tolerance. What Congress gave EPA Instructions on what to evaluate and some of the data required Provided the agency with the standard of safety it must assure Law does not say how to do this kind of assessmentI�ve pulled this from a section specific to infants and children. Similar language appears in a section applying to the general population. This part of the law outlines what must be considered when reviewing a pesticide tolerance. What Congress gave EPA Instructions on what to evaluate and some of the data required Provided the agency with the standard of safety it must assure Law does not say how to do this kind of assessment

4. What US EPA had to do Interpret the FQPA Develop and document approach 24 guidance and Standard Operating Procedures currently on website at http://www.epa.gov/oppfead1/trac/science/ Collect, compile, analyze, and manage data Develop software To implement the charge from Congress, EPA had to� Interpret Operationalize (make it work) To implement the charge from Congress, EPA had to� Interpret Operationalize (make it work)

5. Definitions from Guidance on Cumulative Risk Assessment of Pesticides, 2002 Aggregate risk The risk associated with all pathways and routes of exposure to a single chemical Cumulative risk The risk of a common toxic effect associated with concurrent exposure by all relevant pathways and routes to a group of chemicals that share a common mechanism of action Common mechanism of toxicity Two or more chemicals that cause a common toxic effect(s) by the same sequence of biochemical events. Some of EPA�s interpretation In the following slides I hope to give you a taste of the operational aspects. Some of EPA�s interpretation In the following slides I hope to give you a taste of the operational aspects.

6. Common Mechanism: The Organizing Principle Identifies the pesticides of interest (common mechanism group) Provides a means to quantify and relate each pesticide�s toxic activity to others in the group Common mechanism is fundamental to the pesticide cumulative assessments Identify the common mechanism group Compare toxic activity among members of the group � determine the relative potency (B is twice as potent as A), Make a common unit of evaluation if B = 2A, then A+B = 3A, use additivity to assess multiple chemicals Common mechanism is fundamental to the pesticide cumulative assessments Identify the common mechanism group Compare toxic activity among members of the group � determine the relative potency (B is twice as potent as A), Make a common unit of evaluation if B = 2A, then A+B = 3A, use additivity to assess multiple chemicals

7. Example: Revised Organophosphate Cumulative Risk Assessment (OPCRA) 30 pesticides assessed Nationally representative dietary assessment Regional approach to residential and water Computer program integrates components Exposures in food a concern for children 1-2 years old Nationally representative diet and pesticide data � Continuing Survey of Food Intakes by Individuals, 94-96, 1998 Pesticide Data Program 7 Regions defined � areas with similar pest pressures and therefore pesticide uses for home/garden and agriculture Florida; Northwest;Arid and Semi-Arid Southwest;North East and North Central;Humid Southeast;Lower Midwest;Mid-South In the slides to follow, I�ll try to give you an idea of the work that went into each section of the assessment. Nationally representative diet and pesticide data � Continuing Survey of Food Intakes by Individuals, 94-96, 1998 Pesticide Data Program 7 Regions defined � areas with similar pest pressures and therefore pesticide uses for home/garden and agriculture Florida; Northwest;Arid and Semi-Arid Southwest;North East and North Central;Humid Southeast;Lower Midwest;Mid-South In the slides to follow, I�ll try to give you an idea of the work that went into each section of the assessment.

8. Pathways of Exposure Pathways considered in the organophosphate cumulative risk assessment (Sources of pesticides in these pathways are the various types of pesticide applications/uses) Foods � from a single apple to complex combination foods such as apple pie with multiple ingredients Indoor and outdoor household environments, including pets, gardens, etc Drinking and cooking water Routes of exposure: ingestion, inhalation, dermal absorption Review definitions of aggregate and cumulative: An aggregate assessment evaluates one pesticide through the various sources, pathways, and routes of exposure A cumulative assessment evaluates more than one pesticidePathways considered in the organophosphate cumulative risk assessment (Sources of pesticides in these pathways are the various types of pesticide applications/uses) Foods � from a single apple to complex combination foods such as apple pie with multiple ingredients Indoor and outdoor household environments, including pets, gardens, etc Drinking and cooking water Routes of exposure: ingestion, inhalation, dermal absorption Review definitions of aggregate and cumulative: An aggregate assessment evaluates one pesticide through the various sources, pathways, and routes of exposure A cumulative assessment evaluates more than one pesticide

9. Hazard Identification Identify effects of concern Organophosphate pesticides are neurotoxic Common mechanism - interferes with enzyme Determine how effects will be measured Enzyme inhibition can be measured in blood plasma, red blood cells and in brain Brain is the target organ Hazard identification: The process of determining whether exposure to an agent can cause an increase in the incidence of a health condition. It involves characterizing the nature and strength of the evidence of causation. Risk Assessment in the Federal Government: Managing the Process (Red Book), NRC 1983 Hazard identification: The process of determining whether exposure to an agent can cause an increase in the incidence of a health condition. It involves characterizing the nature and strength of the evidence of causation. Risk Assessment in the Federal Government: Managing the Process (Red Book), NRC 1983

10. Dose-Response How much pesticide exposure leads to how much enzyme inhibition Evaluate animal studies for each pesticide of interest by all routes of exposure Select an index chemical Identify toxicological reference value Determine relative potency Enable additive assumption Dose-Response: the process of characterizing the relation between the dose of an agent administered or received and the incidence of a adverse health effect in exposure populations and estimating the incidence of the effect as a function of human exposure to the agent. Risk Assessment in the Federal Government: Managing the Process (Red Book), NRC 1983 Exposure-Response relationship: The relationship between exposure level and in the incidence of adverse effects. Glossary of The Presidential/Congressional Commission on Risk Assessment and Risk Management, 1997 http://www.riskworld.com/nreports/1996/risk_rpt/RR6ME001.HTM Key questions: How will human exposures be evaluated to indicate risk and how will exposure information on 30 different chemicals be combined? These questions answered based on 94 animal studies Look at all the studies � on which chemical is the data best, most complete, highest quality � this becomes the �index� chemical Call it Chemical A It�s dose-response will determine the dose of concern for health, the toxicological reference value Toxic strength (potency) of all the others will be calculated in comparison to this index chemical Determine the relative potency (e.g. B is twice as potent as A), make a common unit of evaluation (put B in units of A) allows additivity,if B = 2A, then A+B = 3A, allows assessment of 30 chemicals Dose-Response: the process of characterizing the relation between the dose of an agent administered or received and the incidence of a adverse health effect in exposure populations and estimating the incidence of the effect as a function of human exposure to the agent. Risk Assessment in the Federal Government: Managing the Process (Red Book), NRC 1983 Exposure-Response relationship: The relationship between exposure level and in the incidence of adverse effects. Glossary of The Presidential/Congressional Commission on Risk Assessment and Risk Management, 1997 http://www.riskworld.com/nreports/1996/risk_rpt/RR6ME001.HTM Key questions: How will human exposures be evaluated to indicate risk and how will exposure information on 30 different chemicals be combined? These questions answered based on 94 animal studies Look at all the studies � on which chemical is the data best, most complete, highest quality � this becomes the �index� chemical Call it Chemical A It�s dose-response will determine the dose of concern for health, the toxicological reference value Toxic strength (potency) of all the others will be calculated in comparison to this index chemical Determine the relative potency (e.g. B is twice as potent as A), make a common unit of evaluation (put B in units of A) allows additivity,if B = 2A, then A+B = 3A, allows assessment of 30 chemicals

11. Exposure Assessment Measure or estimate how humans come into contact with pesticides (intensity, frequency, duration) Determine where the pesticides are in the environment � in homes, on foods, etc. Understand human behaviors/activity patterns Exposure assessment: The process of measuring or estimating the intensity, frequency and duration of human exposure to an agent currently present in the environment. Risk Assessment in the Federal Government: Managing the Process (Red Book), NRC 1983 Exposure assessment: The process of measuring or estimating the intensity, frequency and duration of human exposure to an agent currently present in the environment. Risk Assessment in the Federal Government: Managing the Process (Red Book), NRC 1983

12. A look at some of the details of the dietary component will give you an idea of the complexity of the cumulative assessment. The residential and water components are similarly complex, combining multiple sources of data. This slide describes the dietary data sources and types of manipulation and modification within the exposure assessment model. Data sources are in red. The left side of the slide outlines how the pesticide residue data collected by the USDA Pesticide Data Program (PDP) are incorporated into the assessment. Residue concentrations on agricultural commodities that become processed foods are modified or adjusted by relevant processing/cooking factors. The right side of this slide tracks how foods reported eaten in the Continuing Survey of Food Intakes by Individuals (CSFII) are broken down into the component agricultural commodities through the recipe translations. A look at some of the details of the dietary component will give you an idea of the complexity of the cumulative assessment. The residential and water components are similarly complex, combining multiple sources of data. This slide describes the dietary data sources and types of manipulation and modification within the exposure assessment model. Data sources are in red. The left side of the slide outlines how the pesticide residue data collected by the USDA Pesticide Data Program (PDP) are incorporated into the assessment. Residue concentrations on agricultural commodities that become processed foods are modified or adjusted by relevant processing/cooking factors. The right side of this slide tracks how foods reported eaten in the Continuing Survey of Food Intakes by Individuals (CSFII) are broken down into the component agricultural commodities through the recipe translations.

13. Risk Characterization Risk relates exposure to hazard Risk characterization involves interpreting the assessment results Is anyone �at risk�? Does any population group have exposures approaching the toxicological dose of concern If yes, by what route, pathway, source? Kids dietary exposure: Analyze 800+ output records After running the computer models� Risk characterization: The process of organizing, evaluating, and communicating information about the nature, strength of evidence, and likelihood of adverse health or ecological effects from particular exposures. (The Presidential/Congressional Commission on Risk Assessment and Risk Management, 1997) Compare exposure estimates to the toxicological reference. Dietary output includes the food(s) that contributed to an individual�s exposure and the pesticides on the food. Analyzing contributors to exposure helps identify the risk mitigation strategy. What pesticide use on what food needs to be changed to reduce children�s dietary exposures.After running the computer models� Risk characterization: The process of organizing, evaluating, and communicating information about the nature, strength of evidence, and likelihood of adverse health or ecological effects from particular exposures. (The Presidential/Congressional Commission on Risk Assessment and Risk Management, 1997) Compare exposure estimates to the toxicological reference. Dietary output includes the food(s) that contributed to an individual�s exposure and the pesticides on the food. Analyzing contributors to exposure helps identify the risk mitigation strategy. What pesticide use on what food needs to be changed to reduce children�s dietary exposures.

14. Ongoing Activities Four more common mechanism groups Triazines (e.g. atrazine), thio-and N-methyl carbamates, chloroacetanilides Data collection/Model refinement Pesticide residues Dietary intake Other concerns Data Quality Act requirements 1) Several more common mechanism of action groups in line for cumulative assessments. 2) Ongoing data collection, management and model improvement efforts Sampling of food commodities for residues Incorporating recipes for new foods 3) A private software developer wrote part of the cumulative assessment computer program so some of the assessment �machinery� is proprietary, not available to the public. The Data Quality Act requirements on public availability of data and models could potentially be used to challenge the results of cumulative assessments. 1) Several more common mechanism of action groups in line for cumulative assessments. 2) Ongoing data collection, management and model improvement efforts Sampling of food commodities for residues Incorporating recipes for new foods 3) A private software developer wrote part of the cumulative assessment computer program so some of the assessment �machinery� is proprietary, not available to the public. The Data Quality Act requirements on public availability of data and models could potentially be used to challenge the results of cumulative assessments.

15. References Office of Pesticide Programs website http://www.epa.gov/pesticides/ Revised Organophosphate Cumulative Risk Assessment http://www.epa.gov/pesticides/cumulative/rra-op/ OPP science policy documents & guidance http://www.epa.gov/oppfead1/trac/science/ The broader cumulative risk framework http://oaspub.epa.gov/eims/eimscomm.getfile?p_download_id=36941 Mfox@oce.usda.gov, 202-720-9000