# Presentation: 035523

## 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

## Outline

- FQPA language on cumulative assessment
- How US EPA interpreted that language
- Review cumulative assessment of organophosphate pesticides
- Ongoing activities
- Selected references

**Notes:**
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 concern

## 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

- *Public Law 104-170, August 3, 1996

**Notes:**
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 assessment

## 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

**Notes:**
To implement the charge from Congress, EPA had to...
Interpret
Operationalize (make it work)

## 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.

**Notes:**
Some of EPA’s interpretation

In the following slides I hope to give you a taste of the operational aspects. 

## 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

**Notes:**
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 

## 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

**Notes:**
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.

## Pathways of Exposure

- Food

- Residential

- Water

**Notes:**
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 pesticide

## 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

**Notes:**
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

## 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

## 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

**Notes:**
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

## Pesticide Residues

- Food Consumption

- Pesticide sprayed on an
- agricultural commodity

- Commodity is processed
- Into another form

- Commodity is available
- to consumer as raw
- agricultural commodity

- Commodity is available
- to consumer as
- a processed food

- Consumer eats some amount of
- a food containing an agricultural
- commodity

- The food is
- a raw
- agricultural
- commodity

- The food contains
- several raw or
- processed
- agricultural
- commodities

- Commodity may be cooked,
- canned, frozen, boiled,
- concentrated, or otherwise
- manipulated or may remain
- raw

- The food’s recipe specifies
- the relative proportions of
- agricultural commodities in
- the food

- Recipe translation to
- agricultural commodity and
- processing/cooking status

- FCCOMMREV
- COM_CODE & COM_AMT

- RT-30  FOOD_CODE

- FCCOMMREV

- FCCOMMREV  COM_CODE & FOODFORM

- RESIDUE  – PDP adjusted by
- PROCESSING OR
- COOKING FACTORS

- SINGLE SERVING PDP DATA

- COMPOSITE  PDP DATA

**Notes:**
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.  

## 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

**Notes:**
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.

## 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

**Notes:**
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.  

## 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