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Revised Cumulative Risk Assessment: Organophosphorus Pesticides Office of Pesticide Programs June 18, 2002 Welcome Lois Rossi, Director Special Review and Reregistration Division Managing Risk From Organophosphorus Pesticides Outline of Presentation Plan for the OPs

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Revised Cumulative Risk Assessment:

Organophosphorus

Pesticides

Office of Pesticide Programs

June 18, 2002


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Welcome

Lois Rossi, Director

Special Review and Reregistration Division


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Managing Risk

From

Organophosphorus

Pesticides


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Outline of Presentation

  • Plan for the OPs

  • Progress to date

  • Achievements in:

    • Risk reduction

    • Methods development

    • Process improvements


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Plan for the OPs

  • Several OP Reregistration Eligibility Decisions completed before August 1996

  • After August 1996 OPs became a major focus of Reregistration and Tolerance Reassessment

  • In the last six years a tremendous amount of resources dedicated to:

    • Risk assessment and risk management of the individual OP chemicals

    • Developing cumulative risk assessment methods and applying them to the OPs

  • It is appropriate to examine the results and the achievements of the last six years


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Implementation of the Plan

  • Refine available exposure methods and data

  • Develop a public process to allow greater stakeholder access to information and to facilitate input on:

    • Science policies

    • Exposure data and assumptions

    • Risk assessments

    • Risk management

  • Develop methods for aggregate risk assessment

  • Develop methods for cumulative risk assessment


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Status of OPs

  • 49 total OPs ever registered

  • 7 cancelled before 1996

    • Chlorfenvinphos, Chlorthiophos, Dialifor, Dioxathion, Monocrotophos, Phosphamidon, Sulprofos

  • 42 started the public participation process


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Status of OPs (continued)

  • 3 early voluntary cancellations

    • Fonofos, Isazophos, Isofenphos

  • 5 recent cancellations

    • Chlorpyrifos methyl, Ethion, Ethyl parathion, Fenamiphos, Sulfotepp

  • 34 OPs remain


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Status of Tolerance Reassessment

FQPA: Must reassess all tolerances by Aug. 2006

  • 33% by August 3, 1999

    • Completed!

    • Goal 3208, 3290 actually reassessed

  • 66% by August 3, 2002

    • On track for completing goal of 6416

  • 100% by August 3, 2006

    • Final goal: 9721


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Status of OP Tolerance Reassessment

  • 1691 at the start of FQPA (1996)

    • 17.4% of all tolerances (9721)

  • 871 reassessed through revocation or other process

  • 98 reassessment underway (revocation)

  • 722 OP tolerances remain to be reassessed


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Public Participation Process

  • Phase 1 -- Registrant "Error Only" Review (30 days) 

  • Phase 2 -- EPA Considers Registrants Comments (up to 30 days)

  • Phase 3 -- Public Comment on Prel. Risk Asmt. (60 days)  

  • Phase 4 -- EPA Revises Risk Assessments; Technical Briefing (up to 90 days) 

  • Phase 5 -- EPA Solicits Risk Mgmt. Ideas (60 days)

  • Phase 6 -- EPA Develops Risk Mgmt. Strategies (60 days)


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Public Participation Process

Individual Reregistration Eligibility Decisions (IREDs)

  • 39 preliminary risk assessments -- public comment

  • 39 revised risk assessments B public comment

  • 32 IREDs/TREDS

  • Communication about each OP: overviews, summaries, fact sheets, comment responses

  • Conference calls and closure calls

  • 18 Technical Briefings

  • Stakeholder meetings B 3 outside DC


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Public Participation Process (continued)

TRAC & CARAT (Advisory Committees)

  • 10 TRAC and 3 CARAT meetings

  • Numerous TRAC and CARAT Workgroup meetings

  • 50+ TRAC/CARAT staff papers


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Public Participation Process (continued)

Development of Cumulative Assessment

  • 5 Technical Briefings

  • Drinking Water Methodology Workshop

  • Numerous Science Advisory Panel meetings

  • Preliminary assessment B public comment

  • The release of the revised assessment


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Achievements in Risk Reduction - Residential -

  • Residential use reduced by >20 million pounds annually

  • Principally as the result of risk mitigation for chlorpyrifos and diazinon


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Residential (continued)

Universe of chemicals

  • Started with 17 OPs with residential/public area uses

  • 7 OPs excluded from cumulative assessment because residential uses were eliminated/reduced to a negligible level (e.g. limited to bait stations, fire ant mounds)

  • Of the remaining 10, two are limited to public health uses (naled, fenthion)

  • 3 OPs with residential/public area uses still under review (DDVP, malathion, tetrachlorvinphos)


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Residential (continued)

Indoor Uses

  • Initially 9 OPs had indoor uses

    • Now only DDVP

  • Initially 6 OPs had pet uses – now only tetrachlorvinphos and DDVP

  • Indoor use of chlorpyrifos, fenitrothion, and trichlorfon limited to pre-packaged child-resistant bait stations (negligible exposure)


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Residential (continued)

Protecting Public Health Uses

  • Public Health uses retained where individual assessments indicate no risks of concern

  • Chlorpyrifos fire ant mound treatment

  • Chlorpyrifos mosquito control

  • Fenthion mosquito control

  • Naled mosquito and black fly control

  • Phosmet fire ant mound treatment


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Residential (continued)

  • For the cumulative assessment:

    • Used daily residential estimates in probabilistic assessment for the first time

    • developed regional assessments to cover spatial variation throughout the U.S.

  • These advances together will likely have a major impact on future residential risk assessment methodology


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Achievements in Risk Reduction- Food -

  • Many chemicals faced a much higher standard as the result of the FQPA safety factor requirement

  • This together with generally very low toxicological endpoints for cholinesterase inhibition resulted in extremely low allowable exposures for most chemicals

  • EPA & USDA increased PDP monitoring of OP residues on foods highly consumed by children

  • Agency quickly implemented use of probabilistic dietary exposure estimates on a routine basis


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Food (continued)

  • Most OPs met these very high standards

  • When dietary risks of concern were identified, risks were mitigated:

    • Use removed from OP/crop combination

    • Use pattern changes

      • e.g., rate, frequency, timing


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Food (continued)

  • Used rigorous methods and high quality data and worked with stakeholders on viable use pattern changes:

    • Addressed dietary risks of concern

    • Limited disruption to agriculture


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Achievements in Risk Reduction- Drinking Water -

  • OPP now routinely addressing drinking water risks

  • Surface water models enhanced to include a scenario representative of a drinking water reservoir

  • Screening level model developed for groundwater

  • Agency moved on several fronts to obtain improved water monitoring data and is continuing that work

  • Effects of drinking water treatment beginning to be addressed


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Drinking Water (continued)

  • OPs are not a major concern for drinking water (relative to some other classes of chemicals)

  • Time generally allowed for data development when concerns were identified

  • Drinking water risks were mitigated through:

    • Use removed from certain OP/crop combinations

    • Use pattern changes

      • e.g., rate, frequency, timing, use area


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Drinking Water (continued)

  • For the cumulative assessment:

    • Used daily drinking water estimates in probabilistic assessment for the first time

    • Developed regional assessments to cover spatial variation throughout the U.S.

  • These advances together with improved modeling and monitoring likely to have a major impact on future drinking water risk assessment methodology


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Achievements in Risk Reduction- Worker Risk -

  • Worker risks are important concern for Ops

  • Very low toxicological endpoints for cholinesterase inhibition often resulted in very low exposures presenting risks of concern

  • Risk/Benefit balancing required an enormous amount of input from stakeholders


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Worker Risk (continued)

Agency worked quickly to complete review of ARTF data

  • Excellent source of extensive, up-to-date data on exposure of re-entry workers

  • Allowed exposures for specific tasks to be calculated separately

    PR notice AWorker Risk Mitigation for Organophosphate [email protected]

  • Focused stakeholder attention on worker risks

  • Leveled playing field by stating EPA’s approach


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Worker Risk (continued)

  • Most chemicals showed some worker risks of concern (handler and/or re-entry)

  • Two chemicals cancelled in large part due to worker risk:

    • Mevinphos (1994)

    • Ethyl parathion (last use date 10/31/03)


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Worker Risk (continued)

Handler risks addressed in several ways:

  • Closed mixing loading systems applied to many chemicals/scenarios

  • Closed cabs with various levels of respiratory protection applied to many chemicals/scenarios

  • Maximum PPE used in some cases where closed systems not feasible


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Worker Risk (continued)

  • Most hand held application methods eliminated

  • Certain formulation types (e.g. dusts) eliminated or restricted

  • Reductions in amount handled

    • Reduced rates/frequency of application

    • Some restrictions on amounts used when mixer/loader/applicator is same person

    • Some restrictions on aerial applications


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Worker Risk (continued)

Re-entry risks addressed in several ways:

  • Tailored to specific problem

  • Significant input from stakeholders

  • Creative solutions in toughest cases (high risks, high benefits), collecting bio-monitoring and will reexamine risks


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Achievements in Risk Reduction- Ecological Risk -

Many risk management actions described above also address ecological risks

  • Chlorpyrifos and diazinon mitigation

  • Azinphos methyl: eliminated use on sugarcane and cotton in large part due to aquatic concerns

  • Decreased rates/application frequency; limited area covered (e.g. on golf courses, change from broadcast to spot treatments)


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Ecological Risks (continued)

Other risk mitigation methods utilized:

  • Watering in/incorporation of granules

  • Altered timing of applications to reduce exposure to wildlife at most vulnerable times (e.g. nesting)

  • Developed new disposal methods for cattle dip vats (coumaphos)

  • Buffer zones (for spray drift)

  • Addressed special risk concerns (e.g. honey bees)

  • Addressed special habitat concerns (fenthion)

  • Improved labeling (e.g. emphasize best management practices)


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Summary

  • Major accomplishment in which many people played an important role

  • Better results when people work together

  • Establishment of an effective public participation process ensures the continuation of a productive working relationship


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Science Assessment

Staff from the Health Effects Division and Environmental Fate and Effects Division


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General Overview and Introduction

Randolph Perfetti, Ph.D

Associate Director,

Health Effects


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Roadmap

  • Background

  • Activities Since the Preliminary Assessment

  • Major Revisions in This Assessment

  • Highlights of Sensitivity Analyses


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Background

  • FQPA 1996 requirements

  • Methods development

  • SAP reviews and public comments, technical briefings

  • Development of Preliminary Assessment

  • Revised Assessment


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What is this Cumulative Assessment

  • Multiple chemicals with common mechanism of toxicity

  • Multiple routes of exposure

  • Multiple pathways of exposure


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Roadmap

  • Background

  • Activities Since the Preliminary Assessment

  • Major Revisions in This Assessment

  • Highlights of Sensitivity Analyses


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Activities Since Preliminary Assessment

  • Addressed the FQPA Safety Factor

  • Incorporation of new food processing factors

  • Sensitivity analyses

  • SAP review

  • Public comments and technical briefing


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Roadmap

  • Background

  • Activities Since the Preliminary Assessment

  • Major Revisions in This Assessment

  • Highlights of Sensitivity Analyses


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Major Differences

  • Hazard/ Dose Response

    • Relative Potency Factors

    • FQPA Factors

  • Food Exposure

    • New processing factors

    • Over- tolerance residues

    • Time frames

    • Populations Considered


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Major Differences

  • Water

    • Number of regions

    • Populations considered in Region A

  • Residential

    • Number of regions

    • Distributions used

    • Populations considered in Region A

    • Pet uses


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Major Differences

  • Regional

    • Preliminary OP CRA – 13 regions

    • Revised OP CRA – 7 regions

    • 7 regions effectively describes geographical/climatological differences





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Risk Characterization

  • Summarizes and integrates all of the information from the various components of the assessment.

  • Looks at:

    • Strengths and weaknesses of the data used including any potential biases in input parameters and the direction of that bias,

    • Reliability and availability of the data, as well as the characteristics of the exposure models, and attempts to bound that uncertainty.

  • The revised assessment discusses in great detail what data have been used; how the data have been used; and the strengths and weaknesses of the resulting analysis.


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Roadmap

  • Background

  • Activities Since the Preliminary Assessment

  • Major Revisions in This Assessment

  • Highlights of Sensitivity Analyses


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Sensitivity Analysis: Definition

Sensitivity analysis is used to increase the confidence in the model and its predictions by providing an understanding of how the model response variables respond to changes in the inputs.


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Highlights of Sensitivity Analyses

  • Food

    • Analysis of consumption and residue extremes

    • Imported crops

    • ½ LOD

    • Translation of residue data

    • Market Basket Survey


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Highlights of Sensitivity Analyses

  • Drinking Water

    • Additional comparisons of monitoring data vs. estimated concentration

    • Water treatment effects/ conversion to active metabolites

    • Typical and maximum application rates

    • Impact of estimated spray drift loading


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Highlights of Sensitivity Analyses

  • Residential

    • Log normal vs. uniform distributions

    • QA/QC of Regional Analyses


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David Miller

Public Health Service

Anna Lowit, Ph.D. Toxicologist

Vicki Dellarco, Ph.D. Senior Science Advisor

Beth Doyle, Ph.D.

Branch Chief

Nelson Thurman

Senior Environmental Scientist

David Hrdy,

Biologist

The Science Team


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The FQPA Safety Factor Analysis

Vicki Dellarco, Ph.D.

Senior Science Advisor

Health Effects Division


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Determination of the Appropriate FQPA Safety Factor(s) in the Organophosphorus Pesticide Cumulative Risk Assessment

Evaluation of Sensitivity and Susceptibility to the Common Mechanism of Toxicity, Acetylcholinesterase Inhibition


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Topics the Organophosphorus Pesticide Cumulative Risk Assessment

  • Background

    • FQPA 10X Safety Factor Provision

    • Science Policy Papers

    • Public Comments on Guidance

  • Analysis of Sensitivity & Susceptibility

    • Key Questions

    • Available Data

    • Conclusions

  • June SAP Meeting

    • Questions


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“in the case of threshold effects…an additional tenfold margin of safety …shall be applied for infants and children …”

“the Administrator may use a different margin of safety for the pesticide chemical residue only if, on the basis of reliable data, such margin will be safe for infants and children.”

FQPA 10X Safety Factor Provision


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FQPA Provision margin of safety …shall be applied for infants and children …”

  • FQPA establishes a presumption in favor of applying an additional 10X safety factor

    • Can depart from default FQPA 10X approach when reliable evidence shows that a different safety factor is protective of infants & children


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“take into account…potential pre- and post-natal toxicity and completeness of the data with respect to exposure and toxicity to infants and children”

FQPA Provision


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Science Policy Papers toxicity and completeness of the data with respect to exposure and toxicity to infants and children”

http://www.epa.gov/oppfead1/trac/science/determ.pdf

http://www.epa.gov/oppfead1/trac/science/consid_draft.pdf


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FQPA Safety Factor Guidance toxicity and completeness of the data with respect to exposure and toxicity to infants and children”

  • Completeness of toxicity data

  • Degree of concern for pre-& postnatal toxicity

  • Completeness of exposure data

Guidance Structured Around 3 Areas of Analysis


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FQPA Safety Factor Determinations: toxicity and completeness of the data with respect to exposure and toxicity to infants and children”Cumulative Risk Assessment

  • Analysis focuses on common mechanism of toxicity & associated effects in the young

Acetylcholinesterase


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FQPA Safety Factor Determination: Cumulative Risk Assessment toxicity and completeness of the data with respect to exposure and toxicity to infants and children”

  • If uncertainty pertains to specific chemical members

    • Use uncertainty factor to adjust relative potency factor (RPF) on a chemical specific basis

  • If uncertainty generally shared by the chemical group

    • Apply uncertainty factor as group factor after determining Margin of Exposures (MOE)


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Public Comments on Guidance toxicity and completeness of the data with respect to exposure and toxicity to infants and children”

  • Public Comment Draft, February 28, 2002

    • “Consideration of the FQPA Safety Factor and Other Uncertainty Factors in Cumulative Risk Assessment of Chemicals Sharing a Common Mechanism of Toxicity;”


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Public Comments toxicity and completeness of the data with respect to exposure and toxicity to infants and children”Uncertainty/Safety Factor: OP CRA

  • 10X intraspecies factor is adequate to protect children from effects of OPs

    • 1X interspecies factor should be used because rats & humans respond similarly to effects of OPs

  • Age-related sensitivity found in rats not relevant to children

    • Direct dosing via gavage

    • Difference between human & rat development

    • Effects found at high toxic doses

Comments Supporting Removal of FQPA Factor


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Public Comments toxicity and completeness of the data with respect to exposure and toxicity to infants and children”Uncertainty/Safety Factor: OP CRA

  • Children are not at a greater risk

    • Will have adult levels of detoxification enzymes by time they are consuming fruits & vegetables

  • Should not impose uncertainty factors for the absence of data from newly required studies (DNT)

Comments Supporting Removal of FQPA Factor


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Public Comments toxicity and completeness of the data with respect to exposure and toxicity to infants and children”Uncertainty/Safety Factors: OP CRA

  • RPFs based on adult data require an FQPA safety factor of at least 10

    • DNT studies not available for many OPs

    • Some OPs have demonstrated developmental effects

    • Exposures at critical windows of neurodevelopment can lead to permanent and adverse effects

  • More distinct age groups need to be considered

Comments Supporting Retention of FQPA Factor


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Public Comments toxicity and completeness of the data with respect to exposure and toxicity to infants and children”Uncertainty/Safety Factors: OP CRA

  • Need to account for effects that could occur below those doses used to calculate RPFs & PoDs

  • Toxic degradate & metabolites need to be considered

  • All sources of exposure need to be considered (violative residues, spray drift, nonagricultural contribution to water, food purchased at farmers markets, etc)

Comments Supporting Retention of FQPA Factor


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II. Analysis of toxicity and completeness of the data with respect to exposure and toxicity to infants and children”Susceptibility & Sensitivity

Prepared jointly by Scientists from

Office of Pesticide Programs &

Office of Research & Development


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FQPA Conclusions toxicity and completeness of the data with respect to exposure and toxicity to infants and children”

  • Completeness of Toxicity Data

    • Apply database uncertainty factor to most OPs to account for potential age-dependent sensitivity in children based on biological evidence

  • Concern for Pre-& Postnatal Toxicity

    • No additional concern if potential age-dependent sensitivity is accounted for

  • Completeness of Exposure Data

    • No additional concern, based on comprehensive & data-specific exposure assessment


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What are the Potential toxicity and completeness of the data with respect to exposure and toxicity to infants and children”Toxicities in the Young?

  • Cholinergic toxicity

  • Neurodevelopmental Effects

Inhibition of AChE can potentially lead to adverse effects in the young

Acetylcholinesterase


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What is the Most Sensitive Endpoint? toxicity and completeness of the data with respect to exposure and toxicity to infants and children”

Important to address age-related sensitivity of ChE inhibition to account for potential pre- & postnatal toxicity

  • When neurodevelopmental effects are found, they do not occur at doses below those that cause ChE inhibition in young and/or dam

Acetylcholinesterase


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Focus: Age Dependent Sensitivity to Cholinesterase Inhibition

  • Will the young show cholinesterase inhibition at lower doses than adults or at the same dose will be inhibited more?

Acetylcholinesterase


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Comparative Cholinesterase Data Available for OP Pesticides in Postnatal versus Adult Rats

Acephate Azinphos-methyl Bensulide

ChlorethoxyfosChlorpyrifosChlorpyrifos-methyl

Diazinon Dichlorvos Dicrotophos

DimethoateDisulfoton Ethoprop

Fenamiphos FenthionMalathion

Methamidophos Metidathion Methyl Parathion

Mevinphos Naled Oxydemeton-methyl

Phorate Phosolone Phosmet

Phostebupirim Pirimiphos-methyl Profenofos

Terbufos Tetrachlorvinphos Tribuphos

Trichlorphon


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Age Dependent Sensitivity in Rats in Postnatal versus Adult Rats

  • Postnatal (direct dosing)

    • Some OPs caused age dependent sensitivity, but not all

  • Fetuses

    • Unknown, but less inhibition in fetus is typically seen compared to dam



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Why is Age Dependent Sensitivity Found In Rat Pups? in Postnatal versus Adult Rats

  • Biological Factor

    • Immature rats appear to be more sensitive to some OP pesticides because they lack detoxification capability via A-esterases and/or carboxylesterases


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Generic OP Metabolic Pathway in Postnatal versus Adult Rats

Oxon

OP Pesticide

Liver Activation

Detoxification

Bind to

CaEs

Detoxification

Hydroylzed by

A-Esterases

Inhibit

AChE


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Summary of Current Knowledge in Postnatal versus Adult Rats

Derived from rat studies


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FQPA Safety Factor Provision in Postnatal versus Adult Rats

  • Issues

    • Potential for age-dependent sensitivity AND

    • Incomplete data for cholinesterase activity in the young for many OP pesticides

  • Approach

    • Address FQPA provision “completeness of the toxicity data” with database uncertainty factor

    • Adjust RPF values, except for those OPs that do not show age-dependent sensitivity


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Chemical by Chemical Adjustment of RPF Values in Postnatal versus Adult Rats

  • Size of Uncertainty Factor


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Developmental Stages in Postnatal versus Adult Rats

  • Acute Dose Rat Study

    • Treatment at Postnatal Day (PND) 7 or 11 (similar to a human infant <6 months)

  • Repeated Dosing Rat Study

    • Treatment from PND 11 to 21 & measured at PND 21 (similar to a 1-2 year old)


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Developmental Stages in Postnatal versus Adult Rats

  • Highly Exposed Children’s Age Group

    • 1 & 2 yr, not infant < 1yr

  • Maturation Profile of A-Esterase

    • Rats

      • Increases from birth to reach adult levels around postnatal day 21

    • Humans

      • After birth steady increase during the first 6 months to about 12 to 15 months of age


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Developmental Stages in Postnatal versus Adult Rats

  • Relative sensitivities found in repeated dosing studies better approximate maturation profile of highly exposed children’s age group (1-2 year olds)


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Why Use Repeated Dose Rat Study Versus Acute Study? in Postnatal versus Adult Rats

  • Exposure to an OP occurs every day via food

  • Following exposure to an OP, re-synthesis of ChE to pre-exposure levels does not occur for days (or weeks)

  • Biomonitoring studies suggest an existing body burden to OP pesticides


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Size of FQPA Safety Factor in Postnatal versus Adult Rats

  • Consideration for selecting 3X FQPA Safety Factor

    • ChE Data on 6 OP Pesticides

      • At relevant ages, sensitivities ranged from 1X (no difference) up to about 3X difference

      • Greater sensitivities (≤10X) occur only at “newborn”, low exposure stage


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Size of FQPA Safety Factor in Postnatal versus Adult Rats(continued)

  • Consideration for selecting 3X FQPA Safety Factor

    • Potential for other OPs to show age dependent sensitivity, but difference is not expected to be great between human 1 & 2 year olds & adult


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Size of FQPA Safety Factor in Postnatal versus Adult Rats(continued)

  • Consideration for selecting 3X FQPA Safety Factor

    • Some human infants will rapidly reach adult levels of blood A-esterases at 6 months, and some uncertainty around 1-2 years


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Comparative Cholinesterase Data Available for OP Pesticides in Postnatal versus Adult Rats

3X-Acephate 3X-Azinphos-methyl 3X-Bensulide

3X-Chlorethoxyfos1X-Chlorpyrifos3X-Chlorpyf-M

3X-Diazinon 3X-Dichlorvos 3X-Dicrotopho

1X-Dimethoate3X-Disulfoton 3X-Ethoprop

3X-Fenamiphos 3X-Fenthion3X-Malathion

1X-Methamidophos 3X-Metidathion3X-MethylPara

3X-Mevinphos 3X-Naled 3X-ODM

3X-Phorate 3X-Phosolone 3X-Phosmet

3X-Phostebupirim 3X-Pirimiphos-methy 3X-Profenofos

3X-Terbufos 3X-Tetrachlorvinphos 3X-Tribuphos

3X-Trichlorphon1X-Omethoate (by extension)


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Relative Potency Factors Based on Adult Rat Brain (Female) Cholinesterase Data

RPF = BMD10 OPx

BMD10 Index

(methadmidophos)


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FQPA Conclusions Cholinesterase Data

  • Completeness of Toxicity Data

    • Apply database uncertainty factor to most OPs to account for potential age-dependent sensitivity in children based on biological evidence

  • Concern for Pre-& Postnatal Toxicity

    • No additional concern if potential age-dependent sensitivity is accounted for

  • Completeness of Exposure Data

    • No additional concern, based on comprehensive & data-specific exposure assessment


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Completeness of Cholinesterase DataExposure Data

Food

Exposure

Drinking Water

Exposure

Residential

Exposure


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Completeness of the Exposure Data Cholinesterase Data

  • Several Different Age Groups

    • All pathways

      • 1-2 yr & 3-5 yr

    • Food

      • Infants < 1 yr; 1-2 yr; 3–5 yr; 6-12 yr, 13-19 yr

    • Florida Regional Residential & Drinking Water

      • Infants < 1 yr; 1-2 yr; 3–5 yr; 6-12 yr, 13-19 yr


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Completeness of the Exposure Data: Food Cholinesterase Data

  • Consumption Data (CSFII &1998 Supplemental Children’s Survey)

  • Residue Monitoring Data (USDA PDP, FDA, Market Basket Surveys)

  • Residues in Commercial Baby Food

  • Baby Formula

  • Breast Milk (qualitatively)

  • OP metabolites


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Completeness of the Exposure Data: Drinking Water Cholinesterase Data

  • PRZM-EXAMS Index Reservoir Model

  • Pesticide Use Data (USDA NASS, CDPR, USDA)

  • Regional approach (12 regions)

    • Captures more vulnerable surface watersheds

  • OP metabolites (oxon forms) qualitatively considered


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Completeness of the Exposure Data: Residential Cholinesterase Data

  • Remaining residential uses

    • Applications to home lawn & garden, pets, golf courses, of public health pests

  • All routes

  • Chemical-specific residue data

  • Activity patterns of children

  • Probabilistic techniques


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FQPA Conclusions Cholinesterase Data

  • Completeness of Toxicity Data

    • Apply database uncertainty factor to most OPs to account for potential age-dependent sensitivity in children based on biological evidence

  • Concern for Pre-& Postnatal Toxicity

    • No additional concern if potential age-dependent sensitivity is accounted for

  • Completeness of Exposure Data

    • No additional concern, based on comprehensive & data-specific exposure assessment


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Sensitivity Analysis of 3X Uncertainty Factor Cholinesterase Data

Impact on MOEs

Food Pathway ( 1-2 yr olds)

99.9 99 95

1.2X 1.3X 1.5X

[1XRPFs versus 3XRPFs for all OPs EXCEPT those that do not show age dependent sensitivity]


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June Scientific Advisory Panel Review Cholinesterase Data

  • Role of AChE in Development

  • Age-Dependent Sensitivity in Animal Studies

  • Relevance of Animal Findings to Children


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Cumulative Hazard and Dose-Response Assessment: Cholinesterase Data

Organophosphorus Pesticides

Anna Lowit, Ph.D.

Toxicologist,

Health Effects Division


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Relative Potency Factor Method Cholinesterase Data

  • Relative toxic potency of each chemical was calculated in comparison to “index chemical”

  • Exposure equivalents of index chemical are combined in the cumulative risk assessment

    • Methamidophos is the Index Chemical


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Preliminary Cumulative Risk Assessment (Dec ’01) Cholinesterase Data

  • Oral Route

    • RPFs calculated for 29 OPs

    • Exponential model used to estimate benchmark doses (BMD10s)

      • Basic Model---Low dose region of dose-response curve is linear.

      • Expanded Model—Low dose region of dose-response curve is flat


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Preliminary Cumulative Risk Assessment (Dec ’01) Cholinesterase Data

  • Dermal and Inhalation Routes: CELs

    • Comparative effect levels

      • Applicable only to the common mechanism effect

    • Dose-response modeling was not performed


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Updates and Revisions to RPFs Cholinesterase Data

  • Oral Route

    • RPFs for 4 Additional OPs:

      • chlorethoxyphos, omethoate, profenofos, and phostebupirim

    • New toxicity studies for:

      • disulfoton, fenamiphos, phosalone, tetrachlorvinphos, and tribufos

    • Updated data set of ChE data can be found at

http://www.epa.gov/pesticides/cumulative/rra-op/


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Updates and Revisions to RPFs Cholinesterase Data

  • Oral Route

    • Benchmark dose calculation errors corrected

    • Results:

      • Basic Model---16 OPs

      • Expanded Model—17 OPs


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Analysis of Power to Detect a BMD Cholinesterase Data10

  • EPA Draft Benchmark Dose Guidance (2000) indicates that the BMD should lie at the low end of the range of the responses but within assay detectability.

  • The BMD10 was selected as the effect level for the RPFs and PODs in the CRA

  • Analyzed the power to detect various degrees of rat brain ChE inhibition


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Analysis of Power to Detect a BMD Cholinesterase Data10

  • Analyzed the power to detect various degrees of rat brain ChE inhibition

    • Power of a Study:

      • Ability of a study to detect a given amount of change

      • In general, depends on the sample size and the variability of the data

    • 1%, 5%, 7.5%, 10%, 15%, and 20%


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Analysis of Power to Detect a BMD Cholinesterase Data10

  • Analyzed the power to detect various degrees of rat brain ChE inhibition

    • Power > 0.80 is the conventional goal for determining adequate power for detecting an effect

    • At 1%, 5%, 7.5%, median power is too low

      (i.e, can not consistently detect)

    • At 10%, median power is 0.89 (i.e, can consistently detect)

    • 10% brain ChE inhibition is indeed in the low end of detectability


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Sensitivity Analysis: Cholinesterase DataIndividual Data vs. Summary Data

  • RPFs and PODs in CRA are based on summary data extracted from toxicology studies

    • Mean, standard deviation, sample size

  • Issue discussed by SAP:

    • What is the impact of summary data on the BMD10 calculations?

    • Would the use of individual animal data impact the BMD10 calculations?


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Sensitivity Analysis: Cholinesterase DataIndividual Data vs. Summary Data

  • Individual animal data for 15 toxicology studies in the CRA were available.

  • Analysis showed that the use of summary data did not impact the BMD10 in CRA

    • Methamidophos:

      • BMD10 s of 0.080 mg/kg/day vs. 0.079 mg/kg/day



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Table of RPFs Cholinesterase Data


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Table of PODs Cholinesterase Data

Points of Departure for Methamidophos, the Index Chemical

Oral

0.08 mg/kg/day

Dermal

2.12 mg/kg/day

Inhalation

0.39 mg/kg/day


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Food Exposure Assessment Process Cholinesterase Data

William O. Smith, Ph.D

Health Effects Division


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Roadmap Cholinesterase Data

  • Review of Food Methods

  • Revisions Since Preliminary Assessment

  • Brief Account of Food Results

  • Some Analysis of Results


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Methods used in Food Assessment Cholinesterase Data

DEEM-FCID™ to estimate cumulative dietary exposure and for analysis of contribution of chemicals and foods to exposure.

Calendex ™ software to estimate aggregate exposures from food, water, and residential exposures over different time intervals.


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Methods used in Food Assessment Cholinesterase Data

Discussions in this sections are limited to one day assessments of food exposure using DEEM-FCID™ in order to best illustrate refinements to the analysis.

Later in this briefing the results from Calendex ™ will be discussed for multiple time frames.


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Methods used in Food Assessment Cholinesterase Data

  • Dietary Exposure Evaluation Model – DEEM-FCID™

  • Probabilistic (Monte-Carlo) procedure

  • Input:

    • Distributions for consumption & residues

  • Output:

    • Distribution of one-day dietary exposures


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Methods use in Food Assessment Cholinesterase Data

  • Input data for DEEM-FCID™ and Calendex ™

    • Food consumption

      • CSFII 1994-96/1998

    • Residues on foods

      • OP CRA Food Residue Database


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CSFII 1994-96/1998 Cholinesterase Data

Food Model-Consumption Data

  • Intakes of 20,607 individual participants interviewed over two discontinuous days

  • 1998 Supplemental Children’s Survey

  • Incorporated in DEEM-FCID™ software


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Food Model-Residue Data Cholinesterase Data

OP CRA Food Residue Database

  • Residue Data

  • Processing Factors

  • Relative Potency Factors

  • Data Translation schemes

  • Algorithms for estimating cumulative residue distributions


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Roadmap Cholinesterase Data

  • Review of Food Methods

  • Revisions Since Preliminary Assessment

  • Brief Account of Food Results

  • Some Analysis of Results


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Revisions in Food Assessment Cholinesterase Data

  • Beans, peas, peaches, pears, spinach, and parsley: All boiled food forms

  • Tomato processed food forms

Changes in Source of Residue Data

PDP-canned

PDP-fresh


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Revisions in Food Assessment Cholinesterase Data

  • Apple sauce residue data changed from PDP fresh apples to apple sauce market basket data

  • Lettuce: Removed 1994 residue data


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Revisions in Food Assessment Cholinesterase Data

Processing Factor changes made for:

17 Chemicals on ~550 Food Forms


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Revisions in Food Assessment Cholinesterase Data

  • Relative potency factors revised

  • FQPA factors incorporated via relative potency factors.

    • 1x for chlorpyrifos, dimethoate/omethoate, and methamidophos

    • 3x for all other chemicals in assessment


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Revisions in Food Assessment Cholinesterase Data

  • Chlorpyifos methyl and femamiphos removed from assessment

  • Selected chemical/crop combinations were added or removed to match currently supported uses and tolerances

  • Tolerance exceeding residues were added back to the assessment base on SAP recommendation


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Revisions in Food Assessment Cholinesterase Data

  • Section 3 Registration

  • Section 24(c) SLN Registration

  • Tolerance for import commodities only

Conditions for Inclusion

in this Assessment


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Revisions in Food Assessment Cholinesterase Data

  • Exposure was assessed over different time frames

    • 1-day

    • 7-day, 14-day and 21-day averages

  • Output distributions are being reported for more age groups (7 groups)


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Revisions in Food Assessment Cholinesterase Data

The data and documentation of changes will be available on internet

http://www.epa.gov/pesticides/cumulative/rra-op/

  • Appendices to the revised risk assessment

  • OP CRA Food Residue Database


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Roadmap Cholinesterase Data

  • Review of Food Methods

  • Revisions Since Preliminary Assessment

  • Brief Account of Food Results

  • Some Analysis of Results



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99 Cholinesterase Datath to 99.99th %tile: Food Exposure (Children 1-2)


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Roadmap Cholinesterase Data

  • Review of Food Methods

  • Revisions Since Preliminary Assessment

  • Brief Account of Food Results

  • Some Analysis of Results


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Analysis of Upper Portion of Exposure Distribution for Children 1-2

DEEM CEC

Top daily exposure records in distribution

  • Provides demographics on individuals

  • Identifies the amount of foods consumed

  • Identifies the residue level in each food


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Analysis of Upper Portion of Exposure Distribution for Children 1-2

OP CRA Food Residue Database

  • Tracks all original data contained in each residue distribution

  • Provides links between chemicals and food forms


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Analysis of Upper Portion of Exposure Distribution for Children 1-2

Food consumption Records for top 0.2

percentile of the exposure distribution

Chemical and sample specific data

contributing to residues in top

consumption records


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Most Significant Chemicals in the Top 0.2 Percentile Children 1-2

Of Exposure for Children 1-2

Chemical

Percentage of

Total

Exposure

Dimethoate/Omethoate

48 %

Azinphos methyl

27%

Acephate/methamidophos

11%

Methamidophos

5%

Phosmet

2.4%

Phorate

2.2%


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Most Significant Foods In Top 0.2 percentile Children 1-2

of Exposure for Children 1-2

Food

Food Form

Fraction of Total Exposure

Grape

Uncooked; Fresh or N/S; Cook Meth N/S

0.33

Pear

Uncooked; Fresh or N/S; Cook Meth N/S

0.16

Apple, fruit with peel

Uncooked; Fresh or N/S; Cook Meth N/S

0.13

Apple, juice

Uncooked; Fresh or N/S; Cook Meth N/S

0.10

Tomato

Uncooked; Fresh or N/S; Cook Meth N/S

0.05

Grape, raisin

Uncooked; Dried; Cook Meth N/S

0.04

Bean, snap, succulent

Cooked; Frozen; Boiled

0.03

Pepper, bell

Uncooked; Fresh or N/S; Cook Meth N/S

0.03

Bean, snap, succulent

Cooked; Canned; Boiled

0.02

All Other Commodities

 0.01


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Most Significant Consumers in the Top 0.2 Percentile of Exposure for Children 1-2

  • OPP has examined various aspects of top consumers

  • Distribution of consumption for foods that contribute to upper portion of exposure distribution

    • Overall “pattern” or distribution of consumption values

    • Magnitude of high-end consumption values

    • Predominance of high-end consumption values


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lndividuals With Highest Reported Consumption Values of the Most Significant Foods (in the top 0.2 Percentile of Exposure)


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Role of Imported Foods in Assessment Most Significant Foods (in the top 0.2 Percentile of Exposure)

  • Comparing Exposure with/without import samples contributing to residues

  • Result: With import samples, 12-18% increase in exposure at upper percentiles.


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Calendar-Based Exposure Assessment Most Significant Foods (in the top 0.2 Percentile of Exposure)

Calendex ™ was used to estimate aggregate exposures from food, water, and residential exposures over different time intervals.

These assessments and related issues will be discussed later in this briefing


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Drinking Water Exposure Assessment for Most Significant Foods (in the top 0.2 Percentile of Exposure)

the Revised OP Cumulative Risk Assessment

Nelson Thurman

Senior Environmental Scientist

Environmental Fate & Effects Division


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Road map Most Significant Foods (in the top 0.2 Percentile of Exposure)

http://www.epa.gov/pesticides/cumulative/rra-op/

  • What we did (I.E. Water OP Cumulative Risk)

    • Brief recap with focus on what’s new

  • What we found (II.A-G. Regional Assessments)

    • Some analyses of results

    • Comparison with monitoring (also Appendices III.E.1, III.E.3)

  • What it means (I.H. Risk Characterization)

    • Follow-up analyses (also Appendix III.E.11)


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EFED Most Significant Foods (in the top 0.2 Percentile of Exposure)

Kevin Costello

Ian Kennedy

Stephanie Irene

Nelson Thurman

Many more…

OP chemical teams

Monitoring reviews

Model development

Treatment effects

Follow-up analyses

HED

Steve Nako

David Miller

David Hrdy

Bernard Schneider

Yuen-Shaung Ng

BEAD

Leo Lasota

Art Grube

SRRD

Laura Parsons

Cumulative drinking water assessment team


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What we needed for the cumulative drinking water exposure Most Significant Foods (in the top 0.2 Percentile of Exposure)

  • Distribution of daily concentrations for probabilistic exposure assessment

  • Variations in time (daily, seasonally, yearly)

  • Variations in place for drinking water

  • Co-occurrence of multiple chemicals as they occur together in place and time


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What we knew from monitoring Most Significant Foods (in the top 0.2 Percentile of Exposure)

  • OPs are found in drinking water sources, often not frequently or at high levels

    • Chlorpyrifos, diazinon, malathion most frequent

    • Most detections in single parts per billion or lower

    • Multiple OPs detected together

  • Surface water sources generally more vulnerable

  • Transformations by drinking water treatment

    • Oxons, sulfoxides and sulfones


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Key components of water exposure Most Significant Foods (in the top 0.2 Percentile of Exposure)

  • Daily distribution over multiple years

  • Started at regional level (7 regions)

  • Watershed-based modeling (PRZM-EXAMS)

    • Multiple fields with multiple chemical uses

    • Adjustments for area treated

  • “Typical” usage patterns

  • Estimates compared with monitoring


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Daily distributions reflected weather variations over multiple years for multiple chemicals

Region G


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Regional approach focused on vulnerable areas multiple years for multiple chemicals

  • Where are OPs used? How much? What crops? What kinds of DW intakes? How vulnerable?

Region B

Region D

Region E

Region C

Region A

Region G

Region F


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Each regional DW location reflects … multiple years for multiple chemicals

  • Geographic area with high potential for combined (cumulative) OP exposure

    • Influenced by relative potency factors

  • Location-specific conditions

    • environmental data (soil/site, weather, crops)

    • Major crop-OP combinations within that area

  • More vulnerable drinking water sources within the region


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Each regional OP cumulative distribution reflects… multiple years for multiple chemicals

  • Amount of each OP used in the watershed

    • Typical rates x acres treated x no. applications

    • Based on current use, including risk management actions

  • Timing of each OP use

    • Application windows

  • Relative potency and safety factors


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Preliminary feedback from SAP (2/02) multiple years for multiple chemicals

  • Scientifically sound; appropriate use of models

  • Approach seems health-protective

    • Further monitoring comparisons, sensitivity analyses needed

  • Issues raised in SAP review

    • Application rates

    • Spray drift contributions

    • Treatment by-products (oxons)


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Regional cumulative OP distributions multiple years for multiple chemicals

Reg A

Regional distributions reflected

short-pulse trends, with peak

concentrations generally no greater

than single ppb and declining

rapidly to near-zero concentrations

Reg G

Reg D

Reg E

Reg F

Reg C

Reg B


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Regional water distributions (Region G) multiple years for multiple chemicals


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Cumulative drivers in each region multiple years for multiple chemicals

  • Typically 1 or 2 OPs were major drivers

  • Generally higher RPF chemicals

    • Terbufos (0.85), phorate (0.39), disulfoton (1.26), dicrotophos (1.91)

  • Tended to be OPs that formed sulfoxides, sulfones rather than oxons


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Cumulative drivers in Regions A and G multiple years for multiple chemicals

Region A

Region G


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Comparisons with monitoring data multiple years for multiple chemicals

  • NAWQA: Appendix III.E-1

    • Different water bodies, not drinking water

    • Different time periods, sample frequencies

    • In each region, estimates comparable to monitoring (within a factor of 10)

      • Some higher (>10X): reflects mobile, persistent sulfoxide/ sulfone degradates (ex., phorate, terbufos)

      • Some lower (<10X): reflects cancelled/phased-out uses (ex., diazinon, azinphos methyl)


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Comparisons with NAWQA monitoring multiple years for multiple chemicals

Chlorpyrifos in Region D


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Comparisons with monitoring data multiple years for multiple chemicals

  • USGS-EPA Reservoir Monitoring: Appendix III.E-3

    • Detections, frequencies generally less than estimated concentrations, but not by orders of magnitude

    • Many reservoirs outside high use areas

    • Small time frame; extreme weather conditions

NY Reservoir; Source: USGS


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Typical vs maximum application rates multiple years for multiple chemicals

Region G

Region A


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Spray drift contributions multiple years for multiple chemicals

Region C

Region G


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Impact of treatment by-products multiple years for multiple chemicals

  • Assessment already accounts for sulfoxide, sulfone transformation products

  • Conversion of OP parents to oxons unlikely to add significantly to the cumulative OP load

    • OP pesticides which form oxons do not contribute significantly to the cumulative “pulse”

    • Oxon-forming OP pesticides frequently detected in water (chlorpyrifos, diazinon, malathion) have low RPFs in comparison to other OP pesticides


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Treatment by-products: Oxons (Region G) multiple years for multiple chemicals

Assumes oxons 10X more toxic

chlorpyrifos, dimethoate, malathion,

methyl parathion, phostebupirim


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What do the analyses tell us? multiple years for multiple chemicals

  • Estimated distributions in each region

    • Generally comparable to monitoring

    • Represent high-exposure water sources

  • Typical application rates

    • Represent actual use

    • Using maximum rates, estimated concentrations no more than 2-4X greater than concentrations estimated using typical rates


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What do the analyses tell us? multiple years for multiple chemicals

  • Spray drift is not a factor in most regions

    • Accounts for no more than 1-2% of total OP load in 6 regions; even less of pulse loads

    • May account for majority of OP load in arid west, where runoff events are rare (to be expected)

  • Conversion to oxons is not expected to be a factor

    • Regional drivers are not oxon-forming OPs

    • Little or no effect (<2X) at 75th percentile or higher


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Residential Exposure Assessment Process multiple years for multiple chemicals

Jeff Evans

Senior Scientist

Health Effects Division


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Residential OP Assessment: Use Changes multiple years for multiple chemicals

Indoor Use: DDVP (pest strip use in closets and cupboards)

Pet Use: Tetrachlorvinphos (spray/dip/powder)

collars: only qualitatively assessed

Home Lawns: Bensulide, Trichlorfon

Golf Course: Acephate, Bensulide,Fenamiphos, Trichlorfon


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Residential OP Assessment: Use Changes multiple years for multiple chemicals

Home Garden: Acephate and Disulfoton ornamental), Malathion (ornamental and edible food)

Malathion dust formulation removed

Public Health: Fenthion, Malathion, Naled


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Age Groups multiple years for multiple chemicals

Assessment performed for the following age groups:

  • Children 1-2 years old

  • Children 3-5 years old

  • Adults 20+

    All ages assessed for Region A (as an appendix)


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Regional Changes multiple years for multiple chemicals

  • PCRA assessments conducted for 12 distinct geographical regions, reflecting climate & pest pressure differences

    • One region split into two residential assessments

  • CRA assessments conducted for 7 distinct geographical regions (combined similar regions)


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Regional Framework multiple years for multiple chemicals

Source: USDA ERS


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Number of regions reduced from 13 to 7 multiple years for multiple chemicals

Region A


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SAP Recommendations multiple years for multiple chemicals

  • Use more descriptive distributions

    • Uniform vs. lognormal

  • Utilize activity pattern information from surveys such as National Human Activity Pattern Survey (NHAPS)


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Lawn: Applicator Exposure Data multiple years for multiple chemicals

  • Application Type:

    • Granular push-type rotary spreaders

    • Hose-end sprayer: removed remaining use of trichlorfon since liquid formulations are applied by LCO’s

  • Clothing Types:

    • PCRA uniform distribution: Range of clothing

    • CRA lognormal distribution Short-sleeved shirt and short pants


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Lawn: Applicator Exposure Data multiple years for multiple chemicals

  • Granular Applicator: Dermal Exposure

    • Preliminary CRA

      • Uniform Distribution: 0.02–7.6 mg/lb ai

    • CRA

      • Lognormal Distribution:

        • Mean: 0.69

        • Std Deviation: 0.36

        • 99th Percentile: 1.93


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Lawn: Post-Application Exposure Data multiple years for multiple chemicals

  • Residue Transfer to Skin (transfer coefficient)

    • Choreographed Activities of Adults Measured Using Biological Monitoring, Vacarro 1996

      • Granular and sprayable formulation

      • Crawling, football, frisbee

    • Non-Scripted Activities of Children Measured Using Fluorescent Tracers, Black 1993

      • Mostly solitary play with toys and books.

      • Also activity such as cartwheels


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Lawn and Public Health: Post-Application multiple years for multiple chemicals

  • Adult TC: 1,930-13,200 cm2/hr

    • PCRA Uniform distribution (n=16 Vacarro)

  • Child TC: 700-6,000 cm2/hr

    • PCRA Uniform distribution: Vacarro (n=16) and Black (n=16)


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Lawn and Public Health: Post- Application multiple years for multiple chemicals

  • CRA: e.g., children

    • Used Black data for spray formulations

      • 3348-16,008 cm2/hr (AM 7265, standard deviation 4621)

      • 99th percentile: 23,769

    • Used Vacarro data for granular formulation

      • 714-4785 cm2/hr (AM 2225, standard deviation 2162)

      • 99th percentile: 10,632


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Golf Courses: Post-Application Exposure Data multiple years for multiple chemicals

  • Dermal Contact

    • PCRA: Uniform distribution: 200 to 760 cm2/hr

    • Includes walking and using a cart

    • CRA: Lognormal distribution (AM 483; Standard Deviation 185)

      • 99th percentile 1066 cm2/hr


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Garden: Applicator Exposure Data multiple years for multiple chemicals

  • Preliminary CRA:

    • shaker can (n-20):

      • uniform, 0.0034-0.356 mg/lb ai

    • small tank sprayer (n-20):

      • uniform, 7.99-354.4 mg/lb ai

  • Similar issues regarding clothing as in lawn applications


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Garden: Applicator Exposure Data multiple years for multiple chemicals

  • CRA:

    • Shaker can:

      • lognormal, AM 0.18, standard deviation 0.29

      • 99th percentile 1.31

    • Small tank sprayer:

      • lognormal, AM 78, standard deviation 76

      • 99th percentile 372


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Indoor: Inhalation Exposure Data multiple years for multiple chemicals

  • Preliminary CRA: Post-application inhalation exposure (adults and children)

    • Pest strips: 0.005-0.11 mg/m3

      • Collins et al., 1973

  • Duration of time spent indoors, and breathing rates

    • Up to 24 hours, at rest to moderate

    • Rest to moderate met value (1-2)


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Indoor: Inhalation Exposure Data multiple years for multiple chemicals

  • E = C x BMR x H x VQ x MET_TIME

  • BMR – Basal Metabolic Rate

    • Specific to CSFII individual

  • MET_TIME – met values x duration

    • PCRA: e.g., 24 hrs x met value (2) = 48


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    Indoor: Inhalation Exposure Data multiple years for multiple chemicals

    • CRA: Consolidated Human Activity Database (CHAD) hhtp://www.epa.gov/chadnet1

      • Compilation of preexisting human activity surveys collected at the national, state and city level

        • Generated random MET values for each indoor activity responses

        • Multiplied MET value by duration and generated distributions


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    CRA: MET_Time Values multiple years for multiple chemicals

    Cumulative

    Percentile

    4-6 yr olds

    18+

    90th

    41

    40

    95th

    47

    49

    99th

    59

    67


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    PETS: Applicator multiple years for multiple chemicals

    • Empirical Cumulative Distributions

      • Applicator data applying TCVP using aerosols, powders and pump sprays

      • Applying to 1 to 4 dogs*

      • Dogs weighing up to 148 pounds*

    * based on 176 dogs


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    PETS: Post-Application multiple years for multiple chemicals

    • Dermal exposure based on exposure while individuals were applying pesticides and grooming treated pets

    • Chemical/formulation specific fur residues

      • Average transfer efficiencies of 2.79%


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    PETS: Post-Application multiple years for multiple chemicals

    • Child Dermal Contact Values

      • Average 673 cm2/hr

      • Range 66 to 1660 cm2/hr

    • Duration of contact based on video tapes of children playing with pets (n=3) Freeman et al., 2001; triangular distribution

      • minimum 0.0333 hrs

      • maximum 1.025 hours

      • mode 0.11


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    + over estimate; - under estimate; ~ neutral multiple years for multiple chemicals

    Characterization

    Input Parameter

    bias

    assumptions uncertainty

    Lawn Applicator: granular

    ~

    high confidence – issues re: clothing. No impact

    Shaker can

    ~ to +

    high confidence, clothing, shrubs only. May overestimate

    Tank sprayer

    ~

    High confidence, clothing. No impact

    Dermal Contact Transfer - lawns

    - to +

    Activities appear to be representative, but distributions may be reflective of study design rather than actual activities

    Children: Spray study is based on a non-toxic substance (not a pesticide), high transfer efficiency (6%), assumed 1% for generating dermal contact values.

    Golf: dermal

    ~

    No impact

    Met_Time

    ~ to +

    May have some very high end individuals, truncation at 99th percentile did not have a significant impact.

    Frequency, contact w/ pets

    - to +

    Based on video-observations of children, small n.

    Dermal contact post appl pets lawn

    ~ to +

    Shampooing and grooming immediately after treatment. Considerable contact.

    Pet fur residues

    ~

    Direct hand measurements. Chemical and formulation specific.

    population exposed: pets

    ~ to +

    Small population of users increased based on use of collars since we did not include a collar assessment.


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    Integrating Pathway-specific Exposures in a Cumulative Risk Assessment:

    Region “A” Example

    David J. Miller

    Health Effects Division


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    Outline Assessment:

    • Background on Region “A”

    • Risk Equation

    • Key Concepts in Aggregation/Cumulation Methodology using DEEM™ /Calendex™

      • Importance of calendar-based Assessment

    • Illustrative step-by-step example of Probabilistic Aggregate/Cumulative Assessment for Food and Residential Exposures

    • Review Output/Results for Region “A” (Exposure Profile Plots)


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    Florida Region (Region A) Assessment:

    • Food (Bill Smith):

      • National estimates (applied to all regions)

      • No seasonal/geographic component

    • Drinking Water (Nelson Thurman):

      • Region-specific estimates

      • PRZM-EXAMS daily water concentrations

      • Typical application rates

      • Accounts for application timing/co-occurrence

    • Residential (Jeff Evans):

      • Region-specific estimates

      • Distributional inputs

      • Accounts for application timing


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    Florida Region, Region “A”: Pesticide/Scenario Combinations

    Table II.A.1. Pesticides and Use Sites/Scenarios Considered in Florida Residential/Non-Occupational and Drinking Water Assessment


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    Residential Scenarios: CombinationsRegion “A” Gaant Chart


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    Risk Equation Combinations

    • Risk = f(Exposure, Hazard)

      • Hazard part derived from toxicological studies

      • Exposure part derived from

        • FOOD: residues and consumption

          • Oral pathway

        • WATER: residues and consumption

          • Oral pathway

        • RESIDENTIAL: residues and contact

          • Oral pathway

          • Dermal pathway

          • Inhalation Pathway


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    Key Concepts in Cumulative Assessment Combinations

    • Important to “integrate” or combine these estimated exposures in an internally consistent manner to develop region-specific risk picture

      • Integrated (or Combined) Exposure = “Total MOE”

      • “Appropriate Matching and Combining”

    1

    • MOEtotal =

    1

    1

    1

    +

    +

    MOEdermal

    MOEoral

    MOEinhalation


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    Key Concepts in Cumulative Assessment: Combinations “Appropriate Matching and Combining”

    • Objective: to appropriately match and subsequently combine estimates of pesticide exposures through food with estimates of pesticide exposures through residential uses and estimates of exposures through drinking water


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    Key Concepts in Cumulative Assessment: CombinationsAppropriate Matching and Combining

    • Matching and combining must appropriately consider temporal and spatial factors associated with exposure

      • Temporal Factors

        • The time of year that pesticide exposures occur

          • E.g., springtime

        • Pesticide exposures on one day can be related to pesticide exposures on previous day

          • E.g. day-to-day relationships

      • Spatial Factors

        • Region of Country in which pesticide exposures occur

          • E.g., South vs. North


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    DEEM™/Calendex™ Cumulative Assessment Combinations

    • DEEM™/Calendex™ provides a probabilistic assessment in which appropriate matching occurs

      • Incorporates concept of a Calendar to evaluate aggregate exposures

      • Looks at each individual day of the year

        • Allows appropriate “temporal matching” of exposures through food, drinking water, and residential pathways.

        • Temporal aspect of exposure through residential and agricultural uses important for OP pesticides due to expected seasonal use-patterns


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    DEEM™/Calendex™ Cumulative Assessment Combinations

    • What would happen if we didn’t use calendar-based approach?

    • For example:

      • Fall dermal exposure through lawn-use could be (incorrectly) combined with dermal exposure through spring flea treatment on pets

      • Oral hand-to-mouth exposure from spring lawn application on one day could be (incorrectly) combined with drinking water concentration characteristic of the winter season


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    Key Concepts in Cumulative Assessment: CombinationsAppropriate Matching and Combining

    • In summary, must track potentially exposed persons on a daily basis in a way that preserves all appropriate linkages in a way that considers time, region, and age groups


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    Calendex™ Concepts Combinations

    • Calendex™ uses probabilistic techniques to appropriately combine exposures from the food, water, and residential pathways in a manner which incorporates:

      • Probabilities of exposure,

      • Use and application practices,

      • Human activity patterns,

      • Etc.

        and considers their associated seasonality and timing

    • Result is a collection (or distribution) of aggregated/cumulated exposures (food, residential, and drinking water combined) for each day of the year for the relevant region

      These exposures can be plotted as a “time-line” or profile of daily exposures for any given percentile in the distribution


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    Illustrative Example of Calendex™ Analysis Combinations

    • 1-day exposure is presented as an example

    • Analysis serves as “building block” for any number of days analysis

    • Only oral pathway is considered


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    Illustrative Example of Calendex™ Analysis Combinations

    • Hypothetical Consumption Profile for CSFII Individual #1

      • 12 kg child

      • Consumed: 260 g food #1

        320 g food #2

        250 g food #3

    • Period of Interest: January 1 through December 31

    • Specific to Region of Interest


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    Illustrative Example of Calendex™ Analysis Combinations

    • STEP 1: Calculate Exposure from Food for Individual #1 on January 1

      • Food Exposure(from DEEM™): = 2.89x 10-5 mg/kg bw/day

    • STEP 2: Select Water Consumption for Individual #1

      • E.g., 1560 mL

    • STEP 3: Randomly select year from multiple years of daily water values


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    Illustrative Example of Calendex™ Analysis Combinations

    • STEP 4 : Assign the Water Concentration from January 1 from that year to Individual #1

    • STEP 5: Calculate Exposure from Water by pairing water consumption value with selected water concentration value for January 1

      Water: (1560 mL x 0.00053 mg/L)/62 kg = 1.33 x 10-5 mg/kg bw/day

    • STEP 6: Aggregate with Food Exposure for January 1

      1.33 x 10-5 + 2.89 x 10-5 = 4.22 x 10-5 mg/kg bw/day


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    Illustrative Example of Calendex™ Analysis Combinations

    • STEP 7: Select Residential Treatments for Individual #1 on January 1

      • Specific to region & time and demographics of individual

      • Assigned probabilistically

        • Were pesticides applied in/around home?

        • If so, which treatments?

          • And how much, how often, during what time frame, with what frequency, and by whom?

    • STEP 8: Calculate Exposure from any assigned new residential uses for January 1


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    Illustrative Example of Calendex™ Analysis Combinations

    • STEP 9: Determine if Exposure is “Active” from any previously assigned use/application

      • by oral (hand to mouth) exposure to children (2 days earlier)

        = 1.33 x 10-5 mg/kg BW/day

    • STEP 10: Aggregate exposures for Day #1 from Food/Water, and (any active) Residential Uses

      = 2.89x 10-5 mg/kg BW/day + 1.33 x 10-5 mg/kg BW/day

      = 4.22x 10-5 mg/kg BW/day


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    Illustrative Example of Calendex™ Analysis Combinations

    • STEP 11 : Repeat Steps 1-10 many additional times for this individual, randomly selecting a series of treatment scenarios for that year, determining if any are applicable or otherwise “active” for Day #1 for that individual, and aggregating (summing) selected food/water and residential exposures

    • STEP 12: Continue steps 1-11 with Individual #2 through Individual # ~20,000

      • Result is a collection (or distribution) of aggregate exposures for January 1 for the relevant region


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    Illustrative Example of Calendex™ Analysis Combinations

    • STEP 13: Repeat steps 1-12 for January 2

      • Result is a collection (or distribution) of aggregate exposures for January 2 for the relevant region

    • STEP 14: Repeat steps 1-13 for January 3 through December 31

      • Result is a collection (or distribution) of aggregate exposures (food, water, and residential combined) for each day of the year for the relevant region

      • These exposures can be converted to MOEs and plotted as a “time-line” or profile of daily exposures for any given percentile in the distribution


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    Example of Calendex™ Analysis Combinations(time based exposure profile)

    Children 1-2

    1-day

    99.9th Percentile

    Day of the Year


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    Example of Calendex™ Analysis Combinations(time based exposure profile)

    Children 1-2

    1-day

    99th Percentile

    Day of the Year


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    Rolling Time-Frame Approach Combinations

    • In a rolling time frame approach, average exposures over multiple days are calculated for each individual

      • e.g., January 1 through 7, then January 2 through 8, January 3 through 9, etc.

      • This series of multi-day average exposures serves as basis of comparison with POD


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    Example of Calendex™ Analysis Combinations(time based exposure profile)

    Children 1-2

    7-day

    99.9th Percentile

    Day of the Year


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    Example of Calendex™ Analysis Combinations(time based exposure profile)

    Children 1-2

    7-day

    99th Percentile

    Day of the Year


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    Summary Combinations

    • Food, water, and residential exposures were considered probabilistically in the cumulative assessment

      • Reflects realistic pesticide use based on pest pressures, weather, activity patterns, etc.

      • Temporal and spatial characteristics were preserved and maintained to produce realistic assessments


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    Summary Combinations

    • Result of Assessment is a time based exposure profile of exposures at any selected percentile

      • Total Exposure

      • Various pathway specific exposures


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    Risk Characterization Combinations

    Margaret J. Stasikowski

    Director,

    Health Effects Division


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    Risk Characterization Combinations

    • Interpretation of the Assessment

    • Particularly important in a complex assessment

    • Synthesis of information about the input data

    • Synthesis of information about the processing of data

    • Interface between the risk assessment and risk management


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    Risk Characterization Combinations

    • Strengths and weaknesses of data used

    • Bias and direction of bias in input parameters

    • Uncertainty surrounding the input data

    • Uncertainty in use of models


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    Risk Characterization Combinations

    No single value in the assessment should be used to independently arrive at the interpretation of the results


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    Road Map to Risk Characterization Combinations

    • Use of Regional Assessments

    • Hazard and Dose-Response

    • Modes of Analyses and use of Calendex™

    • Food

    • Residential

    • Drinking Water

    • Conclusions


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    Use of Regional Assessments Combinations

    • Regional Assessments

      • Regional assessments integrate food, residential, and drinking water assessments into one output

        • Keep in mind, however, that food is nationally assessed

        • Residential and drinking water are regionally assessed

      • Residential and drinking water risk are not of concern

        • Except for residential pest strip use

    • Risk characterization, therefore, concentrates on hazard dose-response and exposures through food


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    Hazard and Dose-Response Combinations

    • Brain Acetylcholinesterase inhibition reflects response in a target tissue relevant to humans

      • Error due to extrapolation from a surrogate tissue eliminated

      • Data have narrow confidence limits

        • Much less variability


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    Hazard and Dose-Response Combinations

    • Relative Potency Factor approach

      • Utilizes entire dose response curve rather than less accurate NOAEL method

      • Biological or pharmacokinetic modeling would be better

        • However, input parameters not available

      • Applied simple dose addition


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    Hazard and Dose-Response Combinations

    • Exponential model used

      • Adjusted to appropriately reflect inhibition at very low doses

      • Modified to generate limiting values for each OP

      • Curve fit empirically


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    Hazard Dose-Response Combinations

    • Dose additivity

      • Additivity assumes dose-response curves are parallel

        • Underlying biological processes for each OP complex

        • Activation and/or deactivation rates differ for some OPs

        • Insufficient data to separate into subgroups

      • Uncertainty exists in assuming additivity because horizontal asymptotes are heterogeneous among the OPs


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    Hazard Dose-Response Combinations

    • Dose additivity assumption uncertainties

      • Does additivity apply to all of the OPs at human exposure levels?

      • Does additivity slightly overestimate or underestimate response because of assumption that response is uniform regardless of the underlying background exposure level?


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    Hazard Dose-Response Combinations

    • BMD10 used as a point of comparison

      • Point in the observed response range

      • Low enough to reduce impact of any lack of proportionality

      • Reliably distinguishable from background


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    Hazard Dose-Response Combinations

    • Index Chemical – Methamidophos

      • Excellent data to support modeling BMD10 for the three routes of exposure

      • BMD10 and BMDL nearly the same


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    Hazard Dose-Response Combinations

    • Use of Steady State Cholinesterase Inhibition

      • Steady state reached about day 21

      • Point at which further ChE inhibition is offset by regeneration of the enzyme and equilibrium has been achieved

      • Stable, reproducible levels of inhibition in all compartments measured

      • EPA assumes no naïve exposures to OPs

        • Consistent with the results of biomonitoring studies

      • Regeneration of ChE in days to weeks expected


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    Hazard Dose-Response Combinations

    • Uncertainties surrounding use of steady state

      • May over- or underestimate risk

      • Extent and direction of the error not known

      • Data pertaining to prior exposure to humans different from that used in rat feeding studies

    • Even with these uncertainties, EPA believes that steady state provides a reasonable endpoint for hazard dose-response

      • SAP agreed that this endpoint is appropriate


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    Use of Calendex™ and the Mode of Analysis Combinations

    • Single day analysis

      • Exposures on consecutive days at the same percentile are unlikely to be the same individual

      • Consecutive single-day estimates of exposure are likely to significantly overestimate multi-day exposures to an individual (at higher percentiles)

    • Seven day rolling average

      • Exposures more directly comparable to multi-day toxicity endpoint

      • Better incorporates variability in exposure for an individual across multiple days

      • Will not capture a single day “spike” exposure

      • Consumption and residue data not designed for linked-series of days analysis

    In both cases associated ChEI level is underestimated because lingering ChEI effect is not accounted for


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    Use of Calendex™ and the Mode of Analysis Combinations

    • 14 and 21 day averaging also possible

      • Incrementally small decreases in the estimated risk

      • With longer averaging time one approaches the mean exposure for the output distribution

        • Obscures time-related variability in exposure


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    Use of Calendex™ and the Mode of Analysis Combinations

    • Use of CSFII Data

      • Single day analysis

        • Consumption diary records for each individual paired with a randomly selected set of residue values

          • Uses each available day of consumption data

        • Arrayed as a distribution from high to low exposures

        • Assumes consumption of foods independent from day to day

        • Overemphasizes variability


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    Use of Calendex™ and the Mode of Analysis Combinations

    • Use of CSFII Data

      • Seven day rolling average

        • One diary for each individual paired with a randomly selected set of residue values

          • Randomly redraws from two available days of consumption data over time period of interest (e.g., seven days)

        • Assumption that diet of every individual is limited to the records in the diaries repeated randomly

        • Variability in the diet may not be fully expressed


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    Use of Calendex™ and the Mode of Analysis Combinations

    • Impact of residual cholinesterase inhibition

      • Inhibition not immediately reversible

      • Any day exposure includes inhibition from previous days (carry-over effect)

      • One day analysis does not incorporate this

      • Seven day captures carryover of exposure but not biological aspect of declining exposure over time

      • Seven day de-emphasizes impact of intermittent high exposure


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    Food Assessment Characterization Combinations

    • Consumption Data

      • 1994 – 96, 98 CSFII realistic estimate

      • Adequate number of samples

        • Increased accuracy and utility

      • Extremes of the distribution less well represented than those reflecting the central tendency

        • Some uncertainty at the tails

        • Consumption records in the tail of the distribution analyzed

          • No indication that any small subset of consumption records dominates the outcome of the assessment


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    Food Assessment Characterization Combinations

    • PDP Monitoring Data

      • Directly measures occurrence of more than one OP in a sample

      • Composite analysis may slightly understate potential risk

      • Samples with non-detectable residues assumed zero values

        • Sensitivity analysis showed negligible impact


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    Food Assessment Characterization Combinations

    • Data translation from PDP

      • Families of commodities with similar cultural practices and insect pests likely have similar pesticide use

      • Perhaps introduces uncertainty

      • Not many commodities translated

        • Translated commodities ~1% of child’s diet


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    Food Assessment Characterization Combinations

    • Other Sources of Residue Data

      • FDA Total Diet Study & monitoring data

        • For meats, seafood and eggs, negligible residues assumed

      • 3% of the foods for 1 – 2 year olds unaccounted for

        • Highly processed and blended

        • Negligible residues assumed

      • Do not expect any impact on the assessment


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    Food Assessment Characterization Combinations

    • Impact of Regulatory Actions

      • Existing agreements on removal of uses

        • Uses taken out of the assessment

      • Changes in use patterns not yet reflected in monitoring data

        • Increased pre-harvest intervals

        • Reduced rates of application

      • Ongoing regulatory process for some chemicals

      • All types of regulatory actions will likely result in further reduction of exposure


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    Food Assessment Characterization Combinations

    • Model Outputs

      • Single-day food assessment using DEEM

      • Seven-day rolling average using Calendex™

      • 14 and 21-day analyses included for Region A


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    Food Assessment Characterization Combinations

    • Based on experience with individual chemical assessments

      • Assumption that OP exposure in food uniform nationally

      • Assumption of no significant seasonal variations

        • Ability to store and preserve food, import of seasonal foods

        • PDP does not suggest different types and magnitude of pesticide use across the year

    • Food assessment uncertainties

      • Does not reflect highly localized consumption

      • Only small percentage of food affected


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    Food Assessment Characterization Combinations

    • Toxicity endpoints developed in consideration of 10X factor for interspecies variability and 10X factor for intraspecies variability

    • The additional FQPA Safety Factor is included as an adjustment to the chemical-specific RPFs

    • For the single day analysis for food, MOEs calculated using DEEM software rather than Calendex™



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    Food Assessment Characterization Combinations

    • MOEs from the 7-day analysis exceed 100 at all percentiles of output distribution

    • MOE for the single day assessment at the 99th percentile of output distribution is 128 for children 1-2 and 158 for children 3-5

    • MOE for the single day assessment at the 99.9th percentile of output distribution is 45 for children 1-2 and 53 for children 3-5

    • MOE reaches 100 at the 99.4th percentile of exposure for the single day analysis for children 1-2


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    Food Assessment Characterization Combinations

    • OPP believes that 99.9th percentile of exposure in the single-day assessment is an upperbound of anticipated exposure

      • Especially when considering that exposure at such a high percentile is not expected to occur often

      • Does not reflect changes in residues from recent mitigation actions

    • MOE at the 99.9th percentile of output distribution for 1-day likely overstates the risk from OPs in food


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    Food Assessment Characterization Combinations

    • EPA believes exposures in the U.S. fall somewhere between the results of the single day and seven day analysis


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    Most Significant Chemicals in the Top 0.2 Percentile Combinations

    Of Exposure for Children 1-2

    Chemical

    Percentage of

    Total

    Exposure

    Dimethoate/Omethoate

    48 %

    Azinphos methyl

    27%

    Acephate/methamidophos

    11%

    Methamidophos

    5%

    Phosmet

    2.4%

    Phorate

    2.2%


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    Most Significant Foods In Top 0.2 percentile Combinations

    of Exposure for Children 1-2

    Food

    Food Form

    Fraction of Total Exposure

    Grape

    Uncooked; Fresh or N/S; Cook Meth N/S

    0.33

    Pear

    Uncooked; Fresh or N/S; Cook Meth N/S

    0.16

    Apple, fruit with peel

    Uncooked; Fresh or N/S; Cook Meth N/S

    0.13

    Apple, juice

    Uncooked; Fresh or N/S; Cook Meth N/S

    0.10

    Tomato

    Uncooked; Fresh or N/S; Cook Meth N/S

    0.05

    Grape, raisin

    Uncooked; Dried; Cook Meth N/S

    0.04

    Bean, snap, succulent

    Cooked; Frozen; Boiled

    0.03

    Pepper, bell

    Uncooked; Fresh or N/S; Cook Meth N/S

    0.03

    Bean, snap, succulent

    Cooked; Canned; Boiled

    0.02

    All Other Commodities

     0.01


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    Food Assessment Characterization Combinations

    • Individual assessments for some of these chemicals still need to be completed

    • All information in risk characterization including sensitivity analyses need to be taken into account


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    Residential Assessment Characterization Combinations

    • Conducted for seven regions

    • Distributional analysis

      • Log normal

    • Factored in seasonal aspects of pesticide use


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    Residential Assessment Characterization Combinations

    • Exposure Contact and Pesticide Residue Dissipation

      • Robust information, OPP has high confidence in the use of these data

    • Specific pesticide use data available and used in distributional analysis

    • Calendex™ inputs adjusted to reflect regional use patterns

    • Non-dietary ingestion assessed

      • Children mouthing behavior (hand-to-mouth)

      • Limited data available describing mouthing behavior

      • EPA believes frequency of hand-to-mouth estimates used in current assessment may overstate risk


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    Residential Assessment Characterization Combinations

    • Results

      • Use of DDVP in No-Pest strips major contributor to exposure

        • Only remaining indoor use of OPs

        • Removal of DDVP from assessment in sensitivity analysis resulted in MOEs approximately the same as for food alone

      • Hand-to-mouth activities by children in conjunction with lawn exposure in southern regions is important

        • Uncertainty regarding the estimate of exposure likely to overestimate


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    Drinking Water Characterization Combinations

    • Represents one of most vulnerable drinking water sources in each region

      • Surface water source (reservoir)

      • High OP use in vicinity of water body vulnerable to pesticide contamination

      • Protective of region

    • Daily distributions estimated using PRZM/EXAMS Index Reservoir

      • Comparisons with monitoring indicate estimates are reasonable


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    Drinking Water Characterization Combinations

    • Represent typical OP uses based on actual use surveys

      • If all OP pesticides were used at maximum rate, distributions may increase by no more than a factor of 2-4X

      • Low likelihood that all OP pesticides would be used at maximum rates in same year

    • Distributions represent variations in expected concentrations due to year-to-year weather variations


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    Drinking Water Characterization Combinations

    • Results

      • OPs in drinking water are not major source of cumulative exposure in most regions

      • In two regions (A, G), drinking water exposure approached food exposure levels on brief periods

        • In A, refined concentrations lower because of sugarcane water management

        • In A and G, regional exposure represent high-end sites that don’t reflect what majority of population drinks


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    Drinking Water Characterization Combinations

    • Drinking water treatment effects

      • Not enough information for quantitative evaluation

      • Evidence suggests transformation to oxons, sulfones, sulfoxides

      • Assessment already accounts for sulfones, sulfoxides

      • “Worst-case” evaluation for oxons (100% conversion, 10X increase in toxicity) found no impact on cumulative exposure from water


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    Risk Characterization Conclusions Combinations

    • OPP advanced risk assessment methods as it developed OP cumulative assessment

      • State of the art

    • Extensive peer review of methods and assessment

    • Assumptions in many parts of the assessment were replaced with data


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    Risk Characterization Conclusions Combinations

    • Refined picture of exposure likely to be encountered in the real world

    • Uses distributions of data wherever possible

      • Permits use of the full range of values for each parameter

    • Results as a range of MOEs using one-day and seven-day rolling averages at different percentiles of exposure distribution


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    Risk Characterization Conclusions Combinations

    • EPA believes real world exposure lies somewhere between the one-day and seven-day rolling average

    • Continued analysis of exposures that are significant at the lower end of the MOE range

    • Important not to focus on a single number


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    Risk Characterization Conclusions Combinations

    • Individual OP assessments and mitigation actions need to be finalized

    • Few uses of OPs on food crops play a larger role in the results of the food assessment


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    Risk Characterization Conclusions Combinations

    • Residential risk assessment

      • OP exposure no longer plays a significant role in the cumulative risk from OPs

      • DDVP pest strip major contributor to the cumulative risk assessment

      • Single chemical risk mitigation underway

    • Drinking water assessment

      • OP exposure does not play a significant role in the cumulative risk


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    Summary and Conclusions Combinations

    Lois Rossi, Director


    Outline of discussion l.jpg
    Outline of Discussion Combinations

    • Background Information

    • Status of Individual Chemical Risk Mitigation

    • Summary of Important Risk Concerns

    • Risk Characterization

      • Risk Management Point of View

    • Next Steps


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    Introduction Combinations

    • Continuing to follow course laid out for the Cumulative Assessment over the last five years

    • Sharing current state of our knowledge to the fullest extent possible

    • Inviting public comment and scientific peer review on remaining risk assessment and science policy issues

    • Prepared extensive risk characterizations


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    Background Information Combinations

    • It appears that exposure from water is not a significant contributor to the OP cumulative risk estimates

    • The only residential use that plays an important role in the risk estimate is the indoor use of DDVP (pest strips)

      • Individual chemical risk management for DDVP has not been completed

      • Currently working with registrants on mitigation

      • EPA is committed to addressing this risk and is hoping to quickly resolve this concern


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    Background Information (Cont.) Combinations

    • Individual chemical risk mitigation for dietary risks has been addressed for all OPs except:

      • Dimethoate/omethoate

      • Malathion

      • DDVP

      • ODM

      • Tetrachlorvinphos

    • Although IREDs have not yet been completed for diazinon and methyl parathion, dietary risks have been addressed in previous mitigation action


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    Key Risk Estimate Elements Combinations

    • Relatively few chemical/crop combinations play a major role in the OP cumulative risk assessment

    • Not meant to imply that risks are such that exposure from any one chemical/crop combination must be addressed or that all of them must be addressed


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    Risk Management Considerations Combinations

    • Integrate all of the information from the various components of the assessment

    • Look at:

      • Strengths and weaknesses of data

      • Potential biases in input parameters and the direction of that bias

      • Uncertainties in the data and exposure models, and try to bound that uncertainty

    • One way to examine uncertainties in data or models is to develop estimates based on other sources of data or other models


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    Summary Combinations

    • Appears that a major factor influencing the results is that a few individual OP risk assessments have not been finalized and resulting risk management actions have not been taken

    • This is particularly true for DDVP and Dimethoate


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    Comments on Revised Assessment Combinations

    • Revised assessment has been released for public comment

    • Assessment relies on extensive set of rich databases and many newly developed methods and model(s)

    • Agency hopes that this discussion of considerations in charactizing the OP cumulative risk will help focus comments

    • It is important to focus on these elements and considerations that really affect the results and are critical to making a regulatory determination


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    Next Steps Combinations

    • CARAT workgroup meeting (June 19)

    • Transition workgroup meeting (June 20)

    • Consultation with SAP (June 25-26) on science issues related to application of FQPA safety factor in the OP cumulative assessment

    • 30 day public comment period

    • Complete remaining individual chemical risk mitigation


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