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Reader’s Guide to the Preliminary Human Health Risk Assessment for Chlorpyrifos

Docket # EPA

- HQ

- OPP

- 2008

- 0850

Publication Date : July 1, 2011

Purpose of This Reader ’s Guide :

The purpose of this note to reader is to highlight what the Agency believes are the key areas of uncertainty and continuing evaluation in its human health assessment of chlorpyrifos.

Health Effects Associated with Chlorpyrifos

Chl orpyrifos is an organophosphate (OP) insecticide that binds to and phosphorylates the

enzyme, acet y l cholinesterase ( AChE ) , in both the central (brain) and peripheral nervous systems leading to accumulation of acetylcholine and, ultimately, to clinical signs of toxicity at sufficiently high doses

. In 2000, the Agency concluded for chlorpyrifos that

i nhibition of AChE was the most sensitive effect in all of the animal species evaluated (rats, mice, rabbits , and dogs) and in humans, regardless of exposure duration. The Agency is maintaining at this time, based on available data, that AChE inhibition

, p articularly in blood, still provides the most sensitive dose

- response data for the chlorpyrifos human health risk assessment.

There is , however, a growing body of literature with laboratory animals (rats and mice) indicating that gestational and/or early postnatal exposure to chlorpyrifos may cause persistent behavioral effects into adulthood. The results of both in vivo and in vitro

studies on chlorpyrifos have led some research groups to propose that changes in brain neurochemistry may underlie behavior al changes into adulthood . Although there are several biologically plausible hypotheses for these changes, a mode of action, including key events, temporal a nd dose

- response concordance , has not yet been described.

In addition, there are three prospectiv e epidemiology cohort studies evaluating pre

- and
post

- natal pesticide

, chlorpyrifos or OP

, exposure in mother

- infant pairs that have reported associations with birth outcomes, childhood neurobehavioral and neurodevelopment outcomes in neonates, infants, and young children. The Agency has not yet performed a comprehensive weight of evidence analysis on these studies , but based on preliminary reviews, there appears to be consiste ncy across th r e e studies in reported behavioral delays in cognitive achievement, motor control, social behavior, and intelligence measures

. The Agency has not completed its integrated analysis of the epidemiologic studies with experimental toxicology stud ies. Thus

, definitive c onclusions regarding to what extent the reported neurodevelopmental effects in the epidemiologic

studies can be attributed to chlorpyrifos exposure are not presented in the preliminary risk

assessment

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Key considerations As You R e view the Prelim inary Risk A ssessment :

Human Health Risk Assessment :

Previously published results from the three epidemiology studies were reviewed and discussed by the FIFRA Scie ntific Advisory Pane l (SAP) in 2008 1 . A t th at time, the SAP concluded the se epidemiological studies have utility for risk

assessment but only in a qualitative manner, and not as the principal basis for quantitative risk assessment. Recently, study results from the same three cohort studies were published for 7 year olds. The Agency is evaluat ing the current epidemiology database with experimental laboratory animal data using the draft framework reviewed by the

SAP in 2010 2

. Th e Agency plans to conduct a full weight of evidence evaluation integrating the epidemiology studies with the experimental toxicology studies for the neurodevelopmental outcomes using the Draft Framework for Incorporating Epidemiologic and Human Incidence Data in Human Health Risk Assessment 3

. Such a weight of evidence analysis requires explicit consideration of such criteria as strength, consistency, specificity, dose response, temporal concordance and biological plausibility

. Due to the preliminary nature of this assessment, the Agency is providing

assessments reflecting both the retention of the 10X FQPA Safety Factor as presented in the previous June 2000 assessment, and a proposal to reduce the FQPA Safety Factor to 1X based on recently submitted data. The Agency will

continue to reevaluat e the existing dat a to determine whether a reduction of the FQPA Safety Factor is appropriate in the final risk assessment.

Drinking W ater Assessment

Estimated concentrations of chlorpyrifos in source water are based on modeling. Currently available monitoring data is judged to be insufficient to capture peak, daily water concentrations and do not represent high use areas of chlorpyrifos. As the Agency moves forward to finalize the risk assessment, the Agency will further characterize estimated chlorpyrifos concentratio ns in source water by considering more typical use rates and agronomic practices for all chlorpyrifos

uses. Laboratory

- scale experiments indicate rapid conversion of chlorpyrifos to chlorpyrifos oxon (more toxic metabolite) during chlorination ; therefore quantitative (100%) conversion of chlorpyrifos to chlorpyrifos oxon is assumed in drinking water utilities. Because chlorpyrifos oxon is more toxic than

1 http://www.epa.gov/scipoly/sap/meetings/2008/091608_mtg.htm

2 http://www.epa.gov/scipoly/sap/meetings/2010/020210meeting.html

3 http://www.regulations .gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2009

- 0851

- 0004Page 3 of 4 chlorpyrifos

, this preliminary assessment considers the oxon metabolite as the

residue of concern in t reated drinking water.

The i mpact of alternative drinking water treatment processes on ch lorpyrifos and chlorpyrifos oxon concentrations in finished drinking water is an area of uncertainty . In the final assessment the Agency will attempt to further characterize the effect of treatment processes on estimated chlorpyrifos oxon concentrations in finished drinking water. The Agency is asking for any pertinent data and information that could inform or possibly revise existing monitoring data , model input data or the assumption that chlorpyrifos is completely oxidized to the oxon metabolite during drinking water

treatment and distribution to end users

.

Residential Bystander Post

- application Inhalation Exposure

Recently, the Agency has begun to explore the development of an approach for assessing inhalation exposure resulting from the field volatilization of conventional pesticides based on recommendation s provided by the SAP in

December 2009 4

. In the preliminary risk assessment, t he Agency has assessed res idential bystander

exposure from field volatilization of applied chlo rpyrifos based on available ambient and application site air monito ring data; applicati on site studies were conducted in California and Washington. The limitations and assumptions have be en highlighted in the assessment and the Agency seeks public comment on those assumptions. In addition, the Agency

will continue to evaluate the 2009 SAP comme nts and where appropriate, the Agency will revise the approach, which may warrant a reanalysis o f the preliminary residential bystander exposure and risk assessment for chlorpyrifos

.

Current Status and Next Steps

This preliminary human health risk assessment on c hlorpyrifos is being presented for public comment for a period of 60

- days to seek input on the above issues

. EPA is asking for any pertinent data and information that will inform or possibly

revise the preliminary human health risk assessment. After the comment period , the Agency plans to fully analyz e and integrate all the

available scientific data and considerations of pub l ic comments to ensure a scientifically sound, technically robust, human health risk assessment for chlorpyrifos.

How to Submit Comments

Comments on risk mitigation options for c hlorpyrifos must be submitted to EPA

no later than September 5, 2011 . Submit your comments, identified by docket number

EPA

- HQ

- OPP

- 200 8

- 0850 , by one of the following methods.

4 http://www.epa.gov/scipoly/sap/meetings/2009/december/120309meetingminutes.pdfPage 4 of 4 Federal eRulemaking Portal, http://www.regulations.gov : Follow the on

- line instructions for submitting comments . Alternatively, paste this address into your

browser: http://www.regulations.gov/#!docketDeta il;D=EPA

- HQ

- OPP

- 2008

- 0 850

Mail: Office of Pesticide Programs (OPP), Regulatory Public Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania Avenue, NW, Washington,

DC 20460

- 0001.

Delivery: OPP Regulatory Public Docket (7502P), Environmental Protection Agency, Room S

- 4400, One Potom ac Yard (South Building), 2777 S. Crystal Drive, Arlington, VA. Deliveries are accepted only during the Docket’s normal hours of operation (8:30 a.m. to 4:00 p.m., Monday through Friday, excluding legal holidays). Special arrangements should be made for deliveries of boxed information. The Docket telephone number is 703

- 305

- 5805.

Contact

For additional inf

ormation about EPA’s Preliminary Human Health Risk

Assessment for Chlorpyrifos , please contact:

Mr. Tom Myers

Pesticide Re

- evaluation Division (75 08P) Office of Pesticide Programs Environmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460

- 0001 Telephone number: 703

- 308

- 8589

F ax number : 703

- 308

- 7070

E mail address : myers.tom@epa.gov