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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

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

enzyme, acetylcholinesterase (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 

inhibition 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, 

particularly 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 behavioral changes into adulthood. Although there are 

several biologically plausible hypotheses for these changes, a mode of action, including 

key events, temporal and dose-response concordance, has not yet been described.

In addition, there are three prospective 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 consistency across three 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 studies. Thus, definitive conclusions 

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 Review the Preliminary Risk Assessment:

Human Health Risk Assessment:

Previously published results from the three epidemiology studies were reviewed 

and discussed by the FIFRA Scientific Advisory Panel (SAP) in 20081. At that

time, the SAP concluded these 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 evaluating the current epidemiology database with 

experimental laboratory animal data using the draft framework reviewed by the 

SAP in 20102.

The 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 Assessment3. 

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 reevaluate the existing data to determine whether a reduction of the 

FQPA Safety Factor is appropriate in the final risk assessment.

Drinking Water 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 concentrations 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-2009-0851-0004
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chlorpyrifos, this preliminary assessment considers the oxon metabolite as the 

residue of concern in treated drinking water.

The impact of alternative drinking water treatment processes on chlorpyrifos 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 recommendations provided by the SAP in 

December 20094.

In the preliminary risk assessment, the Agency has assessed residential bystander 

exposure from field volatilization of applied chlorpyrifos based on available 

ambient and application site air monitoring data; application site studies were

conducted in California and Washington.

The limitations and assumptions have been highlighted in the assessment and the 

Agency seeks public comment on those assumptions. In addition, the Agency 

will continue to evaluate the 2009 SAP comments and where appropriate, the 

Agency will revise the approach, which may warrant a reanalysis of the

preliminary residential bystander exposure and risk assessment for chlorpyrifos.

Current Status and Next Steps

This preliminary human health risk assessment on chlorpyrifos 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 analyze and integrate all the 

available scientific data and considerations of public comments to ensure a 

scientifically sound, technically robust, human health risk assessment for 

chlorpyrifos. 

How to Submit Comments

Comments on risk mitigation options for chlorpyrifos must be submitted to EPA 

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

EPA-HQ-OPP-2008-0850, by one of the following methods. 

 

4

http://www.epa.gov/scipoly/sap/meetings/2009/december/120309meetingminutes.pdf
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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/#!docketDetail;D=EPA-HQ-OPP-2008-0850

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 Potomac 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 information about EPA’s Preliminary Human Health Risk 

Assessment for Chlorpyrifos, please contact:

Mr. Tom Myers

Pesticide Re-evaluation Division (7508P)

Office of Pesticide Programs

Environmental Protection Agency

1200 Pennsylvania Ave., NW

Washington, DC 20460-0001

Telephone number: 703-308-8589

Fax number: 703-308-7070

Email address: myers.tom@epa.gov