Docket Number: EPA-HQ-OPP-2010-0119 

www.regulations.gov

Chlorpyrifos-methyl Final Work Plan 

Registration Review 

July 2010 

CHLORPYRIFOS-METHYL FINAL WORK PLAN 

Introduction: 

This is the Environmental Protection Agency’s (EPA’s) Final Work Plan for the 

registration review of chlorpyifos-methyl. This work plan includes the expected 

registration review timeline. The work plan also addresses public comments received 

concerning the Preliminary Work Plan in the Summary Document, which was posted in 

the chlorpyrifos-methyl registration review docket (EPA-HQ-OPP-2010-0119), and any 

other comments concerning the initial docket postings. The Summary Document

provided information on what EPA knows about the pesticide and what additional risk 

analyses and data or information the Agency believes are needed to make a registration 

review decision. 

The Agency is implementing the registration review program pursuant to Section 3(g) of 

the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each 

registered pesticide every 15 years to determine whether it continues to meet the FIFRA 

standard for registration. Changes in science, public policy, and pesticide use practices 

will occur over time. The registration review program is intended to make sure that, as 

the ability to assess risk evolves and as policies and practices change, all registered 

pesticides continue to meet the statutory standard. The public phase of registration 

review begins when the initial docket is opened for each case. Information on this 

program is provided at: http://www.epa.gov/oppsrrd1/registration_review/. 

Chlorpyrifos-methyl (Case 8011) is an organophosphate (OP) insecticide registered for 

use to control a variety of insects including beetles, weevils, moths, and grain borers. 

Like other OP insecticides, chlorpyrifos-methyl acts through inhibition of 

acetylcholinesterase. Chlorpyrifos-methyl was first registered in 1985 for use on stored 

grain, such as wheat, barley, oats, rice, and sorghum. There are two chlorpyrifos-methyl 

products currently registered: a technical-grade product, and an end-use product. 

Chlorpyrifos-methyl is only registered for use as an indoor treatment for small grains in 

storage bins and warehouses. A Tolerance Reassessment and Risk Management 

Eligibility Decision document (TRED) was issued for chlorpyrifos-methyl in January 

2001; the TRED was finalized with the OP cumulative in 2006. 

Comments Received on Preliminary Work Plan: 

Multiple comments were received during the 60-day public comment period on the 

Preliminary Work Plan. These comments are summarized in this document and changes 

to the work plan set out in the Preliminary Work Plan are explained. In the Preliminary 

Work Plan, EPA also solicited comments on three specific topics: environmental justice, 

water body impairment, and trade irritants. No comments or information were received 

during the comment period concerning these issues. 

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Anticipated Risk Assessment and Data Needs:

The Agency anticipates that no quantitative ecological risk assessment, 

quantitative endangered species assessment, or drinking water assessment will be needed 

for chlorpyrifos-methyl because all registered uses are indoor uses only. Chlorpyrifosmethyl is applied by manual and automatic sprayer in self-contained units with little 

potential for offsite transport. The application method does not allow for drift to 

terrestrial areas or to water bodies. The application is not intended for moist areas and 

does not contain amounts of active ingredient sufficient for runoff to be a concern. In 

addition, the use pattern is unlikely to result in exposure to aquatic resources or 

groundwater and thus drinking water is unlikely to be impacted by this use. 

The Agency anticipates conducting human health risk assessments for chlorpyrifosmethyl. Below is a summary of the issues relevant to the registration review of 

chlorpyrifos-methyl. 

Human Health Risk: 

• A comprehensive human health risk assessment was conducted in April 2000 to 

support the 2001 Tolerance Reassessment and Risk Management Decision 

(TRED). 

• The TRED did not include a residential or drinking water risk assessment. There 

are no registered uses of chlorpyrifos-methyl that result in residential exposure or 

exposure from drinking water. Exposure to chlorpyrifos-methyl may occur via 

food, and occupational activities may result in dermal and inhalation exposures. 

• During the reregistration of chlorpyrifos, the Agency determined that the 

metabolite TCP, common to both chlorpyrifos and chlorpyfios-methyl, is no 

longer considered to be of toxicological concern, and recommended the removal 

of TCP from the tolerance expression of chlorpyrifos-methyl. Tolerances for 

resides in/on plant and animal commodities should be changed to be expressed in 

terms of parent chlorpyrifos-methyl only (40 CFR 180.419). 

• During registration review, the chlorpyrifos-methyl tolerance expression (40 CFR 

180.419) will be reviewed to ensure that it appropriately covers the metabolites 

and degradates of chlorpyrifos-methyl and that it specifies the residues to be 

measured for each commodity. 

• Because of the use pattern for chlorpyrifos-methyl (on stored grains and inside 

grain storage facilities), residues in water are not anticipated. Therefore, a 

drinking water exposure analysis was not conducted and will not be required 

under registration review. If acute and chronic points of departure are revised, the 

Agency will conduct a food-only dietary assessment under registration review.

• The Agency anticipates updated occupational handler and occupational postapplication risk assessments will be needed for chlorpyrifos-methyl. The 

concentration of active ingredient has changed in the single remaining 

chlorpyrifos-methyl end-use product.

• The database is complete with the exception of the following studies, which the 

Agency anticipates requiring in order to conduct a complete human health 

assessment: 

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○ 870 Series acute toxicity studies (acute oral, acute dermal, acute 

inhalation, primary eye irritation, primary skin irritation). The 

dermal sensitization study will not be required.

○ 870.3250 Subchronic inhalation study

○ 870.7800 Immunotoxicity (rats)

○ Non-guideline study: Comparative cholinesterase assay (CCA): 

required for organophosphates including chlorpyrifos-methyl. 

○ 860.1500 Magnitude of the residue data were identified as 

outstanding in the 2000 TRED for aspirated grain fractions. Those 

data will be required in registration review.

• The recent cumulative risk assessment for the organophosphates includes a 

comprehensive assessment of OP exposure and no risks of concern were 

identified for chlorpyrifos-methyl. Should the Agency determine that new 

information on chlorpyrifos-methyl is available which could potentially impact 

the cumulative risk assessment and result in a risk of concern, the Agency will 

revisit the cumulative risk assessment. 

• Please refer to Chlorpyrifos Methyl. Human Health Assessment Scoping 

Document in Support of Registration Review, dated January 12, 2010, located in 

the chlorpyrifos-methyl docket, for a detailed discussion of the anticipated human 

health risk assessment needs. 

Other Data Needs: 

• OPPTS GLN 830.7050 UV/Visible Light Absorption – this study is a new data 

requirement under 40 CFR part 158 (Product Chemistry Data Requirements) for 

registration of a pesticide (food and non-food uses). The Agency anticipates 

requiring this study to obtain basic information about the compound’s 

identity/composition and the wavelengths at which the compound may be 

susceptible to photochemical degradation. 

Endocrine Disruptor Screening Program

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the 

Administrator may designate.” The EDSP employs a two-tiered approach to making the 

statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to 

identify the potential of a chemical substance to interact with the estrogen, androgen, or 

thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and 

are found to have the potential to interact with E, A, or T hormonal systems will proceed 

to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests 

are necessary based on the available data. Tier 2 testing is designed to identify any 

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adverse endocrine related effects caused by the substance, and establish a quantitative 

relationship between the dose and the E, A, or T effect. 

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the 

first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert 

ingredients. This list of chemicals was selected based on the potential for human 

exposure through pathways such as food and water, residential activity, and certain postapplication agricultural scenarios. This list should not be construed as a list of known or 

likely endocrine disruptors. 

Chlorpyrifos-methyl is not among the group of 58 pesticide active ingredients on the 

initial list to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must 

screen all pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP 

orders/data call-ins for all Registration Review cases, including those for which EPA has 

already opened a Registration Review docket for a pesticide active ingredient. 

For further information on the status of the EDSP, the policies and procedures, the list of 

67 chemicals, the test guidelines and the Tier 1 screening battery, please visit our 

website: http://www.epa.gov/endo/. 

Timeline: 

EPA has created the following estimated timeline for completion of the registration 

review for chlorpyrifos-methyl. 

Registration Review for Chlorpyrifos-methyl – Projected Registration Review 

Timeline 

Activities Estimated Date 

Opening the Docket 

Open Docket and Public Comment Period March 2010 

Close Public Comment June 2010 

Case Development 

Issue Final Work Plan (FWP) August 2010 

Issue Data Call-in (DCI) April – June 2011

Data Submission April – June 2013 

Open Public Comment Period for Preliminary Risk 

Assessments October – December 2014 

Close Public Comment Period January – March 2015 

Registration Review Decision 

Open Public Comment Period for Proposed Registration 

Review Decision April – June 2015 

Close Public Comment Period July – September 2015 

Final Registration Review Decision & Begin PostDecision Follow-up 2016 

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Registration Review for Chlorpyrifos-methyl – Projected Registration Review 

Timeline 

Activities Estimated Date 

Total (years) 6 

Summary of Comments and Agency Responses: 

The chlorpyrifos-methyl registration review docket was open for a 60-day comment 

period beginning on March 31, 2010. During the comment period, multiple comments 

were received, which are summarized below. None of the comments received prompted 

a change in the work plan. This document makes final the work plan for the 

chlorpyrifos-methyl registration review process. 

Comments from Dow AgroSciences [EPA-HQ-OPP-2010-0119-0012] 

Comment 1: Dow AgroSciences (DAS) commented that the 1999 and 2002 NASS data 

supporting the chlorpyrifos-methyl preliminary work plan is out of date in light of the 

2004 and 2007 cancellations of chlorpyrifos-methyl sole active ingredient end-use 

products, and the 2004 registration of a chlorpyrifos-methyl/deltamethrin combination 

product. Currently, the only remaining chlorpyrifos-methyl end-use product registered is 

for Storcide II, a combination product of chlorpyrifos-methyl and deltamethrin registered 

during 2004 and with maximum chlorpyrifos-methyl application rate of 3 mg ai/kg on 

grain. Additionally, chlorpyrifos-methyl is only registered in the U.S. for post-harvest 

use on barley, oats, rice, sorghum, and wheat, and there are no uses or tolerances of 

chlorpyrifos-methyl on corn. 

Response 1: The Agency thanks DAS for their comment, which may be considered in 

future chlorpyrifos-methyl assessments. 

Comment 2: DAS cites EPA documents on the toxicity of chlorpyrifos and chlorpyrifosmethyl. DAS states that the intrinsic toxicological profiles and characteristics for 

chlorpyrifos and chlorpyrifos-methyl have not changed, and DAS believes that the 

bridging approach suggested as a course of action by EPA in the 2003 and 2010 

memoranda is relevant and appropriate for the current requests for the subchronic 

inhalation, immunotoxicity, and CCA studies. DAS requests that instead of requiring 

separate studies for each of these guidelines to be conducted with chlorpyrifos-methyl, 

EPA instead refer to studies already on file or about to be submitted to the Agency as part 

of the parallel Registration Review process for chlorpyrifos. 

Response 2: The guideline immunotoxicity (870.7800), subchronic inhalation (870.3465) 

and the non-guideline comparative cholinesterase studies currently remain as data gaps 

for chlorpyrifos methyl. EPA will consider the results as presented in the final reports of 

these study types conducted with the closely related organophosphate chlorpyrifos (ethyl 

analog) when these studies are received as their final report. If these studies with 

chlorpyrifos (ethyl analog) are determined to satisfy the Agency’s standards for 

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acceptable criteria, they will be considered for bridging to satisfying the requirements for 

chlorpyrifos-methyl. 

Comments from Physicians Committee for Responsible Medicine (PCRM) 

[EPA-HQ-OPP-2010-0119-0014] 

Comment 1: The chlorpyrifos-methyl human health scoping document, as well as the 

cited EPA 2003 and 2010 memoranda, state that bridging data from chlorpyrifos (CPY) 

would be considered for purposes of satisfying chlorpyrifos-methyl data requirements. 

PCRM encourages DAS and the Agency to maximize this. The subchronic inhalation, 

immunotoxicity, and CCA studies can be waived using this approach.

Response 1: Please see the EPA response to DAS Comment 2 above. 

Comment 2: For the 870 acute toxicity series (acute oral, acute dermal, acute inhalation, 

primary eye irritation, primary skin irritation) PCRM challenges the Agency to look at a 

number of validated and otherwise scientifically appropriate nonanimal alternatives and 

strategies to fulfill CPM data requirements. 

Response 2: Response 2: Reducing the use of animal-based testing is one of the 

Agency's ongoing goals as EPA is an active member of the Interagency Coordinating 

Committee on the Validation of Alternative Methods (ICCVAM). EPA does currently 

accept the use of several test methods or testing approaches which result in the reduction 

of test animal usage, and the Agency will continue expanding the acceptance of such 

methods as they are approved by ICCVAM and associated international organizations. 

Comments from various university extension agents, crop specialists, and growers

[EPA-HQ-OPP-2010-0119-0009, -0010, -0011, -0013] 

Comment: Each of these comments stress the importance of the use chlorpyrifos-methyl 

on stored grain to protect against insect damage. Several comments mention that 

particularly in the southeastern U.S., alternative stored grain insecticides, including 

fumigants and diatomaceous earth, do not provide adequate protection. 

Response: EPA thanks the commenters for their comments. The comments may be 

considered in future chlorypyrifos-methyl assessments. 

Comment from Bayer CropScience [EPA-HQ-OPP-2010-0119-0015] 

Comment: Bayer CropScience is the registrant for Storicide II, the sole remaining 

chlorpyrifos-methyl end-use product. This comment provides information on the usage 

of Storicide II. 

Response: EPA thanks Bayer CropScience for their comment, which may be considered 

in future chlorypyrifos-methyl assessments. 

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Next Steps: 

o The Agency plans to issue a DCI in mid 2011, requiring the chlorpyrifos-methyl 

studies needed to complete the human health risk assessment.

o The Agency will conduct a human health risk assessment for chlorpyrifos-methyl.

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