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

www.regulations.gov 

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Chlorpyrifos-methyl 

Summary Document 

Registration Review: Initial Docket 

March 2010 

 

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TABLE OF CONTENTS 

I. PRELIMINARY WORK PLAN................................................................................. 4 

II. FACT SHEET ............................................................................................................. 9

Please Note 

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency’s 

current position based on the following documents: 

1. Chlorpyrifos-methyl. Human Health Assessment Scoping Document in Support of 

Registration Review. January 12, 2010. 

2. Registration Review Problem Formulation for Chlorpyrifos-methyl. November 23, 

2009. 

3. Usage/Label Use Report for Chlorpyrifos-methyl. April 24, 2009. 

4. Updated Review of Chlorpyrifos Methyl Incident Reports. November 24, 2009.

These and other supporting documents for the chlorpyrifos-methyl registration review case may 

be found in the docket EPA-HQ-OPP-2010-0119 at http://www.regulations.gov. 
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I. PRELIMINARY WORK PLAN 

Introduction

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review 

program. All pesticides distributed or sold in the United States generally must be registered by 

the U.S. Environmental Protection Agency (EPA or the Agency), based on scientific data 

showing that they will not cause unreasonable risks to human health or the environment when 

used as directed on product labeling. 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 of no unreasonable adverse effects to human 

health or the environment. Changes in science, public policy, and pesticide use practices will 

occur over time. Through the registration review program, the Agency periodically reevaluates 

pesticides to make sure that as change occurs, products in the marketplace can be used safely. 

Information on this program is provided at www.epa.gov/oppsrrd1/registration_review/. 

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. The Agency will consider benefits information and data as required by FIFRA. 

The public phase of registration review begins when the initial docket is opened for each case. 

The docket is the Agency’s opportunity to state what it knows about the pesticide and what 

additional risk analyses and data it believes are needed to make a registration review decision. 

After reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop and commit to a final work plan and schedule for the 

registration review of chlorpyrifos-methyl. 

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. 

Chlorpyrifos-methyl is closely related to chlorpyrifos (case # 0100), a general use OP 

insecticide registered for use for control of foliage and soil-borne insect pests on a variety of 

food and feed crops. The chlorpyrifos preliminary and final work plans incorrectly stated that 

chlorpyrifos-methyl shares the same case number as chlorpyrifos. While the two chemicals are 

closely related, the chlorpyrifos-methyl case is being handled separately (the chlorpyrifos-methyl 

case number is 8011). The chlorpyrifos final work plan is available at 

http://www.regulations.gov. 
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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 chlorpyrifosmethyl because all registered uses are indoor uses only. Chlorpyrifos-methyl 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 chlorpyrifosmethyl. 

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 post-application 

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 chlorpyrifosmethyl 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 chlorpyrifosmethyl 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 (EDSP):

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 adverse endocrine related effects caused by the substance, and 

establish a quantitative relationship between the dose and the E, A, or T effect. 
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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 (ais) 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 post-application 

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 ais 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 ai. 

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 the completion of the chlorpyrifos-methyl 

registration review. 

Registration Review for Chlorpyrifos-Methyl – Projected Registration Review Timeline

Activities Estimated Date 

Opening the docket 

Open Docket and Public Comment Period 2010 – Mar. 

Close Public Comment 2010 – May 

Case Development 

Final Work Plan 2010 – Aug. 

Issue DCI 2011 – Apr.- June 

Data Submission 2013 – Apr. - June 

Open Public Comment Period for Preliminary Risk Assessments 2014 – Oct. - Dec. 

Close Public Comment Period 2015 – Jan. – Mar. 

Registration Review Decision 

Open Public Comment Period for Proposed Registration Review 

Decision 

 2015 – Apr. – June. 

Close Public Comment Period 2015 – July – Sept. 

Final Registration Review Decision and Begin Post-Decision Follow-up 2016 

Total (years) 6 

Guidance for Commenters:

The public is invited to comment on EPA’s preliminary registration review work plan and 

rationale. The Agency will carefully consider all comments as well as any additional 

information or data provided in a timely manner prior to issuing a final work plan for the 

chlorpyrifos-methyl case. 
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Trade Irritants

• Through the registration review process, the Agency intends to solicit information on 

trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. 

Growers and other stakeholders are asked to comment on any trade irritant issues 

resulting from lack of Maximum Residue Levels (MRLs) or disparities between U.S. 

tolerances and MRLs in key export markets, providing as much specificity as possible 

regarding the nature of the concern. 

Water Quality

• Chlorpyrifos-methyl is not identified as a cause of impairment for any water bodies listed 

as impaired under section 303(d) of the Clean Water Act, based on information provided 

at 

http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_grou

p_id=885. In addition, no Total Maximum Daily Loads (TMDL) have been developed 

for [insert pesticide], based on information provided at 

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_gr

oup_id=885&p_pollutant_group_name=PESTICIDES. More information on impaired 

water bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/. The Agency 

invites submission of water quality data for this pesticide. To the extent possible, data 

should conform to the quality standards in Appendix A of the OPP Standard Operating 

Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s 

Registration Review Risk Assessment and Management Process (see: 

http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm) in order to 

ensure they can be used quantitatively or qualitatively in pesticide risk assessments. 

Environmental Justice

• EPA seeks to achieve environmental justice, the fair treatment and meaningful 

involvement of all people, regardless of race, color, national origin, or income, in the 

development, implementation, and enforcement of environmental laws, regulations, and 

policies. To help address potential environmental justice issues, the Agency seeks 

information on any groups or segments of the population who, as a result of their 

location, cultural practices, or other factors, may have atypical, unusually high exposure 

to chlorpyrifos-methyl, compared to the general population. Please comment if you are 

aware of any sub-populations that may have atypical or unusually high exposure 

compared to the general population. 

Additional Information

Stakeholders are also asked to provide information and data that will assist the Agency in 

refining risk assessments. 

Next Steps:

After the 60-day public comment period closes, the Agency will review and respond to any 

comments received in a timely manner and then issue a Final Work Plan for chlorpyrifos-methyl. 
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II. FACT SHEET

 

Background Information:

• Chlorpyrifos-methyl Registration Review Case Number: 8011 

• Chlorpyrifos-methyl PC Code: 059102; CAS#: 5598-13-0 

• Technical Registrant: Dow AgroSciences LLC 

• Chlorpyrifos-methyl was first registered in 1985. 

• A Tolerance Reassessment and Risk Management Eligibility Decision document (TRED) 

for chlorpyrifos-methyl was completed in January 2001 and was finalized with the OP 

cumulative in 2006. 

• Tolerances for chlorpyrifos-methyl range from 0.5 ppm to 130 ppm [40 CFR 180.419] 

• Pesticide Re-evaluation Division (PRD) Chemical Review Manager (CRM) Katie 

Weyrauch (weyrauch.katie@epa.gov) 

• Registration Division (RD) Contact: Marianne Lewis (lewis.marianne@epa.gov)

Use & Usage Information: 

• Chlorpyrifos-methyl is an organophosphate (OP) insecticide registered for use to control 

a variety of insects including beetles, weevils, moths, and grain borers. Chlorpyrifosmethyl is registered for use on stored grain, such as wheat, barley, oats, rice, and 

sorghum. Chlorpyrifos-methyl is registered for use only used as an indoor treatment for 

small grains in storage bins and warehouses 

• According to data from the United States Department of Agriculture’s National 

Agricultural Statistics Service and private market research, approximately 110,000 lbs a.i. 

are used annually. 

Recent Actions

• At the conclusion of the TRED, the chlorpyrifos-methyl registrants requested voluntary 

cancellation of all registrations. A Federal Register Notice announcing the receipt of 

request for registration cancellation was published on April 24, 2002 (FR 67 20118) 

(FRL-6773-1). 

• The Agency received public comments on the request for voluntary cancellation that 

compelled it to change the terms of the cancellation. A Federal Register Notice was 

published on July 7, 2004 (FR 69 40906) (FRL-7363-9) amending the TRED and the 

request for registration cancellation. This FRN extended the phase-out dates for the 

remaining end-use chlorpyrifos-methyl products and maintained the only remaining 

technical product registration (product number 62719-42). EPA requested comment on 

the July 7, 2004 FRN action. 

• On December 5, 2007 (FR 72 68580) (FRL-8155-5), EPA issued a product cancellation 

order further extending the phase-out dates for the remaining end-use products based on 

comments received on the July 7, 2004 FRN. The Agency granted an extension of the 

existing registrations until an equally effective stored grain product was registered. 

Storicide II, a chlorpyrifos-methyl / deltamethrin product was conditionally registered on 
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October 27, 2004 (EPA Reg. No. 264-992). Storicide II contains half the concentration 

of chlorpyrifos-methyl compared to earlier chlorpyrifos-methyl end-use products. 

• There are two currently registered chlorpyrifos-methyl products: a technical-grade 

product, Reldan F Insecticidal Chemical (Reg. No. 62710-42), and an end-use product, 

Storicide II Grain, Bin, and Warehouse Insecticide (Reg. No. 264-992). 

Ecological Risk Assessment Status: 

Please refer to the Registration Review Problem Formulation for Chlorpyrifos-methyl, dated 

November 23, 2009, and located in the chlorpyrifos-methyl docket at regulations.gov (EPA-HQOPP-2010-0119). 

• An ecological risk assessment was completed in 1980 for chlorpyrifos-methyl prior to its 

registration in 1985. 

• No ecological risk has been identified for chlorpyrifos-methyl because all uses are indoor 

uses that do not lead to ecological exposure. According to product toxicity data, all enduse products are toxic to extremely toxic to fish, birds, and other wildlife. Data from 

early risk assessments indicate that chlorpyrifos-methyl is practically nontoxic to 

moderately toxic to avian wildlife based on dosing studies; practically nontoxic to 

slightly toxic to avian wildlife based on dietary studies; moderately toxic to very highly 

toxic to fish based on acute data; slightly to very highly toxic to aquatic invertebrates 

based on acute tests; and very highly toxic to honeybees based on acute studies. 

• No acceptable fate data have been submitted to EPA for chlorpyrifos-methyl. Previous 

data summaries were prepared based on overviews of the environmental fate as captured 

in open literature. 

• All registered chlorpyrifos-methyl uses are indoor uses. Chlorpyrifos-methyl 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. 

Human Health Risk Assessment Status:

Please refer to Chlorpyrifos-methyl. Human Health Assessment Scoping Document in Support of 

Registration Review, dated January 12, 2010, and located in the chlorpyrifos-methyl docket at 

regulations.gov (EPA-HQ-OPP-2010-0119), for a discussion of the key findings of the most 

recent human health risk assessment for chlorpyrifos-methyl. A summary follows: 

Hazard Characterization: 

• In the 2001 TRED, the short-term dermal and inhalation endpoint selected was a no 

observed adverse effect level (NOAEL) of 1.0 mg/kg/day based on cholinesterase 

inhibition from a developmental toxicity study in rats. The intermediate-term dermal and 

inhalation endpoint selected was a NOAEL of 0.1 mg/kg/day based on cholinesterase 

inhibition from a chronic/carcinogenicity study in rats. 
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Dietary (Food Only): 

• The most recent dietary exposure assessment was conducted in association with the 2001 

TRED. Dietary risk estimates for chlorpyrifos-methyl were below EPA’s level of 

concern for the general population and all population subgroups. 

• Because chlorpyrifos-methyl is only used on stored grains inside grain storage facilities, 

residues in drinking water are not anticipated. Therefore a drinking water exposure 

analysis was not conducted. 

Residential: 

• The 2001 TRED did not assess residential scenarios because there are no registered 

residential uses of chlorpyrifos-methyl. 

Aggregate: 

• There are no residential uses of chlorpyrifos-methyl; therefore, aggregate risk estimates 

are equivalent to the dietary estimates and are not of concern. 

Occupational: 

• The 2000 occupational assessment was based on the chlorpyrifos-methyl product Reldan 

4E (43% emulsifiable concentrate) and dust products. Handler estimates were of concern 

for all but one scenario – mixing and loading liquids for direct grain treatment using an 

automated system. 

• In response to those concerns, the registrant requested voluntary cancellation of all dust 

products and agreed to mitigation measures to address risks to handlers of the liquid 

formulation. 

• Post-application risks from liquid applications were expected to be minimal. 

• Dust formulations were cancelled in 2002, and Reldan 4E (43% emulsifiable concentrate 

(EC)) was cancelled in 2007. The only currently registered formulation is a 22% EC 

(Storicide II). The 22% may be applied to stored grains at 3 ppm, whereas the 43% EC 

was applied at 6 ppm. 

• Updated occupational handler and post-application exposure assessment are necessary. 

• Past chlorpyrifos-methyl risk assessments rely in part on data from studies in which adult 

human subjects were intentionally exposed to a pesticide to determine their dermal and 

inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure 

Database (PHED) and the Agricultural Reentry Task Force (ARTF) Database. EPA has 

reviewed all the studies in these multi-pesticide generic exposure databases, and on the 

basis of available evidence has found them to have been neither fundamentally unethical 

nor significantly deficient relative to standards of ethical research conduct prevailing 

when they were conducted. There is no regulatory barrier to continued reliance on these 

studies, and all applicable requirements of EPA’s Rule for the Protection of Human 

Subjects of Research (40 CFR Part 26) have been satisfied. 

Cumulative: 
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• Chlorpyrifos-methyl use was assessed as part of the organophosphate cumulative risk 

assessment, completed in July 2006. No cumulative risks of concern for chlorpyrifosmethyl were identified in that assessment. 

Incidents:

Ecological: 

• Since chlorpyrifos-methyl is registered for indoor use only, EPA did not search the 

Ecological Incident Information System (EIIS) for ecological incidents associated with 

chlorpyrifos-methyl.

Human: 

• The OPP Incident Database System (IDS) was searched for human incidents involving 

chlorpyrifos-methyl in the United States from 2002 to the present. IDS includes reports 

of incidents from various sources, including mandatory FIFRA Section 6 (a) (2) reports 

from registrants, other federal and state health and environmental agencies and individual 

consumers. This review indicates that no incidents were reported. 

Data Call-In Status:

• No chemical-specific data call-ins (DCIs) have been issued for chlorpyrifos-methyl since 

the 2001 TRED. DCIs were issued for chlorpyrifos-methyl in 1992 for product chemistry 

data, 1995 for agricultural handler data, and 1999 for developmental neurotoxicity data. 

All requirements have been satisfied with either a waiver request, bridging of data, or 

data submission. 

• After the 2001 chlorpyrifos-methyl TRED was issued, EPA allowed for several of the 

data gaps identified in the TRED to be satisfied with studies from chlorpyrifos, a closely 

related organophosphate insecticide. The studies expected to be required in this 

registration review are listed in the Preliminary Work Plan under the “Anticipated Risk 

Assessment and Data Needs” section (p. 4). 

Tolerances and International Harmonization: 

• Maximum Residue limits (MRLs) for chlorpyrifos-methyl have been established by the 

Codex Alimentarius Commission. However, the majority of these MRLs are not 

harmonized with U.S. tolerances. Any chlorpyrifos-methyl tolerances reassessed during 

registration review will be considered for possible harmonization with international 

MRLs. Canadian and Mexican MRLs have not been established. 

• Chlorpyrifos-methyl tolerances in 40 CFR 180.419 are currently expressed as the 

combined residues of chlorpyrifos-methyl and TCP (2,5,6-trichloro-2-pyridinol) in or on 

plant commodities. EPA previously concluded that the U.S. tolerance expression should 

be amended to include only chorpyrifos-methyl. Accordingly, the tolerance definition for 

chlorpyrifos-methyl should be amended to include only chlorpyrifos-methyl. 

• 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. 
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Labels: 

Labels can be obtained from the Pesticide Product Label System (PPLS) website: 

http://oaspub.epa.gov/pestlabl/ppls.home.