Federal Register / Vol. 86, No. 165 / Monday, August 30, 2021 / Rules and Regulations 48315 

(2) Tolerances are established for 

residues of thiabendazole, including its 

metabolites and degradates, in or on the 

commodities in table 2 to paragraph 

(a)(2). Compliance with the tolerance 

levels specified to table 2 to paragraph 

(a)(2) is to be determined by measuring 

only the sum of thiabendazole (2-(4- 

thiazolyl)benzimidazole) and its 

metabolite 5-hydroxythiabendazole (free 

and conjugated) calculated as the 

stoichiometric equivalent of 

thiabendazole, in or on the commodity. 

TABLE 2 TO PARAGRAPH (a)(2) 

* * * * * 

[FR Doc. 2021–18390 Filed 8–27–21; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2021–0523; FRL–5993–04– 

OCSPP] 

Chlorpyrifos; Tolerance Revocations 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: On April 29, 2021, the United 

States Court of Appeals for the Ninth 

Circuit ordered EPA to issue a final rule 

concerning the chlorpyrifos tolerances 

by August 20, 2021. Based on the 

currently available data and taking into 

consideration the currently registered 

uses for chlorpyrifos, EPA is unable to 

conclude that the risk from aggregate 

exposure from the use of chlorpyrifos 

meets the safety standard of the Federal 

Food, Drug, and Cosmetic Act (FFDCA). 

Accordingly, EPA is revoking all 

tolerances for chlorpyrifos. 

DATES: This final rule is effective 

October 29, 2021. The tolerances for all 

commodities expire on February 28, 

2022. 

Written objections, requests for 

hearings, or requests for a stay identified 

by the docket identification (ID) number 

EPA–HQ–OPP–2021–0523 must be 

received on or before October 29, 2021, 

and must be filed in accordance with 

the instructions provided in 40 CFR part 

178 (see also Unit I.C. of the 

SUPPLEMENTARY INFORMATION unit in this 

document). 

ADDRESSES: The docket for this action, 

identified by docket identification (ID) 

number EPA–HQ–OPP–2021–0523, is 

available at http://www.regulations.gov 

or at the Office of Pesticide Programs 

Regulatory Public Docket (OPP Docket) 

in the Environmental Protection Agency 

Docket Center (EPA/DC), West William 

Jefferson Clinton Bldg., Rm. 3334, 1301 

Constitution Ave. NW, Washington, DC 

20460–0001. 

Due to public health concerns related 

to COVID–19, the EPA/DC and Reading 

Room are closed to visitors with limited 

exceptions. The staff continues to 

provide remote customer service via 

email, phone, and webform. For the 

latest status information on EPA/DC 

services and docket access, visit http:// 

www.epa.gov/dockets. 

FOR FURTHER INFORMATION CONTACT: 

Elissa Reaves, Pesticide Re-Evaluation 

Division (7508P), Office of Pesticide 

Programs, Environmental Protection 

Agency, 1200 Pennsylvania Ave. NW, 

Washington, DC 20460–0001; telephone 

number: 703–347–0206; email address: 

OPPChlorpyrifosInquiries@epa.gov. 

SUPPLEMENTARY INFORMATION: 

I. General Information 

A. Does this action apply to me? 

You may be potentially affected by 

this action if you are an agricultural 

producer, food manufacturer, or 

pesticide manufacturer. The following 

list of North American Industrial 

Classification System (NAICS) codes is 

not intended to be exhaustive, but rather 

provides a guide to help readers 

determine whether this document 

applies to them. Potentially affected 

entities may include: 

• Crop production (NAICS code 111). 

• Animal production (NAICS code 

112). 

• Food manufacturing (NAICS code 

311). 

• Pesticide manufacturing (NAICS 

code 32532). 

Other types of entities not listed in 

this unit could also be affected. The 

NAICS codes have been provided to 

assist you and others in determining 

whether this action might apply to 

certain entities. To determine whether 

you or your business may be affected by 

this action, you should carefully 

examine the applicability provisions in 

Unit II. If you have any questions 

regarding the applicability of this action 

to a particular entity, consult the contact 

listed under FOR FURTHER INFORMATION

CONTACT. 

B. How can I get electronic access to 

other related information? 

You may access a frequently updated 

electronic version of 40 CFR part 180 

through the Government Printing 

Office’s e-CFR site at http://

www.ecfr.gov/cgi-bin/textidx?&c=ecfr&tpl=/ecfrbrowse/Title40/ 

40tab_02.tpl. 

C. How can I file an objection or hearing 

request? 

Under FFDCA section 408(g), 21 

U.S.C. 346a, any person may file an 

objection to any aspect of this regulation 

and may also request a hearing on those 

objections. You must file your objection 

or request a hearing on this regulation 

in accordance with the instructions 

provided in 40 CFR part 178. To ensure 

proper receipt by EPA, you must 

identify docket ID number EPA–HQ– 

OPP–2021–0523 in the subject line on 

the first page of your submission. All 

objections and requests for a hearing 

must be in writing and must be received 

by the Hearing Clerk on or before 

October 29, 2021. Addresses for mail 

and hand delivery of objections and 

hearing requests are provided in 40 CFR 

178.25(b), although at this time, EPA 

strongly encourages those interested in 

submitting objections or a hearing 

request, to submit objections and 

hearing requests electronically. See 

Order Urging Electronic Service and 

Filing (April 10, 2020), https://

www.epa.gov/sites/production/files/ 

2020-05/documents/2020-04-10_-_

order_urging_electronic_service_and_

filing.pdf. At this time, because of the 

COVID–19 pandemic, the judges and 

staff of the Office of Administrative Law 

Judges (OALJ) are working remotely and 

not able to accept filings or 

correspondence by courier, personal 

deliver, or commercial delivery, and the 

ability to receive filings or 

correspondence by U.S. Mail is 

similarly limited. When submitting 

documents to the U.S. EPA OALJ, a 

person should utilize the OALJ e-filing 

system, at https://yosemite.epa.gov/OA/ 

EAB/EAB-ALJ_upload.nsf. 

Although EPA’s regulations require 

submission via U.S. Mail or hand 

delivery, EPA intends to treat 

submissions filed via electronic means 

as properly filed submissions during 

this time that the Agency continues to 

maximize telework due to the 

pandemic; therefore, EPA believes the 

preference for submission via electronic 

means will not be prejudicial. If it is 


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48316 Federal Register / Vol. 86, No. 165 / Monday, August 30, 2021 / Rules and Regulations 

impossible for a person to submit 

documents electronically or receive 

service electronically, e.g., the person 

does not have any access to a computer, 

the person shall so advise OALJ by 

contacting the Hearing Clerk at (202) 

564–6281. If a person is without access 

to a computer and must file documents 

by U.S. Mail, the person shall notify the 

Hearing Clerk every time it files a 

document in such a manner. The 

address for mailing documents is U.S. 

Environmental Protection Agency, 

Office of Administrative Law Judges, 

Mail Code 1900R, 1200 Pennsylvania 

Ave. NW, Washington, DC 20460. 

In addition to filing an objection or 

hearing request with the Hearing Clerk 

as described in 40 CFR part 178 and 

above, please submit a copy of the filing 

(excluding any Confidential Business 

Information (CBI)) for inclusion in the 

public docket. Information not marked 

confidential pursuant to 40 CFR part 2 

may be disclosed publicly by EPA 

without prior notice. Submit the nonCBI copy of your objection or hearing 

request, identified by docket ID number 

EPA–HQ–OPP–2021–0523, using the 

Federal eRulemaking Portal at http://

www.regulations.gov. Follow the online 

instructions for submitting comments. 

Do not submit electronically any 

information you consider to be CBI or 

other information whose disclosure is 

restricted by statute. 

If you would like to submit CBI with 

your hearing request, please first contact 

the Pesticide Re-Evaluation Division by 

telephone, 703–347–0206, or by email 

address: OPPChlorpyrifosInquiries@

epa.gov. Do not submit CBI to EPA 

through the Federal eRulemaking Portal 

or email. 

D. What can I do if I want the Agency 

to maintain a tolerance that the Agency 

has revoked? 

Any affected party has 60 days from 

the date of publication of this order to 

file objections to any aspect of this order 

with EPA and to request an evidentiary 

hearing on those objections (21 U.S.C. 

346a(g)(2)). A person may raise 

objections without requesting a hearing. 

The objections submitted must 

specify the provisions of the regulation 

deemed objectionable and the grounds 

for the objection (40 CFR 178.25). While 

40 CFR 180.33(i) indicates a fee is due 

with each objection, EPA currently 

cannot collect such fees per 21 U.S.C. 

346a(m)(3). If a hearing is requested, the 

objections must include a statement of 

the factual issue(s) on which a hearing 

is requested, the requestor’s contentions 

on such issues, and a summary of any 

evidence relied upon by the objector (40 

CFR 178.27). 

Although any person may file an 

objection, EPA will not consider any 

legal or factual issue presented in 

objections, if that issue could reasonably 

have been raised earlier in the Agency’s 

review of chlorpyrifos relative to this 

petition. Similarly, if you fail to file an 

objection to an issue resolved in the 

final rule within the time period 

specified, you will have waived the 

right to challenge the final rule’s 

resolution of that issue (40 CFR 

178.30(a)). After the specified time, 

issues resolved in the final rule cannot 

be raised again in any subsequent 

proceedings on this rule. See Nader v 

EPA, 859 F.2d 747 (9th Cir. 1988), cert 

denied 490 U.S. 1931 (1989). 

EPA will review any objections and 

hearing requests in accordance with 40 

CFR 178.30, and will publish its 

determination with respect to each in 

the Federal Register. A request for a 

hearing will be granted only to resolve 

factual disputes; objections of a purely 

policy or legal nature will be resolved 

in the Agency’s final order, and will 

only be subject to judicial review 

pursuant to 21 U.S.C. 346a(h)(1), (40 

CFR 178.20(c) and 178.32(b)(1)). A 

hearing will only be held if the 

Administrator determines that the 

material submitted shows the following: 

(1) There is a genuine and substantial 

issue of fact; (2) There is a reasonable 

probability that available evidence 

identified by the requestor would, if 

established, resolve one or more of such 

issues in favor of the requestor, taking 

into account uncontested claims to the 

contrary; and (3) Resolution of the 

issue(s) in the manner sought by the 

requestor would be adequate to justify 

the action requested (40 CFR 178.30). 

You must file your objection or 

request a hearing on this regulation in 

accordance with the instructions 

provided in 40 CFR part 178. To ensure 

proper receipt by EPA, you must 

identify docket ID number EPA–HQ– 

OPP–2021–0523 in the subject line on 

the first page of your submission. All 

requests must be in writing and must be 

received by the Hearing Clerk as 

required by 40 CFR part 178 on or 

before October 29, 2021. 

II. Background 

A. What action is the Agency taking? 

EPA is revoking all tolerances for 

residues of chlorpyrifos. In 2007, the 

Pesticide Action Network North 

America (PANNA) and the Natural 

Resources Defense Council (NRDC) filed 

a petition with EPA under section 

408(d) of the Federal Food, Drug, and 

Cosmetic Act (FFDCA), 21 U.S.C. 

346a(d), requesting that EPA revoke all 

chlorpyrifos tolerances. (Ref. 1). In an 

April 29, 2021 decision concerning the 

Agency’s orders denying that 2007 

Petition and the subsequent objections 

to that denial, the Ninth Circuit ordered 

EPA to ‘‘(1) grant the 2007 Petition; (2) 

issue a final regulation within 60 days 

following issuance of the mandate that 

either (a) revokes all chlorpyrifos 

tolerances or (b) modifies chlorpyrifos 

tolerances and simultaneously certifies 

that, with the tolerances so modified, 

the EPA ‘has determined that there is a 

reasonable certainty that no harm will 

result from aggregate exposure to the 

pesticide chemical residue, including 

all anticipated dietary exposures and all 

other exposures for which there is 

reliable information,’ including for 

‘infants and children’; and (3) modify or 

cancel related FIFRA registrations for 

food use in a timely fashion consistent 

with the requirements of 21 U.S.C. 

346a(a)(1).’’ League of United Latin Am. 

Citizens v. Regan, 996 F.3d 673 (9th Cir. 

2021) (the LULAC decision). 

In today’s action, EPA is granting the 

2007 Petition, which requested 

revocation of the tolerances. While EPA 

previously responded to and denied the 

individual claims in the original 

petition, the Court found EPA’s denial, 

at least with regard to the issues raised 

in the litigation, to be unsupported by 

the record before the Court and ordered 

EPA to grant the 2007 Petition and issue 

a final rule revoking or modifying 

tolerances. EPA is granting the petition 

by granting the relief sought by the 

petition, i.e., the revocation of the 

chlorpyrifos tolerances, for the reasons 

stated in this rulemaking. Moreover, the 

Court expressly ordered EPA to respond 

to the petition by issuing a final rule 

under FFDCA section 408(d)(4)(A)(i). 

996 F.3d at 702. That provision of the 

statute involves the issuance of a final 

rule ‘‘without further notice and 

without further period for public 

comment.’’ 21 U.S.C. 346a(d)(4)(A)(i). 

While the FFDCA provides an option for 

EPA to respond to a petition with the 

issuance of a proposed rule under 

FFDCA section 408(d)(4)(A)(ii) and 

thereafter to finalize the proposal, the 

Court did not direct EPA to exercise its 

authority to finalize its 2015 proposal to 

revoke tolerances pursuant to 

subparagraph (d)(4)(A)(ii). Nothing in 

the Ninth Circuit’s opinion reflects an 

expectation that, in complying with the 

Court’s order, EPA would or should 

finalize the 2015 proposed rule. As 

such, EPA is viewing this action as 

independent from the 2015 proposal, 

and this final rule is based on the 

Agency’s current assessment of the 

available scientific information, rather 


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Federal Register / Vol. 86, No. 165 / Monday, August 30, 2021 / Rules and Regulations 48317 

than a continuation of and finalization 

of the Agency’s proposal in 2015 to 

revoke chlorpyrifos tolerances. 

In this final rule, EPA is revoking all 

tolerances for residues of chlorpyrifos 

contained in 40 CFR 180.342. This 

includes tolerances for residues of 

chlorpyrifos on specific food and feed 

commodities (180.342(a)(1)); on all food 

commodities treated in food handling 

and food service establishments in 

accordance with prescribed conditions 

(180.342(a)(2) and (a)(3)); and on 

specific commodities when used under 

regional registrations (180.342(c)). 

EPA finds that, taking into 

consideration the currently available 

information and the currently registered 

uses of chlorpyrifos, EPA cannot make 

a safety finding to support leaving the 

current tolerances for residues of 

chlorpyrifos in place, as required under 

the FFDCA section 408(b)(2). 21 U.S.C. 

346a(b)(2). As described in greater detail 

below, the Agency’s analysis indicates 

that aggregate exposures (i.e., exposures 

from food, drinking water, and 

residential exposures), which stem from 

currently registered uses, exceed safe 

levels, when relying on the wellestablished 10% red blood cell 

acetylcholinesterase (RBC AChE) 

inhibition as an endpoint for risk 

assessment and including the statutory 

tenfold (10X) margin of safety to 

account for uncertainties related to the 

potential for neurodevelopmental effects 

to infants, children, and pregnant 

women. Accordingly, the Agency is 

therefore revoking all tolerances because 

given the currently registered uses of 

chlorpyrifos, EPA cannot determine that 

there is a reasonable certainty that no 

harm will result from aggregate 

exposure to residues, including all 

anticipated dietary (food and drinking 

water) exposures and all other 

exposures for which there is reliable 

information. 

B. What is the Agency’s authority for 

taking this action? 

EPA is taking this action pursuant to 

the authority in FFDCA sections 

408(b)(1)(A), 408(b)(2)(A), and 

408(d)(4)(A)(i). 21 U.S.C. 346a(b)(1)(A), 

(b)(2)(A), (d)(4)(A)(i). 

C. Overview of Final Rule 

When assessing pesticides, EPA 

performs a number of analyses to 

determine the risks from aggregate 

exposure to pesticide residues. For 

further discussion of the regulatory 

requirements of section 408 of the 

FFDCA, see https://www.epa.gov/lawsregulations/summary-federal-food-drugand-cosmetic-act, and for a complete 

description of the risk assessment 

process, see https://www.epa.gov/ 

pesticide-science-and-assessingpesticide-risks/overview-riskassessment-pesticide-program and 

https://www.epa.gov/pesticide-scienceand-assessing-pesticide-risks/epas-riskassessment-process-tolerancereassessment. 

In general, to assess the risk of a 

pesticide tolerance, EPA combines 

information on pesticide toxicity with 

information regarding the route, 

magnitude, and duration of exposure to 

the pesticide. The risk assessment 

process involves four distinct steps: (1) 

Identification of the toxicological 

hazards posed by a pesticide; (2) 

Determination of the exposure ‘‘level of 

concern’’ for humans, which includes 

choosing a point of departure (PoD) that 

reflects the adverse health endpoint that 

is most sensitive to the pesticide, as 

well as uncertainty factors; (3) 

Estimation of human exposure to the 

pesticide through all applicable routes; 

and (4) Characterization of human risk 

based on comparison of the estimated 

human exposure to the level of concern. 

For tolerances, if aggregate exposure to 

humans is greater than the Agency’s 

determined level of concern, the 

Agency’s determination is the tolerances 

are not safe. 

The following provides a brief 

roadmap of the Units in this rule. 

• Unit III. contains an overview of the 

statutory background, including the 

safety standard in FFDCA, and the 

registration standard under FIFRA. 

FFDCA provides the statutory basis for 

evaluating tolerances and directs the 

Agency to revoke tolerances that are not 

safe. 

• Unit IV. provides an overview of 

the FFDCA petition that requested that 

EPA revoke chlorpyrifos tolerances on 

the grounds that those tolerances were 

not safe under the FFDCA. While that 

petition raised numerous issues, the 

primary scientific challenge to the 

chlorpyrifos tolerances that was before 

the Ninth Circuit related to whether 

EPA had selected the correct PoD for 

assessing risk. While EPA’s PoD was 

based on inhibition of the enzyme 

acetylcholinesterase (AChE), petitioners 

asserted that the most sensitive health 

endpoint was neurodevelopmental 

outcomes from exposure to chlorpyrifos. 

A summary of that petition, EPA’s 

response to that petition, and the 

subsequent litigation and Ninth 

Circuit’s order directing EPA to revoke 

or modify the chlorpyrifos tolerances is 

included in this section. 

• Unit V. provides an overview of the 

regulatory background for chlorpyrifos, 

including the numerous human health 

risk assessments EPA has conducted 

and FIFRA Scientific Advisory Panels 

(SAPs) that were convened to discuss 

the complex scientific issues associated 

with chlorpyrifos. 

• Units VI. through VIII. summarizes 

EPA’s risk assessment, which reflect the 

four-step process described above. 

• Unit VI, which focuses on the 

hazard assessment of chlorpyrifos, 

combines the first two steps to provide 

a full picture of how EPA conducts its 

hazard assessment. After describing the 

process generally, this unit discusses 

EPA’s analysis of the hazards posed by 

chlorpyrifos, including a discussion of 

the available data on AChE inhibition 

and the potential for 

neurodevelopmental outcomes in the 

young. Unit VI. also discusses the 

Agency’s process for determining the 

endpoint on which to regulate 

chlorpyrifos exposure and the rationale 

for basing the PoD analysis on 10% 

AChE inhibition. Finally, this Unit 

includes a discussion of the FQPA 

safety factor and the Agency’s reasons 

for retaining the default 10X value. 

• Unit VII. describes EPA’s exposure 

assessment for chlorpyrifos. The unit 

includes a description of the general 

approach for estimating exposures to 

pesticide residues in or on food and in 

drinking water, as well as exposures 

that come from non-occupational and 

non-dietary sources, also referred to as 

residential exposures. The unit walks 

through how EPA conducted those 

exposure assessments for chlorpyrifos, 

including a detailed discussion of the 

recent refinements to the drinking water 

analysis conducted by EPA for 

chlorpyrifos. 

• Unit VIII. describes the Agency’s 

process for assessing aggregate risk 

based on the hazard discussed in Unit 

VI. and the exposure discussed in Unit 

VII. and provides the Agency’s rationale 

and conclusions concerning the overall 

risks posed by chlorpyrifos based on the 

currently registered uses. Unit VIII. 

concludes that the aggregate risks 

exceed the level of concern and 

therefore the chlorpyrifos tolerances 

must be revoked. 

Units IX. and X. address procedural 

matters, international obligations, 

statutory and executive order review 

requirements, and the specific revisions 

that will be made to the Code of Federal 

Regulations with this final rule. 

III. Statutory Background 

A. Federal Food, Drug, and Cosmetic 

Act (FFDCA) Tolerances 

A ‘‘tolerance’’ represents the 

maximum level for residues of pesticide 

chemicals legally allowed in or on raw 

agricultural commodities and processed 


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foods. Section 408 of FFDCA, 21 U.S.C. 

346a, authorizes the establishment of 

tolerances, exemptions from tolerance 

requirements, modifications of 

tolerances, and revocation of tolerances 

for residues of pesticide chemicals in or 

on raw agricultural commodities and 

processed foods. Without a tolerance or 

exemption, pesticide residues in or on 

food is considered unsafe, 21 U.S.C. 

346a(a)(1), and such food, which is then 

rendered ‘‘adulterated’’ under FFDCA 

section 402(a), 21 U.S.C. 342(a), may not 

be distributed in interstate commerce, 

21 U.S.C. 331(a). 

Section 408(b)(2) of the FFDCA 

directs that EPA may establish or leave 

in effect a tolerance for a pesticide only 

if it finds that the tolerance is safe, and 

EPA must revoke or modify tolerances 

determined to be unsafe. FFDCA 

408(b)(2)(A)(i) (21 U.S.C. 

346a(b)(2)(A)(i)). Section 408(b)(2)(A)(ii) 

defines ‘‘safe’’ to mean that ‘‘there is a 

reasonable certainty that no harm will 

result from aggregate exposure to the 

pesticide chemical residue, including 

all anticipated dietary exposures and all 

other exposures for which there is 

reliable information.’’ This includes 

exposure through food, drinking water 

and all non-occupational exposures 

(e.g., in residential settings), but does 

not include occupational exposures to 

workers (i.e., occupational). Risks to 

infants and children are given special 

consideration. Specifically, pursuant to 

section 408(b)(2)(C), EPA must assess 

the risk of the pesticide chemical based 

on available information concerning the 

special susceptibility of infants and 

children to the pesticide chemical 

residues, including neurological 

differences between infants and 

children and adults, and effects of in 

utero exposure to pesticide chemicals; 

and available information concerning 

the cumulative effects on infants and 

children of such residues and other 

substances that have a common 

mechanism of toxicity. (21 U.S.C. 

346a(b)(2)(C)(i)(II) and (III)). 

This provision further directs that ‘‘in 

the case of threshold effects, . . . an 

additional tenfold margin of safety for 

the pesticide chemical residue and other 

sources of exposure shall be applied for 

infants and children to take into account 

potential pre- and postnatal toxicity and 

completeness of the data with respect to 

exposure and toxicity to infants and 

children.’’ (21 U.S.C. 346a(b)(2)(C)). 

EPA is permitted to ‘‘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.’’ (21 U.S.C. 

346a(b)(2)(C)). Due to Congress’s focus 

on both pre- and postnatal toxicity, EPA 

has interpreted this additional safety 

factor as pertaining to risks to infants 

and children that arise due to prenatal 

exposure as well as to exposure during 

childhood years. This section providing 

for the special consideration of infants 

and children in section 408(b)(2)(C) was 

added to the FFDCA through the Food 

Quality Protection Act (FQPA) (Pub. L. 

104–170, 110 Stat. 1489 (1996)); 

therefore, this additional margin of 

safety is often referred to as the ‘‘FQPA 

safety factor (SF)’’. 

Section 408(d) of the FFDCA, 21 

U.S.C. 346a(d), authorizes EPA to 

revoke tolerances in response to an 

administrative petition submitted by 

any person. As explained in more detail 

in Unit IV, PANNA and NRDC 

submitted a petition in 2007 requesting 

revocation of all chlorpyrifos tolerances. 

The Ninth Circuit has directed EPA to 

grant that petition and issue a rule 

revoking or modifying those tolerances. 

EPA is issuing this rule in response to 

that petition and revoking all 

chlorpyrifos tolerances because EPA is 

unable to determine, based on data 

available at this time, that aggregate 

exposures to chlorpyrifos are safe. 

B. Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) Registration 

Review 

Under FIFRA, a pesticide may not be 

sold or distributed in the United States 

unless it is registered. (7.U.S.C. 136a(a)). 

EPA must determine that a pesticide 

‘‘will not generally cause unreasonable 

adverse effects on the environment in 

order to register a pesticide.’’ 7 U.S.C. 

136a(c)(5). The term ‘‘unreasonable 

adverse effects on the environment’’ is 

defined to include ‘‘a human dietary 

risk from residues that result from a use 

of a pesticide in or on any food 

inconsistent with the standard under 

section 346a of Title 21.’’ 7 U.S.C. 

136(bb). Thus, the FIFRA registration 

standard incorporates the FFDCA safety 

standard and requires consideration of 

safety at the time of registration and 

during the registration review process. 

Under section 3(g) of FIFRA (7 U.S.C. 

136(a)(g)), EPA is required to re-evaluate 

existing registered pesticides every 15 

years in a process called ‘‘registration 

review.’’ The purpose of registration 

review is ‘‘to ensure that each pesticide 

registration continues to satisfy the 

FIFRA standard for registration,’’ 40 

CFR 155.40(a)(1), taking into account 

changes that have occurred since the 

last registration decision, including any 

new relevant scientific information and 

any changes to risk-assessment 

procedures, methods, and data 

requirements. 40 CFR 55.53(a). To 

ensure that a pesticide continues to 

meet the standard for registration, EPA 

must determine, based on the available 

data, including any additional 

information that has become available 

since the pesticide was originally 

registered or re-evaluated, that the 

pesticide does not cause ‘‘unreasonable 

adverse effects on the environment.’’ 7 

U.S.C. 136a(c)(1), (5); see also 40 CFR 

152.50. 

Chlorpyrifos is currently undergoing 

registration review, which must be 

completed by October 1, 2022. 7 U.S.C. 

136a(g)(1)(A)(iv). For information about 

the ongoing registration review process 

for chlorpyrifos, see https://

www.regulations.gov/docket/EPA-HQOPP-2008-0850. 

IV. FFDCA Petition and Related 

Litigation 

A. 2007 FFDCA Petition 

In 2006, EPA issued the Registration 

Eligibility Decision (RED) for 

chlorpyrifos, which concluded that 

chlorpyrifos was eligible for 

reregistration as it continued to meet the 

FIFRA standard for registration. In 

September 2007, PANNA and NRDC 

submitted to EPA a petition (the 

Petition) seeking revocation of all 

chlorpyrifos tolerances under FFDCA 

section 408 and cancellation of all 

chlorpyrifos pesticide product 

registrations under FIFRA. (Ref. 1). That 

petition raised several claims regarding 

EPA’s 2006 FIFRA reregistration 

decision for chlorpyrifos and the active 

registrations in support of the request 

for tolerance revocations and product 

cancellations. Those claims are 

described in detail in EPA’s earlier 

order denying the petition (82 FR 16581, 

April 5, 2017) (FRL–9960–77). 

B. Agency Responses and 2017 Order 

Denying Petition 

On March 29, 2017, EPA denied the 

Petition in full (82 FR 16581, April 5, 

2017) (FRL–9960–77). Prior to issuing 

that order, EPA provided the Petitioners 

with two interim responses on July 16, 

2012 and July 15, 2014, which denied 

six of the Petition’s claims. EPA made 

clear in both the 2012 and 2014 

responses that, absent a request from 

Petitioners, EPA’s denial of those six 

claims would not be made final until 

EPA finalized its response to the entire 

Petition. Petitioners made no such 

request, and EPA therefore finalized its 

response to those claims in the March 

29, 2017 Denial Order. 

As background, three of the Petition’s 

claims all related to the same issue: 

Whether the potential exists for 

chlorpyrifos to cause 

neurodevelopmental effects in children 


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at exposure levels below EPA’s existing 

regulatory standard (10% RBC AChE 

inhibition). Because the claims relating 

to the potential for neurodevelopmental 

effects in children raised novel, highly 

complex scientific issues, EPA 

originally decided it would be 

appropriate to address these issues in 

connection with the registration review 

of chlorpyrifos under FIFRA section 3(g) 

and decided to expedite that review, 

intending to finalize it in 2015, well in 

advance of the October 1, 2022 

registration review deadline (Ref. 2). 

EPA decided as a policy matter that it 

would address the Petition claims 

raising these matters on a similar 

timeframe. Id. at 16583. 

The complexity of these scientific 

issues precluded EPA from finishing its 

review according to EPA’s original 

timeline, and the Petitioners brought 

legal action in the Ninth Circuit Court 

of Appeals to compel EPA to either 

issue an order denying the Petition or to 

grant the Petition by initiating the 

tolerance revocation process. The result 

of that litigation was that on August 10, 

2015, the Court ordered EPA to ‘‘issue 

either a proposed or final revocation 

rule or a full and final response to the 

administrative [P]etition by October 31, 

2015.’’ In re Pesticide Action Network N. 

Am., 798 F.3d 809, 815 (9th Cir. 2015). 

In response to that 2015 order, EPA 

issued a proposed rule to revoke all 

tolerances for chlorpyrifos on October 

28, 2015 (published in the Federal 

Register on November 6, 2015 (80 FR 

69080)), based on its unfinished 

registration review risk assessment. EPA 

acknowledged that it had had 

insufficient time to complete its 

drinking water assessment and its 

review of data addressing the potential 

for neurodevelopmental effects. 

Although EPA noted that further 

evaluation might enable more tailored 

risk mitigation, EPA was unable to 

conclude, based on the information 

before EPA at the time, that the 

tolerances were safe, since the aggregate 

exposure to chlorpyrifos exceeded safe 

levels. 

On December 10, 2015, the Ninth 

Circuit issued a further order requiring 

EPA to take final action on its proposed 

revocation rule and issue its final 

response to the Petition by December 

30, 2016. In re Pesticide Action Network 

N. Am., 808 F.3d 402 (9th Cir. 2015). In 

response to EPA’s request for an 

extension of the deadline in order to be 

able to fully consider the July 2016 

FIFRA Scientific Advisory Panel (SAP) 

report regarding chlorpyrifos toxicology, 

the Ninth Circuit ordered EPA to 

complete its final action by March 31, 

2017. In re Pesticide Action Network of 

North America v. EPA, 840 F.3d 1014 

(9th Cir. 2016). Following that order, 

EPA published a Notice of Data 

Availability (NODA), seeking comment 

on EPA’s revised risk assessment and 

water assessment and reopening the 

comment period on the proposal to 

revoke tolerances. (81 FR 81049, 

November 17, 2016) (FRL–9954–65). 

On March 29, 2017, and as published 

in the Federal Register on April 5, 2017, 

the EPA issued an order denying the 

Petition (the Denial Order) (82 FR 

16581). The specific responses are 

described in full in that Denial Order 

and summarized again in the Agency’s 

denial of objections (84 FR 35555, July 

24, 2019) (FRL–9997–06). EPA’s Denial 

Order did not issue a determination 

concerning the safety of chlorpyrifos. 

Rather, EPA concluded that, despite 

several years of study, the science 

addressing neurodevelopmental effects 

remained unresolved and that further 

evaluation of the science on this issue 

during the remaining time for 

completion of registration review was 

warranted. EPA therefore denied the 

remaining Petition claims, concluding 

that it was not required to complete— 

and would not complete—the human 

health portion of the registration review 

or any associated tolerance revocation of 

chlorpyrifos without resolution of those 

issues during the ongoing FIFRA 

registration review of chlorpyrifos. 

C. Objections and EPA’s Denial of 

Objections 

In June 2017, several public interest 

groups and states filed objections to the 

Denial Order pursuant to the procedures 

in FFDCA section 408(g)(2). 

Specifically, Earthjustice submitted 

objections on behalf of the following 12 

public interest groups: Petitioners 

PANNA and NRDC, United Farm 

Workers, California Rural Legal 

Assistance Foundation, Farmworker 

Association of Florida, Farmworker 

Justice, GreenLatinos, Labor Council for 

Latin American Advancement, League 

of United Latin American Citizens, 

Learning Disabilities Association of 

America, National Hispanic Medical 

Association and Pineros y Campesinos 

Unidos del Noroeste. Another public 

interest group, the North Coast River 

Alliance, submitted separate objections. 

With respect to the states, New York, 

Washington, California, Massachusetts, 

Maine, Maryland, and Vermont 

submitted a joint set of objections (Ref. 

1). The objections focused on three main 

topics: (1) The Objectors asserted that 

the FFDCA requires that EPA apply the 

FFDCA safety standard in reviewing any 

petition to revoke tolerances and that 

EPA’s decision to deny the Petition 

without making a safety finding failed to 

apply that standard; (2) The Objectors 

contended that the risk assessments 

EPA conducted in support of the 2015 

proposed rule and the 2016 Revised 

Human Health Risk Assessment (HHRA) 

demonstrated that chlorpyrifos results 

in unsafe drinking water exposures and 

adverse neurodevelopmental effects and 

that EPA therefore was required to issue 

a final rule revoking all chlorpyrifos 

tolerances; and (3) The Objectors 

claimed that EPA committed procedural 

error in failing to respond to comments, 

and they specifically pointed to 

comments related to 

neurodevelopmental effects, inhalation 

risk, and Dow AgroSciences’ (now doing 

business as Corteva AgriScience) 

physiologically based pharmacokinetic 

model (PBPK model) used in EPA’s 

2014 and 2015 human health risk 

assessments, which are discussed 

further in Unit V. 

On July 18, 2019, EPA issued a final 

order denying all objections to the 

Denial Order and thereby completing 

EPA’s administrative denial of the 

Petition (the Final Order) (84 FR 35555). 

Again, the Final Order did not issue a 

determination concerning the safety of 

chlorpyrifos. Rather, EPA denied the 

objections in part on the grounds that 

the data concerning 

neurodevelopmental toxicity were not 

sufficiently valid, complete, and reliable 

to meet the petitioners’ burden. 

D. Judicial Challenge to Objections 

Denial and 2021 Ninth Circuit Order 

On August 7, 2019, the Objectors 

(LULAC Petitioners) and States 

petitioned the Ninth Circuit for review 

of the Denial Order and the Final Order. 

The LULAC Petitioners and States 

argued that EPA was compelled to grant 

the 2007 Petition and revoke 

chlorpyrifos tolerances because (1) EPA 

lacked authority to maintain 

chlorpyrifos tolerances without an 

affirmative finding that chlorpyrifos is 

safe, (2) EPA’s findings that chlorpyrifos 

is unsafe in the Agency’s risk 

assessments from 2014 and 2016, 

compel it to revoke chlorpyrifos 

tolerances, and (3) The 2007 Petition 

provided a sufficient basis for EPA to 

reconsider the question of chlorpyrifos’s 

safety and was not required to prove 

that a pesticide is unsafe. 

On April 29, 2021, the Ninth Circuit 

issued its decision, finding that when 

EPA denied the 2007 Petition to revoke 

chlorpyrifos tolerances, it was 

essentially leaving those chlorpyrifos 

tolerances in effect, which, the Court 

noted, the FFDCA only permits if EPA 

has made a determination that such 

tolerances were safe. League of United 


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Latin Am. Citizens v. Regan, 996 F.3d. 

673 (9th Cir. 2021). Although EPA 

argued that it was not compelled to 

reconsider its safety determination 

because the 2007 Petition had failed to 

meet the threshold requirement of 

providing reliable evidence that the 

tolerances were unsafe, the Court found 

that the Petition provided the necessary 

‘‘reasonable grounds,’’ which triggered 

EPA’s duty to ensure the tolerances 

were safe. Id. at 695. Since EPA’s Denial 

Order and Final Order failed to make 

any safety determinations for 

chlorpyrifos, the Court concluded that 

EPA violated the FFDCA by leaving 

those tolerances in place without the 

requisite safety findings. Id. at 695–96. 

Moreover, in light of the record before 

the Court, including the 2016 HHRA 

indicating that the current chlorpyrifos 

tolerances are not safe, the Court found 

EPA’s denial of the 2007 Petition to be 

arbitrary and capricious. Id. at 697. 

Based on the available record, the Court 

concluded that EPA must grant the 

Petition and issue a final rule modifying 

or revoking the tolerances under FFDCA 

section 408(d)(4)(A)(i). Id. at 701. 

The Court recognized that EPA had 

been continuing to evaluate chlorpyrifos 

in registration review and had issued 

additional regulatory documents 

concerning chlorpyrifos after the record 

closed in the litigation, e.g., the 2020 

Proposed Interim Registration Review 

Decision and 2020 SAP, both of which 

are discussed in more detail in Unit V. 

below, and noted that such information 

could be relevant to a safety 

determination. Id. at 703. The Court 

allowed that if the new information 

could support a safety determination, 

EPA might issue a final rule modifying 

chlorpyrifos tolerances rather than 

revoking them, although the Court 

directed EPA to act ‘‘immediately’’ and 

not engage in ‘‘further factfinding.’’ Id. 

at 703. As a result, the Court ordered 

EPA to: (1) Grant the 2007 Petition; (2) 

Issue a final rule within 60 days of the 

issuance of the mandate that either 

revokes all chlorpyrifos tolerances or 

modifies chlorpyrifos tolerances, 

provided that such modification is 

supported by a safety finding, and (3) 

Modify or cancel related FIFRA 

registrations for food use in a timely 

fashion. Id. at 703–04. Since the 

mandate was issued on June 21, 2021, 

the deadline for issuing this final rule is 

August 20, 2021. 

V. Chlorpyrifos Background and 

Regulatory History 

Chlorpyrifos (0,0-diethyl-0–3,5,6- 

trichloro-2-pyridyl phosphorothioate) is 

a broad-spectrum, chlorinated 

organophosphate (OP) insecticide. 

Given the complex scientific nature of 

the issues reflected in this rule, EPA is 

alerting the reader that many of the 

technical terms used in this unit will be 

described more fully in a subsequent 

unit. 

Chlorpyrifos, like other OP pesticides, 

affects the nervous system by inhibiting 

acetylcholinesterase (AChE), an enzyme 

necessary for the proper functioning of 

the nervous system. This can ultimately 

lead to signs of neurotoxicity. As 

discussed in more detail below, while 

there are data that indicate an 

association between chlorpyrifos and 

neurodevelopmental outcomes, there 

remains uncertainty in the doseresponse relationship and the levels at 

which these outcomes occur. In an effort 

to resolve this scientific uncertainty, 

evaluation of toxicology and 

epidemiology studies of chlorpyrifos, 

specific to determining the appropriate 

regulatory endpoint, has been the focus 

of EPA’s work on chlorpyrifos for over 

a decade. 

Chlorpyrifos has been registered for 

use in the United States since 1965. 

Currently registered use sites include a 

large variety of food crops (including 

fruit and nut trees, many types of fruits 

and vegetables, and grain crops), and 

non-food use settings (e.g., golf course 

turf, industrial sites, greenhouse and 

nursery production, sod farms, and 

wood products). Public health uses 

include aerial and ground-based fogger 

mosquito adulticide treatments, roach 

bait products, and individual fire ant 

mound treatments. In 2000, the 

chlorpyrifos registrants reached an 

agreement with EPA to voluntarily 

cancel all residential use products 

except those registered for ant and roach 

baits in child-resistant packaging and 

fire ant mound treatments. See, e.g., 65 

FR 76233, December 6, 2000) (FRL– 

6758–2); 66 FR 47481, September 12, 

2001) (FRL–6799–7). 

In 2006, EPA completed FIFRA 

section 4 reregistration and FFDCA 

tolerance reassessment for chlorpyrifos 

and the OP class of pesticides, 

concluding that the existing tolerances 

were safe and that chlorpyrifos 

continued to meet the FIFRA standard 

for registration. In that effort, EPA relied 

on RBC AChE inhibition as the endpoint 

for examining risk. 

Subsequently, given ongoing 

scientific developments in the study of 

the OPs generally, EPA chose to 

prioritize the FIFRA section 3(g) 

registration review (the subsequent 

round of re-evaluation following 

reregistration) of chlorpyrifos and the 

OP class. The registration review of 

chlorpyrifos and the OPs has presented 

EPA with numerous novel scientific 

issues which the Agency has taken to 

multiple independent FIFRA SAP 

reviews. (Note: The SAP is a federal 

advisory committee created by FIFRA 

section 25(d), 7 U.S.C. 136w(d), and 

serves as EPA’s primary source of peer 

review for significant regulatory and 

policy matters involving pesticides.) 

These SAPs, which have included the 

review of new worker and nonoccupational exposure methods, 

experimental toxicology and 

epidemiology, and the evaluation of a 

chlorpyrifos-specific physiologicallybased pharmacokineticpharmacodynamic (PBPK–PD, see Unit 

VII. for definitions) model. These FIFRA 

SAP reviews have resulted in significant 

developments in EPA’s risk assessments 

generally, and, more specifically, in the 

study of chlorpyrifos’s effects. In 

particular, and partly in response to the 

issues raised in the 2007 Petition, EPA 

has conducted extensive reviews of 

available data to evaluate the possible 

connection between chlorpyrifos and 

adverse neurodevelopmental effects, 

and to assess whether the 

neurodevelopmental effects could be 

used to determine points of departure 

(PoDs) for assessing chlorpyrifos. On 

this particular topic, EPA has convened 

three FIFRA SAP reviews. EPA has 

taken FIFRA SAP recommendations into 

consideration as it has developed risk 

assessments and regulatory documents 

for chlorpyrifos. The remainder of this 

Unit provides a brief regulatory 

overview for chlorpyrifos by presenting 

a summary of the chronology of the 

FIFRA SAPs and Agency assessments of 

chlorpyrifos. 

The 2008 FIFRA SAP evaluated the 

Agency’s preliminary review of 

available literature and research on 

epidemiology in mothers and children 

following exposures to chlorpyrifos and 

other OPs, laboratory studies on animal 

behavior and cognition, AChE 

inhibition, and mechanisms of action. 

(Ref. 3) The 2008 FIFRA SAP 

recommended that AChE inhibition 

remain as the source of data for the 

points of departure (PoDs, see Unit VII. 

for definitions), but noted that despite 

some uncertainties, the Columbia Center 

for Children’s Environmental Health 

(CCCEH) epidemiologic studies ‘‘is 

epidemiologically sound’’ and 

‘‘provided extremely valuable 

information’’ for evaluating the 

potential neurodevelopmental effects of 

chlorpyrifos (Ref. 3). See Unit VI.A.2. 

for neurodevelopmental toxicity. 

The 2010 FIFRA SAP favorably 

reviewed EPA’s 2010 draft 

epidemiology framework. (Ref. 4, 5) 

This draft framework, titled 

‘‘Framework for Incorporating Human 


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Epidemiologic & Incident Data in Risk 

Assessments in Pesticides,’’ described 

the use of the Bradford Hill Criteria as 

modified in the Mode of Action 

Framework to integrate epidemiology 

information with other lines of 

evidence. As suggested by the 2010 

FIFRA SAP, EPA did not immediately 

finalize the draft framework but instead 

used it in several pesticide evaluations 

prior to making revisions and finalizing 

it. EPA’s Office of Pesticide Program’s 

(OPP) finalized this epidemiology 

framework in December 2016 (Ref. 5). 

In 2011, EPA released its preliminary 

human health risk assessment (2011 

HHRA) for the registration review of 

chlorpyrifos. The 2011 HHRA used 10% 

RBC AChE inhibition from laboratory 

rats as the critical effect (or PoD) for 

extrapolating risk. It also used the 

default 10X uncertainty factors for interand intra-species extrapolation. The 10X 

FQPA SF was removed with a note to 

the public that a weight of evidence 

(WOE) evaluation would be 

forthcoming, as described in the 2010 

draft ‘‘Framework for Incorporating 

Human Epidemiologic & Incident Data 

in Health Risk Assessment.’’ 

In 2011, EPA convened a meeting of 

the FIFRA SAP to review the PBPK–PD 

model for chlorpyrifos. The panel made 

numerous recommendations for the 

improvement of the model for use in 

regulatory risk assessment, including 

the inclusion of dermal and inhalation 

routes. From 2011–2014, Dow 

AgroSciences, in consultation with EPA, 

refined the PBPK–PD model, and those 

refinements were sufficient to allow for 

use of the PBPK–PD model in the next 

HHRA. 

In 2012, the Agency convened another 

meeting of the FIFRA SAP to review the 

latest experimental data related to RBC 

AChE inhibition, cholinergic and noncholinergic adverse outcomes, including 

neurodevelopmental studies on 

behavior and cognition effects. The 

Agency also performed an in-depth 

analysis of the available chlorpyrifos 

biomonitoring data and of the available 

epidemiologic studies from three major 

children’s health cohort studies in the 

United States, including those from the 

CCCEH, Mount Sinai, and University of 

California, Berkeley. The Agency 

explored plausible hypotheses on mode 

of actions/adverse outcome pathways 

(MOAs/AOPs) leading to 

neurodevelopmental outcomes seen in 

the biomonitoring and epidemiology 

studies. 

The 2012 FIFRA SAP described the 

Agency’s epidemiology review as ‘‘very 

clearly written, accurate’’ and ‘‘very 

thorough review’’. (Ref. 6 at 50–52, 53) 

It went further to note that it ‘‘believes 

that the [Agency’s] epidemiology review 

appropriately concludes that the studies 

show some consistent associations 

relating exposure measures to abnormal 

reflexes in the newborn, pervasive 

development disorder at 24 or 36 

months, mental development at 7–9 

years, and attention and behavior 

problems at 3 and 5 years of 

age. . . . .’’ The 2012 FIFRA SAP 

concluded that the RBC AChE 

inhibition remained the most robust 

dose-response data, though expressed 

significant concerns about the degree to 

which 10% RBC AChE inhibition is 

protective for neurodevelopmental 

effects, pointing to evidence from 

epidemiology, in vivo animal studies, 

and in vitro mechanistic studies, and 

urged the EPA to find ways to use the 

CCCEH data. 

In 2014, EPA released a revised 

human health risk assessment (2014 

HHRA. (Ref. 7). The revised assessment 

used the chlorpyrifos PBPK–PD model 

for deriving human PoDs for RBC AChE 

inhibition, thus obviating the need for 

the inter-species extrapolation factor (as 

explained later in this Unit) and 

providing highly refined PoDs which 

accounted for gender, age, duration and 

route specific exposure considerations. 

The PBPK–PD model was also used to 

develop data derived intra-species 

factors for some lifestages. The 10X 

FQPA SF was retained based on the 

outcome of the 2012 FIFRA SAP and 

development of a WOE analysis on 

potential for neurodevelopmental 

outcomes according to EPA’s 

‘‘Framework for Incorporating Human 

Epidemiologic & Incident Data in Risk 

Assessments for Pesticides.’’ The 2014 

HHRA, taken together with the Agency’s 

drinking water assessment, identified 

estimated aggregate risks exceeding the 

level of concern for chlorpyrifos. 

On November 6, 2015, EPA issued a 

proposed rule to revoke all tolerances of 

chlorpyrifos, based on the aggregate 

risks exceeding the level of concern (80 

FR 69079) (FRL–9935–92). In this 

proposed rulemaking, EPA specified 

that it was unable to conclude that 

aggregate exposures from use of 

chlorpyrifos met the FFDCA’s 

‘‘reasonable certainty of no harm’’ 

standard due to risks identified from the 

drinking watering using a national-scale 

assessment (i.e., using default values 

and conservative assumptions). At that 

time, the EPA had not completed a 

refined drinking water assessment (i.e., 

a higher-tier and more resourceintensive assessment relying on more 

targeted inputs) or an additional 

analysis of the hazard of chlorpyrifos 

that was suggested by several 

commenters to the 2014 HHRA. Those 

commenters raised the concern that the 

use of 10% RBC AChE inhibition for 

deriving PoDs for chlorpyrifos may not 

provide a sufficiently health protective 

human health risk assessment given the 

potential for neurodevelopmental 

outcomes. 

In 2015, EPA conducted additional 

hazard analyses using data on 

chlorpyrifos levels in fetal cord blood 

reported by the CCCEH study 

investigators. The Agency convened 

another meeting of the FIFRA SAP in 

April 2016 to evaluate a proposal of 

using cord blood data from the CCCEH 

epidemiology studies as the source of 

data for the PoDs. The 2016 SAP did not 

support the ‘‘direct use’’ of the cord 

blood and working memory data for 

deriving the regulatory endpoint, due in 

part to insufficient information about 

timing and magnitude of chlorpyrifos 

applications in relation to cord blood 

concentrations at the time of birth, 

uncertainties about the prenatal 

window(s) of exposure linked to 

reported effects, lack of a second 

laboratory to reproduce the analytical 

blood concentrations, and lack of raw 

data from the epidemiology study. (Ref. 

8) 

Despite its critiques of uncertainties 

in the CCCEH studies, the 2016 FIFRA 

SAP expressed concern that 10% RBC 

AChE inhibition is not sufficiently 

protective of human health. 

Specifically, the FIFRA SAP stated that 

it ‘‘agrees that both epidemiology and 

toxicology studies suggest there is 

evidence for adverse health outcomes 

associated with chlorpyrifos exposures 

below levels that result in 10% RBC 

AChE inhibition (i.e., toxicity at lower 

doses).’’ (Id. at 18). (Ref. 8) 

Taking into consideration the 

conclusions of the 2016 SAP, EPA 

issued another HHRA using a dose 

reconstruction approach to derive the 

PoD based on the neurodevelopmental 

effects observed in the CCCEH study. In 

2016, EPA also issued a revised 

drinking water assessment (2016 DWA). 

EPA issued a Notice of Data Availability 

seeking public comment on the 2016 

HHRA and 2016 DWA. (81 FR 81049, 

November 17, 2016) (FRL–9954–65). 

In 2017, in response to a Ninth Circuit 

order, EPA denied the 2007 Petition on 

the grounds that ‘‘further evaluation of 

the science during the remaining time 

for completion of registration review is 

warranted to achieve greater certainty as 

to whether the potential exists for 

adverse neurodevelopmental effects to 

occur from current human exposures to 

chlorpyrifos.’’ (82 FR at 16583). As part 

of this commitment to further evaluate 

the science, EPA evaluated the new 

laboratory animal studies with results 


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suggesting effects on the developing 

brain occur at doses lower than doses 

that cause AChE inhibition, and 

concluded that they are not sufficient 

for setting a PoD. While EPA sought to 

verify the conclusions of the 

epidemiology studies conducted by 

Columbia University it has been unable 

to confirm the findings of the CCCEH 

papers or conduct alternative statistical 

analyses to evaluate the findings. In 

summary, while EPA sought to address 

the potential neurodevelopmental 

effects associated with chlorpyrifos 

exposure over the past decade, these 

efforts ultimately concluded with the 

lack of a suitable regulatory endpoint 

based on these potential effects. 

However, these efforts do not alleviate 

the Agency’s concerns regarding 

potential neurodevelopmental effects. 

In October 2020, EPA released its 

latest human health risk assessment 

(2020 HHRA) and drinking water 

assessment (2020 DWA). (Ref. 9 and 10) 

Due to the shortcomings of the data 

upon which the 2016 HHRA was based 

and the uncertainty surrounding the 

levels around which 

neurodevelopmental effects may occur, 

the 2020 HHRA uses the same endpoint 

and PoDs as those used in the 2014 

HHRA (i.e., the PBPK–PD model has 

been used to estimate exposure levels 

resulting in 10% RBC AChE inhibition 

following acute (single day, 24 hours) 

and steady state (21-day) exposures for 

a variety of exposure scenarios for 

chlorpyrifos and/or chlorpyrifos oxon). 

The 2020 HHRA retained the default 

10X FQPA SF, but also presented risk 

estimates at a reduced 1X FQPA SF, 

though it did not adopt or attempt to 

justify use of this approach. 

Then, in December 2020, as part of its 

FIFRA registration review, EPA issued 

its Proposed Interim Registration 

Review Decision (2020 PID) for 

chlorpyrifos (85 FR 78849, December 7, 

2020) (FRL–10017–13). The 2020 PID 

was based on comparing estimates in 

the 2020 HHRA with the values from 

the 2020 DWA, and retaining the 10X 

FQPA safety factor, the PID proposed to 

limit applications of chlorpyrifos in this 

country would be reduced to certain 

uses in certain regions of the United 

States. The PID proposed to conclude 

that the Agency could make a safety 

finding for the approach in this path 

forward, as risk would be based on 

limited uses in limited geographic areas, 

as specified. This proposed path 

forward was intended to offer to 

stakeholders a way to mitigate the 

aggregate risk from chlorpyrifos, which 

the Agency had determined would 

exceed risk levels of concern without 

the proposed use restrictions. 

In December 2020, EPA requested 

public comment on the 2020 PID, 2020 

HHRA, and 2020 DWA. EPA extended 

the 60-day comment period by 30 days 

and it closed on March 7, 2021. 

VI. EPA’s Hazard Assessment for 

Chlorpyrifos 

A. General Approach to Hazard 

Identification, Dose-Response 

Assessment, and Extrapolation 

Any risk assessment begins with an 

evaluation of a chemical’s inherent 

properties, and whether those properties 

have the potential to cause adverse 

effects (i.e., a hazard identification). In 

evaluating toxicity or hazard, EPA 

reviews toxicity data, typically from 

studies with laboratory animals, to 

identify any adverse effects on the test 

subjects. Where available and 

appropriate, EPA will also take into 

account studies involving humans, 

including human epidemiological 

studies. The animal toxicity database for 

a conventional, food use pesticide 

usually consists of studies investigating 

a broad range of endpoints including 

potential for carcinogenicity, 

mutagenicity, developmental and 

reproductive toxicity, and neurotoxicity. 

These studies include gross and 

microscopic effects on organs and 

tissues, functional effects on bodily 

organs and systems, effects on blood 

parameters (such as red blood cell 

count, hemoglobin concentration, 

hematocrit, and a measure of clotting 

potential), effects on the concentrations 

of normal blood chemicals (including 

glucose, total cholesterol, urea nitrogen, 

creatinine, total protein, total bilirubin, 

albumin, hormones, and enzymes such 

as alkaline phosphatase, alanine 

aminotransferase and cholinesterases), 

and behavioral or other gross effects 

identified through clinical observation 

and measurement. EPA examines 

whether adverse effects are caused by 

different durations of exposure ranging 

from short-term (acute) to long-term 

(chronic) pesticide exposure and 

different routes of exposure (oral, 

dermal, inhalation). Further, EPA 

evaluates potential adverse effects in 

different age groups (adults as well as 

fetuses and juveniles). (Ref. 11 at 8–10). 

Once a pesticide’s potential hazards 

are identified, EPA determines a 

toxicological level of concern for 

evaluating the risk posed by human 

exposure to the pesticide. In this step of 

the risk assessment process, EPA 

essentially evaluates the levels of 

exposure to the pesticide at which 

effects might occur. An important aspect 

of this determination is assessing the 

relationship between exposure (dose) 

and response (often referred to as the 

dose-response analysis). In evaluating a 

chemical’s dietary risks, EPA uses a 

reference dose (RfD) approach, which 

typically involves a number of 

considerations including: 

• A ‘‘point of departure’’ (PoD): 

Typically, the PoD is the value from a 

dose-response curve that is at the low 

end of the observable data in laboratory 

animals and that is the toxic dose that 

serves as the ‘starting point’ in 

extrapolating a risk to the human 

population, although a PoD can also be 

derived from human data as well. PoDs 

are selected to be protective of the most 

sensitive adverse toxic effect for each 

exposure scenario, and are chosen from 

toxicity studies that show clearly 

defined No Observed Adverse Effect 

Levels (NOAELs) or Lowest Observed 

Adverse Effect Levels (LOAELs), doseresponse relationships, and 

relationships between the chemical 

exposure and effect. EPA will select 

separate PoDs, as needed, for each 

expected exposure duration (e.g., acute, 

chronic, short-term, intermediate-term) 

and route of exposure (e.g., oral, dermal, 

inhalation). For chlorpyrifos, as 

discussed later in this Unit, EPA 

derived PoDs based on 10% RBC AChE 

inhibition. 

• Interspecies extrapolation: Because 

most PoDs are derived from toxicology 

studies in laboratory animals, there is a 

need to extrapolate from animals to 

humans. In typical risk assessments, a 

default tenfold (10X) uncertainty factor 

is used to address the potential for a 

difference in toxic response between 

humans and animals used in toxicity 

tests. For chlorpyrifos, as described 

further below, EPA used a sophisticated 

model called a physiologically based 

pharmacokinetic-pharmacodynamic 

(PBPK–PD) model that accounts for 

differences in laboratory animals and 

humans, thereby obviating the need for 

the default interspecies factor. 

• Intraspecies extrapolation: To 

address the potential for differences in 

sensitivity in the toxic response across 

the human population, EPA conducts 

intraspecies extrapolation. In typical 

risk assessments, a 10X default 

uncertainty factor is used. For 

chlorpyrifos, the PBPK–PD model used 

to derive PoDs also accounts for 

differences in metabolism and toxicity 

response across the human population 

for some age groups and some 

subpopulations, which allows the 

default factor of 10X to be refined in 

accordance with EPA’s 2014 Guidance 

for Applying Quantitative Data to 

Develop Data-Derived Extrapolation 

Factors for Interspecies and Intraspecies 

Extrapolation. 


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• Food Quality Protection Act safety 

factor (FQPA SF)): The FFDCA section 

408(b)(2)(C) instructs EPA, in making its 

‘‘reasonable certainty of no harm’’ 

finding, that in ‘‘the case of threshold 

effects, an additional tenfold margin of 

safety for the pesticide chemical residue 

and other sources of exposure shall be 

applied for infants and children to take 

into account potential pre- and postnatal toxicity and completeness of data 

with respect to exposure and toxicity to 

infants and children.’’ Section 

408(b)(2)(C) further states that ‘‘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.’’ For 

chlorpyrifos, as discussed later in this 

Unit, EPA is retaining the default 10X 

FQPA SF. 

In the human health risk assessment 

process, as indicated above, EPA uses 

the selected PoD to calculate a RfD for 

extrapolating risk. The RfD is calculated 

by dividing the selected PoD by any 

applicable interspecies and intraspecies 

factors and other relevant uncertainty 

factors such as LOAEL to NOAEL factor 

or database uncertainty factor. 

After calculating the RfD, as indicated 

above, EPA retains an additional safety 

factor of 10X to protect infants and 

children (the FQPA safety factor), unless 

reliable data support selection of a 

different factor, as required under the 

FFDCA. As described in EPA’s policy 

for determining the appropriate FQPA 

safety factor, this additional safety factor 

often overlaps with other traditional 

uncertainty factors (e.g., LOAEL to 

NOAEL factor or database uncertainty 

factor), but it might also account for 

residual concerns related to pre- and 

postnatal toxicity or exposure. (Ref. 35 

at 13–16) In implementing FFDCA 

section 408, EPA calculates a variant of 

the RfD referred to as a Population 

Adjusted Dose (PAD), by dividing the 

RfD by the FQPA SF. Risk estimates less 

than 100% of the PAD are safe. 

B. Toxicological Effects of Chlorpyrifos 

Consistent with FFDCA section 

408(b)(2)(D), EPA has reviewed the 

available scientific data and other 

relevant information for chlorpyrifos in 

support of this action. For over a 

decade, EPA has evaluated the scientific 

evidence surrounding the different 

health effects associated with 

chlorpyrifos. The Agency has conducted 

extensive reviews of the scientific 

literature on health outcomes associated 

with chlorpyrifos and presented 

approaches for evaluating and using that 

information to the FIFRA SAP on 

several occasions, as discussed above in 

Unit V. Chlorpyrifos has been tested in 

toxicological studies for the potential to 

cause numerous different adverse 

outcomes (e.g., reproductive toxicity, 

developmental toxicity, cancer, 

genotoxicity, dermal toxicity, endocrine 

toxicity, inhalation toxicity, and 

immunotoxicity). The inhibition of 

AChE leading to cholinergic 

neurotoxicity and the potential for 

effects on the developing brain (i.e., 

neurodevelopmental effects) are the 

most sensitive effects seen in the 

available data. (2020 HHRA p. 6). The 

SAP reports have rendered numerous 

recommendations for additional study 

and sometimes conflicting advice for 

how EPA should consider (or not 

consider) the data in conducting EPA’s 

registration review human health risk 

assessment for chlorpyrifos. 

Unit VI. discusses the Agency’s 

assessment of the science relating to 

AChE inhibition and the potential for 

neurodevelopmental effects. Other 

adverse outcomes besides AChE 

inhibition and neurodevelopment are 

less sensitive and are thus not discussed 

in detail here. Further information 

concerning those effects can be found in 

the 2000 human health risk assessment 

which supported the RED and the 2011 

preliminary human health risk 

assessment. (Ref. 12 and 13). 

1. Acetylcholinesterase (AChE) 

Inhibition 

Chlorpyrifos, like other OP pesticides, 

affects the nervous system by inhibiting 

AChE, an enzyme necessary for the 

proper functioning of the nervous 

system and ultimately leading to signs 

of neurotoxicity. This mode of action, in 

which AChE inhibition leads to 

neurotoxicity, is well-established, and 

thus has been used as basis for the PoD 

for OP human health risk assessments, 

including chlorpyrifos. This science 

policy is based on decades of work, 

which shows that AChE inhibition is 

the initial event in the pathway to acute 

cholinergic neurotoxicity. 

The Agency has conducted a 

comprehensive review of the available 

data and public literature regarding this 

adverse effect from chlorpyrifos. (Ref. 8 

at 24–25, Ref. 13 at 25–27) There are 

many chlorpyrifos studies evaluating 

RBC AChE inhibition or the brain in 

multiple lifestages (gestational, fetal, 

post-natal, and non-pregnant adult), 

multiple species (rat, mouse, rabbit, dog, 

human), methods of oral administration 

(oral gavage with corn oil, dietary, 

gavage via milk) and routes of exposure 

(oral, dermal, inhalation via vapor and 

via aerosol). In addition, chlorpyrifos is 

unique in the availability of AChE data 

from peripheral tissues in some studies 

(e.g., heart, lung, liver). There are also 

literature studies comparing the in vitro 

AChE response to a variety of tissues 

which show similar sensitivity and 

intrinsic activity. Across the database, 

brain AChE tends to be less sensitive 

than RBC AChE or peripheral AChE. In 

oral studies, RBC AChE inhibition is 

generally similar in response to 

peripheral tissues. Thus, the in vitro 

data and oral studies combined support 

the continued use of RBC AChE 

inhibition as the critical effect for 

quantitative dose-response assessment. 

Female rats tend to be more sensitive 

than males to these AChE effects. For 

chlorpyrifos, there are data from 

multiple studies which provide robust 

RBC AChE data in pregnant, lactating, 

and non-pregnant female rats from oral 

exposure (e.g., developmental 

neurotoxicity (DNT), reproductive, and 

subchronic data). 

In addition, studies are available in 

juvenile pups which show agedependent differences, particularly 

following acute exposures, in sensitivity 

to chlorpyrifos and its oxon. As 

discussed above, this sensitivity is not 

derived from differences in the AChE 

enzyme itself but instead are derived 

largely from the immature metabolic 

clearance capacity in the juveniles. 

2. Neurodevelopmental Toxicity 

In addition to information on the 

effects of chlorpyrifos on AChE, there is 

an extensive body of information (in the 

form of laboratory animal studies, 

epidemiological studies, and 

mechanistic studies) studying the 

potential effects on neurodevelopment 

in infants and children following 

exposure to OPs, including chlorpyrifos. 

There are numerous laboratory animal 

studies on chlorpyrifos in the literature 

that have evaluated the impact of 

chlorpyrifos exposure in pre- and postnatal dosing on the developing brain. 

These studies vary substantially in their 

study design, but all involve gestational 

and/or early postnatal dosing with 

behavioral evaluation from adolescence 

to adulthood. The data provide 

qualitative support for chlorpyrifos to 

potentially impact the developing 

mammalian brain with adverse 

outcomes in several neurological 

domains including cognitive, anxiety 

and emotion, social interactions, and 

neuromotor function. It is, however, 

important to note that there is little 

consistency in patterns of effects across 

studies. In addition, most of these 

studies use doses that far exceed EPA’s 

10% benchmark response level for RBC 

AChE inhibition. There are only a few 

studies with doses at or near the 10% 

brain or RBC AChE inhibition levels; 


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among these only studies from Carr 

laboratory at Mississippi State 

University are considered by EPA to be 

high quality. EPA has concluded that 

the laboratory animal studies on 

neurodevelopmental outcomes are not 

sufficient for quantitatively establishing 

a PoD. Moreover, EPA has further 

concluded that the laboratory animal 

studies do not support a conclusion that 

adverse neurodevelopmental outcomes 

are more sensitive than 10% RBC AChE 

inhibition. (Ref. 8 at 25–31, Ref. 9 at 88– 

89). 

EPA evaluated numerous 

epidemiological studies on chlorpyrifos 

and other OP pesticides in accordance 

with the ‘‘Framework for Incorporating 

Human Epidemiologic & Incident Data 

in Health Risk Assessment.’’ (Ref. 8, 14, 

and 15) The most robust epidemiologic 

research comes from three prospective 

birth cohort studies. These include: (1) 

The Mothers and Newborn Study of 

North Manhattan and South Bronx 

performed by the Columbia Children’s 

Center for Environmental Health 

(CCCEH) at Columbia University; (2) the 

Mount Sinai Inner-City Toxicants, Child 

Growth and Development Study or the 

‘‘Mt. Sinai Child Growth and 

Development Study;’’ and (3) the Center 

for Health Assessment of Mothers and 

Children of Salinas Valley 

(CHAMACOS) conducted by researchers 

at University of California Berkeley. 

(Ref. 8 at 32–43). 

In the case of the CCCEH study, 

which specifically evaluated the 

possible connections between 

chlorpyrifos levels in cord blood and 

neurodevelopmental outcomes on a 

specific cohort, there are a number of 

notable associations. (Ref. 8 at 36–38). 

Regarding infant and toddler 

neurodevelopment, the CCCEH authors 

reported statistically significant deficits 

of 6.5 points on the Psychomotor 

Development Index at three years of age 

when comparing high to low exposure 

groups. Notably, these decrements 

persist even after adjustment for group 

and individual level socioeconomic 

variables. These investigators also 

observed increased odds of mental delay 

and psychomotor delay at age three 

when comparing high to low exposure 

groups. The CCCEH authors also report 

strong, consistent evidence of a positive 

association for attention disorders, 

attention deficit hyperactivity disorder 

(ADHD), and pervasive development 

disorder (PDD) when comparing high to 

low chlorpyrifos exposure groups. 

Moreover, it was reported that for 

children in the CCCEH cohort at age 

seven for each standard deviation 

increase in chlorpyrifos cord blood 

exposure, there is a 1.4% reduction in 

Full-Scale IQ and a 2.8% reduction in 

Working Memory. In addition, the 

CCCEH authors evaluated the 

relationship between prenatal 

chlorpyrifos exposure and motor 

development/movement and reported 

elevated risks of arm tremor in children 

around 11 years of age in the CCCEH 

cohort. 

Notwithstanding the observed 

associations, EPA and the 2012 and 

2016 FIFRA SAPs identified multiple 

uncertainties in the CCCEH 

epidemiology studies (Ref. 6 and 8). 

Some of these include the relatively 

modest sample sizes, which limited the 

statistical power; exposure at one point 

in prenatal time with no additional 

information regarding postnatal 

exposures; representativeness of a single 

point exposure where time-varying 

exposures or the ability to define 

cumulative exposures would be 

preferable; lack of specificity of a 

critical window of effect and the 

potential for misclassification of 

individual exposure measures; and lack 

of availability of the raw data from the 

studies that would allow verification of 

study conclusions. 

One of the notable uncertainties in the 

CCCEH epidemiology studies identified 

by EPA and the 2016 FIFRA SAP is the 

lack of specific exposure information on 

the timing, frequency, and magnitude of 

chlorpyrifos application(s) in the 

apartments of the women in the study. 

Despite extensive effort by EPA to 

obtain or infer this exposure 

information from various sources, the 

lack of specific exposure data remains a 

critical uncertainty. EPA made efforts in 

2014 and 2016 to develop dose 

reconstruction of the exposures to these 

women. These dose reconstruction 

activities represent the best available 

information and tools but are highly 

uncertain. In addition, the pregnant 

women and children in the CCCEH 

studies were exposed to multiple 

chemicals, including multiple potent 

AChE inhibiting OPs and N-methyl 

carbamates. Moreover, using EPA’s dose 

reconstruction methods from 2014 

suggest that the pregnant women likely 

did not exhibit RBC AChE inhibition 

above 10%. The 2012 and 2016 FIFRA 

SAP reports expressed concern that it is 

likely that the CCCEH findings occurred 

at exposure levels below those that 

result in 10% RBC AChE inhibition 

(Ref. 6 and 8). However, given the 

available CCCEH exposure information 

and the exposures to multiple potent 

AChE inhibiting pesticides, EPA cannot 

definitively conclude the level of AChE 

inhibition. EPA remains unable to make 

a causal linkage between chlorpyrifos 

exposure and the outcomes reported by 

CCCEH investigators. (Ref. 8) Moreover, 

given the uncertainties, particularly in 

the exposure information available from 

CCCEH (single timepoints, lack of time 

varying exposure, lack of knowledge 

about application timing), uncertainties 

remain about the dose-response 

relationships from the epidemiology 

studies. 

Finally, there are several lines of 

evidence for actions of chlorpyrifos 

distinct from the classical mode of 

action of AChE inhibition. This 

information has been generated from 

model systems representing different 

levels of biological organization and 

provide support for molecular initiating 

events (binding to the morphogenic site 

of AChE, muscarinic receptors, or 

tubulin), cellular responses (alterations 

in neuronal proliferation, 

differentiation, neurite growth, or 

intracellular signaling), and responses at 

the level of the intact nervous system 

(serotonergic tone, axonal transport). 

Among the many in vitro studies on 

endpoints relevant to the developing 

brain available for chlorpyrifos, only 

three have identified outcomes in 

picomole concentrations, including 

concentrations lower than those that 

elicit AChE inhibition in vitro. 

However, as is the case for many other 

developmental neurotoxicants, most of 

these studies have not been designed 

with the specific goal of construction or 

testing an adverse outcome pathway. 

Thus, there are not sufficient data 

available to test rigorously the causal 

relationship between effects of 

chlorpyrifos at the different levels of 

biological organization in the nervous 

system. (Ref. 8 at 27–31) 

Due to the complexity of nervous 

system development involving the 

interplay of many different cell types 

and developmental timelines, it is 

generally accepted that no single in vitro 

screening assay can recapitulate all the 

critical processes of neurodevelopment. 

As a result, there has been an 

international effort to develop a battery 

of new approach methodologies (NAMs) 

to inform the DNT potential for 

individual chemicals. This DNT NAM 

battery is comprised of in vitro assays 

that assess critical processes of 

neurodevelopment, including neural 

network formation and function, cell 

proliferation, apoptosis, neurite 

outgrowth, synaptogenesis, migration, 

and differentiation. In combination the 

assays in this battery provide a 

mechanistic understanding of the 

underlying biological processes that 

may be vulnerable to chemicallyinduced disruption. It is noteworthy, 

however, that to date the quantitative 

relationship between alterations in these 


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neurodevelopmental processes and 

adverse health outcomes has not been 

fully elucidated. Moreover, additional 

assays evaluating other critical 

neurodevelopmental processes such as 

myelination are still being developed 

(Ref. 15). 

In September 2020, EPA convened a 

FIFRA SAP on developing and 

implementing NAMs using methods 

such as in vitro techniques and 

computational approaches. Included in 

that consideration was use of the DNT 

NAM battery to evaluate OP compounds 

as a case study. These methods 

presented to the 2020 FIFRA SAP 

provide a more systematic approach to 

evaluating pharmacodynamic effects on 

the developing brain compared to the 

existing literature studies. Initial data 

from the NAM battery were presented to 

the SAP for 27 OP compounds, 

including chlorpyrifos and its 

metabolite, chlorpyrifos oxon, and, 

when possible, compared to in vivo 

results (by using in vitro to in vivo 

extrapolation). On December 21, 2020, 

the SAP released its final report and 

recommendations on EPA’s proposed 

use of the NAMs data. (Ref. 16). The 

advice of the SAP is currently being 

taken into consideration as EPA 

develops a path forward on NAMs, but 

analysis and implementation of NAMs 

for risk assessment of chlorpyrifos is in 

progress and was unable to be 

completed in time for use in this 

rulemaking. The Agency is continuing 

to explore the use of NAMs for the OPs, 

including chlorpyrifos, and intends to 

make its findings available as soon as it 

completes this work. 

C. Hazard Identification: Using AChE as 

the Toxicological Endpoint for Deriving 

PADs 

The RED for chlorpyrifos was 

completed in 2006 and relied on RBC 

AChE inhibition results from laboratory 

animals to derive PoDs and retained the 

FQPA 10X safety factor due to concerns 

over age-related sensitivity and 

uncertainty associated with potential 

neurodevelopmental effects observed in 

laboratory animals. Based on a review of 

all the studies (guideline data required, 

peer reviewed literature, mechanistic), 

AChE inhibition remains the most 

robust quantitative dose-response data 

and thus continues to be the critical 

effect for the quantitative risk 

assessment. This approach is consistent 

with the advice of the SAP from 2008 

and 2012. The Agency typically uses a 

10% response level for AChE inhibition 

in human health risk assessments. This 

response level is consistent with the 

2006 OP cumulative risk assessment 

and other single chemical OP risk 

assessments. (Ref. 17 and 18). 

In response to the 2015 proposed rule 

to revoke chlorpyrifos tolerances, as 

noted above, the Agency received some 

comments raising a concern that the use 

of the 10% AChE inhibition may not be 

sufficiently health protective. Taking 

those comments into consideration, EPA 

conducted an additional hazard analysis 

and convened the 2016 FIFRA SAP to 

evaluate a proposal of using cord blood 

data from the CCCEH epidemiology 

studies as the source of data for PoDs. 

The 2016 FIFRA SAP did not support 

the ‘‘direct use’’ of the cord blood and 

working memory data for deriving the 

regulatory endpoint, due to insufficient 

information about timing and 

magnitude of chlorpyrifos applications 

in relation to cord blood concentrations 

at the time of birth, uncertainties about 

the prenatal window(s) of exposure 

linked to reported effects, and lack of a 

second laboratory to reproduce the 

analytical blood concentrations. (Ref. 8) 

Despite their critiques regarding 

uncertainties in the CCCEH studies, the 

2016 SAP expressed concern that 10% 

RBC AChE inhibition is not sufficiently 

protective of human health. 

The 2016 FIFRA SAP, however, did 

present an alternative approach for EPA 

to consider. First, it is important to note 

that this SAP was supportive of the 

EPA’s use of the PBPK–PD model as a 

tool for assessing internal dosimetry 

from typical OPP exposure scenarios. 

Use of the PBPK–PD model coupled 

with typical exposure scenarios 

provides the strongest scientific 

foundation for chlorpyrifos human 

health risk assessment. Given that the 

window(s) of susceptibility are 

currently not known for the observed 

neurodevelopmental effects, and the 

uncertainties associated with 

quantitatively interpreting the CCCEH 

cord blood data, this SAP recommended 

that the Agency use a time weighted 

average (TWA) blood concentration of 

chlorpyrifos for the CCCEH study cohort 

as the PoD for risk assessment. Thus, in 

2016 EPA attempted, using the PBPK– 

PD model, to determine the TWA blood 

level expected from post-application 

exposures from the chlorpyrifos indoor 

crack-and-crevice use scenario. Despite 

that effort, EPA’s position is that the 

shortcomings of the data with regard to 

the dose-response relationship and lack 

of exposure information discussed 

above, continue to raise issues that 

make quantitative use of the CCCEH 

data in risk assessment not scientifically 

sound. 

Thus, taking into consideration the 

robustness of the available data at this 

time, EPA has determined that the most 

appropriate toxicological endpoint for 

deriving points of departure for 

assessing risks of chlorpyrifos is 10% 

RBC AChE inhibition. The Agency is 

not ignoring or dismissing the extensive 

data concerning the potential for 

adverse neurodevelopmental outcomes, 

however. As discussed later in this Unit, 

the Agency is addressing the 

uncertainties surrounding the potential 

for adverse neurodevelopmental 

outcomes by retaining the default 10X 

FQPA safety factor. 

1. Durations of Exposure 

As noted in Unit VI.A., EPA 

establishes PoDs for each expected 

exposure duration likely to result from 

pesticide exposure. For chlorpyrifos, 

exposure can occur from a single event 

or on a single day (e.g., eating a meal) 

or from repeated days of exposure (e.g., 

residential). With respect to AChE 

inhibition, effects can occur from a 

single exposure or from repeated 

exposures. For OPs, repeated exposures 

generally result in more AChE 

inhibition at a given administered dose 

compared to acute exposures. Moreover, 

AChE inhibition in repeated dosing 

guideline toxicology studies with most 

OPs show a consistent pattern of 

inhibition reaching a ‘‘steady state’’ of 

inhibition at or around 2–3 weeks of 

exposure in adult laboratory animals 

(Ref. 19). This pattern observed with 

repeated dosing is a result of the amount 

of inhibition coming to equilibrium 

with production of new enzyme. As 

such, AChE studies of 2–3 weeks 

generally show the same degree of 

inhibition with those of longer duration 

(i.e., up to 2 years of exposure). Thus, 

for most of the human health risk 

assessments for the OPs, the Agency is 

focusing on the critical durations 

ranging from a single day up to 21 days 

(i.e., the approximate time to reach 

steady state for most OPs). As such, EPA 

has calculated PoDs for the acute and 

steady-state durations. As described 

below, these PoDs have been derived for 

various lifestages, routes, and exposure 

scenarios. 

2. Deriving PODs, Inter- and IntraSpecies Extrapolation: Use of the PBPK 

Model 

The process for developing RfDs and 

PADs typically involves first deriving 

PoDs directly from laboratory animal 

studies, followed by dividing the PoD 

by the default uncertainty factors of 10X 

for interspecies extrapolation and 

intraspecies extrapolation, and the 

FQPA safety factor. For chlorpyrifos, as 

discussed previously in Unit V, there is 

a sophisticated PBPK–PD model 

available for chlorpyrifos. Numerous 


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Federal Advisory Committees and 

external review panels have encouraged 

the use of such a modeling approach to 

reduce inherent uncertainty in the risk 

assessment and facilitate more 

scientifically sound extrapolations 

across studies, species, routes, and dose 

levels. The PBPK–PD model for 

chlorpyrifos has undergone extensive 

peer review by various individual or 

groups, including the FIFRA SAPs. 

Significant improvements have been 

made to the model over the years in 

response to recommendations from the 

2008, 2011, and 2012 FIFRA SAPs and 

comments from both internal and 

external peer reviewers. (Ref. 9 at 20). 

As a result, EPA has concluded that the 

current PBPK–PD model is sufficiently 

robust and is using it for deriving PoDs 

for chlorpyrifos. 

a. Derivation of PoDs 

As noted above, the PoDs for 

chlorpyrifos are based on the levels at 

which 10% RBC AChE inhibition is 

observed. The PBPK–PD model 

accounts for pharmacokinetic and 

pharmacodynamic characteristics to 

derive age-, duration-, and route-specific 

PoDs. Separate PoDs have been 

calculated for dietary (food, drinking 

water) and residential exposures by 

varying inputs on types of exposures 

and populations exposed. Specifically, 

the following characteristics have been 

evaluated: Duration [24-hour (acute), 21- 

day (steady state)]; route (dermal, oral, 

inhalation); body weights which vary by 

lifestage; exposure duration (hours per 

day, days per week); and exposure 

frequency [events per day (eating, 

drinking)]. For each exposure scenario, 

the appropriate body weight for each 

age group or sex was modeled as 

identified from the Exposure Factors 

Handbook (Ref. 21) for residential 

exposures and from the U.S. Department 

of Agriculture’s (USDA) National Health 

and Nutrition Examination Survey 

(NHANES)/What We Eat in America 

(WWEIA) Survey for dietary exposures. 

Within the PBPK–PD model, the 

Agency evaluated the following 

exposure scenarios: Oxon (chlorpyrifos 

metabolite) exposures via drinking 

water (acute and steady-state exposures 

for infants, children, youths, and female 

adults); chlorpyrifos exposures via food 

(acute and steady-state exposures for 

infants, children, youths, and female 

adults); steady-state residential 

exposures to chlorpyrifos via skin for 

children, youths, and female adults; 

steady-state residential exposures to 

chlorpyrifos via hand-to-mouth 

ingestion for children 1–2 years old; 

steady-state residential exposures to 

chlorpyrifos via inhalation for children 

1–2 years old and female adults. (Ref. 9 

at 22–25). 

Steady-state dietary exposure was 

estimated daily for 21 days. For 

drinking water exposure, infants and 

young childrens (infants <1 year old, 

children between 1–2 years old, and 

children between 6–12 years old) were 

assumed to consume water 6 times per 

day, with a total consumption volume of 

0.69 L/day. For youths and female 

adults, they were assumed to consume 

water 4 times per day, with a total 

consumption volume of 1.71 L/day. 

For all residential dermal exposures 

to chlorpyrifos the dermal PoDs were 

estimated assuming 50% of the skin’s 

surface was exposed. Exposure times for 

dermal exposure assessment were 

consistent with those recommended in 

the 2012 Residential Standard Operating 

Procedures (SOPs) (Ref. 18). For 

residential inhalation exposures 

following public health mosquitocide 

application, the exposure duration was 

set to 1 hour per day for 21 days. The 

incidental oral PoDs for children 1 to <2 

years old for other turf activities were 

estimated assuming that there were six 

events, 15 minutes apart, per day. 

The PBPK-modeled PoDs derived for 

the various lifestages, routes, and 

exposure scenarios discussed above, can 

be found in Table 4.2.2.1.2 of the 2020 

HHRA (Ref 8). 

b. Inter-Species Extrapolation 

As indicated above, the PBPK–PD 

model directly predicts human PoDs 

based on human physiology and 

biochemistry, and thus there is no need 

for an inter-species uncertainty factor to 

extrapolate from animal PoDs. 

c. Intra-Species Extrapolation 

The PBPK–PD model can account for 

variability of critical physiological, 

pharmacokinetic, and 

pharmacodynamic parameters in a 

population to estimate, using the Monte 

Carlo analysis, the distribution of doses 

that result in 10% RBC AChE inhibition. 

Therefore, Data-Derived Extrapolation 

Factors (DDEF) for intra-species 

extrapolation have been estimated to 

replace the default intra-species 

uncertainty factor for some groups (Ref. 

22). 

According to EPA’s DDEF guidance 

(Ref. 22), when calculating a DDEF 

intra-species extrapolation factor, 

administered doses leading to the 

response level of interest (in the case of 

chlorpyrifos, the 10% change in RBC 

AChE inhibition) are compared between 

a measure of average response and 

response at the tail of the distribution 

representing sensitive individuals. The 

tail of the distribution may be selected 

at the 95th, 97.5th, and 99th percentile. 

As to chlorpyrifos, the 99th percentile 

was used in risk assessment to provide 

the most conservative measure (Ref. 7). 

In addition to estimating DDEF using 

the above approach for specific age 

groups, intra-species DDEF was also 

calculated by comparing between 

average responses between adults and 6- 

month old infants. For the 2020 HHRA, 

the largest calculated DDEFs, 4X for 

chlorpyrifos and 5X for the oxon 

metabolite, were used for intraspecies 

extrapolation for all groups except 

women of childbearing age. There was 

a slightly higher variability between 

adults and infants when considering the 

distributions for the oxon metabolite, 

thus, the slightly higher intra-species 

factor. For women of childbearing age, 

the Agency is applying the standard 10X 

intra-species extrapolation factor due to 

limitations in the PBPK–PD model to 

account for physiological, anatomical, 

and biochemical changes associated 

with pregnancy. (Ref. 9 at 21–22). 

d. Summarizing the PoDs, Inter- and 

Intra-Species Extrapolation Factors 

In summary, for assessing the risks 

from exposure to chlorpyrifos, the 

human PBPK–PD model has been used 

to derive PoDs based on 10% RBC AChE 

inhibition for various populations, 

durations, and routes. The model, 

which calculates a human PoD directly, 

obviates the need for an interspecies 

extrapolation factor since animal data 

are not used. To account for variations 

in sensitivities, the Agency has 

determined that an intra-species factor 

of 4X for chlorpyrifos and 5X for the 

oxon is appropriate for all groups except 

women of childbearing age. For women 

of childbearing age, the typical 10X 

intra-species factor is being applied, due 

the lack of appropriate information and 

algorithms to characterize physiological 

changes during pregnancy. 

3. FQPA Safety Factor 

As noted above, the FFDCA requires 

EPA, in making its ‘‘reasonable certainty 

of no harm’’ finding, that in ‘‘the case 

of threshold effects, an additional 

tenfold margin of safety for the pesticide 

chemical residue and other sources of 

exposure shall be applied for infants 

and children to take into account 

potential pre- and postnatal toxicity and 

completeness of data with respect to 

exposure and toxicity to infants and 

children.’’ 21 U.S.C. 346A(b)(2)(C). 

Section 408(b)(2)(C) further states that 

‘‘the Administrator may use a different 

margin of safety for the pesticide 

chemical residue only if, on the basis of 


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reliable data, such margin will be safe 

for infants and children.’’ 

In applying the FQPA safety factor 

provision, EPA has interpreted it as 

imposing a presumption in favor of 

retaining it as an additional 10X safety 

factor. (Ref. 5 at 4, 11). Thus, EPA 

generally refers to the 10X factor as a 

presumptive or default 10X factor. EPA 

has also made clear, however, that this 

presumption or default in favor of the 

10X is only a presumption. The 

presumption can be overcome if reliable 

data demonstrate that a different factor 

is safe for children. (Id.). In determining 

whether a different factor is safe for 

children, EPA focuses on the three 

factors listed in FFDCA section 

408(b)(2)(C)—the completeness of the 

toxicity database, the completeness of 

the exposure database, and potential 

pre- and post-natal toxicity. In 

examining these factors, EPA strives to 

make sure that its choice of a safety 

factor, based on a weight-of-theevidence evaluation, does not 

understate the risk to children. (Id. at 

24–25, 35). 

EPA’s 2020 HHRA assessed the 

potential risks from exposures to 

chlorpyrifos in two ways—with one 

scenario being the retention of the 

default 10X FQPA SF, and the other 

scenario being the reduction of the 

FQPA SF to 1X. The purpose of using 

both values was to provide an 

indication of what the potential risk 

estimates would be under either 

scenario. The 2020 document, however, 

retained the 10X and did not adopt or 

offer support for reducing to 1X. To 

reduce the FQPA safety factor to 1X, the 

FFDCA requires that EPA determine 

that reliable data demonstrate that the 

1X would be safe for infants and 

children. The 2020 document did not 

make that determination. For 

chlorpyrifos, of the three factors 

mentioned in the previous paragraph, 

the primary factor that undercuts a 

determination that a different safety 

factor would be safe for children is the 

uncertainty around the potential for preand post-natal toxicity for infants and 

children in the area of 

neurodevelopmental outcomes. 

Based on the weight of the evidence 

concerning the potential for 

neurodevelopmental outcomes as 

discussed in Unit VI.B.2. above, there is 

ample qualitative evidence of a 

potential effect on the developing brain; 

however, there remains uncertainty 

around the levels at which these 

potential neurodevelopmental outcomes 

occur. Although the laboratory animal 

studies do not support a conclusion that 

neurodevelopmental outcomes are more 

sensitive than AChE inhibition, the 

mechanistic data are, at this time, 

incomplete in their characterization of 

dose-response. This conclusion may be 

further evaluated upon EPA’s 

completion of the review of the 2020 

FIFRA SAP report concerning NAMs; 

however, due to the time constraints of 

this rule, EPA has not been able to 

include that information in the current 

assessment of chlorpyrifos. Finally, 

while the epidemiology data indicates 

an association between chlorpyrifos and 

adverse neurodevelopmental outcomes, 

there remains some uncertainty in the 

dose-response relationship. As such, 

because the data available at this time 

indicate remaining uncertainties 

concerning pre- and post-natal toxicity 

due to insufficient clarity on the levels 

at which these outcomes occur, the 

Agency is unable to conclude, at this 

time, that a different safety factor would 

be safe for infants and children; thus, 

the Agency is retaining the default 10X 

FQPA safety factor. 

4. Total Uncertainty Factors and PADs 

In conclusion, the Agency used a total 

uncertainty factor of 100X for 

determining the food and drinking 

water PADs for females of childbearing 

age (1X interspecies factor, 10X intraspecies factor, and 10X FQPA safety 

factor); 40X for determining the food 

PADs for remaining populations (1X 

interspecies factor, 4X intra-species 

factor, and 10X FQPA safety factor); and 

50X for determining the PADs for 

drinking water for remaining 

populations (1X interspecies factor, 5X 

intra-species factor, and 10X FQPA 

safety factor). 

Taking into consideration the PoDs, 

intra-species extrapolation factors, and 

FQPA safety factor, the Agency 

calculated acute PADs (aPADs) and 

steady state PADs (ssPADs) for infants 

(less than 1 year old), children (1 to 2 

years old), children (6 to 12 years old), 

youths (13 to 19 years old), and females 

(13–49 years old); these subpopulations 

will be protective of other 

subpopulations. (Ref. 9 at 30–32.) 

Values may be found in table 5.0.1 in 

the 2020 HHRA. 

VII. EPA’s Exposure Assessment for 

Chlorpyrifos 

Risk is a function of both hazard and 

exposure. Thus, equally important to 

the risk assessment process as 

determining the hazards posed by a 

pesticide and the toxicological 

endpoints for those hazards is 

estimating human exposure. Under 

FFDCA section 408, EPA must evaluate 

the aggregate exposure to a pesticide 

chemical residue. This means that EPA 

is concerned not only with exposure to 

pesticide residues in food but also 

exposure resulting from pesticide 

contamination of drinking water 

supplies and from use of pesticides in 

the home or other non-occupational 

settings. (See 21 U.S.C. 

346a(b)(2)(D)(vi)). 

Pursuant to FFDCA section 408(b), 

EPA has evaluated chlorpyrifos’s risks 

based on ‘‘aggregate exposure’’ to 

chlorpyrifos. By ‘‘aggregate exposure,’’ 

EPA is referring to exposure to 

chlorpyrifos by multiple pathways of 

exposure, i.e., food, drinking water, and 

residential. EPA uses available data and 

standard analytical methods, together 

with assumptions designed to be 

protective of public health, to produce 

separate estimates of exposure for a 

highly exposed subgroup of the general 

population, for each potential pathway 

and route of exposure. 

The following reflect a summary of 

the Agency’s exposure assessment from 

the 2020 HHRA unless otherwise 

specified. (Ref. 10). 

A. Exposure From Food 

1. General Approach for Estimating 

Food Exposures 

There are two critical variables in 

estimating exposure in food: (1) The 

types and amount of food that is 

consumed; and (2) The residue level in 

that food. Consumption is estimated by 

EPA based on scientific surveys of 

individuals’ food consumption in the 

United States conducted by the U.S. 

Department of Agriculture (USDA), (Ref. 

11 at 12). Information on residue values 

can come from a range of sources 

including crop field trials; data on 

pesticide reduction (or concentration) 

due to processing, cooking, and other 

practices; information on the extent of 

usage of the pesticide; and monitoring 

of the food supply. (Id. at 17). 

Data on the residues of chlorpyrifos in 

foods are available from both field trial 

data and monitoring data, primarily the 

USDA’s Pesticide Data Program (PDP) 

monitoring data. Monitoring data 

generally provide a characterization of 

pesticide residues in or on foods 

consumed by the U.S. population that 

closely approximates real world 

exposures because they are sampled 

closer to the point of consumption in 

the chain of commerce than field trial 

data, which are generated to establish 

the maximum level of legal residues that 

could result from maximum permissible 

use of the pesticide immediately after 

harvest. 

EPA uses a computer program known 

as the Dietary Exposure Evaluation 

Model and Calendex software with the 

Food Commodity Intake Database 


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(DEEM–FCID version 3.16/Calendex) to 

estimate exposure by combining data on 

human consumption amounts with 

residue values in food commodities. 

The model incorporates 2003–2008 

consumption data from USDA’s 

NHANES/WWEIA. The data are based 

on the reported consumption of more 

than 20,000 individuals over two nonconsecutive survey days. Foods ‘‘as 

consumed’’ (e.g., apple pie) are linked to 

EPA-defined food commodities (e.g., 

apples, peeled fruit—cooked; fresh or N/ 

S (Not Specified); baked; or wheat 

flour—cooked; fresh or N/S, baked) 

using publicly available recipe 

translation files developed jointly by 

USDA Agricultural Research Service 

(ARS) and EPA. For chronic exposure 

assessment (or in the case of 

chlorpyrifos, for steady-state exposure 

assessment), consumption data are 

averaged for the entire U.S. population 

and within population subgroups; 

however, for acute exposure assessment, 

consumption data are retained as 

individual consumption events. Using 

this consumption information and 

residue data, the exposure estimates are 

calculated for the general U.S. 

population and specific subgroups 

based on age, sex, ethnicity, and region. 

For chlorpyrifos, EPA determined that 

acute and steady-state exposure 

durations were relevant for assessing 

risk from food consumption. EPA 

calculates potential risk by using 

probabilistic techniques to combine 

distributions of potential exposures in 

sentinel populations. The resulting 

probabilistic assessments present a 

range of dietary exposure/risk estimates. 

Because probabilistic assessments 

generally present a realistic range of 

residue values to which the population 

may be exposed, EPA’s starting point for 

estimating exposure and risk for such 

assessments is the 99.9th percentile of 

the population under evaluation. When 

using a probabilistic method of 

estimating acute dietary exposure, EPA 

typically assumes that, when the 99.9th 

percentile of acute exposure is equal to 

or less than the aPAD, the level of 

concern for acute risk has not been 

exceeded. By contrast, where the 

analysis indicates that estimated 

exposure at the 99.9th percentile 

exceeds the aPAD, EPA would generally 

conduct one or more sensitivity 

analyses to determine the extent to 

which the estimated exposures at the 

high-end percentiles may be affected by 

unusually high food consumption or 

residue values. (The same assumptions 

apply to estimates for steady state 

dietary exposure and the ssPAD.) To the 

extent that one or a few values seem to 

‘‘drive’’ the exposure estimates at the 

high-end of exposure, EPA would 

consider whether these values are 

reasonable and should be used as the 

primary basis for regulatory decision 

making (Ref. 20). 

2. Estimating Chlorpyrifos Exposures in 

Food 

The residue of concern, for tolerance 

expression and risk assessment, in 

plants (food and feed) and livestock 

commodities is the parent compound 

chlorpyrifos. EPA has determined that 

the metabolite chlorpyrifos oxon is not 

a residue of concern in food or feed, 

based on available field trial data and 

metabolism studies that indicate that 

the oxon is not present in the edible 

portions of the crops. In addition, the 

chlorpyrifos oxon is not found on 

samples in the USDA PDP monitoring 

data. Furthermore, the oxon metabolite 

was not found in milk or livestock 

tissues (Ref. 9 at 33). 

Acute and steady-state dietary (food 

only) exposure analyses for chlorpyrifos 

were conducted using the DEEM–FCID 

version 3.16/Calendex software (Ref. 

23). These analyses were performed for 

the purpose of obtaining food exposure 

values for comparison to the 

chlorpyrifos doses predicted by the 

PBPK–PD model to cause RBC AChE 

Inhibition. The acute and steady-state 

dietary (food only) exposure analyses do 

not include drinking water exposures, 

which were assessed separately, see 

Unit VII.B.2. 

Both the acute and steady state 

dietary exposure analyses are highly 

refined. The large majority of food 

residues used were based upon PDP 

monitoring data except in a few 

instances where no appropriate PDP 

data were available. In those cases, field 

trial data or tolerance level residues 

were assumed. EPA also used food 

processing factors from submitted 

studies as appropriate. In addition, 

EPA’s acute and steady state dietary 

exposure assessments used percent crop 

treated (PCT) information. (Ref. 23) 

The chlorpyrifos acute dietary 

exposure analysis was conducted using 

the DEEM–FCID, version 3.16, which 

incorporates 2003–2008 survey 

consumption data from USDA’s 

NHANES/WWEIA. The acute risk 

estimates were presented for the 

sentinel populations for infants (less 

than 1 yr old); children (1–2 years old); 

youths (6–12 years old); and adults 

(females 13–49 years old). The 

assessment of these index lifestages is 

protective of other population 

subgroups. 

The chlorpyrifos steady-state dietary 

exposure analysis was conducted using 

the Calendex component of DEEM–FCID 

(with 2003–2008 survey consumption 

data from USDA’s NHANES/WWEIA). 

Calendex provides a focus detailed 

profile of potential exposures to 

individuals across a calendar year. A 

calendar-based approach provides the 

ability to estimate daily exposures from 

multiple sources over time to an 

individual and is in keeping with two 

key tenets of aggregate risk assessment: 

(1) That exposures when aggregated are 

internally consistent and realistic; and 

(2) that appropriate temporal and 

geographic linkages or correlations/ 

associations between exposure scenarios 

are maintained. 

The chlorpyrifos steady state 

assessment considers the potential risk 

from a 21-day exposure duration using 

a 3-week rolling average (sliding by day) 

across the year. For this assessment, the 

same food residue values used in the 

acute assessment were used for the 21- 

day duration. In the Calendex software, 

one diary for each individual in the 

WWEIA is selected to be paired with a 

randomly selected set of residue values 

for each food consumed. The steadystate analysis calculated exposures for 

the sentinel populations for infants (less 

than 1 year old); children (1–2 years 

old); youths (6–12 years old); and adults 

(females 13–49 years old). The 

assessment of these index lifestages is 

protective of other population 

subgroups. 

B. Exposure From Drinking Water 

1. General Approach for Assessing 

Exposure From Drinking Water 

a. Modeling and Monitoring Data 

Monitoring and modeling are both 

important tools for estimating pesticide 

concentrations in water and can provide 

different types of information. 

Monitoring data can provide estimates 

of pesticide concentrations in water that 

are representative of the specific 

agricultural or residential pesticide 

practices in specific locations, under the 

environmental conditions associated 

with a sampling design (i.e., the 

locations of sampling, the times of the 

year samples were taken, and the 

frequency by which samples were 

collected). Although monitoring data 

can provide a direct measure of the 

concentration of a pesticide in water, it 

does not always provide a reliable basis 

for estimating spatial and temporal 

variability in exposures because 

sampling may not occur in areas with 

the highest pesticide use, and/or when 

the pesticides are being used and/or at 

an appropriate sampling frequency to 

detect high concentrations of a pesticide 

that occur over the period of a day to 

several days. 


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Because of the limitations in most 

monitoring studies, EPA’s standard 

approach is to use water exposure 

models as the primary means to 

estimate pesticide exposure levels in 

drinking water. Modeling is a useful 

tool for characterizing vulnerable sites 

and can be used to estimate upper-end 

pesticide water concentrations from 

infrequent, large rain events. EPA’s 

computer models use detailed 

information on soil properties, crop 

characteristics, and weather patterns to 

estimate water concentrations in 

vulnerable locations where the pesticide 

could be used according to its label (Ref. 

24 at 27–28). EPA’s models calculate 

estimated water concentrations of 

pesticides using laboratory data that 

describe how fast the pesticide breaks 

down to other chemicals and how it 

moves in the environment at these 

vulnerable locations. The modeling 

provides an estimate of pesticide 

concentrations in ground water and 

surface water. Depending on the 

modeling algorithm (e.g., surface water 

modeling scenarios), daily 

concentrations can be estimated 

continuously over long periods of time, 

and for places that are of most interest 

for any particular pesticide. 

EPA relies on models it has developed 

for estimating pesticide concentrations 

in both surface water and groundwater. 

The most common model used to 

conduct drinking water assessments is 

the Pesticide in Water Calculator (PWC). 

PWC couples the Pesticide Root Zone 

Model (PRZM) and Variable Volume 

Water Model (VVWM) models together 

to simulate pesticide fate and transport 

from the field of application to an 

adjacent reservoir. (Ref. 24 at 27–28). 

The PWC estimates pesticide 

concentrations for an index reservoir 

that is modeled for site-specific 

scenarios (i.e., weather and soil data) in 

different areas of the country. A detailed 

description of the models routinely used 

for exposure assessment is available 

from the EPA OPP Aquatic Models 

website: https://www.epa.gov/pesticidescience-and-assessing-pesticide-risks/ 

models-pesticide-riskassessment#aquatic. 

In modeling potential surface water 

concentrations, EPA attempts to model 

areas of the country that are vulnerable 

to surface water contamination rather 

than simply model ‘‘typical’’ 

concentrations occurring across the 

nation. Consequently, EPA models 

exposures occurring in small highly 

agricultural watersheds in different 

growing areas throughout the country, 

over a 30-year period. The scenarios are 

designed to capture residue levels in 

drinking water from reservoirs with 

small watersheds with a large 

percentage of land use in agricultural 

production. EPA believes these 

assessments are likely reflective of a 

small subset of the watersheds across 

the country that maintain drinking 

water reservoirs, representing a drinking 

water source generally considered to be 

more vulnerable to frequent high 

concentrations of pesticides than most 

locations that could be used for crop 

production. 

When monitoring data meet certain 

data quantity criteria, EPA has tools 

available to quantify the uncertainty in 

available monitoring data such that it 

can be used quantitively to estimate 

pesticide concentrations in drinking 

water. (Ref. 25) Furthermore, monitoring 

data can be used in a weight of evidence 

approach with model estimated 

concentrations to increase confidence in 

the conclusions of a drinking water 

assessment. 

b. Drinking Water Level of Comparison 

(DWLOC) 

The drinking water level of 

comparison (DWLOC) is a benchmark 

that can be used to guide refinements of 

the drinking water assessment (DWA). 

This value relates to the concept of the 

‘‘risk cup,’’ which EPA developed to 

facilitate risk refinement when 

considering aggregate human health risk 

to a pesticide. (Ref. 26). The risk cup is 

the total exposure allowed for a 

pesticide considering its toxicity and 

required safety factors. The risk cup is 

equal to the maximum safe exposure for 

the duration and population being 

considered. Exposures exceeding the 

risk cup are of potential concern. There 

are risk cups for each pertinent duration 

of exposure (e.g., acute, short-term, 

chronic). The exposure durations most 

commonly of interest for acute or shortterm pesticide exposure risk 

assessments are 1-day, 4-day, and 21- 

day averages. For example, the relevant 

exposure duration for AChE reversible 

inhibition from exposure to carbamate 

insecticides is 1-day, while AChE 

irreversible inhibition resulting from 

exposure to OP insecticides is usually 

21-days based on steady-state kinetics. 

(Ref. 19) 

In practice, EPA calculates the total 

exposure from food consumption and 

residential (or other non-occupational) 

exposures and subtracts this value from 

the maximum safe exposure level. The 

resulting value is the allowable 

remaining exposure without the 

potential for adverse health effect. 

Knowing this allowable remaining 

exposure and the water consumption for 

each population subgroup (e.g., infants), 

the Agency can calculate the DWLOC, 

which is the estimate of safe 

concentrations of pesticides in drinking 

water. Using this process of DWLOC 

calculation allows EPA to determine a 

target maximum safe drinking water 

concentration, thereby identifying 

instances where drinking water 

estimates require refinement. (Ref. 24 at 

19–20). 

c. Scale of Drinking Water Assessment 

Although food is distributed 

nationally, and residue values are 

therefore not expected to vary 

substantially throughout the country, 

drinking water is locally derived and 

concentrations of pesticides in source 

water fluctuate over time and location 

for a variety of reasons. Pesticide 

residues in water fluctuate daily, 

seasonally, and yearly because of the 

timing of the pesticide application, the 

vulnerability of the water supply to 

pesticide loading through runoff, spray 

drift and/or leaching, and changes in the 

weather. Concentrations are also 

affected by the method of application, 

the location, and characteristics of the 

sites where a pesticide is used, the 

climate, and the type and degree of pest 

pressure, which influences the 

application timing, rate used, and 

number of treatments in a crop 

production cycle. 

EPA may conduct a drinking water 

assessment (DWA) for a national scale 

depending on the pesticide use under 

evaluation. A national scale DWA may 

use a single upper-end pesticide 

concentration as a starting point for 

assessing whether additional 

refinements are needed or estimated 

pesticide concentrations for certain sitespecific scenarios that are associated 

with locations in the United States 

vulnerable to pesticide contamination 

based on pesticide use patterns. (Ref. 24 

at 22.) 

EPA may also conduct a regional scale 

DWA to focus on areas where pesticide 

concentrations may be higher than the 

DWLOC. Under this assessment, EPA 

estimates pesticide concentrations 

across different regions in the United 

States that are subdivided into different 

areas called hydrologic units (HUCs). 

There are 21 HUC 2 regions with 18 in 

the contiguous United States. These 

areas contain either the drainage area of 

a major river or a combined drainage of 

a series of rivers. This information can 

eb found at: https://water.usgs.gov/GIS/ 

huc.html. Estimated pesticide 

concentrations under this approach 

would be associated with a vulnerable 

pesticide use area somewhere within 

the evaluated region. (Ref. 24 at 23). 


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d. Drinking Water Refinements 

EPA has defined four assessment tiers 

for drinking water assessments. Lower 

tiered assessments are more 

conservative based on the defaults or 

upper bound assumptions and may 

compound conservatisms, while higher 

tiers integrate more available data and 

provide more realistic estimates of 

environmental pesticide concentrations. 

These four tiers are generally based on 

the level of effort, the amount of data 

considered, the spatial scale, and the 

certainty in the estimated pesticide 

concentration. Tier 1 requires the least 

amount of effort and the least amount of 

data, whereas Tier 4 is resource 

intensive, considers a wide range of 

sources and types of data, and is 

spatially explicit, resulting in high 

confidence in the reported pesticide 

concentration. Each successive tier 

integrates more focused pesticide, 

spatial, temporal, agronomic, and cropspecific information. The order in 

which refinements are considered (i.e., 

the order in which the assessment is 

refined) is pesticide-specific and 

depends on the nature and quality of the 

available data used to support the 

refinement. Additional information on 

the conduct of drinking water 

assessments can be found in the 

‘‘Framework for Conducting Pesticide 

Drinking Water Assessment for Surface 

Water’’ (USEPA, 2020). 

As discussed in the Framework 

document, EPA can incorporate several 

refinements in higher tiered modeling. 

Two such refinements are the percent 

cropped area (PCA) and the percent 

crop treated (PCT). These are described 

in the recently completed document 

titled ‘‘Integrating a Distributional 

Approach to Using Percent Crop Area 

(PCA) and Percent Crop Treated (PCT) 

into Drinking Water Assessment’’ (Ref. 

27) The PCA refers to the amount of area 

in a particular community water system 

that is planted with the crop of interest 

(e.g., the default assumption is that the 

entire watershed is planted with a crop 

of interest). The PCT refers to the 

amount of the cropped area that is 

treated with the pesticide of interest 

(e.g., the default is that the entire 

cropped area is treated with the 

pesticide of interest). With additional 

use and usage data, EPA can refine 

assumptions about the application rate 

and PCT for use in modeling to generate 

estimated drinking water concentrations 

(EDWCs) that are appropriate for human 

health risk assessment and more 

accurately account for the contribution 

from individual use patterns in the 

estimation of drinking water 

concentrations. 

2. Drinking Water Assessment for 

Chlorpyrifos. 

For the chlorpyrifos drinking water 

assessment, the metabolite chlorpyrifos 

oxon, which forms because of drinking 

water treatment and is more toxic than 

chlorpyrifos, was chosen as the residue 

of concern. (Ref. 28 and 29) The range 

of conversion from parent to oxon 

depends upon the type of water 

treatment and other conditions. Based 

on available information regarding the 

potential effects of certain water 

treatments (e.g., chlorination appears to 

hasten transformation of chlorpyrifos to 

chlorpyrifos oxon), EPA assumed that 

all chlorpyrifos in source water is 

converted to chlorpyrifos oxon upon 

treatment. 

The Agency used a DWLOC approach 

for assessing aggregate risk from 

chlorpyrifos. As such, EPA calculated 

DWLOCs for different age groups for 

both the acute aggregate assessment and 

the steady-state aggregate assessment, 

taking into consideration the food and 

residential contributions to the risk cup. 

These numbers were provided as a 

benchmark for evaluating drinking 

water contributions from uses of 

chlorpyrifos across the United States, 

and whether such concentrations would 

result in aggregate exposures to 

chlorpyrifos that exceeded the Agency’s 

levels of concern. The lowest acute 

DWLOC calculated was for exposure to 

chlorpyrifos oxon to infants (<1 year 

old) at 23 ppb; the lowest steady state 

DWLOC calculated was also for 

exposure to chlorpyrifos oxon to infants 

(<1 year old) at 4.0 ppb. (Ref. 9 at 45– 

45). In other words, EDWCs of 

chlorpyrifos oxon greater than 4.0 ppb 

for a 21-day average would exceed 

EPA’s DWLOC and present a risk that 

exceeds the Agency’s level of concern. 

In its 2014 drinking water assessment, 

EPA concluded that there were multiple 

uses of chlorpyrifos that could lead to 

exposures to chlorpyrifos oxon in 

drinking water that exceed the DWLOC 

identified at that time. (Ref. 29). This 

assessment provided the basis for the 

Agency’s proposal to revoke tolerances 

in 2015. (Ref. 30). In 2016, EPA 

conducted a refined drinking water 

assessment that estimated drinking 

water concentrations based on modeling 

of all registered uses, as well as all 

available surface water monitoring data. 

That assessment considered several 

refinement strategies in a two-step 

process to derive exposure estimates for 

chlorpyrifos and chlorpyrifos oxon 

across the country. The first step was an 

assessment of potential exposure based 

on the current maximum label rates at 

a national level. This indicated that the 

EDWCs could be above the DWLOC. 

Because estimated concentrations at 

the national level exceeded the DWLOC, 

the Agency conducted a more refined 

assessment of uses on a regional level. 

(Ref. 28 at 73–86). This more refined 

analysis derived EDWCs using the PWC 

modeling for maximum labeled rates 

and 1 pound per acre by region for each 

use. The analysis indicated that 

approved uses of chlorpyrifos in certain 

vulnerable watersheds in every region of 

the country would result in EDWCs that 

exceed the DWLOC. For example, Table 

25 of EPA’s 2016 DWA, which provides 

the range of estimated concentrations of 

chlorpyrifos in drinking water from uses 

on golf courses and agricultural or 

production crops, shows EDWCs that 

exceed the DWLOC in vulnerable 

watersheds in every region in the 

country. While the lower end of some of 

the ranges provided in that table are 

below the DWLOC, those lower 

numbers reflect a single use (i.e., single 

crop) and do not reflect potential 

exposure from other uses where 

applications occur at higher rates, more 

frequently, or in more locations made 

more vulnerable due to soil type, 

weather, or agronomic practices. The 

relevant estimated concentration for risk 

assessment purposes is the highest 

concentration across all uses because it 

reflects concentrations that may occur 

in vulnerable sources of drinking water 

(Ref. 28 at 73–74). 

In addition, a robust quantitative 

analysis of the monitoring data was 

conducted resulting in concentrations 

consistent with model-estimated 

concentrations above the DWLOC. (Ref. 

28 at 90–121). Considering both 

monitoring data and modeling estimates 

together supports the conclusion that 

drinking water concentrations in regions 

across the country will exceed the 

DWLOC. (Ref. 28 at 121–123). 

After the EPA’s 2016 DWA showed 

that the DWLOC exceedances are 

possible from several uses, EPA 

developed refinement strategies to 

examine those estimated regional/ 

watershed drinking water 

concentrations to pinpoint community 

drinking water systems where exposure 

to chlorpyrifos oxon as a result of 

chlorpyrifos applications may pose an 

exposure concern. At that time, EPA 

was anticipating that a more refined 

drinking water assessment might allow 

EPA to better identify where at-risk 

watersheds are located throughout the 

country to support more targeted risk 

mitigation through the registration 

review process. The refinements better 

account for variability in the use area 

treated within a watershed that may 


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contribute to a drinking water intake 

(referred to as PCA or percent use area 

when considering non-agricultural uses) 

and incorporate data on the amount of 

a pesticide that is actually applied 

within a watershed for agricultural and 

non-agricultural uses (referred to as 

PCT). These refinement approaches 

underwent external peer review and 

were issued for public comment in 

January 2020: https://www.epa.gov/ 

pesticide-science-and-assessingpesticide-risks/about-water-exposuremodels-used-pesticide. In addition, EPA 

used average application rates, average 

numbers of annual applications for 

specific crops, and estimated typical 

application timing at the state-level 

based on pesticide usage data derived 

from a statistically reliable private 

market survey database, publicly 

available survey data collected by the 

USDA, and state-specific scientific 

literature from crop extension experts. 

The recently developed refinements 

were integrated in the Updated 

Chlorpyrifos Refined Drinking Water 

Assessment for Registration Review, 

which was issued in September 2020. 

(2020 DWA) (Ref. 10) The updated 

assessment applied the new methods for 

considering the entire distribution of 

community water systems PCA 

adjustment factors, integrated state level 

PCT data, incorporated refined usage 

and application data, and included 

quantitative use of surface water 

monitoring data in addition to 

considering state level usage rate and 

data information. In addition, given the 

2016 DWA calculation of estimated 

drinking water concentrations 

exceeding the DWLOC of 4.0 ppb, the 

Agency decided to focus its refinements 

for the 2020 updated drinking water 

assessment on a subset of uses in 

specific regions of the United States. 

The purpose of the focus on this subset 

of uses was to determine, if these were 

the only uses permitted on the label, 

whether or not the resulting estimated 

drinking water concentrations would be 

below the DWLOC. The subset of uses 

assessed were selected because they 

were identified as critical uses by the 

registrant and/or high-benefit uses to 

growers. That subset of currently 

registered uses included alfalfa, apple, 

asparagus, cherry, citrus, cotton, peach, 

soybean, sugar beet, strawberry, and 

wheat in specific areas of the country. 

The results of this analysis indicated 

that the EDWCs from this subset of uses 

limited to certain regions are below the 

DWLOC. (Ref. 10 at 16–17). However, 

the 2020 DWA refined estimates did not 

include chlorpyrifos exposures from 

uses beyond that subset. In the 2020 

DWA, EPA stated that if additional uses 

were added or additional geographic 

areas included, a new separate 

assessment would need to be prepared 

in order to evaluate whether 

concentrations would remain below the 

DWLOC. In addition to the modeling of 

the EDWCs for the specific subset of 

uses, the 2020 DWA conducted a 

quantitative surface water monitoring 

data analysis. That analysis indicated 

that monitored chlorpyrifos 

concentrations, which reflect existing 

uses, are above the DWLOC. (Ref. 10 at 

62, 75). These data would need to be 

considered in the context of any 

additional uses beyond the subset 

evaluated. 

C. Residential Exposure to Pesticides 

1. General Approach to Assessing NonOccupational Exposures 

Residential assessments examine 

exposure to pesticides in nonoccupational or residential settings (e.g., 

homes, parks, schools, athletic fields or 

any other areas frequented by the 

general public), based on registered uses 

of the pesticide. Exposures to pesticides 

may occur to persons who apply 

pesticides (which is referred to as 

residential handler exposure) or to 

persons who enter areas previously 

treated with pesticides (which is 

referred to as post-application 

exposure). Such exposures may occur 

through oral, inhalation, or dermal 

routes and may occur over different 

exposure durations (e.g., short-term, 

intermediate-term, long-term), 

depending on the type of pesticide and 

particular use pattern. 

Residential assessments are 

conducted through examination of 

significant exposure scenarios (e.g., 

children playing on treated lawns or 

homeowners spraying their gardens) 

using a combination of generic and 

pesticide-specific data. To regularize 

this process, EPA has prepared SOPs for 

conducting residential assessments on a 

wide array of scenarios that are 

intended to address all major possible 

means by which individuals could be 

exposed to pesticides in a nonoccupational environment (e.g., homes, 

schools, parks, athletic fields, or other 

publicly accessible locations). (Ref. 18) 

The SOPs identify relevant generic data 

and construct algorithms for calculating 

exposure amounts using these generic 

data in combination with pesticidespecific information. The generic data 

generally involve survey data on 

behavior patterns (e.g., activities 

conducted on turf and time spent on 

these activities) and transfer coefficient 

data. Transfer coefficient data measure 

the amount of pesticide that transfers 

from the environment to humans from 

a defined activity (e.g., hand contact 

with a treated surface or plant). Specific 

information on pesticides can include 

information on residue levels as well as 

information on environmental fate such 

as degradation data. 

Once EPA assesses all the potential 

exposures from all applicable exposure 

scenarios, EPA selects the highest 

exposure scenario for each exposed 

population to calculate representative 

risk estimates for use in the aggregate 

exposure assessment. Those specific 

exposure values are then combined with 

the life stage appropriate exposure 

values provided for food and drinking 

water to determine whether a safety 

finding can be made. 

2. Residential Exposure Assessment for 

Chlorpyrifos 

Most chlorpyrifos products registered 

for residential treatment were 

voluntarily cancelled or phased out by 

the registrants between 1997 and 2001; 

however, some uses of chlorpyrifos 

remain that may result in nonoccupational, non-dietary (i.e., 

residential) exposures. Based on the 

remaining registered uses, the Agency 

has determined that residential handler 

exposures are unlikely. Chlorpyrifos 

products currently registered for 

residential use are limited to roach bait 

products or ant mound treatments. 

Exposures from the application of roach 

bait products are expected to be 

negligible. The roach bait product is 

designed such that the active ingredient 

is contained within a bait station, which 

eliminates the potential for contact with 

the chlorpyrifos containing bait 

material. Since the ant mound 

treatments can only be applied 

professionally, residential handler 

exposure is also not anticipated. (Ref. 9 

at 36–44). 

There is a potential for residential 

post-application exposures. 

Chlorpyrifos is registered for use on golf 

courses and as an aerial and groundbased ultra-low volume (ULV) mosquito 

adulticide applications made directly in 

residential areas. Based on the 

anticipated use patterns reviewed under 

the SOP, EPA assessed these exposures 

as steady-state residential postapplication exposures, which would be 

protective of shorter durations of 

exposure. There is a potential for dermal 

post-application exposures from the golf 

course uses for adults (females 13–49 

years old); youths (11 to less than 16 

years old); and children (6 to less than 

11 years old). There is also a potential 

for dermal, incidental oral, and 

inhalation post-application exposures 


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for children (1 to less than 2 years old) 

and dermal and inhalation postapplication exposures for adults from 

exposure to mosquitocide uses. The 

Agency combined post-application 

exposures for children (1 to less than 2 

years old) for dermal, inhalation, and 

incidental oral exposure routes because 

these routes all share a common 

toxicological endpoint. EPA used the 

post-application exposures and risk 

estimates resulting from the golfing 

scenarios in its aggregate exposure and 

risk assessment. 

VIII. Aggregate Risk Assessment and 

Conclusions Regarding Safety for 

Chlorpyrifos 

The final step in the risk assessment 

is the aggregate exposure assessment 

and risk characterization. In this step, 

EPA combines information from the first 

three steps (hazard identification, level 

of concern (LOC)/dose-response 

analysis, and human exposure 

assessment) to quantitatively estimate 

the risks posed by a pesticide. The 

aggregated exposure assessment process 

considers exposure through multiple 

pathways or routes of exposure (e.g., 

food, water, and residential) for 

different sub-populations (e.g., infants, 

children ages 1–6) and exposure 

duration or types of effects (e.g., acute 

noncancer effects (single dose), chronic 

noncancer effects, and cancer). The 

aggregated exposure assessments can be 

deterministic (levels of exposure for 

each pathway are point estimates), 

probabilistic (levels of exposure are a 

distribution for a given population), or 

a combination of the two and are 

dependent on the level of refinement or 

assessment tier. 

As noted above, EPA evaluates 

aggregate exposure by comparing 

combined exposure from all relevant 

sources to the safe level. Where 

exposures exceed the safe level, those 

levels exceed the risk cup and are of 

potential concern. There are risk cups 

for each pertinent duration of exposure 

for a pesticide because the amount of 

exposure that can be incurred without 

adverse health effects will vary by 

duration (e.g., acute, short-term, 

chronic). The risk cup is equal to the 

PAD (either acute, chronic, or steadystate), or the maximum safe exposure for 

short- and intermediate-term durations. 

Whether risks will exceed the risk cup 

(i.e., whether exposures are expected to 

exceed safe levels) is expressed 

differently, depending on the type of 

level of concern the Agency has 

identified. For dietary assessments, the 

risk is expressed as a percentage of the 

acceptable dose (i.e., the dose which 

EPA has concluded will be ‘‘safe’’). 

Dietary exposures greater than 100% of 

the percentage of the acceptable dose 

are generally cause for concern and 

would be considered ‘‘unsafe’’ within 

the meaning of FFDCA section 

408(b)(2)(B). For non-dietary (and 

combined dietary and non-dietary) risk 

assessments of threshold effects, the 

toxicological level of concern is 

typically not expressed as an RfD/PAD, 

but rather in terms of an acceptable (or 

target) Margin of Exposure (MOE) 

between human exposure and the PoD. 

The ‘‘margin’’ that is being referred to in 

the term MOE is the ratio between the 

PoD and human exposure which is 

calculated by dividing human exposure 

into the PoD. An acceptable MOE is 

generally considered to be a margin at 

least as high as the product of all 

applicable safety factors for a pesticide. 

For example, when the Agency retains 

the default uncertainty factors for 

dietary or aggregate risk (a 10X 

interspecies uncertainty factor, a 10X 

intraspecies uncertainty factor, and a 

10X FQPA safety factor), the total 

uncertainty factors (or level of concern) 

is 1000, and any MOE above 1000 

represents exposures that are not of 

concern. Like RfD/PADs, specific target 

MOEs are selected for exposures of 

different durations and routes. For nondietary exposures, EPA typically 

examines short-term, intermediate-term, 

and long-term exposures. Additionally, 

target MOEs may be selected based on 

both the duration of exposure and the 

various routes of non-dietary 

exposure—dermal, inhalation, and oral. 

Target MOEs for a given pesticide can 

vary depending on the characteristics of 

the studies relied upon in choosing the 

PoD for the various duration and route 

scenarios. 

In addition, in a DWLOC aggregate 

risk assessment, the calculated DWLOC 

is compared to the EDWC. Where EPA 

has calculated a DWLOC, EPA can 

determine whether drinking water 

exposures will result in aggregate risks 

of concern by comparing estimated 

pesticide concentrations in drinking 

water to the DWLOC. As noted above, 

an aggregate DWLOC represents the 

amount of allowable safe residues of 

pesticide in drinking water because it 

represents the room remaining in the 

risk cup after accounting for the food 

and residential exposures. The DWLOC 

provides an estimate of the allowable 

safe concentrations of pesticides in 

drinking water for comparison to 

EDWCs. When the EDWC is less than 

the DWLOC, there are no risk concerns 

for aggregate exposures because the 

Agency can conclude that the 

contribution from drinking water when 

aggregated with food and nonoccupational exposures will not exceed 

save levels of exposure. Conversely, an 

EDWC at or exceeding the DWLOC 

would indicate a risk of concern, as 

those exposures to chlorpyrifos in 

drinking water, when aggregated with 

exposures from food and residential 

exposures, would exceed safe levels of 

exposure. (Ref. 31). 

A. Dietary Risks From Food Exposures 

As noted above, EPA’s acute and 

steady state dietary exposures 

assessments for chlorpyrifos were 

highly refined and incorporated 

monitoring data for almost all foods. 

The Agency assessed food exposures 

based on approved registered uses of 

chlorpyrifos. This includes field uses of 

chlorpyrifos but not potential exposure 

from food handling establishment uses 

since the Agency did not identify any 

registered food handling establishment 

uses. (Ref. 9 at 33–36). 

Considering food exposures alone, the 

Agency did not identify risks of concern 

for either acute or steady state 

exposures. Acute dietary (food only) 

risk estimates, which are based on risk 

from a single exposure event in the 2020 

HHRA were all below 100 percent of the 

acute population adjusted dose for food 

(aPADfood) at the 99.9th percentile of 

exposure and are not of concern. The 

population with the highest risk 

estimate was females (13–49 years old) 

at 3.2% aPADfood. Steady-state dietary 

(food only) risk estimates, which are 

based on the potential risk from a 21- 

day exposure duration using a 3-week 

rolling average (sliding by day) across 

the year, were also all below 100% of 

the steady state PAD for food (ssPADfood) 

at the 99.9th percentile of exposure and 

are not of concern. The population with 

the highest risk estimate was children 

(1–2 years old) at 9.7% ssPADfood. 

Although EPA’s most recent risk 

assessment calculated two sets of risk 

estimates as a result of the dual 

approach to assess the range of risks that 

would occur if the Agency determined 

reliable data existed to support a 1X 

FQPA safety factor, EPA has determined 

that it is appropriate to retain the 10X 

FQPA safety factor, see Unit VI.C.3. 

Therefore, the risk estimates associated 

with the 1X FQPA are not relevant to 

today’s action. 

B. Non-Occupational, Non-Dietary 

(Residential) Risks 

Because there are some uses of 

chlorpyrifos that may result in 

residential exposures, EPA assessed risk 

from those uses. All residential postapplication risk estimates for the 

registered uses of chlorpyrifos were 


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below the Agency’s level of concern. 

(Ref. 9 at 38). The residential postapplication LOC for children is 40, and 

the lowest risk estimate for children (11 

to less than 16 years old) was 1,200; the 

residential post-application LOC for 

adults is 100, and the MOE is 1,000. 

Because the calculated MOEs are above 

the Agency’s level of concern, there are 

no risks of concern from residential 

exposures. 

C. Risks From Drinking Water 

As noted above, the Agency 

aggregated exposures to chlorpyrifos 

from food and residential exposures and 

calculated the DWLOC, i.e., the amount 

of drinking water exposures that would 

be considered safe. The Agency 

calculated acute and steady state 

DWLOCs for infants (less than 1 year 

old); children (1 to 2 years old); youths 

(6–12 years old), and adults (females 

13–49 years old), which would be 

protective of other subpopulations. The 

most sensitive acute DWLOC was 23 

ppb chlorpyrifos oxon, and the most 

sensitive steady state DWLOC was 4 

ppb. 

As indicated above in Unit VII.B.2., 

the Agency estimated drinking water 

contributions from registered uses of 

chlorpyrifos in its 2016 DWA. That 

document indicated that EDWCs exceed 

the DWLOC of 4.0 ppb on a national 

level and in every region of the United 

States. (Ref. 28). 

While the 2020 DWA produced 

estimated drinking water concentrations 

that were below the DWLOC of 4.0 ppb, 

those EDWCs were contingent upon a 

limited subset of chlorpyrifos use. When 

assessing different combinations of only 

those 11 uses in specific geographic 

regions, the modeling assumed that 

chlorpyrifos would not be labeled for 

use on any other crops and would not 

otherwise be used in those geographic 

regions. At this time, however, the 

currently registered chlorpyrifos uses go 

well beyond the 11 uses in the specific 

regions assessed in the 2020 DWA. 

Because the Agency is required to assess 

aggregate exposure from all anticipated 

dietary, including food and drinking 

water, as well as residential exposures, 

the Agency cannot rely on the 2020 

DWA to support currently labeled uses. 

When one assesses the potential of all 

currently registered uses nationwide 

and in specific geographical areas, as 

was done in the 2016 DWA, the 

estimates of drinking water 

concentrations exceed the DWLOC of 

4.0 ppb, in certain vulnerable 

watersheds across the United States. 

D. Aggregate Exposure and 

Determination Concerning Safety 

As noted above, in accordance with 

FFDCA section 408(b)(2), EPA must, 

when establishing or leaving in effect 

tolerances for residues of a pesticide 

chemical, determine that the tolerances 

are safe. That is, EPA must determine 

that ‘‘there is a reasonable certainty that 

no harm will result from aggregate 

exposure to the pesticide chemical 

residue, including all anticipated 

dietary exposures and all other 

exposures for which there is reliable 

information.’’ (21 U.S.C. 346a(b)(2)). 

As discussed earlier in this Unit, 

exposures from food and nonoccupational exposures individually or 

together do not exceed EPA’s levels of 

concern. The Agency determined that 

risks from exposures to chlorpyrifos 

residues in food comprised 3.2% of the 

aPAD for females (13–49 years old) and 

9.7% of the ssPAD for children (1–2 

years old), the highest exposed 

subpopulations. Combining those 

exposures with relevant residential 

exposures, the Agency calculated the 

allowable levels of drinking water 

concentrations. Based on the Agency’s 

assessment of drinking water 

concentrations based on the currently 

registered uses, however, drinking water 

exposures significantly add to those 

risks. When considering the drinking 

water contribution from currently 

registered uses, the Agency’s levels of 

concern are exceeded when combined 

with food and residential exposures. 

As indicated above, the Agency 

calculated acute and steady-state 

DWLOCs, and the lowest DWLOC is for 

steady-state exposures to infants at 4.0 

ppb; therefore, any EDWCs of 

chlorpyrifos oxon exceeding 4.0 ppb 

indicate that aggregate exposures of 

chlorpyrifos would be unsafe. The 

Agency’s 2016 DWA demonstrates that 

DWLOC will be exceeded for some 

people whose drinking water is derived 

from certain vulnerable watersheds 

throughout the United States, which 

means that drinking water contributions 

will result in aggregate exposures that 

exceed the Agency’s determined safe 

level of exposure. When taking into 

consideration aggregate exposures based 

on current labeled uses, the EDWCs 

exceed the DWLOC of 4.0 ppb. For 

example, as noted above in Unit 

VII.B.2., the 2016 DWA presented 

EDWCs for uses of chlorpyrifos, 

including concentrations based on use 

on golf courses and agricultural crops. 

For those uses alone, the Agency 

estimated concentrations exceeding 4.0 

ppb in every region in the country; See 

Table 25 of the 2016 DWA. (Ref. 28 at 

73–74.) Comparing the calculated 

EDWCs from the 2016 DWA with the 

DWLOC calculated in the 2020 HHRA 

shows that drinking water 

concentrations from chlorpyrifos uses 

will exceed the safe allowable level for 

contributions from drinking water. This 

means that aggregate exposure (food, 

drinking water, and residential 

exposures) exceeds the Agency’s safe 

level for chlorpyrifos exposure. Because 

the FFDCA requires EPA to aggregate all 

dietary and non-occupational exposure, 

EPA cannot conclude that there is a 

reasonable certainty that no harm will 

result from aggregate exposure to 

chlorpyrifos residues when taking into 

consideration all labeled uses. 

It is worth noting that the Agency’s 

Proposed Interim Registration Review 

Decision (PID) recognized that there 

might be limited combinations of uses 

in certain geographic areas that could be 

considered safe, if the assessment only 

includes those specific uses in those 

areas. The PID noted that ‘‘[w]hen 

considering all currently registered 

agricultural and non-agricultural uses of 

chlorpyrifos, aggregate exposures are of 

concern. If considering only the uses 

that result in DWLOCs below the 

EDWCs, aggregate exposures are not of 

concern.’’ (Ref. 32 at 19). The PID 

proposed limiting chlorpyrifos 

applications to specific crops in certain 

regions where the EDWCs for those uses 

were calculated to be lower than the 

DWLOC. (Id. at 40). The Agency’s 

ability to make the safety finding for any 

remaining uses would be contingent 

upon significant changes to the existing 

registrations, including use 

cancellations, geographical limitations, 

and other label changes. 

Consequently, while the 2020 PID 

suggested that there may be limited 

combinations of uses that could be safe, 

FFDCA section 408(b)(2) requires EPA 

to aggregate all dietary and nonoccupational exposures to chlorpyrifos 

in making a safety finding. Without 

effective mitigation upon which to base 

a reduced aggregate exposure 

calculation, the products as currently 

registered present risks above the 

Agency’s levels of concern. Based on the 

data available at this time and the 

aggregate exposures expected from 

currently registered uses, the Agency 

cannot, at this time, determine that 

aggregate exposures to residues of 

chlorpyrifos, including all anticipated 

dietary exposures and all other nonoccupational exposures for which there 

is reliable information, are safe. 

Accordingly, as directed by the statute 

and in compliance with the Court’s 

order, EPA is revoking all chlorpyrifos 

tolerances. 


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IX. Procedural Matters 

A. When do these actions become 

effective? 

The revocations of the tolerances for 

all commodities will become effective 

on February 28, 2022. The Agency has 

set the expiration date for these 

tolerances to satisfy its international 

trade obligations described in Unit X. 

Any commodities listed in this rule 

treated with the pesticide subject to this 

rule, and in the channels of trade 

following the tolerance revocations, 

shall be subject to FFDCA section 

408(l)(5). Under this section, any 

residues of these pesticides in or on 

such food shall not render the food 

adulterated so long as it is shown to the 

satisfaction of the Food and Drug 

Administration that: 

1. The residue is present as the result 

of an application or use of the pesticide 

at a time and in a manner that was 

lawful under FIFRA, and 

2. The residue does not exceed the 

level that was authorized at the time of 

the application or use to be present on 

the food under a tolerance or exemption 

from tolerance that was in effect at the 

time of the application. Evidence to 

show that food was lawfully treated may 

include records that verify the dates 

when the pesticide was applied to such 

food. 

B. Response to Comments 

Today’s action responds to the Ninth 

Circuit’s order to issue a final rule in 

response to the 2007 Petition. As such 

this rule is not finalizing the proposal 

published in the Federal Register issue 

of November 6, 2015, nor is it 

implementing or resolving any 

registration review activity. Thus, this 

document is not responding to 

comments received on the 2015 

proposal or the most recent registration 

review documents. Those activities are 

separate and apart from the procedural 

posture of this final rule action. 

Moreover, as the registration review 

process is ongoing, including a separate 

review of the comments submitted, the 

Agency intends to respond to the most 

recent comments in as part of that 

process, rather than in this rule. 

C. Are the Agency’s actions consistent 

with international obligations? 

The tolerance revocations in this final 

rule are not discriminatory and are 

designed to ensure that both 

domestically produced and imported 

foods meet the food safety standard 

established by the FFDCA. The same 

food safety standards apply to 

domestically produced and imported 

foods. 

EPA considers Codex Maximum 

Residue Limits (MRLs) in setting U.S. 

tolerances and in reassessing them. 

Codex MRLs are established by the 

Codex Committee on Pesticide 

Residues, a committee within the Codex 

Alimentarius Commission, an 

international organization formed to 

promote the coordination of 

international food standards. The 

FFDCA requires EPA to take Codex 

MRLs into consideration when 

establishing new tolerances, and it is 

EPA’s policy to harmonize U.S. 

tolerances with Codex MRLs to the 

extent possible, provided that the MRLs 

achieve the level of protection required 

under FFDCA. In the current instance, 

EPA has determined that the current 

U.S. tolerances for chlorpyrifos are not 

safe and must be revoked. EPA has 

developed guidance concerning 

submissions for import tolerance 

support (65 FR 35069, June 1, 2000) 

(FRL–6559–3). 

Under the World Trade Organization 

Agreement on the Application of 

Sanitary and Phytosanitary Measures 

(SPS Agreement), to which the United 

States is a party, Members are required 

to, except in urgent circumstances, 

‘‘allow a reasonable interval between 

the publication of a sanitary or 

phytosanitary regulation and its entry 

into force in order to allow time for 

producers in exporting Members, and 

particularly in developing country 

Members, to adapt their products and 

methods of production to the 

requirements of the importing Member.’’ 

(Ref. 33). The WTO has interpreted the 

phrase ‘‘reasonable interval’’ to mean 

normally a period of not less than six 

months. (Ref. 34). In accordance with its 

obligations, EPA intends to notify the 

WTO of this regulation and is providing 

a ‘‘reasonable interval’’ by establishing 

an expiration date for the existing 

tolerances to allow those tolerances to 

remain in effect for a period of six 

months after the effective date of this 

final rule. After the six-month period 

expires, the tolerances for residues 

chlorpyrifos in or on food will no longer 

be in effect. 

X. Statutory and Executive Order 

Reviews 

Additional information about these 

statutes and Executive Orders can be 

found at https://www.epa.gov/lawsregulations-and-executive-orders. 

A. Executive Order 12866: Regulatory 

Planning and Review and Executive 

Order 13563: Improving Regulations 

and Regulatory Review 

The Office of Management and Budget 

(OMB) has exempted tolerance 

regulations from review under 

Executive Order 12866, entitled 

Regulatory Planning and Review (58 FR 

51735, October 4, 1993). Because this 

action has been exempted from review 

under Executive Order 12866, this final 

rule is not subject to Executive Order 

13563 (76 FR 3821, January 21, 2011). 

B. Paperwork Reduction Act (PRA) 

This final rule does not contain any 

information collection activities subject 

to OMB review and approval under the 

PRA, 44 U.S.C. 3501 et seq. An agency 

may not conduct or sponsor, and a 

person is not required to respond to a 

collection of information that requires 

OMB approval under PRA, unless it has 

been approved by OMB and displays a 

currently valid OMB control number. 

The OMB control numbers for EPA’s 

regulations in title 40 of the CFR, after 

appearing in the Federal Register, are 

listed in 40 CFR part 9, and included on 

the related collection instrument or 

form, if applicable. 

C. Regulatory Flexibility Act (RFA) 

The RFA, 5 U.S.C. 601 et seq., 

generally requires an agency to prepare 

a regulatory flexibility analysis of any 

rule subject to notice and comment 

rulemaking requirements under the 

Administrative Procedures Act or any 

other statute. Since this rule, which is 

issued under FFDCA section 

408(d)(4)(A)(i) (21 U.S.C. 

346a(d)(4)(A)(i)) directly in response to 

a petition under FFDCA section 408(d), 

does not require the issuance of a 

proposed rule, the RFA requirements do 

not apply. 

D. Unfunded Mandates Reform Act 

(UMRA) 

EPA has determined that this action 

does not impose any enforceable duty, 

contain any unfunded mandate, or 

otherwise have any effect on small 

governments subject to the requirements 

of UMRA sections 202, 203, 204, or 205 

(2 U.S.C. 1501 et seq.). 

E. Executive Order 13132: Federalism 

This action will not have federalism 

implications because it is not expected 

to have a substantial direct effect on 

States, on the relationship between the 

national government and the States, or 

on the distribution of power and 

responsibilities among the various 

levels of government, as specified in 

Executive Order 13132 (64 FR 43255, 

August 10, 1999). This final rule 

directly regulates growers, food 

processors, food handlers and food 

retailers, not States. This action does not 

alter the relationships or distribution of 

power and responsibilities established 


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by Congress in the preemption 

provisions of section 408(n)(4) of the 

FFDCA. 

F. Executive Order 13175: Consultation 

and Coordination With Indian Tribal 

Governments 

For the same reasons, this action will 

not have Tribal implications because it 

is not expected to have substantial 

direct effects on Indian Tribes, 

significantly or uniquely affect the 

communities of Indian Tribal 

governments, and does not involve or 

impose any requirements that affect 

Indian Tribes. Accordingly, the 

requirements of Executive Order 13175 

(65 FR 67249, November 9, 2000), do 

not apply to this action. 

G. Executive Order 13045: Protection of 

Children From Environmental Health 

and Safety Risks 

This action is not subject to Executive 

Order 13045 (62 FR 19885, April 23, 

1997), because this is not an 

economically significant regulatory 

action as defined by Executive Order 

12866, and this action does not address 

environmental health or safety risks 

disproportionately affecting children. 

H. Executive Order 13211: Actions 

Concerning Regulations That 

Significantly Affect Energy Supply, 

Distribution, or Use 

This action is not subject to Executive 

Order 13211 (66 FR 28355, May 22, 

2001), because this action is not a 

significant regulatory action under 

Executive Order 12866. 

I. National Technology Transfer and 

Advancement Act (NTTAA) 

In addition, since this action does not 

involve any technical standards, 

NTTAA section 12(d), 15 U.S.C. 272 

note, does not apply to this action. 

J. Executive Order 12898: Federal 

Actions To Address Environmental 

Justice in Minority Populations and 

Low-Income Populations 

This action does not entail special 

considerations of environmental justice 

related issues as delineated by 

Executive Order 12898 (59 FR 7629, 

February 16, 1994). Nevertheless, the 

revocation of the tolerances will reduce 

exposure to the pesticide and lead to a 

reduction in chlorpyrifos use on food 

crops. While EPA has not conducted a 

formal EJ analysis for this rule, the 

revocation of tolerances will likely 

reduce disproportionate impacts on EJ 

communities that are impacted by 

chlorpyrifos applications on crops. 

K. Congressional Review Act (CRA) 

This action is subject to the CRA (5 

U.S.C. 801 et seq.), and EPA will submit 

a rule report containing this rule and 

other required information to each 

House of the Congress and to the 

Comptroller General of the United 

States. This action is not a ‘‘major rule’’ 

as defined by 5 U.S.C. 804(2). 

XI. References 

The following is a list of the 

documents that are specifically 

referenced in this document. The 

docket, identified by docket ID number 

docket number EPA–HQ–OPP–2021– 

0523, includes these documents and 

other information considered by EPA, 

including documents that are referenced 

within the documents that are included 

in the docket, even if the referenced 

document is not physically located in 

the docket. All records in docket are 

part of the record for this rulemaking. 

For assistance in locating these other 

documents, please consult the technical 

person listed under FOR FURTHER

INFORMATION CONTACT. 

1. The Petition from NRDC and PANNA, 

EPA’s various responses to it, and the 

objections submitted on the Petition 

denial are available in docket number 

EPA–HQ–OPP–2007–1005 available at 

https://www.regulations.gov. 

2. U.S. EPA. Chlorpyrifos Final Work Plan. 

2009. Available at: https://

www.regulations.gov/document/EPA– 

HQ-OPP-2008-0850-0020. 

3. FIFRA Scientific Advisory Panel (2008). 

‘‘The Agency’s Evaluation of the Toxicity 

Profile of Chlorpyrifos.’’ Report from the 

FIFRA Scientific Advisory Panel Meeting 

of September 16–19, 2008. Available at: 

https://www.regulations.gov/docket/ 

EPA-HQ-OPP-2008-0274/document. 

4. U.S. EPA (2010). Draft Framework and 

Case Studies on Atrazine, Human 

Incidents, and the Agricultural Health 

Study: Incorporation of Epidemiology 

and Human Incident Data into Human 

Health Risk Assessment available at: 

https://www.regulations.gov/document/ 

EPA-HQ-OPP-2009-0851-0004. 

5. U.S. EPA (2016). Office of Pesticide 

Programs’ Framework for Incorporating 

Human Epidemiologic & Incident Data in 

Risk Assessments for Pesticides. (2016) 

Available at: https://www3.epa.gov/ 

pesticides/EPA-HQ-OPP-2008-0316- 

DRAFT-0075.pdf. 

6. FIFRA Scientific Advisory Panel (2012). 

‘‘Scientific Issues Associated with 

Chlorpyrifos’’. Available at: https://

www.regulations.gov/document/EPAHQ-OPP-2012-0040-0029. 

7. U.S. EPA (2014). Chlorpyrifos: Revised 

Human Health Risk Assessment for 

Registration Review. Available in docket 

number EPA–HQ–OPP–2008–0850, 

https://www.regulations.gov/document/ 

EPA-HQ-OPP-2008-0850-0195. 

8. U.S. EPA (2016). Scientific Advisory Panel 

for Chlorpyrifos: Analysis of 

Biomonitoring Data. Available at: https:// 

www.epa.gov/sites/default/files/2016-07/ 

documents/chlorpyrifos_sap_april_

2016_final_minutes.pdf. 

9. U.S. EPA (2020). Chlorpyrifos Human 

Health Risk Assessment. Available at: 

https://www.regulations.gov/document/ 

EPA-HQ-OPP-2008-0850-0944. 

10. U.S. EPA (2020). Updated Chlorpyrifos 

Refined Drinking Water Assessment for 

Registration Review. Available at: 

https://www.regulations.gov/document/ 

EPA-HQ-OPP-2008-0850-0941. 

11. A User’s Guide to Available EPA 

Information on Assessing Exposure to 

Pesticides in Food (June 21, 2000). 

Available at: https://www.doh.wa.gov/ 

Portals/1/Documents/4000/PASW_

exposurefood.pdf. 

12. U.S. EPA (2000). Chlorpyrifos Human 

Health Risk Assessment. Available at: 

https://archive.epa.gov/scipoly/sap/ 

meetings/web/pdf/hed_ra.pdf. 

13. U.S. EPA (2011). Chlorpyrifos: 

Preliminary Human Health Risk 

Assessment for Registration Review. 

Available in docket number EPA–HQ– 

OPP–2008–0850, https://

www.regulations.gov/document/EPAHQ-OPP-2008-0850-0025. 

14. U.S. EPA (2016). Summary Reviews for 

Additional Epidemiological Literature 

Studies from Prospective Birth Cohort 

Studies. Available in docket number 

EPA–HQ–OPP–2015–0653 at https://

www.regulations.gov/document/EPAHQ-OPP-2015-0653-0438. 

15. U.S. EPA (2020). The Use of New 

Approach Methodologies (NAMs) to 

Derive Extrapolation Factors and 

Evaluate Developmental Neurotoxicity 

for Human Health Risk Assessment. 

Available in docket number EPA–HQ– 

OPP–2020–0263 at https://

www.regulations.gov/document/EPAHQ-OPP-2020-0263-0033. 

16. U.S. EPA (2020). Transmittal of Meeting 

Minutes and Final Report of the Federal 

Insecticide, Fungicide, and Rodenticide 

Act, Scientific Advisory Panel (FIFRA 

SAP) Virtual Meeting held on September 

15–18, 2020. Available in docket number 

EPA–HQ–2020–0263 at https://

www.regulations.gov/document/EPAHQ-OPP-2020-0263-0054. 

17. U.S. EPA (2006). Revised 

Organophosphorous Pesticide 

Cumulative Risk Assessment. Available 

at http://www.epa.gov/pesticides/ 

cumulative/2006-op/index.htm. 

18. U.S. EPA (2012). Standard Operating 

Procedures for Residential Pesticide 

Exposure Assessment https://

www.epa.gov/sites/default/files/2015-08/ 

documents/usepa-opp-hed_residential_

sops_oct2012.pdf. 

19. FIFRA Scientific Advisory Panel (2002). 

‘‘Organophosphate Pesticides: 

Preliminary OP Cumulative Risk 

Assessment.’’ Information on how to 

obtain the meeting report is available at 

http://www2.epa.gov/sap/fifra-scientificadvisory-panel-meetings. 

20. U.S. EPA (2000). Choosing a Percentile of 

Acute Dietary Exposure as a Threshold 

of Regulatory Concern. Available at: 


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48336 Federal Register / Vol. 86, No. 165 / Monday, August 30, 2021 / Rules and Regulations 

https://www.epa.gov/sites/production/ 

files/2015-07/documents/trac2b054_

0.pdf. 

21. EPA’s Exposure Factors Handbook. 

Available at: https://www.epa.gov/ 

expobox/about-exposure-factorshandbook. 

22. U.S. EPA (2014). Guidance for Applying 

Quantitative Data to Develop DataDerived Extrapolation Factors for 

Interspecies and Intraspecies 

Extrapolation. Available at: https://

www.epa.gov/sites/default/files/2015-01/ 

documents/ddef-final.pdf. 

23. U.S. EPA (2014). Chlorpyrifos Acute and 

Steady Dietary (Food Only) Exposure 

Analysis to Support Registration Review. 

Available at: https://

www.regulations.gov/document/EPAHQ-OPP-2008-0850-0197. 

24. U.S. EPA (2020). Framework for 

Conducting Pesticide Drinking Water 

Assessments for Surface Water. 

Environmental Fate and Effects Division. 

Office of Pesticide Programs. Office of 

Chemical Safety and Pollution 

Prevention. U.S. Environmental 

Protection Agency. Available at: https:// 

www.epa.gov/sites/default/files/2020-09/ 

documents/framework-conductingpesticide-dw-sw.pdf. 

25. FIFRA Scientific Advisory Panel (2019) 

‘‘Approaches for Quantitative Use of 

Surface Water Monitoring Data in 

Pesticide Drinking Water Assessments.’’ 

Available at: https://

www.regulations.gov/document/EPAHQ-OPP-2019-0417-0019. 

26. U.S. EPA (2001). General Principles for 

Performing Aggregate Exposure and Risk 

Assessments. Available at: https://

www.epa.gov/sites/default/files/2015-07/ 

documents/aggregate.pdf. 

27. U.S. EPA (2020). Appendix B. Case Study 

for Integrating a Distributional Approach 

to Using Percent Crop Area (PCA) and 

Percent Crop Treated (PCT) into 

Drinking Water Assessment. Available 

at: https://www.regulations.gov/ 

document/EPA-HQ-OPP-2020-0279- 

0002. 

28. U.S. EPA (2016). Chlorpyrifos Refined 

Drinking Water Assessment for 

Registration Review. Available at: 

https://www.regulations.gov/document/ 

EPA-HQ-OPP-2015-0653-0437. 

29. U.S. EPA (2014). Chlorpyrifos Updated 

Drinking Water Assessment for 

Registration Review. Available at: 

https://www.regulations.gov/document/ 

EPA-HQ-OPP-2008-0850-0198. 

30. U.S. EPA (2015). Proposed Rule: 

Tolerance Revocations: Chlorpyrifos. 

Available at: https://

www.regulations.gov/document/EPAHQ-OPP-2015-0653-0001. 

31. U.S. EPA (2011). Finalization of Guidance 

on Incorporation of Water Treatment 

Effects on Pesticide Removal and 

Transformations in Drinking Water 

Exposure Assessments. Available at: 

https://www.epa.gov/pesticide-scienceand-assessing-pesticide-risks/ 

finalization-guidance-incorporationwater-treatment. 

32. U.S. EPA (2020). Chlorpyrifos Proposed 

Interim Registration Review Decision. 

Available at: https://

www.regulations.gov/document/EPAHQ-OPP-2008-0850-0971. 

33. For more information on World Trade 

Organization’s Agreement on the 

Application of Sanitary and 

Phytosanitary Measures (SPS 

Agreement), please see: https://

www.wto.org/english/tratop_e/sps_e/ 

spsagr_e.htm. 

34. For more information on World Trade 

Organization (2001) ImplementationRelated Issues and Concerns, please see: 

https://docs.wto.org/dol2fe/Pages/SS/ 

directdoc.aspx?filename=Q:/WT/Min01/ 

17.pdf&Open=True. 

List of Subjects in 40 CFR Part 180 

Environmental protection, 

Administrative practice and procedure, 

Agricultural commodities, Pesticides 

and pests, Reporting and recordkeeping 

requirements. 

Dated: August 18, 2021. 

Edward Messina, 

Director, Office of Pesticide Programs. 

Therefore, for the reasons set forth in 

the preamble, 40 CFR part 180 is 

amended as follows: 

PART 180—[AMENDED] 

■ 1. The authority citation for part 180 

continues to read as follows: 

Authority: 21 U.S.C. 321(q), 346a and 371. 

■ 2. In § 180.342, add introductory text 

to read as follows: 

§ 180.342 Chlorpyrifos; tolerances for 

residues. 

This section and all tolerances 

contained herein expire and are revoked 

on February 28, 2022. 

* * * * * 

[FR Doc. 2021–18091 Filed 8–27–21; 8:45 am] 

BILLING CODE 6560–50–P 

DEPARTMENT OF DEFENSE 

Defense Acquisition Regulations 

System 

48 CFR Parts 212, 225 and 252 

[Docket DARS–2020–0039] 

RIN 0750–AL15 

Defense Federal Acquisition 

Regulation Supplement: Improved 

Energy Security for Main Operating 

Bases in Europe (DFARS Case 2020– 

D030) 

AGENCY: Defense Acquisition 

Regulations System, Department of 

Defense (DoD). 

ACTION: Final rule. 

SUMMARY: DoD is issuing a final rule 

amending the Defense Federal 

Acquisition Regulation Supplement 

(DFARS) to implement a section of the 

National Defense Authorization Act for 

Fiscal Year 2020. This section prohibits 

contracts for the acquisition of 

furnished energy for a covered military 

installation in Europe that is sourced 

from inside the Russian Federation. 

DATES: Effective August 30, 2021. 

FOR FURTHER INFORMATION CONTACT: Ms. 

Kimberly Bass, telephone 571–372– 

6174. 

SUPPLEMENTARY INFORMATION: 

I. Background 

DoD published a proposed rule in the 

Federal Register at 86 FR 3935 on 

January 15, 2021, to amend the DFARS 

to implement section 2821 of the 

National Defense Authorization Act 

(NDAA) for Fiscal Year (FY) 2020 (Pub. 

L. 116–92). Section 2821 prohibits use 

of energy sourced from inside the 

Russian Federation in an effort to 

promote energy security in Europe. The 

prohibition applies to all forms of 

energy ‘‘furnished to a covered military 

installation’’ as that term is defined in 

the statute. No public comments were 

received in response to the proposed 

rule. 

II. Discussion and Analysis 

A. Summary of Significant Changes 

No changes are made to the final rule 

as a result of public comments. 

B. Other Changes 

One change is made to the rule as 

proposed to clarify the same language 

that appears in section 225.7019–2, 

paragraph (b); the provision 252.225– 

7053, paragraph (b)(2); and clause 

252.225–7054, paragraph (b)(2). In all 

three locations, the statement ‘‘Does not 

apply to a third party that uses it to 

create some other form of energy (e.g., 

heating, cooling, or electricity)’’ is 

changed to read ‘‘Does not apply to 

energy converted by a third party into 

another form of energy and not directly 

delivered to a covered military 

installation.’’ No other changes are 

made to the rule. 

III. Applicability to Contracts At or 

Below the Simplified Acquisition 

Threshold and for Commercial Items, 

Including Commercially Available Offthe-Shelf Items 

This DFARS rule implements section 

2821 of the NDAA for FY 2020 (Pub. L. 

116–92). Section 2821 prohibits use of 

energy sourced from inside the Russian 

Federation unless a waiver is approved 

by the head of the contracting activity. 

To implement section 2821, this rule 

creates a new solicitation provision and 


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