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SETTLEMENT AGREEMENT

 This Settlement Agreement is entered into by and among Petitioners Natural 

Resources Defense Council, Inc., Pesticide Action Network North America, Pineros y 

Campesinos Unidos Del Noroeste, Physicians for Social Responsibility - San Francisco, 

Farm Labor Organizing Committee, AFL-CIO, and Migrant Clinicians Network 

(collectively “Petitioners”) and the U.S. Environmental Protection Agency ("EPA"). 

 WHEREAS, on February 6, 2006, EPA published in the Federal Register a 

final rule entitled “Protections for Subjects in Human Research.” See 71 Fed. Reg. 6138 

(Feb. 6, 2006) (the “2006 final rule”); 

 WHEREAS, the Petitioners filed four petitions for review of the 2006 final 

rule, which were consolidated in the United States Court of Appeals for the Second 

Circuit, Case Nos. 06-0820-ag, 06-1895-ag, 06-2149-ag, 06-2360-ag (2nd Cir.); 

 WHEREAS, the Petitioners and EPA (collectively, “the Parties”) briefed 

the case and presented oral argument before the court on January 17, 2008; 

 WHEREAS, the Parties wish to settle the Petitioners’ petitions for review; 

 WHEREAS, settlement of the Petitioners’ petitions is in the public interest; 

 NOW, THEREFORE, without admission of any issues of fact or law, or 

waiver of any claim or defense, either factual or legal, the Parties agree as follows: 

Specific Provisions

 1. EPA agrees to conduct notice-and-comment rulemaking in accordance 

with the Administrative Procedure Act on the issue of whether the 2006 final rule 

should be amended. 

 2. No later than seven months after this Settlement Agreement is filed with 

the court, EPA agrees to sign a notice of proposed rulemaking that proposes, at a 
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minimum, the amendments to the 2006 final rule as substantially consistent with 

Exhibit A. After considering any public comments received, EPA agrees to take final 

action on the proposed rule, which may include signing a notice of final rulemaking. 

EPA will take such final action no later than eighteen months after this settlement 

agreement is filed with the court. 

 

Procedural Matters

 3. Upon execution of this Settlement Agreement by the Parties, the Petitioners 

and EPA agree to file a joint motion requesting that the court extend the stay in Case 

Nos. 06-0820-ag, 06-1895-ag, 06-2149-ag, 06-2360-ag (2nd Cir.), pending completion of 

the activities set forth in paragraphs 1 and 2. This Settlement Agreement shall be 

appended to that joint motion. This Settlement Agreement will take effect only if the 

court grants the requested stay. 

 4. If EPA takes the actions described in paragraph 2, by the schedule contained 

in paragraph 2, then the Petitioners and EPA agree to file a joint motion in accordance 

with Rule 42 of the Federal Rules of Appellate Procedure for dismissal with prejudice of 

Case Nos. 06-0820-ag, 06-1895-ag, 06-2149-ag, 06-2360-ag (2nd Cir.). 

Petitioners' Remedies

5. If EPA fails to take the actions described in paragraph 2, by the schedule 

contained in paragraph 2, then the Petitioners’ sole remedy shall be the right to 

reactivate their petitions for review of the 2006 final rule and request that the Court 
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proceed to issue a decision in the consolidated cases. The Petitioners agree to give EPA 

thirty days’ notice prior to exercising their rights under this paragraph. 

6. Any challenge to any amendments to the 2006 final rule must be brought in a 

new action, and Petitioners reserve whatever rights they may have to bring such a 

challenge, except as specifically provided below. Notwithstanding the foregoing 

sentence, if EPA amends the 2006 final rule by adopting the language of Exhibit A 

without making any material changes to the language of Exhibit A, Petitioners will not 

exercise whatever rights they may have to seek judicial review of those amendments 

pursuant to 21 U.S.C. § 346a(h)(1) or otherwise. Nothing in this settlement agreement 

shall restrict Petitioners’ rights to comment on or otherwise participate in the APA 

rulemaking discussed in paragraph 1. 

General Provisions

 7. Nothing in the terms of this Settlement Agreement shall be construed to 

limit or modify the discretion accorded EPA by the Department of the Interior, 

Environment and Related Agencies Appropriations Act, 2006; the Federal Food, Drug, 

and Cosmetic Act; the Federal Insecticide, Fungicide and Rodenticide Act; or general 

principles of administrative law. 

 8. Nothing in this Settlement Agreement shall be construed to limit or 

modify EPA's discretion to alter, amend, or revise 40 C.F.R. Parts 26 and 150 through 

180, or to promulgate superseding rules or subsequent guidance. Nothing in this 

Settlement Agreement shall be construed to limit or modify EPA’s discretion to propose 
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additional regulatory changes in the same notice of proposed rulemaking signed 

pursuant to paragraph 2 and to finalize additional or different regulatory changes in the 

same notice of final rulemaking signed pursuant to paragraph 2. 

 9. Until any amendments to the 2006 final rule become effective, the 2006 

final rule remains in effect. 

 10. This is the entire Settlement Agreement between the Parties with respect 

to the Petitioners’ petitions for review of the 2006 final rule. All prior conversations, 

meetings, discussions, drafts, and writings of any kind are specifically superseded by 

this Settlement Agreement and may not be used by the Parties to vary or contest the 

terms of this Settlement Agreement, or as evidence of the Parties' intent in entering into 

this Settlement Agreement. 

 11. The Parties may agree in writing to modify any provision of this 

Settlement Agreement. 

 12. Nothing in this Settlement Agreement shall be construed to constitute an 

admission of any issue of fact, law, or liability by any of the Parties. Except as expressly 

provided in this Settlement Agreement, none of the Parties waives or relinquishes any 

legal rights, claims, or defenses it may have. 

 13. EPA agrees to pay Petitioners $ 135,000 in full satisfaction of Petitioners’ 

claims for attorney fees and costs in this litigation. 

 14. The undersigned representatives of each Party certify that they are fully 

authorized by the Party or Parties they represent to bind the respective Parties to the 
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terms of this Settlement Agreement. This Settlement Agreement may be signed in 

counterparts, which, taken together, shall constitute the whole. This Settlement 

Agreement will be deemed to be executed and shall become effective when it has been 

signed by all of the representatives of the Parties set forth below. 

 15. No provision of this Settlement Agreement shall be interpreted as or 

constitute a commitment or requirement that EPA obligate or pay funds in 

contravention of the Anti-Deficiency Act, 31 U.S.C. § 1341, or take actions in 

contravention of the Administrative Procedure Act, 5 U.S.C. §§ 551-559, 701-706, or any 

other law or regulation, either substantive or procedural. 

 16. It is hereby expressly understood and agreed that this Settlement 

Agreement was jointly drafted by the Parties. Accordingly, the Parties hereby agree 

that any and all rules of construction to the effect that ambiguity is construed against 

the drafting party shall be inapplicable in any dispute concerning the terms, meaning, 

or interpretation of this Settlement Agreement. 

 17. Circumstances that are not reasonably foreseeable and that are outside 

the reasonable control of EPA could possibly delay compliance with the schedule 

established in paragraphs 2. Such situations include, but are not limited to, a 

government shut-down such as occurred in 1995 and 1996, or catastrophic 

environmental events requiring immediate and/or time-consuming response by EPA. 

Should a delay occur due to such circumstances, any resulting failure to meet the 

timetables set forth herein shall not constitute a failure to comply with the terms of this 


EXHIBIT A TO SETTLEMENT AGREEMENT 

TITLE 40--PROTECTION OF ENVIRONMENT 

CHAPTER I--ENVIRONMENTAL PROTECTION AGENCY 

PART 26: PROTECTION OF HUMAN SUBJECTS--Table of Contents 

 

Subpart K: Basic Ethical Requirements for Third-Party Human Research for Pesticides 

Involving Intentional Exposure of Non-pregnant, Non-nursing Adults 

§ 26.1101 To what does this subpart apply? 

(a) Except as provided in paragraph (c) of this section, subpart K of this part applies to all 

research initiated after [insert effective date of amended rule] involving intentional exposure 

of a human subject to a pesticide if, at any time prior to initiating such research, any person 

who conducted or supported such research intended either to submit results of the research to 

EPA for consideration in connection with any action that may be performed by EPA under 

any regulatory statute administered by EPA or to hold the results of the research for later 

inspection by EPA under any regulatory statute administered by EPA. 

(b) For purposes of determining a person’s intent under paragraph (a), EPA may consider any 

available and relevant information. EPA shall rebuttably presume the existence of intent 

if: 

(1) The person or the person’s agent has submitted or made available for inspection the 

results of such research to EPA; or 

(2) The person is a member of a class of people who, or whose products or activities, are 

regulated by EPA and, at the time the research was initiated, the results of such 

research would be relevant to EPA’s exercise of its regulatory authority with respect 

to that class of people, products, or activities. 

(c) Unless otherwise required by the Administrator, research is exempt from this subpart if it 

involves only the collection or study of existing data, documents, records, pathological 

specimens, or diagnostic specimens from previously conducted studies, and if these sources 

are publicly available or if the information is recorded by the investigator in such a manner 

that subjects cannot be identified, directly or through identifiers linked to the subjects. 

(d) The Administrator retains final judgment as to whether a particular activity is covered by this 

subpart. 

(e) Compliance with this subpart requires compliance with pertinent Federal laws or regulations 

which provide additional protections for human subjects. 
Exhibit A to Settlement Agreement 2 

(f) This subpart does not affect any State or local laws or regulations which may otherwise be 

applicable and which provide additional protections for human subjects. Reference to State 

or local laws in this subpart is intended to include the laws of federally recognized American 

Indian and Alaska Native Tribal Governments. 

(g) This subpart does not affect any foreign laws or regulations which may otherwise be 

applicable and which provide additional protections to human subjects of research. 

§ 26.1102 Definitions. 

(a) Administrator means the Administrator of the Environmental Protection Agency (EPA) and 

any other officer or employee of EPA to whom authority has been delegated. 

(b) Institution means any public or private entity or agency (including Federal, State, and other 

agencies). 

 (c) Initiation of research involving human subjects is considered to occur as of the enrollment of 

the first subject in the research. 

(d) Research means a systematic investigation, including research, development, testing and 

evaluation, designed to develop or contribute to generalizable knowledge. Activities which 

meet this definition constitute research for purposes of this subpart, whether or not they are 

considered research for other purposes. For example, some demonstration and service 

programs may include research activities. 

(e) Human subject means a living individual about whom an investigator (whether professional 

or student) conducting research obtains: 

 (1) Data through intervention or interaction with the individual, or 

 (2) Identifiable private information. 

 (3) “Intervention” includes both physical procedures by which data are gathered (for 

example, venipuncture) and manipulations of the subject or the subject’s environment 

that are performed for research purposes. Interaction includes communication or 

interpersonal contact between investigator and subject. “Private information” includes 

information about behavior that occurs in a context in which an individual can reasonably 

expect that no observation or recording is taking place, and information which has been 

provided for specific purposes by an individual and which the individual can reasonably 

expect will not be made public (for example, a medical record). Private information must 

be individually identifiable (i.e., the identity of the subject is or may readily be 

ascertained by the investigator or associated with the information) in order for obtaining 

the information to constitute research involving human subjects. 
Exhibit A to Settlement Agreement 3 

(f) IRB means an institutional review board established in accord with and for the purposes 

expressed in this part. 

(g) IRB approval means the determination of the IRB that the research has been reviewed and 

may be conducted at an institution within the constraints set forth by the IRB and by other 

institutional and Federal requirements. 

(h) Minimal risk means that the probability and magnitude of harm or discomfort anticipated in 

the research are not greater in and of themselves than those ordinarily encountered in daily 

life or during the performance of routine physical or psychological examinations or tests. 

(i) Research involving intentional exposure of a human subject means a study of a substance in 

which the exposure to the substance experienced by a human subject participating in the 

study would not have occurred but for the human subject’s participation in the study. 

(j) Person means any person, as that term is defined in FIFRA section 2(s) (7 U.S.C. 136), 

except: 

(1) A federal agency that is subject to the provisions of the Federal Policy for the Protection 

of Human Subjects of Research, and 

(2) A person when performing human research supported by a federal agency covered by 

paragraph (j)(1) of this section. 

(k) Pesticide means any substance or mixture of substances meeting the definition in 7 U.S.C. 

136(u) [Federal Insecticide, Fungicide and Rodenticide Act sec. 2(u)]. 

§§ 26.1103-26.1106 [Reserved] 
Exhibit A to Settlement Agreement 4 

§ 26.1107 IRB membership. 

(a) Each IRB shall have at least five members, with varying backgrounds to promote complete 

and adequate review of research activities which are presented for its approval. The IRB shall 

be sufficiently qualified through the experience and expertise of its members, and the 

diversity of the members, including consideration of race, gender, and cultural backgrounds 

and sensitivity to such issues as community attitudes, to promote respect for its advice and 

counsel in safeguarding the rights and welfare of human subjects. In addition to possessing 

the professional competence necessary to review specific research activities, the IRB shall be 

able to ascertain the acceptability of proposed research in terms of institutional commitments 

and regulations, applicable law, and standards of professional conduct and practice. The IRB 

shall therefore include persons knowledgeable in these areas. If an IRB regularly reviews 

research that involves a vulnerable category of subjects, such as prisoners or handicapped or 

mentally disabled persons, consideration shall be given to the inclusion of one or more 

individuals who are knowledgeable about and experienced in working with these subjects. 

(b) Every nondiscriminatory effort will be made to ensure that no IRB consists entirely of men 

or entirely of women, including the institution’s consideration of qualified persons of both 

sexes, so long as no selection is made to the IRB on the basis of gender. No IRB may consist 

entirely of members of one profession. 

(c) Each IRB shall include at least one member whose primary concerns are in scientific areas 

and at least one member whose primary concerns are in nonscientific areas. 

(d) Each IRB shall include at least one member who is not otherwise affiliated with the 

institution and who is not part of the immediate family of a person who is affiliated with the 

institution. 

(e) No IRB may have a member participate in the IRB’s initial or continuing review of any 

project in which the member has a conflicting interest, except to provide information 

requested by the IRB. 

(f) An IRB may, in its discretion, invite individuals with competence in special areas to assist in 

the review of issues which require expertise beyond or in addition to that available on the 

IRB. These individuals may not vote with the IRB. 

§ 26.1108 IRB functions and operations. 

In order to fulfill the requirements of this subpart each IRB shall: 

(a) Follow written procedures: 

 (1) For conducting its initial and continuing review of research and for reporting its findings 

and actions to the investigator and the institution; 
Exhibit A to Settlement Agreement 5 

(2) For determining which projects require review more often than annually and which 

projects need verification from sources other than the investigator that no material 

changes have occurred since previous IRB review; 

(3) For ensuring prompt reporting to the IRB of proposed changes in research activity; and 

(4) For ensuring that changes in approved research, during the period for which IRB 

approval has already been given, may not be initiated without IRB review and approval 

except where necessary to eliminate apparent immediate hazards to the human subjects. 

(b) Follow written procedures for ensuring prompt reporting to the IRB, appropriate institutional 

officials, and the Environmental Protection Agency of: 

 

(1) Any unanticipated problems involving risks to human subjects or others; 

(2) Any instance of serious or continuing noncompliance with this subpart of the 

requirements or determinations of the IRB; or 

(3) Any suspension or termination of IRB approval. 

(c) Except when an expedited review procedure is used (see Sec. 26.1110), review proposed 

research at convened meetings at which a majority of the members of the IRB are present, 

including at least one member whose primary concerns are in nonscientific areas. In order for 

the research to be approved, it shall receive the approval of a majority of those members 

present at the meeting. 

§ 26.1109 IRB review of research. 

(a) An IRB shall review and have authority to approve, require modifications in (to secure 

approval), or disapprove all research activities covered by this subpart. 

(b) An IRB shall require that information given to subjects as part of informed consent is in 

accordance with Sec. 26.1116. The IRB may require that information, in addition to that 

specifically mentioned in Sec. 26.1116 be given to the subjects when, in the IRB’s 

judgment, the information would meaningfully add to the protection of the rights and welfare 

of subjects. 

(c) An IRB shall require documentation of informed consent in accordance with Sec. 26.1117. 

(d) An IRB shall notify investigators and the institution in writing of its decision to approve or 

disapprove the proposed research activity, or of modifications required to secure IRB 

approval of the research activity. If the IRB decides to disapprove a research activity, it shall 

include in its written notification a statement of the reasons for its decision and give the 

investigator an opportunity to respond in person or in writing. 
Exhibit A to Settlement Agreement 6 

(e) An IRB shall conduct continuing review of research covered by this subpart at intervals 

appropriate to the degree of risk, but not less than once per year, and shall have authority to 

observe or have a third party observe the consent process and the research. 

§ 26.1110 Expedited review procedures for certain kinds of research involving no more 

than minimal risk, and for minor changes in approved research. 

(a) The Secretary, HHS, has established, and published as a Notice in the Federal Register, a list 

of categories of research that may be reviewed by the IRB through an expedited review 

procedure. The list will be amended, as appropriate after consultation with other departments 

and agencies, through periodic republication by the Secretary, HHS, in the Federal Register. 

A copy of the list is available from the Office for Human Research Protections, HHS, or any 

successor office. 

(b) (1) An IRB may use the expedited review procedure to review either or both of the 

following: 

(i) Some or all of the research appearing on the list and found by the reviewer(s) to 

involve no more than minimal risk, 

(ii) Minor changes in previously approved research during the period (of 1 year or less) 

for which approval is authorized. 

(2) Under an expedited review procedure, the review may be carried out by the IRB 

chairperson or by one or more experienced reviewers designated by the chairperson from 

among members of the IRB. In reviewing the research, the reviewers may exercise all of 

the authorities of the IRB except that the reviewers may not disapprove the research. A 

research activity may be disapproved only after review in accordance with the nonexpedited procedure set forth in Sec. 26.1108(c). 

(c) Each IRB which uses an expedited review procedure shall adopt a method for keeping all 

members advised of research proposals which have been approved under the procedure. 

(d) The Administrator may restrict, suspend, or terminate, an institution’s or IRB’s use of the 

expedited review procedure for research covered by this subpart. 

§ 26.1111 Criteria for IRB approval of research. 

(a) In order to approve research covered by this subpart the IRB shall determine that all of the 

following requirements are satisfied: 

(1) Risks to subjects are minimized: 
Exhibit A to Settlement Agreement 7 

(i) By using procedures which are consistent with sound research design and which do 

not unnecessarily expose subjects to risk, and 

(ii) Whenever appropriate, by using procedures already being performed on the subjects 

for diagnostic or treatment purposes. 

 

(2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and 

the importance of the knowledge that may reasonably be expected to result. In evaluating 

risks and benefits, the IRB should consider only those risks and benefits that may result 

from the research (as distinguished from risks and benefits subjects would receive even if 

not participating in the research). The IRB should not consider possible long-range 

effects of applying knowledge gained in the research (for example, the possible effects of 

the research on public policy) as among those research risks that fall within the purview 

of its responsibility. 

(3) Selection of subjects is equitable. In making this assessment the IRB should take into 

account the purposes of the research and the setting in which the research will be 

conducted and should be particularly cognizant of the special problems of research 

involving vulnerable populations, such as prisoners, mentally disabled persons, or 

economically or educationally disadvantaged persons. 

 (4) Informed consent will be sought from each prospective subject, in accordance with, and 

to the extent required by Sec. 26.1116. 

(5) Informed consent will be appropriately documented, in accordance with, and to the extent 

required by Sec. 26.1117. 

(6) When appropriate, the research plan makes adequate provision for monitoring the data 

collected to ensure the safety of subjects. 

(7) When appropriate, there are adequate provisions to protect the privacy of subjects and to 

maintain the confidentiality of data. 

(b) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, 

such as prisoners, mentally disabled persons, or economically or educationally disadvantaged 

persons, additional safeguards have been included in the study to protect the rights and 

welfare of these subjects. 

§ 26.1112 Review by institution. 

Research covered by this subpart that has been approved by an IRB may be subject to further 

appropriate review and approval or disapproval by officials of the institution. However, those 

officials may not approve the research if it has not been approved by an IRB. 
Exhibit A to Settlement Agreement 8 

§ 26.1113 Suspension or termination of IRB approval of research. 

An IRB shall have authority to suspend or terminate approval of research that is not being 

conducted in accordance with the IRB’s requirements or that has been associated with 

unexpected serious harm to subjects. Any suspension or termination of approval shall include a 

statement of the reasons for the IRB’s action and shall be reported promptly to the investigator, 

appropriate institutional officials, and the Administrator of EPA. 

§ 26.1114 Cooperative research. 

In complying with this subpart, sponsors, investigators, or institutions involved in multiinstitutional studies may use joint review, reliance upon the review of another qualified IRB, or 

similar arrangements aimed at avoidance of duplication of effort. 

§ 26.1115 IRB records. 

(a) An IRB shall prepare and maintain adequate documentation of IRB activities, including the 

following: 

(1) Copies of all research proposals reviewed, scientific evaluations, if any, that accompany 

the proposals, approved sample consent documents, progress reports submitted by 

investigators, and reports of injuries to subjects. 

(2) Minutes of IRB meetings which shall be in sufficient detail to show attendance at the 

meetings; actions taken by the IRB; the vote on these actions including the number of 

members voting for, against, and abstaining; the basis for requiring changes in or 

disapproving research; and a written summary of the discussion of controverted issues 

and their resolution. 

(3) Records of continuing review activities. 

(4) Copies of all correspondence between the IRB and the investigators. 

(5) A list of IRB members identified by name; earned degrees; representative capacity; 

indications of experience such as board certifications, licenses, etc., sufficient to describe 

each member’s chief anticipated contributions to IRB deliberations; and any employment 

or other relationship between each member and the institution, for example, full-time 

employee, a member of governing panel or board, stockholder, paid or unpaid consultant. 

(6) Written procedures for the IRB in the same detail as described in Sec. 26.1108(a) and 

Sec. 26.1108(b). 

(7) Statements of significant new findings provided to subjects, as required by Sec. 

26.1116(b)(5). 
Exhibit A to Settlement Agreement 9 

(b) The records required by this subpart shall be retained for at least 3 years, and records relating 

to research which is conducted shall be retained for at least 3 years after completion of the 

research. All records shall be accessible for inspection and copying by authorized 

representatives of EPA at reasonable times and in a reasonable manner. 

§ 26.1116 General requirements for informed consent. 

No investigator may involve a human being as a subject in research covered by this subpart 

unless the investigator has obtained the legally effective informed consent of the subject. An 

investigator shall seek such consent only under circumstances that provide the prospective 

subject sufficient opportunity to consider whether or not to participate and that minimize the 

possibility of coercion or undue influence. The information that is given to the subject shall be in 

language understandable to the subject. No informed consent, whether oral or written, may 

include any exculpatory language through which the subject is made to waive or appear to waive 

any of the subject’s legal rights, or releases or appears to release the investigator, the sponsor, the 

institution or its agents from liability for negligence. 

(a) Basic elements of informed consent. In seeking informed consent the following information 

shall be provided to each subject: 

(1) A statement that the study involves research, an explanation of the purposes of the 

research and the expected duration of the subject’s participation, a description of the 

procedures to be followed, and identification of any procedures which are experimental; 

(2) A description of any reasonably foreseeable risks or discomforts to the subject; 

(3) A description of any benefits to the subject or to others which may reasonably be 

expected from the research; 

(4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that 

might be advantageous to the subject; 

(5) A statement describing the extent, if any, to which confidentiality of records identifying 

the subject will be maintained; 

(6) For research involving more than minimal risk, an explanation as to whether any 

compensation and an explanation as to whether any medical treatments are available if 

injury occurs and, if so, what they consist of, or where further information may be 

obtained; 

(7) An explanation of whom to contact for answers to pertinent questions about the research 

and research subjects’ rights, and whom to contact in the event of a research-related 

injury to the subject; and 
Exhibit A to Settlement Agreement 10 

(8) A statement that participation is voluntary, refusal to participate will involve no penalty 

or loss of benefits to which the subject is otherwise entitled, and the subject may 

discontinue participation at any time without penalty or loss of benefits to which the 

subject is otherwise entitled. 

(b) Additional elements of informed consent. When appropriate, one or more of the following 

elements of information shall also be provided to each subject: 

(1) A statement that the particular treatment or procedure may involve risks to the subject (or 

to the embryo or fetus, if the subject may become pregnant) which are currently 

unforeseeable; 

(2) Anticipated circumstances under which the subject’s participation may be terminated by 

the investigator without regard to the subject’s consent; 

(3) Any additional costs to the subject that may result from participation in the research; 

(4) The consequences of a subject’s decision to withdraw from the research and procedures 

for orderly termination of participation by the subject; 

(5) A statement that significant new findings developed during the course of the research 

which may relate to the subject’s willingness to continue participation will be provided to 

the subject; and 

(6) The approximate number of subjects involved in the study. 

(c) The informed consent requirements in this subpart are not intended to preempt any applicable 

Federal, State, or local laws which require additional information to be disclosed in order for 

informed consent to be legally effective. 

(d) Nothing in this subpart is intended to limit the authority of a physician to provide emergency 

medical care, to the extent the physician is permitted to do so under applicable Federal, State, 

or local law. 

(e) The subjects of the research must be informed of the identity of the pesticide and the nature 

of its pesticidal function. 
Exhibit A to Settlement Agreement 11 

§ 26.1117 Documentation of informed consent. 

(a) Informed consent shall be documented by the use of a written consent form approved by the 

IRB and signed by the subject. A copy shall be given to the subject. 

(b) The consent form may be either of the following: 

(1) A written consent document that embodies the elements of informed consent required by 

Sec. 26.1116. This form may be read to the subject, but in any event, the investigator 

shall give the subject adequate opportunity to read it before it is signed; or 

(2) A short form written consent document stating that the elements of informed consent 

required by Sec. 26.1116 have been presented orally to the subject. When this method is 

used, there shall be a witness to the oral presentation. Also, the IRB shall approve a 

written summary of what is to be said to the subject. Only the short form itself is to be 

signed by the subject. However, the witness shall sign both the short form and a copy of 

the summary, and the person actually obtaining consent shall sign a copy of the summary. 

A copy of the summary shall be given to the subject, in addition to a copy of the short 

form. 

§§ 26.1118-26.1122 [Reserved] 

§ 26.1123 Early termination of research. 

The Administrator may require that any project covered by this subpart be terminated or 

suspended when the Administrator finds that an IRB, investigator, sponsor, or institution has 

materially failed to comply with the terms of this subpart. 

§ 26.1124 [Reserved] 

§ 26.1125 Prior submission of proposed human research for EPA review. 

Any person or institution who intends to conduct or sponsor human research covered by Sec. 

26.1101(a) shall, after receiving approval from all appropriate IRBs, submit to EPA prior to 

initiating such research all information relevant to the proposed research specified by Sec. 

26.1115(a), and the following additional information, to the extent not already included: 

(a) A discussion of: 

(1) The potential risks to human subjects; 

(2) The measures proposed to minimize risks to the human subjects; 
Exhibit A to Settlement Agreement 12 

(3) The nature and magnitude of all expected benefits of such research, and to whom they 

would accrue; 

(4) Alternative means of obtaining information comparable to what would be collected 

through the proposed research; and 

(5) The balance of risks and benefits of the proposed research. 

(b) All information for subjects and written informed consent agreements as originally provided 

to the IRB, and as approved by the IRB. 

(c) Information about how subjects will be recruited, including any advertisements proposed to 

be used. 

(d) A description of the circumstances and methods proposed for presenting information to 

potential human subjects for the purpose of obtaining their informed consent. 

(e) All correspondence between the IRB and the investigators or sponsors. 

(f) Official notification to the sponsor or investigator, in accordance with the requirements of 

this subpart, that research involving human subjects has been reviewed and approved by an 

IRB. 

Subpart L: Prohibition of Third-Party Research Involving Intentional Exposure of Human 

Subjects to a Pesticide who are Children or Pregnant or Nursing Women 

§ 26.1201 To what does this subpart apply? 

Subpart L applies to any research subject to subpart K of this part. 

§ 26.1202 Definitions. 

The definitions in Sec. 26.1102 apply to this subpart as well. In addition, the definitions at 

45 CFR 46.202(a) through (f) and at 45 CFR 46.202(h) apply to this subpart. In addition, a child

is a person who has not attained the age of 18 years. 

§ 26.1203 Prohibition of research involving intentional exposure of any human subject 

who is a pregnant woman (and therefore her fetus), a nursing woman, or a child to a 

pesticide. 

 Notwithstanding any other provision of this part, under no circumstances shall a person 

conduct or support research covered by Sec. 26.1201 that involves intentional exposure of any 

human subject who is a pregnant woman (and therefore her fetus), a nursing woman, or a 
Exhibit A to Settlement Agreement 13 

child to a pesticide. 

Subpart M: Requirements for Submission of Information on the Ethical Conduct of 

Completed Human Research 

§ 26.1301 To what does this subpart apply? 

 This subpart applies to any person who submits to EPA after [insert effective date of amended 

rule] either of the following: 

(a) a report containing the results of any human research on or with a pesticide for consideration 

in connection with any action that may be performed by EPA under any regulatory statute 

administered by EPA. 

(b) a report containing the results of any human research for consideration in connection with an 

action that may be performed by EPA under the Federal Insecticide, Fungicide, and 

Rodenticide Act (7 U.S.C. §§ 136-136y) or section 408 of the Federal Food, Drug, and 

Cosmetic Act (21 U.S.C. § 346a). 

§ 26.1302 Definitions. 

 The definitions in sec. 26.1102 apply to this subpart as well. 

§ 26.1303 Submission of information pertaining to ethical conduct of completed human 

research. 

Any person who submits to EPA data derived from human research covered by this subpart 

shall provide at the time of submission information concerning the ethical conduct of such 

research. To the extent available to the submitter and not previously provided to EPA, such 

information should include: 

(a) Copies of all of the records relevant to the research specified by Sec. 26.1115(a) to be 

prepared and maintained by an IRB. 

(b) Copies of all of the records relevant to the information identified in Sec. 26.1125(a) through 

(f). 

(c) Copies of sample records used to document informed consent as specified by Sec. 26.1117, 

but not identifying any subjects of the research. 

(d) If any of the information listed in paragraphs (a) through (c) of this section is not provided, 

the person shall describe the efforts made to obtain the information. 
Exhibit A to Settlement Agreement 14 

Subpart N [Reserved] 

Subpart O: Administrative Actions for Noncompliance 

§ 26.1501 To what does this subpart apply? 

 This subpart applies to any human research subject to subparts A through L of this part. 

References to State or local laws in this subpart are intended to include the laws of federally 

recognized American Indian and Alaska Native Tribal Governments. 

§ 26.1502 Lesser administrative actions. 

(a) If apparent noncompliance with the applicable regulations in subparts A through L of this 

part concerning the operation of an IRB is observed by an officer or employee of EPA or of 

any State duly designated by the Administrator during an inspection. EPA may send a letter 

describing the noncompliance to the IRB and to the parent institution. EPA will require that 

the IRB or the parent institution respond to this letter within a reasonable time period 

specified by EPA and describe the corrective actions that will be taken by the IRB, the 

institution, or both to achieve compliance with these regulations. 

(b) On the basis of the IRB’s or the institution’s response, EPA may schedule a reinspection to 

confirm the adequacy of corrective actions. In addition, until the IRB or the parent institution 

takes appropriate corrective action, EPA may: 

(1) Withhold approval of new studies subject to the requirements of this part that are 

conducted at the institution or reviewed by the IRB; 

(2) Direct that no new subjects be added to ongoing studies subject to this part; 

(3) Terminate ongoing studies subject to this part when doing so would not endanger the 

subjects; or 

(4) When the apparent noncompliance creates a significant threat to the rights and welfare of 

human subjects, notify relevant State and Federal regulatory agencies and other parties 

with a direct interest of the deficiencies in the operation of the IRB. 

(c) The parent institution is presumed to be responsible for the operation of an IRB, and EPA 

will ordinarily direct any administrative action under this subpart against the institution. 

However, depending on the evidence of responsibility for deficiencies, determined during the 

investigation, EPA may restrict its administrative actions to the IRB or to a component of the 

parent institution determined to be responsible for formal designation of the IRB. 
Exhibit A to Settlement Agreement 15 

§ 26.1503 Disqualification of an IRB or an institution. 

(a) Whenever the IRB or the institution has failed to take adequate steps to correct the 

noncompliance stated in the letter sent by EPA under Sec. 26.1502(a) and the Administrator 

determines that this noncompliance may justify the disqualification of the IRB or of the 

parent institution, the Administrator may institute appropriate proceedings. 

(b) The Administrator may disqualify an IRB or the parent institution from studies subject to this 

part if the Administrator determines that: 

(1) The IRB has refused or repeatedly failed to comply with any of the regulations set forth 

in this part, and 

(2) The noncompliance adversely affects the rights or welfare of the human subjects of 

research. 

(c) If the Administrator determines that disqualification is appropriate, the Administrator will 

issue an order that explains the basis for the determination and that prescribes any actions to 

be taken with regard to ongoing human research, covered by subparts A through L of this 

part, conducted under the review of the IRB. EPA will send notice of the disqualification to 

the IRB and the parent institution. Other parties with a direct interest, such as sponsors and 

investigators, may also be sent a notice of the disqualification. In addition, EPA may elect to 

publish a notice of its action in the Federal Register. 

(d) EPA may refuse to consider in support of a regulatory decision the data from human 

research, covered by subparts A through L of this part, that was reviewed by an IRB or 

conducted at an institution during the period of disqualification, unless the IRB or the parent 

institution is reinstated as provided in Sec. 26.1505, or unless such research is deemed 

scientifically sound and crucial to the protection of public health, under the procedure 

defined in Sec. 26.1706. 

§ 26.1504 Public disclosure of information regarding revocation. 

A determination that EPA has disqualified an institution from studies subject to this part and 

the administrative record regarding that determination are discloseable to the public under 40 

CFR part 2. 

§ 26.1505 Reinstatement of an IRB or an institution. 

An IRB or an institution may be reinstated to conduct studies subject to this part if the 

Administrator determines, upon an evaluation of a written submission from the IRB or institution 

that explains the corrective action that the institution or IRB has taken or plans to take, that the 

IRB or institution has provided adequate assurance that it will operate in compliance with the 
Exhibit A to Settlement Agreement 16 

standards set forth in this part. Notification of reinstatement shall be provided to all persons 

notified under Sec. 26.1502(b)(4). 

§ 26.1506 Debarment. 

If EPA determines that an institution or investigator repeatedly has not complied with or has 

committed an egregious violation of the applicable regulations in subparts A through L of this 

part, EPA may recommend that institution or investigator be declared ineligible to participate in 

EPA-supported research (debarment). Debarment will be initiated in accordance with procedures 

specified at 2 CFR part 1532. 

§ 26.1507 Actions alternative or additional to disqualification. 

Disqualification of an IRB or of an institution is independent of, and neither in lieu of nor a 

precondition to, other statutorily authorized proceedings or actions. EPA may, at any time, on its 

own initiative or through the Department of Justice, institute any appropriate judicial 

proceedings (civil or criminal) and any other appropriate regulatory action, in addition to or in 

lieu of, and before, at the time of, or after, disqualification. EPA may also refer pertinent matters 

to another Federal, State, or local government agency for any action that that agency determines 

to be appropriate. 

Subpart P: Review of Proposed and Completed Human Research 

§ 26.1601 To what does this subpart apply?

This subpart applies to both of the following: 

(a) Reviews by EPA and by the Human Studies Review Board of proposals to conduct new 

research subject to 40 CFR 26.1125, and 

(b) Reviews by EPA after [insert effective date of the revised rule] and, to the extent required by 

sec. 26.1604, by the Human Studies Review Board of reports of completed research subject 

to 40 CFR 26.1701. 

§ 26.1602 Definitions. 

 The definitions in sec. 26.1102 apply to this subpart as well. 
Exhibit A to Settlement Agreement 17 

§ 26.1603 EPA review of proposed human research. 

(a) EPA shall review all proposals for new human research submitted under Sec. 26.1125 of this 

part in a timely manner. 

(b) In reviewing proposals for new human research covered by subpart K, the Administrator 

shall consider and make determinations regarding the proposed research, including: 

(1) Whether the research would be likely to produce data that address an important scientific 

or policy question that cannot be resolved on the basis of animal data or human 

observational research; 

(2) Whether the proposed research is designed in accordance with current scientific standards 

and practices to: 

(i) Address the research question; 

(ii) Include representative study populations for the endpoint in question; and 

(iii) Have adequate statistical power to detect appropriate effects. 

(3) Whether the investigator proposes to conduct the research in accordance with recognized 

good research practices, including, when appropriate, good clinical practice guidelines 

and monitoring for the safety of subjects. 

(c) In reviewing proposals for new research covered by subpart K, the Administrator shall 

consider and make determinations regarding ethical aspects of the proposed research 

including: 

(1) Whether adequate information is available from prior animal studies or from other 

sources to assess the potential risks to subjects in the proposed research; 

(2) Whether the research proposal adequately identifies anticipated risks to human subjects 

and their likelihood of occurrence, minimizes identified risks to human subjects, and 

identifies likely benefits of the research and their distribution. 

(3) Whether the proposed research presents an acceptable balance of risks and benefits. In 

making this determination for research intended to reduce the interspecies uncertainty 

factor in a pesticide risk assessment, the Administrator shall consider Recommendation 

4-1 of the National Research Council as contained in its report entitled Intentional 

Human Dosing Studies for EPA Regulatory Purposes: Scientific and Ethical Issues 

(2004). 

(4) Whether subject selection will be equitable; 

(5) Whether subjects’ participation would follow free and fully informed consent; 
Exhibit A to Settlement Agreement 18 

(6) Whether an appropriately constituted Institutional Review Board or its foreign equivalent 

has approved the proposed research; 

(7) If any person from a vulnerable population may become a subject in the proposed 

research, whether there is a convincing justification for selection of such a person, and 

whether measures taken to protect such human subjects are adequate; 

(8) If any person with a condition that would put them at increased risk for adverse effects 

may become a subject in the proposed research, whether there is a convincing 

justification for selection of such a person, and whether measures taken to protect such 

human subjects are adequate; 

(9) Whether any proposed payments to subjects are consistent with the principles of justice 

and respect for persons, and whether they are so high as to constitute undue inducement 

or so low as to be attractive only to individuals who are socioeconomically 

disadvantaged; and 

(10) Whether the sponsor or investigator would provide needed medical care for injuries 

incurred in the proposed research, without cost to the human subjects. 

(d) With respect to any research or any class of research, the Administrator may recommend 

additional conditions which, in the judgment of the Administrator, are necessary for the 

protection of human subjects. 

(e) In reviewing proposals covered by this section, the Administrator may take into account 

factors such as whether the submitter has been subject to a termination or suspension under 

Sec. 26.123(a) or Sec. 26.1123 and whether the submitter or the person or persons who 

would direct or has/have directed the scientific and technical aspects of an activity has/have, 

in the judgment of the Administrator, materially failed to discharge responsibility for the 

protection of the rights and welfare of human subjects (whether or not the research was 

subject to Federal regulation). 

(f) When research covered by subpart K takes place in foreign countries, procedures normally 

followed in the foreign countries to protect human subjects may differ from those set forth in 

subpart K. (An example is a foreign institution which complies with guidelines consistent 

with the World Medical Assembly Declaration of Helsinki, issued either by sovereign states 

or by an organization whose function for the protection of human research subjects is 

internationally recognized.) In these circumstances, if the Administrator determines that the 

procedures prescribed by the institution afford protections that are at least equivalent to those 

provided in subpart K, the Administrator may approve the substitution of the foreign 

procedures in lieu of the procedural requirements provided in subpart K. 

(g) Following initial evaluation of the protocol, EPA shall submit the protocol and all supporting 

materials, together with the staff evaluation, to the Human Studies Review Board. 
Exhibit A to Settlement Agreement 19 

(h) EPA shall provide the submitter of the proposal copies of the EPA and Human Studies 

Review Board reviews. 

§ 26.1604 EPA review of completed human research. 

(a) When considering, under any regulatory statute it administers, data from completed research 

involving intentional exposure of humans to a pesticide, EPA shall thoroughly review the 

material submitted under Sec. 26.1303, if any, and other available, relevant information and 

document its conclusions regarding the scientific and ethical conduct of the research. 

(b) EPA shall submit its review of data from human research covered by subpart Q, together 

with the available supporting materials, to the Human Studies Review Board if EPA decides 

to rely on the data and: 

(1) The data are derived from research initiated after April 7, 2006, or 

(2) The data are derived from research initiated before April 7, 2006, and the research was 

conducted for the purpose of identifying or measuring a toxic effect. 

(c) In its discretion, EPA may submit data from research not covered by paragraph (b) of this 

section to the Human Studies Review Board for their review. 

(d) EPA shall provide the submitter of the research copies of the EPA and Human Studies 

Review Board reviews. 

§ 26.1605 Operation of the Human Studies Review Board. 

EPA shall establish and operate a Human Studies Review Board as follows: 

(a) Membership. The Human Studies Review Board shall consist of members who are not 

employed by EPA, who meet the ethics and other requirements for special government 

employees, and who have expertise in fields appropriate for the scientific and ethical review 

of human research, including research ethics, biostatistics, and human toxicology. 

(b) Responsibilities. The Human Studies Review Board shall comment on the scientific and 

ethical aspects of research proposals and reports of completed research with human subjects 

submitted by EPA for its review and, on request, advise EPA on ways to strengthen its 

programs for protection of human subjects of research. 

§ 26.1606 Human Studies Review Board review of proposed human research. 

In commenting on proposals for new research submitted to it by EPA, the Human Studies 

Review Board shall consider the scientific merits and ethical aspects of the proposed research, 
Exhibit A to Settlement Agreement 20 

including all elements listed in section 26.1603(b) and (c) and any additional conditions 

recommended pursuant to sec. 26.1603(d). 

§ 26.1607 Human Studies Review Board review of completed human research. 

In commenting on reports of completed research submitted to it by EPA, the Human Studies 

Review Board shall consider the scientific merits and ethical aspects of the completed research, 

and shall apply the appropriate standards in Subpart Q. 

Subpart Q: Ethical Standards for Assessing Whether To Rely on the Results of Human 

Research in EPA Actions 

§ 26.1701 To what does this subpart apply? 

(a) Except as provided in paragraph (b), this subpart applies to EPA’s decisions whether to 

rely, in actions taken under any regulatory statute it administers, on scientifically valid 

and relevant data from research involving intentional exposure of human subjects to a 

pesticide. 

(b) In actions taken under the Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 

§§ 136-136y) or section 408 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 

346a), this subpart applies to EPA’s decisions whether to rely on scientifically valid and 

relevant data from research involving intentional exposure of human subjects. 

§ 26.1702 Definitions. 

 The definitions in Sec. 26.1102 and Sec. 26.1202 shall apply to this subpart as well. 

§ 26.1703 Prohibitions 

(a) Prohibition of reliance on scientifically invalid research involving intentional exposure 

of a human subject to a pesticide. 

EPA shall not rely on data from research involving intentional exposure of a human 

subject to a pesticide unless EPA determines that the data are relevant to a scientific or policy 

question important for EPA decision-making, that the data were derived in a manner that 

makes them scientifically reliable, and that it is appropriate to use the data for the purpose 

proposed by EPA. In making such determinations, EPA shall consider: 

(1) Whether the research was designed and conducted in accordance with appropriate 

scientific standards and practices prevailing at the time the research was conducted; 
Exhibit A to Settlement Agreement 21 

(2) The extent to which the research subjects are representative of the populations for the 

endpoint or endpoints in question; and 

(3) The statistical power of the data to support the scientific conclusion EPA intends to 

draw from the data 

(4) In a study that reports only a No Observed Effect Level (NOEL) or a No Observed 

Adverse Effect Level (NOAEL), whether a dose level in the study gave rise to a 

biological effect, thereby demonstrating that the study had adequate sensitivity to 

detect an effect of interest. 

(b) Prohibition of reliance on research involving intentional exposure to a pesticide of human 

subjects who are pregnant women (and therefore their fetuses), nursing women, or children. 

Except as provided in Sec. 26.1706, EPA shall not rely on data from any research 

involving intentional exposure to a pesticide of any human subject who is a pregnant woman 

(and therefore her fetus), a nursing woman, or a child. 

§ 26.1704 Prohibition of reliance on unethical human research with non-pregnant, nonnursing adults not covered by section 26.1705. 

(a) This section applies to decisions covered by section 26.1701 that are not covered by 

section 26.1705. 

(b) Except as provided in Sec. 26.1706, EPA shall not rely on data from any research 

involving intentional exposure of any human subject to a pesticide, where that research was not 

covered by subparts A through L, if there is clear and convincing evidence that the conduct of 

the research was fundamentally unethical (e.g., the research was intended to seriously harm 

participants or failed to obtain informed consent), or was deficient relative to the ethical 

standards prevailing at the time the research was conducted in a way that placed participants at 

increased risk of harm (based on knowledge available at the time the study was conducted) or 

impaired their informed consent. This prohibition is in addition to the prohibitions in Sec. 

26.1703. 

§ 26.1705 Prohibition of reliance on unethical human research with non-pregnant, nonnursing adults initiated after April 7, 2006, and subject to subparts A through L or another 

codification of the Common Rule. 

(a) This section applies to decisions covered by section 26.1701, if the research on which 

EPA intends to rely meets both of the following conditions: 

 

(1) the research was initiated after April 7, 2006. 
Exhibit A to Settlement Agreement 22 

(2) the research was subject, at the time the research was conducted, either to 

subparts A through L of this part or to another codification of the Basic 

Policy for the Protection of Subjects in Human Research Conducted or 

Supported by a Federal Agency (generally referred to as the “Common 

Rule”). 

(b) Except as provided in Sec. 26.1706, EPA shall not rely on data from any research, 

unless EPA determines that the research was conducted in substantial compliance with 

one of the following: 

(1) all applicable provisions of subparts A through L of this part or another 

codification of the Common Rule, whichever is applicable. 

(2) under procedures at least as protective of subjects as those in subparts A 

through L of this part or another codification of the Common Rule, 

whichever is applicable, if the research was conducted in a foreign country. 

(c) Except as provided in Sec. 26.1706, EPA shall not rely on data from any research, unless 

EPA determines that the research was conducted in substantial compliance with one of 

the following: 

(1) a proposal that was found to be acceptable under Sec. 26.1603(c), and no 

amendments to or deviations from that proposal placed participants at 

increased risk of harm (based on knowledge available at the time the study 

was conducted) or impaired their informed consent. If EPA discovers that 

the submitter of the proposal materially misrepresented or knowingly 

omitted information that would have altered the outcome of EPA’s 

evaluation of the proposal under Sec. 26.1603(c), EPA shall not rely on that 

data. 

(2) a proposal that would have been found to be acceptable under Sec. 

26.1603(c), if it had been subject to review under that section, and no 

amendments to or deviations from that proposal placed participants at 

increased risk of harm (based on knowledge available at the time the study 

was conducted) or impaired their informed consent. 

(d) This prohibition is in addition to the prohibitions in Sec. 26.1703. 

§ 26.1706 Criteria and procedure for decisions to protect public health by relying on 

otherwise unacceptable research. 

This section establishes the exclusive criteria and procedure by which EPA may decide to 

rely on data from research that is not acceptable under the standards in §§ 26.1703 through 

26.1705. EPA may rely on such data only if all the conditions in paragraphs (a) through (d) of 

this section are satisfied: 
Exhibit A to Settlement Agreement 23 

(a) EPA has obtained the views of the Human Studies Review Board concerning the proposal to 

rely on the otherwise unacceptable data, 

(b) EPA has provided an opportunity for public comment on the proposal to rely on the 

otherwise unacceptable data, 

(c) EPA has determined that relying on the data is crucial to a decision that would impose a more 

stringent regulatory restriction that would improve protection of public health, such as a 

limitation on the use of a pesticide, than could be justified without relying on the data, and 

(d) EPA publishes a full explanation of its decision to rely on the otherwise unacceptable data, 

including a thorough discussion of the scientific and ethical deficiencies of the underlying 

research and the full rationale for finding that the standard in paragraph (c) of this section 

was met.