-1- 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 (2 nd Cir.);

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

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

WHEREAS, the Parties wish to settl e 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 th is Settlement Agreement is filed with

the court, EPA agrees to sign a notice of proposed rulemaking that proposes, at a-2- minimum, the amendments to the 2006 final rule as substantially consistent with

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

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

EPA will take such final action no later th an 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 requesti ng that the court extend the stay in Case

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

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

appended to that joint motion. This Settlem ent 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 Petitio ners 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 (2 nd Cir.).

Petitioners' Remedies

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

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

reactivate their petitions for review of th e 2006 final rule and request that the Court-3- proceed to issue a decision in the consolidated cases. The Petitioners agree to give EPA

thirty days’ notice prior to exercising th eir 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 otherwis e. 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 Settl ement Agreement shall be construed to

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

Environment and Related Agencies Appropri ations 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 Agreem ent 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 li mit or modify EPA’s discretion to propose-4- additional regulatory change s in the same notice of proposed rulemaking signed

pursuant to paragraph 2 and to finalize addition al 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 Ag reement 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 eviden ce 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 Agreemen t 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 $ 13 5,000 in full satisfaction of Petitioners’

claims for attorney fees and costs in this litigation.

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

authorized by the Party or Parties they repr esent to bind the respective Parties to the-5- 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 an d 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 requiremen t 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 Proc edure 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 th e 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 po ssibly delay compliance with the schedule

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

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

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

Should a delay occur due to such circumst ances, 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--ENVIRONMENTA L PROTECTION AGENCY

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

Subpart K: Basic Ethical Requi rements for Third-Party Huma n 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 paragra ph (c) of this section, subpart K of this part applies to all research initiated after [inser t effective date of amended ru le] involving intentional exposure of a human subject to a pesticid e if, at any time prior to initi ating such research, any person who conducted or supported such re search intended either to subm it results of the research to

EPA for consideration in conn ection with any action that ma y be performed by EPA under any regulatory statute administer ed by EPA or to hold the resu lts of the research for later inspection by EPA under any regulatory statute administ ered by EPA.

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

available and relevant information. EPA sha ll 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 pe ople who, or whose products or activities, are regulated by EPA and, at the time the rese arch was initiated, the results of such

research would be relevant to EPA’s exerci se 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 exis ting data, documents, records, pathological specimens, or diagnostic specimens from previ ously 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 identif ied, directly or through identi fiers linked to the subjects.

(d) The Administrator retains final judgment as to whether a particular ac tivity is covered by this subpart.

(e) Compliance with this subpart requires compli ance with pertinent Federa l laws or regulations which provide additional prot ections for human subjects.Exhibit A to Settlement Agreement 2 (f) This subpart does not affect any State or lo cal laws or regulations which may otherwise be applicable and which provide additional protec tions 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 prot ections to human subjects of research.

§ 26.1102 Definitions.

(a) Administrator means the Administrator of the Envi ronmental 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 ag ency (including Federal, State, and other agencies).

(c) Initiation of research involving human s ubjects is considered to o ccur as of the enrollment of the first subject in the research.

(d) Research means a systematic investigation, incl uding research, development, testing and evaluation, designed to develop or contribute to generalizab le knowledge. Activities which meet this definition constitute research for purpos es of this subpart, whether or not they are considered research for other purposes. Fo r 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 in teraction with th e individual, or

(2) Identifiable pr ivate information.

(3) “Intervention” includes both physical procedures by wh ich data are gathered (for example, venipuncture) and manipulations of the subject or the subject’s environment that are performed for res earch purposes. Interacti on includes communication or interpersonal contact between investigator a nd subject. “Private in formation” 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 subj ect is or may readily be ascertained by the investigator or associated with the inform ation) in order for obtaining

the information to constitute re search 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 themselv es than those ordinarily encountered in daily life or during the performance of routine physical or psychologi cal examinations or tests.

(i) Research involving intentional exposure of a human subject means a study of a substance in which the exposure to the subs tance experienced by a human s ubject participating in the study would not have occurred but for the hum an subject’s particip ation in the study.

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

except:

(1) A federal agency that is subject to the pr ovisions of the Federal Policy for the Protection of Human Subjects of Research, and

(2) A person when performing human resear ch supported by a federal agency covered by paragraph (j)(1) of this section.

(k) Pesticide means any substance or mixture of substa nces 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 member s, with varying backgrounds to promote complete and adequate review of research activities whic h are presented for its approval. The IRB shall be sufficiently qualified through the experien ce and expertise of its members, and the diversity of the members, including considera tion of race, gender, and cultural backgrounds and sensitivity to such issues as community at titudes, to promote respect for its advice and counsel in safeguarding the right s and welfare of human subjects. In addition to possessing the professional competence necessary to review specific research activi ties, the IRB shall be able to ascertain the acceptabi lity of proposed research in te rms of institutional commitments and regulations, applicable law, and standard s of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas. If an IRB regularly reviews

research that involves a vulnerab le category of subjects, such as prisoners or handicapped or mentally disabled persons, consideration shal l be given to the incl usion of one or more individuals who are knowledgeable about and experienced in wo rking 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 th e IRB on the basis of gender. No IRB may consist entirely of member s 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 primar y concerns are in nonscientific areas.

(d) Each IRB shall include at least one memb er who is not otherwise affiliated with the institution and who is not part of the immediat e 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 conflicti ng interest, except to provide information requested by the IRB.

(f) An IRB may, in its discreti on, invite individuals with competen ce in special area s to assist in the review of issues which require expertise be yond or in addition to that available on the

IRB. These individuals ma y 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 resear ch and for reporting its findings and actions to the investig ator 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 othe r 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 cha nges 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 procedur e is used (see Sec. 26.1110), review proposed research at convened meetings at which a majo rity of the members of the IRB are present, including at least one member whose primary con cerns 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 modifi cations in (to secure approval), or disapprove all research activities covere d by this subpart.

(b) An IRB shall require that information given to subjects as part of in formed 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 gi ven to the subjects when, in the IRB’s judgment, the information would meaningfully a dd to the protection of the rights and welfare of subjects.

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

(d) An IRB shall notify investigators and the instit ution in writing of its decision to approve or disapprove the proposed research activity, or of modifications re quired to secure IRB approval of the research activity. If the IRB decides to disapprove a research activity, it shall

include in its written notificat ion a statement of the reasons for its decision and give the investigator an opportunity to re spond in person or in writing.Exhibit A to Settlement Agreement 6 (e) An IRB shall conduct conti nuing review of research covere d by this subpart at intervals appropriate to the degree of ri sk, 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 cert ain kinds of research involving no more than minimal risk, and for mino r changes in approved research.

(a) The Secretary, HHS, has esta blished, and published as a Notice in the Federal Register, a list of categories of research that may be revi ewed by the IRB through an expedited review procedure. The list will be amended, as appropr iate 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 Offi ce for Human Research Pr otections, HHS, or any

successor office.

(b) (1) An IRB may use the e xpedited review proce dure to review eith er or both of the following:

(i) Some or all of the re search appearing on the list and found by the reviewer(s) to involve no more than minimal risk,

(ii) Minor changes in previously approved re search 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 re viewers designated by the chairperson from among members of the IRB. In reviewing the re search, the reviewers may exercise all of the authorities of the IRB except that the reviewers may not disa pprove 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 whic h have been approved under the procedure.

(d) The Administrator may restrict, suspend, or te rminate, an institution’s or IRB’s use of the expedited review procedure for re search 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 consis tent with sound research design and which do not unnecessarily expose subjects to risk, and

(ii) Whenever appropriate, by using procedures already be ing performed on the subjects for diagnostic or treatment purposes.

(2) Risks to subjects are reasona ble in relation to anticipated be nefits, if any, to subjects, and the importance of the knowledge that may reas onably be expected to result. In evaluating risks and benefits, the IRB should consider on ly those risks and benefits that may result from the research (as distingui shed from risks and benefits su bjects would rece ive even if not participating in the re search). The IRB should not consider possible long-range effects of applying knowledge gain ed in the research (for exam ple, the possible effects of the research on public policy) as among those re search risks that fall within the purview of its responsibility.

(3) Selection of subjects is e quitable. In making this assessm ent the IRB should take into account the purposes of the research and th e setting in which th e research will be conducted and should be particularly cognizan t of the special problems of research involving vulnerable populations, such as pr isoners, mentally disabled persons, or economically or educationa lly 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 docum ented, in accordance with, and to the extent required by Sec. 26.1117.

(6) When appropriate, the rese arch plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

(7) When appropriate, there are ad equate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

(b) When some or all of the s ubjects are likely to be vulnerabl e 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 term inate approval of resear ch that is not being conducted in accordance with the IRB’s require ments or that has been associated with unexpected serious harm to subjects. Any suspen sion 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, relian ce upon the review of another qualified IRB, or similar arrangements aimed at av oidance of duplication of effort.

§ 26.1115 IRB records.

(a) An IRB shall prepare and maintain adequa te 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 vot e on these actions incl uding the number of members voting for, against, and abstaining; the basis for requiring changes in or disapproving research; and a wr itten summary of the discussi on of controverted issues

and their resolution.

(3) Records of conti nuing review activities.

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

(5) A list of IRB members identified by name ; earned degrees; representative capacity; indications of experience such as board certificati ons, 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 boa rd, 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 re tained for at least 3 ye ars, and records relating

to research which is conducted shall be retain ed 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 obtaine d the legally effective informed consent of the subject. An investigator shall seek such consent only unde r circumstances that provide the prospective subject sufficient opportunity to consider whethe r or not to participate and that minimize the possibility of coercion or undue influence. The inform ation that is given to the subject shall be in language understandable to the subject. No info rmed consent, whether oral or written, may include any exculpatory language through which the s ubject is made to waive or appear to waive any of the subject’s legal rights, or releases or appear s to release the inves tigator, 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 res earch, an explanation of the purposes of the research and the expected duration of the s ubject’s participation, a description of the procedures to be followed, and identification of any procedures which are experimental;

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

(3) A description of any bene fits to the subject or to ot hers which may reasonably be expected from the research;

(4) A disclosure of appropriate alternative pr ocedures or courses of treatment, if any, that might be advantageous to the subject;

(5) A statement describing the extent, if any, to which confidentialit y of records identifying the subject will be maintained;

(6) For research involving more than minima l risk, an explanation as to whether any compensation and an explanation as to whet her any medical treatme nts are available if injury occurs and, if so, what they consis t of, or where further information may be obtained;

(7) An explanation of whom to contact for an swers 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; andExhibit A to Settlement Agreement 10 (8) A statement that participa tion is voluntary, refusal to part icipate 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 al so be provided to each subject:

(1) A statement that the partic ular 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 ma y result from participation in the research;

(4) The consequences of a subject’s decision to withdraw from the re search and procedures for orderly termination of participation by the subject;

(5) A statement that significa nt new findings developed during the course of the research which may relate to the subject’s willingness to continue participati on will be provided to the subject; and

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

(c) The informed consent requirements in this s ubpart are not intended to preempt any applicable Federal, State, or local laws which require addi tional 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 perm itted 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 th e 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 su bject, but in any event, the investigator shall give the subject ade quate opportunity to read it before it is signed; or

(2) A short form written consent document sta ting that the elements of informed consent required by Sec. 26.1116 have been presented or ally 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 th at any project cove red by this subpart be terminated or suspended when the Administrator finds that an IRB, investigator, spons or, or institution has materially failed to comply w ith the terms of this subpart.

§ 26.1124 [Reserved]

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

Any person or institution who inte nds to conduct or sponsor huma n research covered by Sec. 26.1101(a) shall, after receiving approval from a ll appropriate IRBs, submit to EPA prior to initiating such research all info rmation relevant to the proposed research specified by Sec. 26.1115(a), and the following additional informa tion, to the extent no t already included:

(a) A discussion of:

(1) The potential risks to human subjects;

(2) The measures proposed to mini mize 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 informa tion comparable to what would be collected through the proposed research; and

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

(b) All information for subjects and written info rmed consent agreements as originally provided to the IRB, and as approved by the IRB.

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

be used.

(d) A description of the circ umstances and methods proposed for presenting information to potential human subjects for the purpose of obtaining their informed consent.

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

(f) Official notification to the sponsor or i nvestigator, in accordance with the requirements of this subpart, that research i nvolving human subjects has been reviewed and approved by an

IRB.

Subpart L: Prohibition of Third-Party Resear ch 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 su bject to subpart K of this part.

§ 26.1202 Definitions.

The definitions in Sec. 26.1102 apply to this subpa rt as well. In additi on, 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 atta ined the age of 18 years.

§ 26.1203 Prohibition of research involving in tentional 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 inten tional exposure of any human subject who is a pregnant woman (and th erefore her fetus), a nursing woman, or aExhibit 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 a ny 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 wi th 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 re search for consideration in connection with an action that may be performed by EPA under the Federal Insectic ide, 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 pertaini ng to ethical conduct of completed human

research.

Any person who submits to EPA data derived fr om human research covered by this subpart shall provide at the time of submission inform ation 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 reco rds relevant to the research sp ecified 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 c onsent 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 effort s 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 subpa rt are intended to include the laws of federally recognized American Indian and Al aska Native Tribal Governments.

§ 26.1502 Lesser administrative actions.

(a) If apparent noncompliance with the applicab le regulations in subparts A through L of this part concerning the operation of an IRB is obser ved by an officer or employee of EPA or of any State duly designated by the Administrato r 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 ac tions that will be taken by the IRB, the institution, or both to achieve co mpliance with these regulations.

(b) On the basis of the IRB’s or the instituti on’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 subj ects be added to ongoing studies subject to this part;

(3) Terminate ongoing studies subj ect to this part when doi ng so would not endanger the subjects; or

(4) When the apparent noncompliance creates a significant threat to th e rights and welfare of human subjects, notify relevant State and Fe deral regulatory agenci es and other parties

with a direct interest of the defici encies in the operation of the IRB.

(c) The parent institution is presumed to be re sponsible for the operati on of an IRB, and EPA will ordinarily direct any administrative action under this subpart against the institution. However, depending on the evidence of responsib ility for deficiencies, determined during the investigation, EPA may restrict it s administrative actions to the IRB or to a component of the parent institution determined to be responsible for form al 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 fa iled to take adequate steps to correct the noncompliance stated in the letter sent by EP A under Sec. 26.1502(a) and the Administrator determines that this noncompliance may justif y the disqualification of the IRB or of the parent institution, the Ad ministrator may institute appropriate proceedings.

(b) The Administrator may disqualify an IRB or th e 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 righ ts or welfare of th e human subjects of

research.

(c) If the Administrator determines that disqua lification is appropriate, the Administrator will issue an order that explains the basis for the de termination and that prescribes any actions to be taken with regard to ongoing human rese arch, 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 addi tion, 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 th is part, that was re viewed by an IRB or conducted at an institution during the period of disqualif ication, unless the IRB or the parent institution is reinstated as provided in S ec. 26.1505, or unless such research is deemed scientifically sound and crucial to the prot ection of public health, under the procedure

defined in Sec. 26.1706.

§ 26.1504 Public disclosure of in formation regarding revocation.

A determination that EPA has disqualified an ins titution from studies subject to this part and the administrative record regard ing that determination are disc loseable 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 acti on that the institution or IRB has ta ken or plans to take, that the IRB or institution has provided adequate assuran ce that it will operate in compliance with theExhibit 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 inves tigator repeatedly has not complied with or has committed an egregious violation of the applicab le regulations in subparts A through L of this part, EPA may recommend that instit ution or investigator be declared ineligible to participate in EPA-supported research (debarment). Debarment w ill be initiated in accordance with procedures specified at 2 CFR part 1532.

§ 26.1507 Actions alternative or a dditional 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 acti ons. EPA may, at any time, on its own initiative or through the De partment of Justice, instit ute any appropria te judicial proceedings (civil or criminal) and any other appr opriate 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 lo cal government agency for any acti on 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 comple ted 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 hu man research submitted under Sec. 26.1125 of this part in a timely manner.

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

shall consider and make determinations re garding the proposed re search, including:

(1) Whether the research would be likely to produce data that a ddress 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 curren t scientific standards and practices to:

(i) Address the research question;

(ii) Include representative study populati ons 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 appr opriate, good clinical practice guidelines and monitoring for the safety of subjects.

(c) In reviewing proposals for new research covered by subpart K, th e Administrator shall consider and make determinations regardi ng ethical aspects of the proposed research including:

(1) Whether adequate information is availabl e from prior animal studies or from other sources to assess the pote ntial risks to subjects in the proposed research;

(2) Whether the research proposal adequately identifie s anticipated risks to human subjects and their likelihood of occurrence, minimizes identified risks to human subjects, and identifies likely benefits of th e research and their distribution.

(3) Whether the proposed research presents an acceptable balance of ri sks 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 cont ained in its report entitled Intentional Human Dosing Studies for EPA Regulatory Pu rposes: Scientific and Ethical Issues (2004).

(4) Whether subject selecti on will be equitable;

(5) Whether subjects’ partic ipation would follow free and fully informed consent;Exhibit A to Settlement Agreement 18 (6) Whether an appropriately constituted Institu tional Review Board or its foreign equivalent has approved the pr oposed research;

(7) If any person from a vulnerable populat ion may become a subject in the proposed research, whether there is a convincing justif ication for selection of such a person, and whether measures taken to protect such human subjects are adequate;

(8) If any person with a conditi on that would put them at incr eased risk for adverse effects may become a subject in the proposed re search, whether ther e 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 ar e 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 w ould provide needed medical care for injuries incurred in the proposed research, wi thout cost to the human subjects.

(d) With respect to any research or any cla ss 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 cove red by this section, the Administ rator 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 th e submitter or the person or persons who

would direct or has/have directed the scientific and techni cal aspects of an activity has/have, in the judgment of the Administrator, materia lly failed to discharge responsibility for the protection of the rights and we lfare of human subjects (wheth er or not the research was subject to Federal regulation).

(f) When research covered by subpart K take s 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 instituti on 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 pr otections that are at l east equivalent to those provided in subpart K, the Administrator may approve the substitution of the foreign procedures in lieu of the procedural requirements provide d in subpart K.

(g) Following initial evaluation of the protocol , EPA shall submit the protocol and all supporting materials, together with the staff eval uation, to the Human St udies Review Board.Exhibit A to Settlement Agreement 19 (h) EPA shall provide the su bmitter 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 scien tific and ethical conduc t of the research.

(b) EPA shall submit its review of data from human research covered by subpart Q, together with the available supporting ma terials, to the Human Studies Review Board if EPA decides to rely on the data and:

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

(2) The data are derived from research initi ated before April 7, 2006, and the research was conducted for the purpose of identif ying 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 re search 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 a nd other requirements fo r special government employees, and who have expertise in fields appr opriate for the scientif ic and ethical review of human research, including research ethi cs, biostatistics, and human toxicology.

(b) Responsibilities. The Human Studies Revi ew 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 hu man 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 as pects of the proposed research,Exhibit A to Settlement Agreement 20 including all elements listed in section 26.1603(b) and (c) an d 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 resear ch 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 Wh ether 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 s ubpart applies to EPA’s decisions whether to rely, in actions taken under any regulatory st atute 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 Fede ral Insecticide, Fu ngicide, and Rodenticide Act (7 U.S.C. §§ 136-136y) or section 408 of the Federal F ood, Drug, and Cosmetic Act (21 U.S.C. § 346a)

, this subpart applies to EPA’s decisions wh ether to rely on scie ntifically 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 th is subpart as well.

§ 26.1703 Prohibitions

(a) Prohibition of reliance on sc ientifically 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 prevaili ng at the time the rese arch was conducted;Exhibit A to Settlement Agreement 21 (2) The extent to which the research subjects ar e representative of the populations for the endpoint or endpoints in question; and

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

draw from the data

(4) In a study that report s 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 th at the study had adequate sensitivity to

detect an effect of interest.

(b) Prohibition of reliance on re search involving intentional expo sure to a pesticide of human subjects who are pregnant women (and therefor e 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 subj ect who is a pregnant woman (and therefore her fetus), a nur sing woman, or a child.

§ 26.1704 Prohibition of reliance on unethic al 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 S ec. 26.1706, EPA shall not rely on data from any research involving intentional exposur e of any human subject to a pestic ide, where that research was not covered by subparts A through L, if there is clea r 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 cons ent), or was deficient relative to the ethical standards prevailing at the time the research was conducted in a way that pl aced participants at increased risk of harm (based on knowledge av ailable 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 unethic al 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 de cisions covered by section 26.1701, if the research on which EPA intends to rely meets both of the following conditions:

(1) the research was init iated 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 (gener ally referred to as the “Common Rule”).

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

unless EPA determines that the research wa s 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 conducte d 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 rese arch 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 knowl edge available at the time the study was conducted) or impaired their inform ed 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 knowl edge 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 decision s 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 Bo ard 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 th at would impose a more stringent regulatory restricti on that would improve protection of public health, such as a limitation on the use of a pesticide, than coul d be justified without relying on the data, and

(d) EPA publishes a full explanati on 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.