Document ID: EPA-HQ-OPP-2003-0132-0666
Agency: epa
Document Type: Rule
Title: Protections for Subjects in Human Research; Nursing Women
Posted Date: 2006-06-23T18:24:31Z

[Federal Register: June 23, 2006 (Volume 71, Number 121)]
[Rules and Regulations]               
[Page 36171-36176]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr23jn06-13]                         

[[Page 36171]]

-----------------------------------------------------------------------

Part II

Environmental Protection Agency

-----------------------------------------------------------------------

 40 CFR Part 26

Protections for Subjects in Human Research; Nursing Women; Direct Final 
Rule and Proposed Rule

[[Page 36172]]

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 26

[EPA-HQ-OPP-2003-0132; FRL-8071-6]
RIN 2070-AD57

 
Protections for Subjects in Human Research; Nursing Women

AGENCY: Environmental Protection Agency (EPA).

ACTION: Direct final rule.

-----------------------------------------------------------------------

SUMMARY: EPA is taking direct final action to explicitly ban research 
for pesticides involving intentional exposure of human subjects who are 
nursing women, and therefore providing protection to any nursing 
infants who may also be exposed. The direct final rule also prohibits 
EPA reliance in actions under the pesticide laws on research involving 
intentional exposure of nursing women.

DATES: This direct final rule is effective on August 22, 2006 without 
further notice, unless EPA receives adverse comment on or before July 
24, 2006. If EPA receives adverse comments to the direct final rule, 
EPA will publish a timely withdrawal document in the Federal Register 
informing the public that this direct final rule rule will not take 
effect.

ADDRESSES: Submit your comments, identified by docket identification 
(ID) number EPA-HQ-OPP-2003-0132, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 

Follow the on-line instructions for submitting comments.
     Mail: Office of Pesticide Programs (OPP) Regulatory Public 
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.
     Delivery: OPP Regulatory Public Docket (7502P), 
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South 
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only 
accepted during the Docket's normal hours of operation (8:30 a.m. to 4 
p.m., Monday through Friday, excluding legal holidays). Special 
arrangements should be made for deliveries of boxed information. The 
Docket Facility telephone number is (703) 305-5805.
    Instructions: Direct your comments to docket ID number EPA-HQ-OPP-
2003-0132. EPA's policy is that all comments received will be included 
in the docket without change and may be made available on-line at 
http://www.regulations.gov, including any personal information 

provided, unless the comment includes information claimed to be 
Confidential Business Information (CBI) or other information whose 
disclosure is restricted by statute. Do not submit information that you 
consider to be CBI or otherwise protected through regulations.gov. The 
regulations.gov website is an ``anonymous access'' system, which means 
EPA will not know your identity or contact information unless you 
provide it in the body of your comment. If you submit an electronic 
comment, EPA recommends that you include your name and other contact 
information in the body of your comment and with any disk or CD-ROM you 
submit. If EPA cannot read your comment due to technical difficulties 
and cannot contact you for clarification, EPA may not be able to 
consider your comment. Electronic files should avoid the use of special 
characters, any form of encryption, and be free of any defects or 
viruses.
    Docket: EPA has established a docket for this action under docket 
ID number EPA-HQ-OPP-2003-0132. All documents in the docket are listed 
in the index for the docket. Although listed in the docket index, some 
information is not publicly available, e.g., CBI or other information 
whose disclosure is restricted by statute. Certain other material, such 
as copyrighted material, is not available through the electronic docket 
and will be publicly available only in hard copy form. Publicly 
available docket materials are available either electronically at 
http://www.regulations.gov or, if only available in hard copy, at the 

Office of Pesticide Programs (OPP) Public Regulatory Docket, in Rm. S-
4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, 
VA. The hours of operation for this Docket Facility are from 8:30 a.m. 
to 4 p.m., Monday through Friday, excluding legal holidays. The Docket 
Facility telephone number is (703) 305-5805.

FOR FURTHER INFORMATION CONTACT: William L. Jordan, Office of Pesticide 
Programs (7501P), Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001; telephone number: (703) 305-1049; 
fax number: (703) 308-4776; e-mail address: jordan.william@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. What Does this Direct Final Rule Do?

    With this direct final rule, EPA clarifies the protections for 
subjects of ``third-party'' human research (i.e., research that is not 
conducted or supported by either EPA or by another Federal Department 
or Agency under the ``Common Rule'') by prohibiting new research 
involving intentional exposure of nursing women, intended for 
submission to EPA under the pesticide laws, thereby providing 
protection to any nursing infants who may also be exposed. This direct 
final rule also prohibits any EPA research involving intentional 
exposure of human subjects who are nursing women to pesticides or any 
other substances. (Research conducted by EPA is referred to as ``first-
party'' research, and ``second-party'' research refers to research 
supported by EPA but performed by others. ``Third-party'' research 
refers to any research that is not ``first-party'' or ``second-party'' 
research.) Finally, this rule prohibits EPA reliance, in actions under 
the pesticide laws, on human research involving intentional exposure of 
nursing women as subjects.

B. Legal Authority

    This direct final rule is authorized under provisions of the 
following statutes that EPA administers: Section 25(a) of the Federal 
Insecticide, Fungicide, and Rodenticide Act (FIFRA) (7 U.S.C. 136-
136y), which authorizes the Administrator to ``prescribe regulations to 
carry out the purposes of [FIFRA],'' and section 408(e)(1)(C) of the 
Federal Food, Drug, and Cosmetic Act (FFDCA) (21 U.S.C. 346a). FFDCA 
authorizes the Administrator to issue a regulation establishing 
``general procedures and requirements to implement [Section 408].'' In 
addition, the portions of this regulation supplementing EPA's 
codification of the Common Rule regarding first- and second-party 
research are authorized pursuant to 5 U.S.C. 301 and 42 U.S.C. 300v-
1(b).
    This direct final rule amends the recently promulgated 
``Protections for Subjects in Human Research Rule'' (hereinafter 
referred to as the ``January 2006 rule'') to extend critical 
protections for human research subjects contained in that rule to 
nursing women and their nursing children. The January 2006 rule 
published in the Federal Register on February 6, 2006 (71 FR 6138) 
(FRL-7759-8). EPA is publishing this direct final rule without prior 
proposal because the Agency believes that these amendments are non-
controversial and does not expect to receive adverse comments. 
Nevertheless, EPA is also publishing a separate document in the 
``Proposed Rules'' section of this issue of the Federal Register that 
serves as the proposal to extend these critical protections for 
subjects of human

[[Page 36173]]

research to nursing women and their nursing children, in the event that 
adverse comments are submitted to EPA on or before July 24, 2006.
    This direct final rule is effective on August 22, 2006 without 
further notice, unless EPA receives comments that are adverse to the 
direct final rule on or before July 24, 2006. If EPA receives comments 
that are adverse to this direct final rule, the Agency will publish a 
timely withdrawal document in the Federal Register informing the public 
that the direct final rule will not take effect on August 22, 2006. EPA 
will then address all public comments received in a subsequent final 
rule based on the proposed rule that is published in the ``Proposed 
Rules'' section of this issue of the Federal Register. The Agency will 
not institute a second comment period on this action. Any parties 
interested in commenting must do so at this time and must submit 
comments by the date indicated in this unit and in the proposed rule.

C. Does this Action Apply to Me?

    You may be potentially affected by this action if you conduct human 
research on substances regulated by EPA. Potentially affected entities 
may include, but are not limited to, entities that conduct or sponsor 
research involving intentional exposure of human subjects that may be 
submitted to EPA under FIFRA or FFDCA. Although EPA has in the past 
received such third-party research from pesticide registrants, other 
entities could submit such information to EPA.
     Pesticide and other Agricultural Chemical Manufacturing 
(NAICS code 325320).
    This listing is not intended to be exhaustive, but rather provides 
a guide regarding entities likely to be affected by this action. Other 
types of entities not listed in this unit could also be affected. The 
North American Industrial Classification System (NAICS) codes have been 
provided to assist you and others in determining whether this action 
might apply to certain entities. To determine whether you or your 
business may be affected by this action, you should carefully examine 
the applicability provisions of 40 CFR part 26. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

D. How Can I Access Electronic Copies of this Document and Other 
Related Information?

    You may access an electronic copy of this Federal Register document 
and the associated electronic docket at http://www.regulations.gov, or 

you may access this Federal Register document electronically through 
the EPA Internet under the ``Federal Register'' listings at http://www.epa.gov/fedrgstr.
 A frequently updated electronic version of the 

Code of Federal Regulations (CFR) is available at http://www.gpoaccess.gov/ecfr
.

II. EPA's January 2006 Promulgation of Protections for Subjects of 
Human Research

    On January 26, 2006, EPA issued a final rule significantly 
strengthening and expanding the protections for subjects of human 
research. For ``third-party'' human research (i.e., research that is 
not conducted or supported by either EPA or by another Federal 
Department or Agency under the Common Rule), that rule:
    1. Prohibited new research involving intentional exposure of 
pregnant women or children, intended for submission to EPA under the 
pesticide laws.
    2. Extended the provisions of the Federal Policy for the Protection 
of Human Subjects of Research (the ``Common Rule'') to other human 
research involving intentional exposure of non-pregnant adults, 
intended for submission to EPA under the pesticide laws.
    3. Required submission to EPA of protocols and related information 
about covered human research before it is initiated.
    4. Established an independent Human Studies Review Board to review 
both proposals for new research and reports of covered human research 
on which EPA proposes to rely under the pesticide laws.
 The January 2006 rule also contained other, similar requirements for 
first- and second-party research, as well as standards to guide EPA 
decisionmaking under the pesticide laws involving reliance on the 
results of completed intentional dosing human research.

III. Protections for Children Potentially Exposed Through Nursing Women 
Who Are Subjects in Human Research

    In the January 2006 rule, EPA provided additional protections for 
children, to prohibit their being intentionally exposed to test 
materials through human research. The Agency believed that it had 
achieved this goal by establishing a prohibition against the use of 
children as subjects in certain types of research involving intentional 
exposure of subjects. Since promulgation of the January 2006 rule, 
however, the Agency has been asked whether the final rule prohibits 
investigators from conducting, or EPA from relying on, research 
involving intentional exposure of nursing women, since use of nursing 
women as subjects of research could potentially result in exposure of 
nursing infants to the test material in nursing women's breast milk.
    The Agency notes that it has not conducted or supported intentional 
dosing studies targeted at nursing women and has no intention to do so 
in the future. Moreover, under the January 2006 rule, if, in accordance 
with 40 CFR 26.1125, a third-party researcher submitted to EPA a 
proposal to perform such research, EPA would not approve the proposal. 
The Agency has concluded that such research should never be performed 
because of the potential that it might result in exposure of nursing 
children. Accordingly, EPA is amending the January 2006 rule to clarify 
that the prohibitions in the January 2006 rule against conduct of new 
research involving intentional exposure of pregnant women and children, 
and the prohibition of the Agency's reliance on completed research 
involving intentional exposure of pregnant women or children, apply as 
well to research involving intentional exposure of nursing women. The 
rule explicitly prohibits research involving intentional exposure of 
nursing women. EPA would consider a woman to be nursing if she is 
providing her breast milk to a child either during or after the 
research when the test material could be detected in her breast milk. 
(For purposes of applying the rule to research conducted after the 
effective date of this action, an investigator could document 
compliance by obtaining a statement from a female subject that she is 
not providing and does not intend to provide her breast milk to a child 
during the research and for a period of time after the research ends 
during which the test material could reasonably be detected in her 
breast milk. The Agency does not intend, however, to prohibit research 
involving intentional exposure of a woman as a research subject simply 
because at some indefinite, future time the woman hopes to breast-feed 
a child.)
    In sum, the Agency believes that the kinds of explicit protections 
for children and pregnant women established by the January 2006 rule 
are equally appropriate for nursing women. Data indicate that some 
pesticides and other environmental substances pass into breast milk, 
but adequate data do not exist to characterize the fate of all 
substances that might be used in human research covered by the January 
2006 rule. Therefore, consistent with the intent of the January 2006 
rule to protect

[[Page 36174]]

children from exposure to test materials through intentional dosing 
studies, EPA is reinforcing the protection for children by prohibiting 
the following:
    1. New research involving intentional exposure of nursing women 
conducted or supported by EPA.
    2. New research involving intentional exposure of nursing women 
conducted by third-party investigators who intend to submit the results 
to EPA under the pesticide laws.
    3. Reliance by EPA in its actions under the pesticide laws on 
research involving intentional exposure of nursing women.
(EPA notes that the absence of information about the nursing status of 
female subjects in a completed study does not justify application of 
the prohibition in Sec.  26.1703.)

IV. FIFRA Review Procedures for the Direct Final Rule

    FIFRA section 25(a)(2)(B) provides: ``[a]t least 30 days prior to 
signing any regulation in final form for publication in the Federal 
Register, the Administrator shall provide the Secretary of Agriculture 
a copy of such regulation.'' This section also authorizes the Secretary 
to waive the opportunity to review and comment on final regulations. 
FIFRA section 25(d)(1) states that ``[t]he Administrator shall submit 
to an advisory panel for comment [the] final form of regulations issued 
under section 25(a) within the same time periods as provided for the 
comments of the Secretary of Agriculture . . .'' This subsection also 
authorizes the FIFRA Scientific Advisory Panel (SAP) to waive the 
opportunity for review. Both, the FIFRA SAP and the U.S. Department of 
Agriculture (USDA) have waived the opportunity under FIFRA to review 
the direct final rule.
    In addition, FIFRA section 25(a)(3) states that ``[a]t such time as 
the Administrator is required under paragraph (2) to provide the 
Secretary of Agriculture with . . . a copy of the final form of 
regulations, the Administrator shall also furnish a copy of such 
regulations to the Committee on Agriculture in the House of 
Representatives, and the Committee on Agriculture, Nutrition, and 
Forestry in the United States Senate.'' Because USDA waived review 
under FIFRA section 25(a)(2)(B), EPA is not required to furnish a copy 
of the final regulations to the specified committees 30 days prior to 
signature of the direct final rule.

V. Statutory and Executive Order Reviews

A. Executive Order 12866

    Under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993), the Office of Management and 
Budget (OMB) has determined that this direct final rule is not a 
``significant regulatory action'' under section 3(f) of the Executive 
Order.
    The amendments contained in this rule are not expected to result in 
a significant increase, if any, to the estimated impacts of the January 
2006 rule, which are presented in a document entitled Economic Analysis 
of the Human Studies Final Rule (Economic Analysis), a copy of which is 
available in the docket for this rule.
    Based on the relatively small economic impact of the January 2006 
rule, EPA believes that this direct final rule will have a minimal--if 
any--impact on industry, regardless of the size of the entity.

B. Paperwork Reduction Act

    This rule contains no new information collection requirements. 
Therefore no further analysis, review or OMB approval is required under 
the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq. The 
information collection requirements contained in the January 2006 rule 
have been approved by OMB under OMB control number 2070-0169 
(identified under EPA ICR No. 2195.02). A copy of the approved 
information collection request document is available in the docket for 
this rule.

C. Regulatory Flexibility Act

    The Regulatory Flexibility Act (RFA) generally requires an agency 
to prepare a regulatory flexibility analysis of any rule subject to 
notice and comment rulemaking requirements under the Administrative 
Procedure Act or any other statute unless the agency certifies that the 
rule will not have a significant economic impact on a substantial 
number of small entities. Small entities include small businesses, 
small organizations, and small governmental jurisdictions.
    After considering the potential economic impacts of the January 
2006 rule on small entities, the Agency concluded pursuant to section 
605(b) of RFA that the January 2006 rule did not have a significant 
adverse economic impact on a substantial number of small entities. EPA 
has determined that the potential additional impact from this direct 
final rule, if any, is minimal. For purposes of assessing the impacts 
of the January 2006 rule on small entities, small entity was defined in 
accordance with the RFA as:
    1. A small business as defined by the Small Business 
Administration's (SBA) regulations at 13 CFR 121.201.
    2. A small governmental jurisdiction that is a government of a 
city, county, town, school district, or special district with a 
population of less than 50,000.
    3. A small organization that is any not-for-profit enterprise which 
is independently owned and operated and is not dominant in its field.
    After considering the economic impacts of this direct final rule on 
small entities, I certify that this action will not have a significant 
economic impact on a substantial number of small entities. The Agency's 
determination is based on the economic analysis performed for the 
January 2006 rule, a copy of which is available in the docket for this 
action.

D. Unfunded Mandates Reform Act

    Under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) 
(Public Law 104-4), EPA has determined that this action does not 
contain a Federal mandate that may result in expenditures of $100 
million or more for State, local, and tribal governments, in the 
aggregate, or the private sector in any 1 year. This rule is expected 
to result in no more than a minor increase, if any, to the estimated 
impact of the January 2006 rule. The estimated total costs associated 
with the January 2006 rule are approximately $38,837 per year. Based on 
historical submissions, EPA has determined that State, local, and 
tribal governments rarely perform human research intended for 
submission to EPA under FIFRA or FFDCA. In addition, the direct final 
rule is not expected to significantly or uniquely affect small 
governments. Accordingly, this action is not subject to the 
requirements of sections 202 and 205 of UMRA.

E. Executive Order 13132

    Executive Order 13132, entitled Federalism (64 FR 43255, August 10, 
1999), does not apply to this rule. EPA has determined that this rule 
does not have ``federalism implications'' because it will not have 
substantial direct effects on the States, on the relationship between 
the national government and the States, or on the distribution of power 
and responsibilities among the various levels of government, as 
specified in the Executive Order. As indicated earlier, instances where 
a State performs human research intended for submission to EPA under 
FIFRA or FFDCA are rare. Therefore, this direct

[[Page 36175]]

final rule may seldom affect a State government.

F. Executive Order 13175

    Executive Order 13175, entitled Consultation and Coordination with 
Indian Tribal Governments (59 FR 22951, November 6, 2000), does not 
apply to this rule. EPA has determined that this rule does not have 
``tribal implications'' because it will not have substantial direct 
effects on tribal governments, on the relationship between the Federal 
Government and the Indian tribes, or on the distribution of power and 
responsibilities between the Federal Government and Indian tribes, as 
specified in the Executive Order. As indicated previously, instances 
where a tribal government performs human research intended for 
submission to EPA under FIFRA or FFDCA are extremely rare.

G. Executive Order 13045

    Executive Order 13045, entitled Protection of Children from 
Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 
1997), does not apply to this rule because this action is not 
designated as an ``economically significant'' regulatory action as 
defined by Executive Order 12866. Furthermore, this rule does not 
establish an environmental standard that is intended to have a 
negatively disproportionate effect on children. To the contrary, this 
action will provide added protections for children with regard to the 
research covered by the rule.

H. Executive Order 13211

    This rule is not subject to Executive Order 13211, entitled Actions 
Concerning Regulations that Significantly Affect Energy Supply, 
Distribution, or Use (66 FR 28355, May 22, 2001) because this rule does 
not have any significant adverse effect on the supply, distribution, or 
use of energy.

I. National Technology Transfer and Advancement Act

    This rule does not impose any technical standards that would 
require Agency consideration of voluntary consensus standards under 
section 12(d) of the National Technology Transfer and Advancement Act 
of 1995 (NTTAA) (15 U.S.C. 272 note) because it does not require 
specific methods or standards to generate data. The NTTAA directs EPA 
to use voluntary consensus standards in its regulatory activities 
unless to do so would be inconsistent with applicable law or 
impractical. Voluntary consensus standards are technical standards 
(e.g., materials specifications, test methods, sampling procedures) 
that are developed or adopted by voluntary consensus standards bodies. 
NTTAA directs EPA to provide Congress, through OMB, with explanations 
when the Agency decides not to use available and applicable voluntary 
consensus standards.

J. Executive Order 12898

    This rule does not have an adverse impact on the environmental and 
health conditions in low-income and minority communities. Therefore, 
under Executive Order 12898, entitled Federal Actions to Address 
Environmental Justice in Minority Populations and Low-Income 
Populations (59 FR 7629, February 16, 1994), the Agency is not required 
to consider environmental justice-related issues.

VI. Congressional Review Act

    The Congressional Review Act, 5 U.S.C. 801 et seq., generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report that includes a copy of the rule to 
each House of the Congress and the Comptroller General of the United 
States. EPA will submit a report containing this rule and other 
required information to the U.S. Senate, the U.S. House of 
Representatives, and the Comptroller General of the United States prior 
to publication of the rule in the Federal Register. This rule is not a 
``major rule'' as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 26

    Environmental protection, Human research subjects, Reporting and 
recordkeeping requirements.

    Dated: June 20, 2006.
Stephen L. Johnson,
Administrator.

0
Therefore, 40 CFR chapter I is amended as follows:

PART 26--[AMENDED]

0
1. The authority citation for part 26 continues to read as follows:

    Authority: 5 U.S.C. 301; 7 U.S.C. 136w(a)(1); 21 U.S.C. 
346a(e)(1)(C); section 201 of Public Law No. 109-54; and 42 U.S.C. 
300v-1(b).

0
2. By revising the heading of subpart B to read as follows:

Subpart B--Prohibition of Research Conducted or Supported by EPA 
Involving Intentional Exposure of Human Subjects who are Children 
or Pregnant or Nursing Women

0
3. By revising Sec.  26.203 to read as follows:

Sec.  26.203  Prohibition of research conducted or supported by EPA 
involving intentional exposure of any human subject who is a pregnant 
woman (and therefore her fetus), a nursing woman, or child.

    Notwithstanding any other provision of this part, under no 
circumstances shall EPA conduct or support research involving 
intentional exposure of any human subject who is a pregnant woman (and 
therefore her fetus), a nursing woman, or a child.

0
4. By revising the heading of subpart K to read as follows:

Subpart K--Basic Ethical Requirements for Third-Party Human 
Research for Pesticides Involving Intentional Exposure of Non-
pregnant, Non-nursing Adults

0
5. By revising the heading of subpart L to read as follows:

Subpart L--Prohibition of Third-Party Research for Pesticides 
Involving Intentional Exposure of Human Subjects who are Children 
or Pregnant or Nursing Women

0
6. By revising Sec.  26.1203 to read as follows:

Sec.  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.

    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 child.

0
7. By revising Sec.  26.1703 to read as follows:

Sec.  26.1703  Prohibition of reliance on research involving 
intentional exposure of human subjects who are pregnant women (and 
therefore their fetuses), nursing women, or children.

    Except as provided in Sec.  26.1706, in actions within the scope of 
Sec.  26.1701 EPA shall not rely on data from any research involving 
intentional exposure of any human subject who is a pregnant woman (and 
therefore her fetus), a nursing woman, or a child.

0
8. By revising the heading of Sec.  26.1704 to read as follows:

[[Page 36176]]

Sec.  26.1704  Prohibition of reliance on unethical human research with 
non-pregnant, non-nursing adults conducted before April 7, 2006.

0
9. By revising the heading of Sec.  26.1705 to read as follows:

Sec.  26.1705  Prohibition of reliance on unethical human research with 
non-pregnant, non-nursing adults conducted after April 7, 2006.

[FR Doc. 06-5649 Filed 6-22-06; 8:45 am]

BILLING CODE 6560-50-S