Page 1 of 4 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES AND

TOXIC SUBSTANCES

December 5, 2008

MEMORANDUM

SUBJECT : Ethics Review of Anti-Fouling Paint Study

TO: Timothy Leighton

Antimicrobial Division

FROM: Kelly Sherman

Human Research Ethics Reviewer Office of Pesticide Programs

REF: Anderson, I., Sherratt, R. (2005) Cruiser Uno: Determination of Dermal and Inhalation Exposure to Hazardous Substances During Amateur Use of Yacht Anti-Fouling Coatings. Unpublished study prepared by Inveresk under Study No. 683732. 132 p. (MRID 46511801)

I have reviewed the referenced document and determined that all applicable requirements of EPA’s Rule for the Protection of Human Subj ects of Research (40 CFR Part 26) have been

satisfied.

Summary Characteristics of the Research

In this research, 15 subjects applied copper-based antifouling paint to yachts using brushes and rollers, and 5 subjects wet-sanded the surface of a yacht previously treated with antifouling paint. Subjects wore whole body outer and inner dosimeters and personal air sampling pumps for monitoring dermal and inhalation exposure. The research was conducted in March 2004 at Port Edgar Marina, South Queensferry, Scotland.Page 2 of 4 1. Value of the Research to Society: The purpose of this study was to monitor and quantify copper exposure levels to “amateurs” (people who do not work on yachts or other water craft for their occupation) during application or sanding of anti-fouling paint on yachts. The study was funded by International Paint Limited. It contributes to the assessment of exposure due to applying and sanding anti-fouling paint on yachts and other similar types of water craft.

2. Subject Selection : No information is provided about how the subjects were recruited or selected. The twenty subjects included 17 men and 3 women who ranged in age from 19 to 77. The pregnancy and nursing status of th e female subjects is not reported. There is no indication any subjects came from an especially vulnerable group.

3. Risk-Benefit Ratio : Neither risks to the subjects nor actions taken to minimize those risks are reported. The report does not identify societal benefits of the research or how they would be distributed, or how the inve stigators weighed likely benefits of the research against the risks to individual subjects.

4. Independent Ethics Review : The study does not report any independent ethics oversight or review of the protocol or of the conduct of the research.

5. Informed Consent : The report states that each subject was provided with a full explanation of the study, its requirements, and potential risks, and signed a consent form prior to commencement of the research.

6. Respect for Potential and Enrolled Subjects : There is no identifying information about any of the subjects in the report. It is not reported whether s ubjects were free to

withdraw from the research.

Applicable Standards

This research was initiated in March 2004, so the research occurred before the effective date of EPA’s amended Rule for the Protection of Human Subjects of Research on April 7, 2006. Because this research involved application of product provided by the sponsors at rates and under conditions specified by the investigators, it meets the definition of “research involving intentional exposure of a human subject” in the rule at 40 CFR §26.1102(i).

The report of this research was submitted to EPA on March 30, 2005, before the effective

date of EPA’s Amended Rule for the Protection of Human Subjects of Research, and thus it is not subject to the requirement of 40 CFR §26.1303 to document the ethical conduct of the

research.

The Agency’s rule defines standards that EPA must apply in deciding whether to rely on research—like this study—which may have involved intentional exposure of human subjects.Page 3 of 4 (See 40 CFR §26 subpart Q.) Because this study was initiated before the effective date of the rule, the applicable acceptance standards from 40 CFR §26 are these:

§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 §26.1706, in actions within the scope of §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.

§26.1704. Prohibition of reliance on unethical human research with nonpregnant adults conducted before April 7, 2006. Except as provided in §26.1706, in actions within the scope of §26.1701, EPA shall not rely on data from any research initiated before April 7, 2006, 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 significantly deficient relative to the ethical standards prevailing at the time the research was conducted. This prohibition is in addition to the prohibition in §26.1703.

FIFRA §12(a)(2)(P) also applied to this research. This provision reads:

In general, [i]t shall be unlawful for any person . . . to use any pesticide in tests on human beings unless such human beings (i) are fully informed of the nature and purposes of the test and of any physical and mental health consequences which are reasonably foreseeable therefrom, and (ii) freely volunteer to participate in the test.

Compliance with Applicable Standards

The twenty subjects in the study were all adults. The study is silent with respect to the pregnancy and nursing status of the three female subjects, but there is no indication that any of the subjects were pregnant or nursing women. In the absence of any information suggesting that pregnant or nursing women were among the subjects, the Agency’s interpretation is that reliance on the study is not prohibited by 40 CFR 26.1703.

40 CFR §26.1704 forbids EPA to rely on data from pre-rule research—such as this study—if there is “clear and convincing evidence that the conduct of the research was fundamentally unethical..., or was significantly deficient relative to the ethical standards prevailing at the time the research was conducted.” Although there are significant gaps in the documentation of the ethical conduct of this research, these gaps do not in themselves amount to “clear and convincing evidence.” I found no evidence that this research was fundamentally unethical, or that its conduct was significantly deficient relative to standards prevailing when it was conducted. 40 CFR §26.1704 does not prohibit EPA reliance on this research.Page 4 of 4 FIFRA §12(a)(2)(P) requires that human subjects of research with pesticides be “fully informed of . . . any physical and mental health consequences which are reasonably foreseeable” from their participation in research. The reported descriptions of the consent process appear to meet the substantive requirements of FIFRA §12(a)(2)(P) for fully voluntary participation.

Conclusion

Although there are many significant gaps in the documentation of the ethical conduct of this study, there is no clear evidence that the research was intended to harm participants, or that it was fundamentally unethical in other ways. Deficient documentation does not itself constitute evidence that the ethical conduct of this study was deficient relative to standards prevailing when

it was conducted.

I find no barrier in law or regulation to reliance on MRID 46511801 in actions taken

under FIFRA or §408 of FFDCA. I defer to others fo r a full review of the scientific validity of this study. If it were determined not to have scientific validity, it would also not be ethically acceptable.