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 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

 WASHINGTON, D.C. 20460 

OFFICE OF 

PREVENTION, PESTICIDES AND 

 TOXIC SUBSTANCES

December 5, 2008

MEMORANDUM 

SUBJECT: Ethics Review of Zinc Pyrithione Worker Exposure Study 

TO: Timothy Leighton 

 Antimicrobial Division 

FROM: Kelly Sherman 

 Human Research Ethics Reviewer 

 Office of Pesticide Programs 

REF: Wu, M. (2005) Assessment of Potential Inhalation and Dermal Exposure to Zinc 

Pyrithione During Outdoor Painting of Ship Hulls with Commercial Antifouling 

Paint Containing ZINC OMADINE®. Unpublished study prepared by Arch 

Chemicals Inc. under Study Identification No. BWE03001. 630 p. (MRID 

46707001) 

 

I have reviewed the referenced document and determined that all applicable requirements 

of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been 

satisfied. 

Summary Characteristics of the Research 

In this research, 31 dry dock workers were monitored as they performed tasks associated 

with the commercial application of antifouling paint to the hulls of commercial cargo and 

passenger ships. The research was conducted between November 2004 and April 2005 in 

Boston, Massachusetts and Freeport, Grand Bahama Island. Subjects wore whole-body 

dosimeters under fresh work clothes and Tyvek® hooded coveralls, dosimeter gloves under work 

gloves, dosimeter patches on the back of their work shirts and on the front of their coveralls, and 

personal air sampling pumps for monitoring dermal and inhalation exposure. 

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Some of the 31 workers were monitored more than once, for a total of 49 “replicates.” 

All of the subjects were professional dry dock workers who normally performed tasks associated 

with the commercial application of antifouling paint to ship hulls. No information is provided 

about how the subjects were recruited, or what they were told of the purposes, procedures, risks, 

benefits, costs, and other aspects of the research. The report does not indicate whether the 

subjects consented to participate, or what form their consent took. The research was not reported 

to have been overseen by an IRB or any comparable independent ethics review entity. 

1. Value of the Research to Society: The purpose of this study was to monitor and 

quantify the exposure levels of zinc pyrithione to dry dock workers as they perform tasks 

associated with applying antifouling paint to the hulls of commercial cargo or passenger 

ships. The study was funded by Arch Chemicals Inc. It contributes to the assessment of 

worker exposure while mixing, loading, and applying zinc pyrithione and possibly other 

types of antifouling paint to commercial cargo and passenger ships. 

2. Subject Selection: Although participating shipyards were reportedly selected to 

represent a typical range of circumstances and practices, no information is given about 

how the subjects were recruited or selected. Their gender, age, and pregnancy or nursing 

status is not reported. There is no indication that 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 discussed. Since subjects were performing their usual jobs and wearing both 

PPE and whole-body dosimeters, the risks associated with their participation in the 

research were low. The report does not identify societal benefits of the research or how 

they would be distributed, or how the investigators 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 is silent about whether informed consent was obtained 

from the subjects. Because subjects wore extensive dosimetry, it is implausible that their 

participation was not consensual. What is less clear is whether it was adequately 

informed. 

6. Respect for Potential and Enrolled Subjects: The report does not contain identifying 

information about any of the subjects. It is not reported whether subjects were free to 

withdraw from the research.

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Applicable Standards 

This research was initiated in December 2003, well before April 7, 2006, the effective 

date of EPA’s amended Rule for the Protection of Human Subjects of Research. The report was 

submitted to EPA on December 5, 2005, before the effective date of EPA’s Amended Rule, and 

thus it was not subject to the requirement of 40 CFR §26.1303 to document the ethical conduct 

of the research. 

The amount of active ingredient handled was not manipulated by the investigators, nor 

was subject behavior or the equipment they used influenced by the investigators. Therefore, the 

research may not constitute “research involving intentional exposure of a human subject” as that 

phrase is defined in the rule at 40 CFR §26.1102(i). However, documentation of how 

cooperating employees and employers were recruited is inadequate to support a definitive 

finding. 

 

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. 

(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. 

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Compliance with Applicable Standards 

All subjects were adults. The study is silent with respect to the age, sex, and pregnancy 

or nursing status of the 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 view 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 (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 study had a clear research purpose and 

was not designed with the intent to seriously harm the subjects. There is no direct evidence that 

the subjects provided consent, but it is unlikely that the workers could have been compelled to 

wear the dosimeters and air sampling equipment without their consent. 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 at the time it was conducted. 40 CFR §26.1704 does not prohibit EPA reliance on this 

research. 

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 the research. The study does not report what the subjects were told 

about the potential health effects of participating in this research, or whether they consented to 

participate. The lack of documentation regarding informed consent is a significant deficiency, 

but this deficiency does not, in my judgment, necessarily indicate that the subjects were not 

properly informed or that their participation was non-consensual, in violation of FIFRA 

§12(a)(2)(P). Uncertainty in this respect could be removed if further information were obtained 

about the process and content of informed consent in this study. 

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 therefore conclude that, whether or not the reported research met the regulatory 

definition of “research involving intentional exposure of a human subject,” there is no barrier in 

law or regulation to EPA’s relying on this research in its actions taken under FIFRA or §408 of 

FFDCA. I defer to others for 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. 

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