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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

October 14, 2014 

MEMORANDUM

SUBJECT: Materials for Review by the Human Studies Review Board for its 

 November 5, 2014 Meeting

TO: Jim Downing 

 Designated Federal Official 

 Human Studies Review Board 

 Office of Science Advisor (8105R) 

FROM: William L. Jordan 

 Deputy Director 

 Office of Pesticide Programs (7501P) 

This memorandum describes the materials that the Environmental Protection Agency’s 

(EPA’s) Office of Pesticide Programs is providing for review by the Human Studies Review 

Board (HSRB or Board) at the meeting scheduled for November 5, 2014. At this meeting, EPA 

will ask the Board to address scientific and ethical issues surrounding two topics. 

1. AHETF Protocol (AHE170) – Open Pour Loading of Granules: 

First, the Board will consider a new scenario design and associated protocol the 

Agricultural Handler Exposure Task Force, LLC (AHETF) describing proposed research to 

monitor dermal and inhalation exposure during open pour loading of granular pesticide products. 

Because the proposed research involves scripted exposure, it meets the regulatory definition of 

“research involving intentional exposure of a human subject” and thus is covered by subparts K 

and L of EPA’s amended rule for the protection of human subjects of research. The rule at 40 

CFR §26.1125 requires a sponsor or investigator to submit to EPA, before conducting a study 

involving intentional exposure of human subjects, the protocol and related materials describing 

the proposed human research. In addition, EPA’s regulation at 40 CFR §26.1601 requires EPA to 

perform science and ethics reviews of the submitted proposal and to seek HSRB review of the 

proposed research. EPA has reviewed the scenario design and protocol, and has concluded that 

the research is likely to generate scientifically sound, useful information and likely to meet the 

applicable provisions of the EPA regulations in 40 CFR part 26, subparts K and L. The charge 

questions and documents being transmitted to the HSRB for review are listed below. 
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Charge Questions: 

If the research described in the scenario design and protocol submission AHE170 is 

performed as described: 

1. Is this research is likely to generate scientifically reliable data, useful for assessing the 

exposure of those who perform open pour loading of granular pesticide products? 

2. Is the research likely to meet the applicable requirements of 40 CFR part 26, subparts 

K and L? 

Documents for AEATF-II Solid Pour Protocol Review: 

EPA is providing for HSRB review the following 4 files concerning the AHETF protocol 

AHE170. 

a. AHETF Scenario and Protocol Submission for Granular Open-Pour Loading 

(AHE170) (dated July 25, 2014) (659 pages) 

b. EPA Science and Ethics Review of AHETF submission (dated October 8, 2014) (52 

pages) 

c. Schulman Associates IRB Standard Operating Procedures 

d. Schulman Associates IRB roster for review of AHE170 

2. Frampton et al. (2002): 

Second, EPA will ask the Board to address scientific and ethical issues surrounding the 

following completed human study with nitrogen dioxide that appears in the published literature: 

Frampton, M.W. et al. Nitrogen Dioxide Exposure: Effects on Airway and Blood 

Cells. Am J Physiol Lung Cell Mol Physiol. 282: L155-L165, 2002. (MRID 

49420001) 

The Agency’s regulation, 40 CFR §26.1602, requires EPA to seek HSRB review if EPA intends 

to rely on the results of a pre-rule study, such as this one, which identifies or quantifies a toxic 

effect. The ethical standards from EPA’s rule at 40 CFR part 26 subpart Q that apply to 

completed pre-rule studies are as follows: 

§26.1703. Except as provided in §26.1706, EPA must not rely on data from any research 

subject to this subpart involving intentional exposure of any human subject who is a 

pregnant woman (and therefore her fetus), a nursing woman, or a child. 
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§26.1704. EPA must not rely on data from any research subject to this section if there is 

clear and convincing evidence that: (1) 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 (2) The conduct of the research was deficient relative to the ethical 

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

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

was conducted) or impaired their informed consent. 

Charge Questions – Frampton et al. (2002): 

1. Is this study scientifically sound, providing reliable data? 

2. If so, is this study adequate for quantitative use in support of an inhalation risk 

assessment for the use of nitrogen dioxide as a medical equipment sterilant? 

3. Does the study meet the applicable requirements of 40 CFR part 26 subpart Q? 

Documents for Frampton review:

The following information has been compiled into one file. 

1. Copy of the published article 

2. EPA science review 

3. EPA ethics review 

a. Attachment 1: Response from Mark Frampton 

b. Attachment 2: Documents from IRB