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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 Huma n 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 th at the Environmental Protection Agency’s (EPA’s) Office of Pesticide Pr ograms is providing for review by the Human Studies Review Board (HSRB or Board) at the meeting schedul ed 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 scen ario design and associated protocol the Agricultural Handler Exposure Task Force, LLC (AHETF) desc ribing proposed research to monitor dermal and inhalation exposure during ope n pour loading of granul ar pesticide products. Because the proposed research involves scripted exposure, it meets the regulatory definition of “research involving inten tional 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 expos ure 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 subm itted proposal and to seek HSRB review of the proposed research. EPA has reviewed the scenar io design and protocol, and has concluded that the research is likely to genera te 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.Page 2 of 3 Charge Questions:

If the research described in the scenar io design and protocol submission AHE170 is performed as described:

1. Is this research is likely to generate scient ifically reliable data, useful for assessing the exposure of those who perform open pour lo ading of granular pesticide products?

2. Is the research likely to meet the applicab le 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 followi ng 4 files concerning the AHETF protocol

AHE170.

a. AHETF Scenario and Protocol Submi ssion 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 Sta ndard Operating Procedures

d. Schulman Associates IRB rost er for review of AHE170

2. Frampton et al. (2002):

Second, EPA will ask the Board to address sc ientific 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-ru le study, such as this one, which identifies or quantifies a toxic

effect. The ethical standards from EPA’s rule at 40 CFR part 26 subpa rt 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 invol ving intentional expo sure of any human subject who is a pregnant woman (and therefore her fe tus), a nursing woman, or a child.Page 3 of 3 §26.1704. EPA must not rely on data from any resear ch subject to this section if there is clear and convincing evidence th at: (1) The conduct of the research was fundamentally unethical (e.g., the research was intended to se riously harm participants or failed to obtain informed consent); or (2) The c onduct of the research was defi cient relative to the ethical standards prevailing at the time the resear ch 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 quantita tive 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 re quirements of 40 CFR part 26 subpart Q?

Documents for Frampton review:

The following information has been compiled into one file.

1. Copy of the pub lished article

2. EPA science review

3. EPA ethics review

a. Attachment 1: Response from Mark Frampton

b. Attachment 2: Documents from IRB