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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

December 30, 2014

MEMORANDUM

SUBJECT: Materials for Review by the Huma n Studies Review Board for its January 14, 2015 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 sche duled for January 14, 2015. At this meeting, EPA

will ask the Board to address scientific a nd ethical issues surrounding the following three completed human toxicity studi es that appear in the published literature. The Agency’s regulation at 40 CFR §26.1604 requires EPA to seek HSRB review if EPA intends to rely on

these studies in decisions under the Federal Inse cticide Fungicide and Ro denticide Act (FIFRA)

or Section 408 of the Federa l Food Drug and Cosmetic Act.

1. Ezratty, Veronique et al. ( 2014) Repeated Nitrogen Dioxi de Exposures and Eosinophilic airway Inflammation in Asthmatic s: A Randomized Crossover Study. Environmental Health Perspectives. Volume 122, Number 8, August 2014. (MRID 49519201)

2. Spak, C.J. et al. (1989) Tissue Response of Gastric Mucosa after Ingestion of Fluoride. Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden. British Medical

Journal. 298:1686-7. (MRID 49489101)

3. Hansson, T. and Roos, B. (1987). The Effect of Fluoride and Calc ium on Spinal Bone Mineral Content: A Controlled, Prospective (3 years) study. Sahlgren’s Hospital, University of Gothenberg, Sweden. Calcified Tissue International. 40:315-317. (MRID 49489102)Page 2 of 3 The ethical standards from EPA’s rule at 40 CFR part 26 subpart Q that apply to these

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.

§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.

Background Materials:

The background information for each of thes e studies consists of three documents:

1. Copy of the pub lished article

2. EPA data evaluation record (the EPA science review)

3. EPA ethics review

4. (For Ezratty only) – copies of protocol, consent form, and ethics review approval

Charge Questions:

The charge questions for each of these studies are provided below.

Charge questions for Ezratty et al. (2014)

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?

Charge questions for Spak et al. (1989)

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

2. If so, is this study adequate for quantitativ e use in support of an acute dietary risk

assessment for fluoride?

3. Does the study meet the applicable re quirements of 40 CFR part 26 subpart Q?Page 3 of 3 Charge questions for Hansson and Roos et al. (1987)

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

2. If so, is this study adequate for qualitativ e use in support of an acute dietary risk

assessment for fluoride?

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