**6/12/06**

**DRAFT**

**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

**HUMAN STUDIES REVIEW BOARD (HSRB)**

**JUNE 27-30, 2006 \***

**PUBLIC MEETING**

**Tuesday, June 27, 2006**

**One Potomac Yard (South Building)**

**2777 Crystal Drive**

**Arlington, VA 22202**

**703-305-7090**

**HSRB WEB SITE http://www.epa.gov/osa/hsrb/**

**Docket Telephone: (202) 566 1752**

**Docket Number: EPA-HQ-ORD-2006-0384**

**1:00 PM Introduction and Identification of Board Members** -- Celia
Fisher, Ph.D. (HSRB Chair)

**1:15 PM Welcome --** George Gray, Ph.D. (EPA Science Advisor)

**1:25 PM Opening Remarks --** Ms. Susan Hazen (Acting Assistant
Administrator, Office of Prevention, Pesticides and Toxic Substances,
EPA)

**1:35 PM Meeting Administrative Procedures** - Paul Lewis, Ph.D.
(Designated Federal Officer \[DFO\], HSRB, OSA, EPA)

**1:40 PM Meeting Process --** Celia Fisher, Ph.D. (HSRB Chair)

**1:55 PM Update on EPA Follow-up of HSRB Recommendations --** Mr. John
Carley (EPA, OPP)

**2:10 PM Informational Presentation of Proposed Workshop on Best
Practices for EPA, National Exposure Research Laboratory Observational
Human Exposure Measurement Studies** - Roy Fortmann, Ph.D. (NERL, Office
of Research and Development, EPA)

**Chloropicrin**

**2:30 PM Science and Ethics of Chloropicrin Human Studies --** Elissa
Reaves, Ph.D. (OPP, EPA) and Mr. John Carley (OPP, EPA)

**3:15 PM Break**

**3:30 PM Public Comments**

**4:00 PM Board Discussion**

Chloropicrin is a non-selective soil fumigant whose primary toxic effect
is sensory irritation in which stimulated free nerve endings mediate
sensations and clinical signs in the nose, eyes, throat, and upper
respiratory tract. Chloropicrin is a unique soil fumigant in that it is
also used as an indicator chemical or warning agent (2% or less by
weight in formulations). The Agency is developing an assessment to
estimate inhalation risk to bystanders and workers from acute exposures
to chloropicrin.

> *1. Scientific considerations*:
>
> The Agency's "Weight of Evidence" (WOE) document and Data Evaluation
> Records (DER) for chloropicrin describe the study design of the acute
> inhalation, human toxicity study. The Agency has concluded that the
> human toxicity study is appropriate for developing a point of
> departure for extrapolation of inhalation risk to bystanders and
> workers exposed to chloropicrin.
>
> Please comment on whether the study is sufficiently sound, from a
> scientific perspective, to be used to estimate a safe level of
> inhalation exposure to chloropicrin.
>
> *2. Ethical considerations*:
>
> The Agency requests that the Board provide comment on the following:
>
> a\. Is there clear and convincing evidence that the conduct of the
> Nethercott study was fundamentally unethical?

b\. Is there clear and convincing evidence that the conduct of the study
was significantly deficient relative to the ethical standards prevailing
at the time the research was conducted?

**Insect Repellent Product Performance Testing Guideline**

**5:00 PM Science and Ethics of Insect Repellent Efficacy Guidelines**
-- Mr. Kevin Sweeney (OPP, EPA), Clara Fuentes, Ph.D. (OPP, EPA) and Mr.
John Carley (OPP, EPA)

**6:00 PM Adjournment**

**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

**HUMAN STUDIES REVIEW BOARD (HSRB)**

**JUNE 27-30, 2006 \***

**PUBLIC MEETING**

**Wednesday, June 28, 2006**

**One Potomac Yard (South Building)**

**2777 Crystal Drive**

**Arlington, VA 22202**

**703-305-7090**

**HSRB WEB SITE http://www.epa.gov/osa/hsrb/**

**Docket Telephone: (202) 566 1752**

**Docket Number: EPA-HQ-ORD-2006-0384**

**8:30 AM Convene Meeting** -- Celia Fisher, Ph.D. (HSRB Chair)

**8:40 AM Follow-up From Previous Day's Discussion --** Mr. John Carley
(OPP, EPA)

**Insect Repellent Product Performance Testing Guideline**

**8:50 AM Public Comments**

**9:15 AM Board Discussion**

> The U.S. EPA Office of Pesticide Programs requests that the HSRB
> review and comment on the draft "Product Performance of Skin-Applied
> Repellents of Insects and Other Arthropods" Testing Guideline in order
> to determine what changes, if any, are necessary for the guideline to
> be made consistent with the requirements for protection of human
> research subjects set forth in 40 CFR part 26. Below is a list of
> questions that focus on these topics.
>
> a\. What actions should an investigator routinely take to minimize the
> risks to human subjects exposed during laboratory and field research
> on the efficacy of repellents?
>
> b\. What types of toxicity data should be routinely generated before
> an investigator conducts repellent efficacy testing on human subjects
> with a new product?

**10:15 AM Break**

**10:30 AM Board Discussion**

> c\. In private and university research laboratories, investigators
> themselves have sometimes served as research subjects when assessing
> chemicals for insect repellent activity. What scientific and ethical
> issues would such a practice raise? Under what conditions, if any,
> would such a practice be acceptable?
>
> d\. Please comment on the scientific and ethical issues arising from
> the use of (or decision not to use) negative controls groups in
> repellent efficacy studies, in both laboratory and field studies.
>
> e\. Please comment on the scientific and ethical issues raised by the
> design of studies to collect data sufficient to support assessment of
> repellent efficacy using the two different efficacy metrics: time to
> first confirmed bite (TFCB), and time providing x% protection of
> treated subjects from bites relative to untreated controls (RP).
>
> f\. Please comment on appropriate approaches for estimating the
> minimum number of subjects needed to evaluate the level of efficacy of
> a repellent in laboratory and field studies.
>
> g\. Please comment on whether or not investigators should have an
> ethical obligation to provide subjects of repellent efficacy research
> with insurance to cover possible future medical costs or other losses
> that result from injury or illness experienced by the subjects as a
> consequence of their participation in the research.

**12:30 PM Lunch**

**1:30 PM Board Discussion**

> h\. Please comment on any special considerations that should be
> addressed in the informed consent materials provided people who are
> candidates to become subjects in insect repellent efficacy research.
>
> i\. Does the HSRB recommend that the draft guideline be revised? If
> so, please explain what aspects or sections might improve with
> revision.

**Human Studies Research Protocols**

**2:15 PM Introduction** -- EPA/OSA

**HSRB Review of Protocol Criteria**

**2:45 PM HSRB Science and Ethics Criteria of Human Studies Protocols
--** Celia Fisher, Ph.D. (HSRB Chair)

**3:30 PM Break**

**3:45 PM HSRB Science and Ethics Criteria of Human Studies Protocols
--** Celia Fisher, Ph.D. (HSRB Chair)

**Research on the Efficacy of Insect Repellents**

**4:15 PM Science and Ethics of Research on the Efficacy of Insect
Repellents --** Mr. Kevin Sweeney (OPP, EPA), Clara Fuentes, Ph.D. (OPP,
EPA) and Mr. John Carley (OPP, EPA)

**5:15 PM Adjournment**

**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

**HUMAN STUDIES REVIEW BOARD (HSRB)**

**PUBLIC MEETING**

**Thursday, June 29, 2006**

**One Potomac Yard (South Building)**

**2777 Crystal Drive**

**Arlington, VA 22202**

**703-305-7090**

**HSRB WEB SITE http://www.epa.gov/osa/hsrb/**

**Docket Telephone: (202) 566 1752**

**Docket Number: EPA-HQ-ORD-2006-0310**

**8:30 AM Convene Meeting** -- Celia Fisher, Ph.D. (HSRB Chair)

**8:40 AM Follow-up From Previous Day's Discussion --** Mr. John Carley
(OPP, EPA)

**Research on the Efficacy of Insect Repellents**

**8:50 AM Public Comments**

**9:20 AM Board Discussion**

> *Study EMD-003 from Carroll-Loye Biological Research*
>
> a\. Does the proposed research described in \[name / designation of
> the protocol\] appear likely to generate scientifically reliable data,
> \[useful for assessing the efficacy of the repellent\] / \[useful
> (together with other data) assessing the potential levels of pesticide
> exposure received by people when mixing, loading or applying a
> pesticides\]?
>
> b\. Does the proposed research described in Study EMD-003 from
> Carroll-Loye Biological Research appear to comport with the applicable
> requirements of 40 CFR part 26, subparts K and L?

**10:15 AM Break**

**10:30 AM Board Discussion**

> *Study EMD-004 from Carroll-Loye Biological Research*
>
> a\. Does the proposed research described in Study EMD-004 from
> Carroll-Loye Biological Research appear likely to generate
> scientifically reliable data, useful for assessing the efficacy of a
> test substance for repellent ticks?
>
> b\. Does the proposed research described in Study EMD-004 from
> Carroll-Loye Biological Research appear to comport with the applicable
> requirements of 40 CFR part 26, subparts K and L?

**11:45 AM Lunch**

**Research on Agricultural Handlers' Exposure to Pesticides**

**12:45 PM Science and Ethics of Research on Agricultural Handler's
Exposure to Pesticides -** Mr. Jeffrey Dawson, Mr. Jeffrey Evans (OPP,
EPA) and Mr. John Carley (OPP, EPA)

**1:45 PM Public Comments**

**2:15 PM Board Discussion**

The Agricultural Handlers Exposure Task Force (AHETF) has submitted
protocols for five pesticide exposure studies that are part of a larger
research program the AHETF is conducting. The premise of the AHETF
research program is that data can be used generically by various
stakeholders (e.g., applicants, registrants, EPA, and others) for
calculating exposures for the occupational handlers of pesticides. The
scope of the AHETF research program is very broad in that it intends to
address exposures related to many job functions in agriculture and also
to assess generally the impacts of various parameters on exposure (e.g.,
How do changes in the pounds of pesticide handled or acres treated
affect exposure levels?). The protocols submitted for HSRB review
describe studies to measure exposures for five specific scenarios (i.e.,
closed or open system mixing/loading , airblast applications to trellis
and orchard crops, or pilot exposures from fixed wing agricultural
aircraft).

The Agency believes these studies improve EPA's ability to assess the
risks of using pesticides because the data will reflect current
agricultural practices, equipment and techniques and will allow for more
refined exposure estimates. Further, the monitoring techniques to be
used for these studies also have been standardized for use across the
AHETF research program.. These more refined and reliable data will allow
the Agency to estimate better how worker exposure levels are affected by
changes in various factors such as the amount of active ingredient
handled, type of application equipment used, application rate used,
volumes handled, and personal protective equipment used.

It should be noted, however, that the use of the data generated in this
study by the U.S. EPA and other stakeholders will depend upon the nature
of the results. For example, the adequacy of the field or laboratory
quality control data may dictate that correction factors are applied to
adjust monitored exposure levels to account for losses from field
samplers or low performing analytical methods.

> *1. AHETF Closed System Mixing/ Loading of Liquids Protocol*
>
> a\. Does the proposed research described in Study No. AHE34 from the
> Agricultural Handlers Exposure Task Force appear likely to generate
> scientifically reliable data, which will be useful, together with
> other data, for assessing the potential levels of pesticide exposure
> received by people when mixing, loading or applying a liquid pesticide
> with closed systems? \[Note: In a few cases, corresponding application
> events are also to be monitored; the same question applies to those
> elements of the study.\]
>
> b\. Does the proposed research described in Study No. AHE34 from the
> Agricultural Handlers Exposure Task Force appear to comport with the
> applicable requirements of 40 CFR part 26, subparts K and L?

**3:15 PM Break**

**3:15 PM Board Discussion**

> *2. AHETF Airblast Application to Trellis Crops in the West Protocol*
>
> a\. Does the proposed research described in Study No. AHE36 from the
> Agricultural Handlers Exposure Task Force appear likely to generate
> scientifically reliable data, which will be useful, together with
> other data, for assessing the potential levels of pesticide exposure
> received by people when making an airblast application of a pesticide
> to a trellis crop under conditions found in the western United States?
> \[Note: In a few cases, corresponding mixing/loading events are also
> to be monitored; the same question applies to those elements of the
> study.\]
>
> b\. Does the proposed research described in Study No. AHE36 from the
> Agricultural Handlers Exposure Task Force appear to comport with the
> applicable requirements of 40 CFR part 26, subparts K and L?
>
> *3. AHETF Airblast Application to Trellis Crops in the East Protocol*
>
> a\. Does the proposed research described in Study No. AHE37 from the
> Agricultural Handlers Exposure Task Force appear likely to generate
> scientifically reliable data, which will be useful, together with
> other data, for assessing the potential levels of pesticide exposure
> received by people when making an airblast application of a pesticide
> to a trellis crop under conditions found in the eastern United States?
> \[Note: In a few cases, corresponding mixing/loading events are also
> to be monitored; the same question applies to those elements of the
> study.\]
>
> b\. Does the proposed research described in Study No. AHE37 from the
> Agricultural Handlers Exposure Task Force appear to comport with the
> applicable requirements of 40 CFR part 26, subparts K and L?

**5:00 PM Adjournment**

**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

**HUMAN STUDIES REVIEW BOARD (HSRB)**

**PUBLIC MEETING**

**Friday, June 30, 2006**

**One Potomac Yard**

**2777 Crystal Drive**

**Arlington, VA 22202**

**703-305-7090**

**8:30 AM Convene Meeting** -- Celia Fisher, Ph.D. (HSRB Chair)

**8:40 AM Follow-up From Previous Day's Discussion --** Mr. John Carley
(OPP, EPA)

**Research on Agricultural Handlers'Exposure to Pesticides**

**9:00 AM Board Discussion**

> *4. AHETF Closed Cab Airblast Application to Orchards Protocol*
>
> a\. Does the proposed research described in Study No. AHE38 from the
> Agricultural Handlers Exposure Task Force appear likely to generate
> scientifically reliable data, which will be useful, together with
> other data, for assessing the potential levels of pesticide exposure
> received by people when making an airblast application of a pesticide
> to orchard crops? \[Note: In a few cases, corresponding mixing/loading
> events are also to be monitored; the same question applies to those
> elements of the study.\]
>
> b\. Does the proposed research described in Study No. AHE38 from the
> Agricultural Handlers Exposure Task Force appear to comport with the
> applicable requirements of 40 CFR part 26, subparts K and L?
>
> *5. AHETF Fixed-Wing Aerial Application Protocol*
>
> a\. Does the proposed research described in Study No. AHE42 from the
> Agricultural Handlers Exposure Task Force appear likely to generate
> scientifically reliable data, which will be useful, together with
> other data, for assessing the potential levels of pesticide exposure
> received by people making an aerial application of a pesticide from
> fixed-wing aircraft? \[Note: In a few cases, corresponding
> mixing/loading events are also to be monitored; the same question
> applies to those elements of the study.\]
>
> b\. Does the proposed research described in Study No. AHE42 from the
> Agricultural Handlers Exposure Task Force appear to comport with the
> applicable requirements of 40 CFR part 26, subparts K and L?

**10:30 AM Break**

**May 2-3, 2006 HSRB Meeting Report\*\***

**10:45 AM HSRB Review of May 2-3, 2006 HRSB Meeting Report --** Celia
Fisher, Ph.D. (HSRB Chair)

**11:00 AM Public Comments**

**11:30 AM Lunch**

**12:30 PM Board Discussion and Decision on Report**

**Chromium**

**Methyl Isothiocyanate**

**Carbofuran**

**2:00 PM Summary and Next Steps** -- Celia Fisher, Ph.D. (HSRB Chair)
and Paul Lewis, Ph.D. (HSRB DFO)

**2:30 PM Adjournment**

\* Agenda times are approximate

\*\* Board review of the May 2-3, 2006 HSRB meeting report is tentative,
pending Board completion of proposed final draft report

For further information, please contact the Designated Federal Officer
for this meeting, Paul Lewis, via telephone: (202) 564-8381 or email:
lewis.paul@epa.gov