E7-9426. FIFRA Scientific Advisory Panel; Notice of Public Meeting

AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Notice.

SUMMARY:

There will be a 4-day meeting of the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP) to review a set of issues being considered by the Agency pertaining to two separate topics. On August 14-15, 2007, the Panel will consider a Review of EPA/ORD/NERL's SHEDS-Multimedia Model, aggregate version 3. On August 16-17, 2007, the Panel will review Assessing Approaches for the Development of PBPK Models of Pyrethroid Pesticides.

DATES:

The meeting will be held on August 14-17, 2007, from 8:30 a.m. to 5 p.m, eastern standard time (est.)

Comments. The Agency encourages that written comments be submitted by July 31, 2007 and requests for oral comments be submitted by August 7, 2007. However, written comments and requests to make oral comments may be submitted until the date of the meeting. For additional instructions, see Unit I.C. of the SUPPLEMENTARY INFORMATION.

Nominations. Nominations of candidates to serve as ad hoc members of the FIFRA SAP for this meeting should be provided on or before May 29, 2007.

Special accommodations. For information on access or services for individuals with disabilities, and to request accommodation of a disability, please contact the Designated Federal Official (DFO) listed under FOR FURTHER INFORMATION CONTACT at least 10 days prior to the meeting to give EPA as much time as possible to process your request.

ADDRESSES:

The meeting will be held at the Environmental Protection Agency Conference Center, Lobby Level, One Potomac Yard (South Bldg.), 2777 Crystal Dr., Arlington, VA 22202.

Comments. Submit your comments, identified by docket ID number EPA-HQ-OPP-2007-0388, by one of the following methods:

• Federal eRulemaking Portal: http://www.regulations.gov. Follow the on-line instructions for submitting comments. Your use of the Federal eRulemaking Portal to submit comments to EPA electronically is EPA's preferred method for receiving comments.

• Mail. Office of Pesticide Programs (OPP) Regulatory Public Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001.

• Delivery. OPP Regulatory Public Docket (7502P), Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South Bldg), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only accepted during the Docket's normal hours of operation 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. Special arrangements should be made for deliveries of boxed information. The Docket Facility telephone number is [phone].

Instructions. Direct your comments to docket ID number EPA-HQ-OPP-2007-0388. If your comments contain any information that you consider to be CBI or otherwise protected, please contact the DFO listed under FOR FURTHER INFORMATION CONTACT to obtain special instruction before submitting your comments. EPA's policy is that all comments received will be included in the docket without change and may be made available on-line at http://www.regulations.gov, including any personal information provided, unless the comment includes information claimed to be Confidential Business Information (CBI) or other information whose disclosure is restricted by statute. Do not submit information that you consider to be CBI or otherwise protected through regulations.gov or e-mail. The regulations.gov website is an “anonymous access” system, which means EPA will not know your identity or contact information unless you provide it in the body of your comment. If you send an e-mail comment directly to EPA without going through regulations.gov, your e-mail address will be automatically captured and included as part of the comment that is placed in the docket and made available on the Internet. If you submit an electronic comment, EPA recommends that you include your name and other contact information in the body of your comment and with any disk or CD ROM you submit. If EPA cannot read your comment due to technical difficulties and cannot contact you for clarification, EPA may not be able to consider your comment. Electronic files should avoid the use of special characters, any form of encryption, and be free of any defects or viruses.

Docket. All documents in the docket are listed in a docket index available in regulations.gov. To access the electronic docket, go to http://www.regulations.gov, select “Advanced Search,” then “Docket Search.” Insert the docket ID number where indicated and select the “Submit” button. Follow the instructions on the regulations.gov web site to view the docket index or access available documents. Although, listed in a docket index, some information is not publicly available, e.g., CBI or other information whose disclosure is restricted by statute. Certain other material, such as copyrighted material, is not placed on the Internet and will be publicly available only in hard copy form. Publicly available docket materials are available in the electronic docket at http://www.regulations.gov, or if only available in hard copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac Yard (South Bldg), 2777 S. Crystal Dr., Arlington, VA. The hours of operation of this Docket Facility are from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The Docket Facility telephone number is [phone].

Nominations, requests to present oral comments, and requests for special accommodations. Submit nominations to serve as an ad hoc member of the FIFRA SAP, requests for special seating accommodations, or requests to present oral comments to the DFO listed under FOR FURTHER INFORMATION CONTACT.

FOR FURTHER INFORMATION CONTACT:

Steve M. Knott, DFO, Office of Science Coordination and Policy (7201M), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: [phone]; fax number: [phone]; e-mail addresses: [e-mail].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

This action is directed to the public in general. This action may, however, be of interest to persons who are or may be required to conduct testing of chemical substances under the Federal Food, Drug, and Cosmetic Act (FFDCA), FIFRA, and the Food Quality Protection Act of 1996 (FQPA). Since other entities may also be interested, the Agency has not attempted to describe all the specific entities that may be affected by this action. If you have any questions regarding the applicability of this action to a particular entity, consult the DFO listed under FOR FURTHER INFORMATION CONTACT.

B. What Should I Consider as I Prepare My Comments for EPA?

When submitting comments, remember to:

1. Identify the document by docket ID number and other identifying information (subject heading, Federal Register date and page number).

2. Follow directions. The Agency may ask you to respond to specific questions or organize comments by referencing a Code of Federal Regulations (CFR) part or section number.

3. Explain why you agree or disagree; suggest alternatives and substitute language for your requested changes.

4. Describe any assumptions and provide any technical information and/or data that you used.

5. If you estimate potential costs or burdens, explain how you arrived at your estimate in sufficient detail to allow for it to be reproduced.

6. Provide specific examples to illustrate your concerns and suggest alternatives.

7. Explain your views as clearly as possible, avoiding the use of profanity or personal threats.

8. Make sure to submit your comments by the comment period deadline identified.

C. How May I Participate in this Meeting?

You may participate in this meeting by following the instructions in this unit. To ensure proper receipt by EPA, it is imperative that you identify docket ID number EPA-HQ-OPP-2007-0388 in the subject line on the first page of your request.

1. Written comments. The Agency encourages that written comments be submitted, using the instructions in ADDRESSES, no later than July 31, 2007, to provide FIFRA SAP the time necessary to consider and review the written comments. However, written comments are accepted until the date of the meeting. Persons wishing to submit written comments at the meeting should contact the DFO listed under FOR FURTHER INFORMATION CONTACT and submit 30 copies. There is no limit on the extent of written comments for consideration by FIFRA SAP.

2. Oral comments. The Agency encourages that each individual or group wishing to make brief oral comments to FIFRA SAP submit their request to the DFO listed under FOR FURTHER INFORMATION CONTACT no later than August 7, 2007, in order to be included on the meeting agenda. Requests to present oral comments will be accepted until the date of the meeting and, to the extent that time permits, the Chair of the FIFRA SAP may permit the presentation of oral comments at the meeting by interested persons who have not previously requested time. The request should identify the name of the individual making the presentation, the organization (if any) the individual will represent, and any requirements for audiovisual equipment (e.g., overhead projector, 35 mm projector, chalkboard). Oral comments before FIFRA SAP are limited to approximately 5 minutes unless prior arrangements have been made. In addition, each speaker should bring 30 copies of his or her comments and presentation slides for distribution to the FIFRA SAP at the meeting.

3. Seating at the meeting. Seating at the meeting will be on a first-come basis.

4. Request for nominations to serve as ad hoc members of the FIFRA SAP for this meeting. As part of a broader process for developing a pool of candidates for each meeting, the FIFRA SAP staff routinely solicits the stakeholder community for nominations of prospective candidates for service as ad hoc members of the FIFRA SAP. Any interested person or organization may nominate qualified individuals to be considered as prospective candidates for a specific meeting. Individuals nominated for this meeting should have expertise in one or more of the following areas: Dietary and residential exposure modeling, probabilistic exposure assessment, statistics, risk assessment with experience understanding the data needed for risk assessment purposes, how to interpret the data, and issues concerning intra-species and inter-species extrapolation, pharmacokinetics with experience in the development and application of PBPK models, and metabolism with experience in the use of in vitro approaches for species extrapolation. Nominees should be scientists who have sufficient professional qualifications, including training and experience, to be capable of providing expert comments on the scientific issues for this meeting. Nominees should be identified by name, occupation, position, address, and telephone number. Nominations should be provided to the DFO listed under FOR FURTHER INFORMATION CONTACT on or before May 29, 2007]. The Agency will consider all nominations of prospective candidates for this meeting that are received on or before this date. However, final selection of ad hoc members for this meeting is a discretionary function of the Agency.

The selection of scientists to serve on the FIFRA SAP is based on the function of the panel and the expertise needed to address the Agency's charge to the panel. No interested scientists shall be ineligible to serve by reason of their membership on any other advisory committee to a Federal department or agency or their employment by a Federal department or agency except the EPA. Other factors considered during the selection process include availability of the potential panel member to fully participate in the panel's reviews, absence of any conflicts of interest or appearance of lack of impartiality, independence with respect to the matters under review, and lack of bias. Although, financial conflicts of interest, the appearance of lack of impartiality, lack of independence, and bias may result in disqualification, the absence of such concerns does not assure that a candidate will be selected to serve on the FIFRA SAP. Numerous qualified candidates are identified for each panel. Therefore, selection decisions involve carefully weighing a number of factors including the candidates' areas of expertise and professional qualifications and achieving an overall balance of different scientific perspectives on the panel.

In order to have the collective breadth of experience needed to address the Agency's charge for this meeting, the Agency anticipates selecting approximately 10 ad hoc scientists for each topic. FIFRA SAP members are subject to the provisions of 5 CFR part 2634, Executive Branch Financial Disclosure, as supplemented by the EPA in 5 CFR part 6401. In anticipation of this requirement, prospective candidates for service on the FIFRA SAP will be asked to submit confidential financial disclosure information which shall fully disclose, among other financial interests, the candidate's employment, stocks and bonds, and where applicable, sources of research support. The EPA will evaluate the candidates financial disclosure form to assess whether there are financial conflicts of interest, appearance of a lack of impartiality or any prior involvement with the development of the documents under consideration (including previous scientific peer review) before the candidate is considered further for service on the FIFRA SAP. Those who are selected from the pool of prospective candidates will be asked to attend the public meetings and to participate in the discussion of key issues and assumptions at these meetings. In addition, they will be asked to review and to help finalize the meeting minutes. The list of FIFRA SAP members participating at this meeting will be posted on the FIFRA SAP web site at http://epa.gov/​scipoly/​sap or may be obtained from the OPP Regulatory Public Docket at http://www.regulations.gov.

II. Background

A. Purpose of the FIFRA SAP

The FIFRA SAP serves as the primary scientific peer review mechanism of EPA, Office of Prevention, Pesticides and Toxic Substances and is structured to provide scientific advice, information and recommendations to the EPA Administrator on pesticides and pesticide-related issues as to the impact of regulatory actions on health and the environment. The FIFRA SAP is a Federal advisory committee established in 1975 under FIFRA that operates in accordance with requirements of the Federal Advisory Committee Act. The FIFRA SAP is composed of a permanent panel consisting of seven members who are appointed by the EPA Administrator from nominees provided by the National Institutes of Health and the National Science Foundation. FIFRA, as amended by the FQPA of 1996, established a Science Review Board consisting of at least 60 scientists who are available to the Scientific Advisory Panel on an ad hoc basis to assist in reviews conducted by the Panel. As a peer review mechanism, the FIFRA SAP provides comments, evaluations and recommendations to improve the effectiveness and quality of analyses made by Agency scientists. Members of the FIFRA SAP are scientists who have sufficient professional qualifications, including training and experience, to provide expert advice and recommendation to the Agency.

B. Public Meeting

The FQPA amended laws under which EPA evaluates the safety of pesticide residues in food. Section 408(b)(2)(D)(v) and (vi) of the FFDCA as amended by FQPA, specifies that when determining the safety of a pesticide chemical, EPA shall consider aggregate exposure (i.e., total dietary (food and water), residential, and other non-occupational) and available information concerning the cumulative effects to human health that may result from exposure to other substances that have a common mechanism of toxicity.

Pyrethroid pesticides are currently undergoing evaluation to determine if a cumulative risk assessment is warranted for this class of chemicals. As part of this evaluation, EPA will utilize the SHEDS probabilistic model to estimate cumulative exposure to pyrethroid pesticides; also, EPA is developing physiologically-based pharmacokinetic (PBPK) models to aid in quantitatively assessing exposure dose response relationships for individual pyrethroids and mixtures.

The FIFRA SAP will meet to review the following scientific issues:

1. Review of EPA/ORD/NERL's SHEDS-Multimedia Model, aggregate version 3: The purpose of this review is to request input from the SAP on EPA/ORD/NERL's Stochastic Human Exposure and Dose Simulation for Multimedia, Multipathway Pollutants (SHEDS-Multimedia), aggregate version 3. SHEDS-Multimedia version 3 is a state-of-science computer model for simulating human exposures to multimedia, multipathway environmental pollutants including pesticides. It is a physically-based, probabilistic model that predicts, for user-specified population cohorts, exposures incurred via eating contaminated foods or drinking water, inhaling contaminated air, touching contaminated surface residues, and ingesting residues from hand- to-mouth or object- to-mouth activities. To do this, it combines information on chemical usage, human activity data (e.g., from Consolidated Human Activity Database (CHAD) time/activity diary surveys and videography studies), environmental residues and concentrations, and exposure factors to generate time series of exposure for simulated individuals. One-stage or two-stage Monte Carlo simulation is used to produce distributions of exposure for various population cohorts (e.g., age/gender groups) that reflect the variability and/or uncertainty in the input parameters. While the core of SHEDS-Multimedia is the concentration-to-exposure module, there are various options (built-in source-to-concentration module; user-entered time series from other models or field study measurements) for obtaining concentration inputs, and SHEDS-Multimedia exposure outputs can be used as inputs to PBPK models.

Finally, the SHEDS-Multimedia version 3 single chemical model can address many useful aspects of aggregate and cumulative risk assessment, related to population aggregate exposures for different multimedia chemicals and the important contributing pathways and factors. Such information will be useful in identifying populations and exposure scenarios of greatest concern for this class of chemicals. These populations and exposure scenarios will in turn be used to determine the most relevant chemical/pyrethroid combinations for which hazard/exposure factors information will need further development in order to support a PBPK dose modeling approach. EPA plans to extend the current single chemical aggregate version of SHEDS to a cumulative version. The cumulative version of SHEDS will be used to estimate exposure resulting from cumulative exposure to pyrethroid pesticides.

At this meeting, the FIFRA SAP panel will be asked to review the following: The dietary module of SHEDS version 3; the residential module of SHEDS version 3; and planned methodologies for extending SHEDS-Multimedia version 3 (aggregate) to SHEDS-Multimedia version 4 (cumulative).

Review of the dietary module will include the methodology and model evaluation. Review of the residential module will include the SAS code, graphic user interface (GUI), technical manual, and user manual. Review of the planned methodologies to extend the single chemical aggregate version of SHEDS (version 3) to the cumulative version (version 4) will include: Algorithms for multiple chemicals and co-occurrence; fugacity-based module for residential concentration predictions; new methodologies for enhanced longitudinal activity diary simulation; Sobol methodology for enhanced sensitivity analyses; planned approach for combining residential and dietary modules; and planned coding and GUI changes for version 4. The panel members will not be asked to review chemical-specific inputs or evaluate outputs at this SAP meeting.

This SAP review is part of the Agency's ongoing process to enhance probabilistic exposure, dose, and risk assessments, and OPP's ongoing efforts to consider available probabilistic exposure and dose models to address FQPA. To assist the FIFRA SAP in their review, each FIFRA SAP member will be provided technical reports describing the SHEDS-Multimedia version 3 model, annotated SHEDS code, GUI, a user guide for the GUI, a technical document describing planned methodologies for extending version 3 to version 4, and several relevant journal articles for reference.

2. Assessing Approaches for the Development of PBPK Models of Pyrethroid Pesticides: The development of these models offers many challenges, including:

a. As a class, pyrethroid pesticides have many structural similarities such that a “generic” model structure, with chemical specific adjustments as needed, can be developed. Chemical specific parameters are anticipated to include partition coefficients, hepatic clearance rates and others.

b. It is anticipated that the PBPK models will be used for cross-species extrapolation of internal dose metrics for assessing the risk of pyrethroid neurotoxicity. Based on the results of in vivo experiments in rats, blood and brain concentrations of parent compound correlate with pyrethroid toxicity as measured by motor activity; either of these metrics could be a model output for use in a cumulative risk assessment.

c. Pyrethroids may have one or more chiral centers resulting in numerous stereoisomers. There is limited information on the toxicity and pharmacokinetics of the different stereoisomers. EPA proposes to evaluate three modeling assumptions in order to address the uncertainties due to chiral chemistry of the pyrethroids.

d. Finally, there is limited human data to calibrate and evaluate these models for extrapolation to humans. EPA proposes to develop the human model through the use of computational and in vitro experimental approaches using human tissue. To evaluate this approach, EPA plans to develop equivalent rodent and human in vitro databases for metabolic and physiological parameters for use in the PBPK models. The utility of this approach will be assessed by comparing rodent model predictions to in vivo data. It is likely that scaling factors will be used in order to incorporate these in vitro parameters into the rodent model. When calibrating the human data, the scaling factors used in the rodent models will be used in the human models.

The purpose of this review is to request input from the SAP on:

i. The appropriateness of a generic PBPK model,

ii. Potential dose metrics that are relevant for a cumulative risk assessment,

iii. The proposed approach for the incorporation of chiral chemistry into model structure, and

iv. The proposed approach for developing these models with limited human dosimetry data. Planned methodologies for linking exposure to PBPK will also be discussed.

C. FIFRA SAP Documents and Meeting Minutes

EPA's background paper, related supporting materials, charge/questions to the FIFRA SAP, FIFRA SAP composition (i.e., members and ad hoc members for this meeting), and the meeting agenda will be available by late July. In addition, the Agency may provide additional background documents as the materials become available. You may obtain electronic copies of these documents, and certain other related documents that might be available electronically, at http://www.regulations.gov and the FIFRA SAP homepage at http://www.epa.gov/​scipoly/​sap.

The FIFRA SAP will prepare meeting minutes summarizing its recommendations to the Agency approximately 90 days after the meeting. The meeting minutes will be posted on the FIFRA SAP web site or may be obtained from the OPP Regulatory Public Docket at http://www.regulations.gov.

List of Subjects

• Environmental protection
• Pesticides and pests

Dated: May 10, 2007.

Clifford J. Gabriel,

Director, Office of Science Coordination and Policy.