82 FR 26086 - FIFRA Scientific Advisory Panel; Notice of Public Meeting; Request for Ad Hoc Expert Nominations

ENVIRONMENTAL PROTECTION AGENCY

Federal Register Volume 82, Issue 107 (June 6, 2017)

There will be a 4-day meeting of the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP) to consider and review physiologically based pharmacokinetic modeling to address pharmacokinetic differences between and within species.

[Federal Register Volume 82, Number 107 (Tuesday, June 6, 2017)]
[Notices]
[Pages 26086-26089]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2017-11697]


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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPP-2017-0180; FRL-9962-78]


FIFRA Scientific Advisory Panel; Notice of Public Meeting; 
Request for Ad Hoc Expert Nominations

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: There will be a 4-day meeting of the Federal Insecticide, 
Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP) to 
consider and review physiologically based pharmacokinetic modeling to 
address pharmacokinetic differences between and within species.

DATES: The meeting will be held on October 24, 2017 to October 27, 
2017, from approximately 9 a.m. to 5 p.m.
    Comments. Written comments should be submitted on or before 
September 11, 2017. FIFRA SAP may not be able to fully consider written 
comments submitted after September 11, 2017. Requests to make oral 
comments should be submitted on or before September 25, 2017 by 
contacting the Designated Federal Official (DFO) listed under FOR 
FURTHER INFORMATION CONTACT. For additional instructions, see Unit I.C. 
of the SUPPLEMENTARY INFORMATION.
    Nominations. Nominations of candidates to serve as ad hoc members 
of FIFRA SAP for this meeting should be provided on or before July 21, 
2017.
    Webcast. This meeting may be webcast. Please refer to the FIFRA SAP 
Web site at https://www.epa.gov/sap for information on how to access 
the webcast. Please note that the webcast is a supplementary public 
process provided only for convenience. If difficulties arise resulting 
in webcasting outages, the meeting will continue as planned.
    Special accommodations. For information on access or services for 
individuals with disabilities, and to request accommodation of a 
disability, please contact the DFO listed under FOR FURTHER INFORMATION 
CONTACT at least 10 days prior to the meeting to allow EPA time to 
process your request.

ADDRESSES: Meeting: The meeting will be held at the Environmental 
Protection Agency, Conference Center, Lobby Level, One Potomac Yard 
(South Bldg.), 2777 S. Crystal Dr., Arlington, VA 22202.
    Comments. Submit your comments, identified by docket identification 
(ID) number EPA-HQ-OPP-2017-0180, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the online

[[Page 26087]]

instructions for submitting comments. Do not submit electronically any 
information you consider to be Confidential Business Information (CBI) 
or other information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at http://www.epa.gov/dockets/contacts.html.
    Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at http://www.epa.gov/dockets.
    Nominations, requests to present oral comments, and requests for 
special accommodations. Submit nominations to serve as ad hoc members 
of FIFRA SAP, requests for special accommodations, or requests to 
present oral comments to the DFO listed under FOR FURTHER INFORMATION 
CONTACT.

FOR FURTHER INFORMATION CONTACT: Dr. Marquea D. King, DFO, Office of 
Science Coordination and Policy (7201M), Environmental Protection 
Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; 
telephone number: (202) 564-3626; email address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    This action is directed to the public in general. This action may 
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) and FIFRA. 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.

B. What should I consider as I prepare my comments for EPA?

    1. Submitting CBI. Do not submit CBI information to EPA through 
regulations.gov or email. 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 
instructions before submitting your comments.
    2. Tips for preparing your comments. When preparing and submitting 
your comments, see the commenting tips at http://www.epa.gov/dockets/comments.html.

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-2017-0180 in the subject line 
on the first page of your request.
    1. Written comments. Written comments should be submitted, using 
the instructions in ADDRESSES and Unit I.B., on or before September 11, 
2017, to provide FIFRA SAP the time necessary to consider and review 
the written comments. FIFRA SAP may not be able to fully consider 
written comments submitted after September 11, 2017.
    2. Oral comments. The Agency encourages each individual or group 
wishing to make brief oral comments to FIFRA SAP to submit their 
request to the DFO listed under FOR FURTHER INFORMATION CONTACT on or 
before September 25, 2017, in order to be included on the meeting 
agenda. Requests to present oral comments will be accepted until 
September 25, 2017 and, to the extent that time permits, the Chair of 
FIFRA SAP may permit the presentation of oral comments at the meeting 
by interested persons who have not previously requested time. Oral 
comments before FIFRA SAP are limited to approximately 5 minutes unless 
arrangements have been made prior to September 25, 2017. 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. In addition, each speaker 
should bring 15 copies of his or her oral remarks and presentation 
slides (if required) for distribution to FIFRA SAP at the meeting by 
the DFO.
    3. Seating at the meeting. Seating at the meeting will be open and 
on a first-come basis.
    4. Request for nominations to serve as ad hoc expert members of 
FIFRA SAP for this meeting. As part of a broader process for developing 
a pool of candidates, both U.S. citizens and permanent residents who 
can demonstrate that they are actively seeking U.S. citizenship will be 
considered. For each meeting, FIFRA SAP staff routinely solicits the 
stakeholder community for nominations of prospective candidates for 
service as ad hoc members of 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: Physiologically-based pharmacokinetic (PBPK) modeling, 
pharmacokinetics, pharmacodynamic (PD) modeling, in vitro to in vivo 
extrapolation, human health risk assessment, neurotoxicity, 
organophosphate pesticides, pyrethroids pesticides, N-methyl carbamate 
pesticides, fungicides, acetylcholinesterase inhibition, and exposure 
assessment. 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, email address, and telephone number. Nominations should be 
provided to the DFO listed under FOR FURTHER INFORMATION CONTACT on or 
before July 21, 2017. The Agency will consider all nominations of 
prospective candidates for this meeting that are received on or before 
that 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 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 EPA. Other factors considered during the 
selection process include availability of the potential Panel member to 
fully participate in the Panel's review, 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 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 peer review charge for this meeting, the Agency 
anticipates selecting approximately 13 ad hoc scientists.

[[Page 26088]]

    FIFRA SAP members are subject to the provisions of 5 CFR part 
2634--Executive Branch Financial Disclosure, Qualified Trusts, and 
Certificates of Divestiture, as supplemented by EPA in 5 CFR part 6401. 
In anticipation of this requirement, prospective candidates for service 
on FIFRA SAP will be asked to submit confidential financial information 
which shall fully disclose, among other financial interests, the 
candidate's employment, stocks, and bonds, and where applicable, 
sources of research support. EPA will evaluate the candidate's 
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 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 and the final 
meeting report. The list of FIFRA SAP members participating at this 
meeting will be posted on the FIFRA SAP Web site at https://www.epa.gov/sap or may be obtained from the OPP Docket at http://www.regulations.gov.

II. Background

A. Purpose of FIFRA SAP

    FIFRA SAP serves as the primary scientific peer review mechanism of 
EPA's Office of Chemical Safety and Pollution Prevention (OCSPP) 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. FIFRA SAP is a Federal advisory committee established in 
1975 under FIFRA that operates in accordance with requirements of the 
Federal Advisory Committee Act (5 U.S.C. Appendix). 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. The 
FIFRA SAP is assisted in their reviews by ad hoc participation from the 
Science Review Board (SRB). As a scientific peer review mechanism, 
FIFRA SAP provides comments, evaluations, and recommendations to 
improve the effectiveness and quality of analyses made by Agency 
scientists.

B. Public Meeting

    The 2009 National Research Council's report ``Science and 
Decisions'' recommends that the EPA use the best, most current science 
to support or revise the default assumptions in risk assessment. In 
addition, the 2013 Institute of Medicine's report on ``Environmental 
Decisions in the Face of Uncertainty'' further recommends that 
replacing default uncertainty factors with data-derived extrapolation 
factors (DDEFs) that delineate the differences between species would 
reduce uncertainty in risk assessment. Such inter- and intra-species 
extrapolation factors can be derived using a PBPK modeling approach to 
organize mechanistic data on properties that determine the absorption, 
distribution, metabolism, and excretion (ADME) of chemicals that enter 
the body. In the 2006 document on ``Approaches for the Application of 
Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data 
in Risk Assessment'', the Agency recognizes that PBPK model analysis is 
a scientifically sound approach that allows for estimating the internal 
dose of a chemical or its metabolite at a target site, and can act as a 
means to evaluate and describe the uncertainty in a risk assessment.
    PBPK models incorporate the relevant physiology, chemistry, 
biochemistry that determines the ADME processes, and thus, they are 
useful for predicting internal dosimetry related to a certain chemical 
within and outside the testing conditions (e.g., species, dose ranges). 
PBPK models have been used to assist high-to-low dose, route-to-route, 
aggregation of exposure from multiple routes, and inter-species 
extrapolations that are necessary for estimating human health risks 
based on the results of animal toxicity studies. The physiological 
structure of PBPK models also allows for examining the effects of 
changing physiology, such as aging, early life-stage, or pregnancy. The 
temporal change in the dose metric simulated by a PBPK model can also 
be linked to a PD model to predict quantitative changes in biological 
effects, such as acetylcholinesterase (AChE) inhibition.
    Several registrants, including the Council for the Advancement of 
Pyrethroid Human Health Risk Assessment (CAPHRA), Tessenderlo Kerley 
Inc. (TKI), FMC/Cheminova, and Syngenta, are developing PBPK (or PBPK-
PD) models for the chemicals: Acibenzolar, carbaryl, deltamethrin, 
dimethoate, malathion, and permethrin. All six models will include 
life-stage physiological changes from birth to adulthood, so that dose 
metrics can be predicted at any age. These life-stage models, however, 
will not include gestation and lactational phases, therefore; it is not 
expected that these models will have the capability to predict dose 
metrics in pregnant women or fetuses or breastfeeding exposures. These 
models are intended as a means to estimating inter- and intra-species 
data derived extrapolation factors and/or human points of departure 
(PoD) for various exposure scenarios (e.g., routes of exposure). For 
dimethoate, malathion, and carbaryl, the PBPK models will be coupled 
with PD models to predict AChE inhibition in red blood cells (RBCs) and 
other tissues (e.g., brain).
    The purpose of the October 2017 SAP will be to review five PBPK or 
PBPK-PD models (carbaryl, deltamethrin, dimethoate, malathion, and 
permethrin) for the purposes of model structures, mathematical 
representations, parameter estimations, computer implementations, 
variability and uncertainty analysis, and model predictive 
capabilities, as well as the appropriateness of their applications in 
human health risk assessments. The details for each model, including 
their inputs, parameters and associated distributions, and the model 
code, written in software program acslX or R, will be provided for five 
(not including acibenzolar) chemicals as part of the background 
materials for the meeting. The agency will solicit comments from the 
SAP members on the evaluation of these PBPK (or PBPK-PD) models 
regarding their capability to predict appropriate internal dose metrics 
in humans. In addition, the SAP members will be asked to evaluate the 
appropriateness of using these models for intended risk assessment 
purposes, such as deriving chemical-specific DDEFs to replace default 
uncertainty factors, or estimating human PoDs for various exposure 
scenarios (e.g., dietary, drinking water, and worker exposures). 
Finally, the SAP members will be asked to comment on the potential for 
using these models as a basis for extrapolation to other chemicals 
within the same chemical class.
    For the sixth PBPK model (acibenzolar), developed in Simcyp, 
details including inputs, parameters and associated distributions, will 
be provided as background materials. The SAP members, however, will not 
be asked to review the Simcyp model code. Instead, the agency will 
solicit comments from the SAP members as a consultation on this model 
as primarily

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a proof-of-concept study, highlighting newer in vitro and in silico 
based approaches. This model is not anticipated to be used in a risk 
assessment by the Agency.

C. FIFRA SAP Documents and Meeting Minutes

    EPA's background paper, charge/questions to FIFRA SAP, and related 
supporting materials will be available on or before August 11, 2017. In 
addition, a list of candidates under consideration as prospective ad 
hoc panelists for this meeting will be available for public comment by 
mid to late August (see link for listing of nominees to appear in mid 
to late August at https://www.epa.gov/sap). Comments should be provided 
to the DFO listed under FOR FURTHER INFORMATION CONTACT on or before 
the deadline listed on the Web site given above. Your comments will be 
placed in the public docket by the DFO. You may obtain electronic 
copies of most meeting documents, including FIFRA SAP composition 
(i.e., members and ad hoc members for this meeting) and the meeting 
agenda, at http://www.regulations.gov and the FIFRA SAP Web site at 
https://www.epa.gov/sap.
    FIFRA SAP will prepare meeting minutes summarizing its 
recommendations to the Agency approximately 90 days after the meeting. 
The meeting minutes and final report will be posted on the FIFRA SAP 
Web site or may be obtained from the OPP Docket at http://www.regulations.gov.

    Authority: 7 U.S.C. 136 et. seq.; 21 U.S.C. 301 et seq.

    Dated: May 25, 2017.
Stanley Barone Jr.,
Director, Office of Science Coordination and Policy.
[FR Doc. 2017-11697 Filed 6-5-17; 8:45 am]
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