[Federal Register Volume 63, Number 101 (Wednesday, May 27, 1998)]
[Notices]
[Pages 29008-29011]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-13993]
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ENVIRONMENTAL PROTECTION AGENCY
[FRL-6102-7]
Science Advisory Board, Environmental Health Committee;
Notification of Public Meeting, June 9-10, 1998
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: Pursuant to the Federal Advisory Committee Act, Pub. L. 92-
463, notification is hereby given that the Environmental Health
Committee (EHC) (henceforth, the ``Committee'') of the Science Advisory
Board (SAB) will meet on Tuesday June 9 and Wednesday June 10, 1998,
beginning no earlier than 8:30 am and ending no later than 5:00 pm on
each day. The meeting will be held in the Main Auditorium, U.S. EPA,
Environmental Research Center, Route 54 and Alexander Drive, Research
Triangle Park, North Carolina 27711. The meeting is open to the public,
however, due to limited space, seating will be on a first-come basis.
The purpose of the meeting is for the Committee to review: (a) Case
studies on the application of the Inhalation Reference Concentrations
(RfC) Methods; and (b) the Acute Reference Exposure Methodology (ARE).
Both the RfC Methods and the ARE Methods were developed by the U.S. EPA
Office of Research and Development (ORD), National Center for
Environmental Assessment (NCEA).
Charge for the RfC Methods Case Studies Review
The Methodology document provides the general conceptual framework
for evaluation of inhalation toxicity, as well as the specifics and
operational procedures for this evaluation. The procedures of the
methodology will continue to develop as the state-of-science changes.
The general charge to the Committee is to conduct a review on the
utility of the conceptual framework through examination of case studies
of chemicals across various types of agents (particle versus gas
category) and data base (human versus laboratory animal; incomplete or
comprehensively complete). The Committee is also charged to comment on
specific aspects
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of this framework, notably, consistency in the conceptual approach
regarding: hazard identification; designation of effect levels; choice
of critical effect; choice of principal study; duration and dosimetry
adjustment; response modeling; application of UF; and characterization
of uncertainty (confidence statements).
The Committee has also been asked to comment on the level of
documentation used to support RfC estimates. In addition, the Committee
has been asked to respond to the following specific questions: (a)
Overall, are the concepts and applications of the RfC methodology
clearly articulated in the documentation provided for the case studies?
Do the decisions and choices in these files attain the Agency's goal of
being ``transparent, clear, and reasonable''? If not, what are specific
examples within these files that could be instituted to better attain
this goal?; (b) In derivation of the RfC in the specific case studies,
(1) are the study summaries presented in sufficient detail for reader
evaluation?, (2) are the designations of the critical effect and
effects levels (NOAEL/LOAEL/BMC) based on rationales that are clear and
reasonable?, (3) of the studies presented in either the IRIS Summary or
Toxicological Review of each chemical, has the Principal study/ies been
selected in a consistent and rational manner? Does this choice reflect
consideration on the current knowledge of potential human response?,
(4) have the underlying assumptions of the duration and dosimetry
adjustments been presented clearly?, (5) are the rationales presented
for use of uncertainty factors clear, reasonable and consistent?, (6)
do the confidence statements reflect the strengths and limitations
(e.g., relevancy to humans, comprehensiveness of the data base) of the
RfC assessment in a manner consistent with the Agency's goals?; and (c)
In the IRIS Summaries for the specific cases, numerous studies are
included under the heading ``Supporting/Additional Studies'' that are
meant to provide further support for designation of the critical effect
(e.g., mechanistic data, human data) or for the effect level chosen in
the Principal study, or to establish the completeness of the data base.
Is the depth of presentation in this section sufficiently comprehensive
to provide information supportive of the decisions made in the
assessment (such as uncertainty factors and confidence levels)?
Charge for the Acute Reference Exposure Methods Review
The Committee has been asked to respond to the following Charge
questions for the Acute Reference Exposure Methodology review: (a) The
ARE methodology recommends three approaches for deriving ARE values and
describes the types and amount of data that should be used to support
each approach. Are these approaches appropriate for deriving acute
exposure values? Are the recommendations for types and amount of data
appropriate?; (b) The ARE methodology recommends using dosimetric
adjustments to derive human equivalent concentrations from animal
exposures. The ARE methodology departs from the RfC methodology by
recommending default dosimetric adjustment factors of one for all
categories of gases. For particulates, the same adjustments used for
developing RfCs are recommended. Does the documentation provide
sufficient rationale for these recommendations? If not, please comment
on the elements that are lacking. Are the recommended dosimetric
adjustments applicable to acute exposure scenarios? If not, please
recommend dosimetric adjustments that are more applicable to acute
exposures; (c) The categorical regression option of the ARE methodology
involves assigning ordinal severity categories to effect data from
toxicity studies that use a variety of species, exposure concentrations
and exposure durations. Regression analysis is then used to relate the
severity of response to exposure concentration and duration for the
entire array of data. For determining the severity category of acute
health effects, the ARE methodology document recommends using
toxicological judgment rather than a well-defined scheme as schemes are
unlikely to be applicable to a variety of toxic endpoints. Is the
expert system for categorizing severity sufficient? If not, how can it
be improved?; (d) The ARE methodology recommends using severe effect
data, including lethality, for the categorical regression approach, but
advises against using lethality and other nonsensitive endpoints when
using No-Observed-Adverse-Effect Level (NOAEL) and benchmark
concentration approaches. The categorical regression model uses severe
effect data to determine the slopes of the probability curves for each
severity, the intercepts for the curves and the distance between the
various severity curves. Is the guidance offered for including lethal
and severe effect data for ARE derivation sufficient? Can the Committee
suggest ways in which severe effect data could be better utilized?; (e)
CatReg software allows individual data and data reported as group
information to be combined in a single analysis. The CatReg Software
User Manual offers three alternatives for placing group and individual
data on ``equal footing'': the use of a scaling factor, g; converting
individual data to group data; and estimating individual responses from
group information. No alternative is described as preferred. Does the
Committee have an opinion as to which alternative may be preferable?;
(f) In categorical regression, the rules of probability constrain the
probability curves for the various severities to be parallel. Although
parallelism is a mathematical constraint, it implies the biological
interpretation that similar mechanisms of action and kinetics are
active in all severity categories. Does the Committee view this as a
limitation to the categorical regression approach? If so, how should
the use of categorical regression be constrained?; and (g) Of the
approaches recommended for ARE derivation, categorical regression is
the only approach for which duration extrapolation is not required. The
NOAEL and benchmark dose/concentration methods (BMC) approaches can
only be applied to exposure durations for which data are available.
AREs for other exposure durations must be derived by duration
extrapolations. AREs for other exposure durations must be derived by
duration extrapolations. For extrapolation from short duration values
to longer durations, a concentration x time adjustment is recommended.
For extrapolations from long durations to shorter durations, use of the
same concentration identified at the longer duration is recommended.
These are conservative duration adjustments. Are these duration
adjustments appropriate for the approaches to which they are applied?
Can the Committee suggest other adjustments that may be more
appropriate?
Background for RfC Methods Case Studies Review
The Clean Air Act Amendments (CAAA) of 1990 require sources to
demonstrate negligible risk and lack of residual risk (after
implementation of control technology) based on health risk estimates.
Inhalation Reference Concentrations (RfCs) are developed as dose-
response estimates for noncancer effects. The RfC is an estimate (with
uncertainty spanning perhaps an order of magnitude) of a daily
inhalation exposure to the human population (including sensitive
subgroups) that is
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likely to be without an appreciable risk of deleterious noncancer
effects during a lifetime. It is anticipated that RfCs will be used for
CAAA regulatory activities as a part of the determination of negligible
and residual risk for noncancer health effects of air toxics.
Additionally, Regional, State and local air pollution control offices
utilize RfC values in risk management programs.
The inhalation RfC methodology was developed according to the oral
reference dose (RfD) paradigm with an added emphasis on portal-of-entry
considerations of comparative toxicity and inhalation dosimetry for
particles and gases. Extrapolation modeling was added in which factors
are derived for adjustment of exposure concentrations that account for
dosimetric differences between experimental animal species and humans.
The methodology is considered to be a ``living'' document. Previous
versions have undergone external peer review, including an expert peer
review in October 1987 and a Science Advisory Board review in 1990
(EPA-SAB-EC-91-008). The current version of the methodology (Methods
for Derivation of Inhalation Reference Concentrations and Application
of Inhalation Dosimetry, EPA/600/8-90/066F, October 1994) represents
the Agency's response to comments made at the 1990 SAB review including
revisions to allow flexibility in the methods employed for dosimetry
adjustments that reflect the state-of-the-science such as substitution
of ``optimal'' approaches (e.g., PB-PK) when validated models are
available. The current version of the Methodology and a category scheme
for gases was reviewed by two additional external workgroups in August
and September 1993. Revisions are already underway in the dosimetry
adjustments to allow for contemporary mechanistic data to inform the
choice of alternative dose metrics across noncancer and cancer
toxicities where appropriate.
At its review of the inhalation methodology, the SAB requested the
opportunity to review case studies using the methods to demonstrate the
application of the dosimetric adjustments and to illustrate the
methodology applied to chemicals representative of the typical range of
data available including those with human occupational or clinical
information and those with databases considered to be insufficient for
quantitative dose-response estimation (``not-verifiable''). The review
requested by the SAB is not intended to be a review of the RfC methods
themselves but rather one of the conceptual framework of the approach
as applied to representative data. The accompanying documents and
related references (Jarabek, 1994; 1995a,b) provide definitions of
uncertainty factors and details on the RfC derivation procedures. Case
studies will be presented in one of four groups: (1) Particle case
studies, (2) category 1 gas case studies, (3) category 3 gas case
studies, and (4) not-verifiable case studies.
Another concern that had been voiced in a 1990 EHC report to the
Agency (EPA-SAB-EHC-90-005) regarding the RfD Methodology was the
reliance on the NOAEL/LOAEL approach for designation of the effect
levels used in the derivation. Since that time, the Agency has
advocated the use of the benchmark dose/concentration (BMD/C) approach
as preferred or at least complimentary to the NOAEL/LOAEL approach (The
Use of the Benchmark Dose Approach in Health Risk Assessment, EPA/630/
R-94/007, February 1995) when the data allow. Some of the case studies
to be reviewed (MDI, phosphoric acid, antimony trioxide, carbon
disulfide) present BMC analyses.
Background documentation describing the derivation of the RfC for
each of the chemical files has been provided. In some cases this is
embodied by the IRIS Summary (i.e., on-line IRIS file) alone. The newer
files (1997 and 1998) are accompanied by a Toxicological Review from
which the actual on-line IRIS assessments are derived in addition to
the summary sheet. The complete IRIS file for the compounds reviewed
(and any other compound on IRIS) is available at http://www.epa.gov/
iris. The differences in level of documentation reflect changes made
during a pilot program of the Integrated Risk Information System (IRIS)
process which will be described at the meeting and is reviewed in Mills
and Foureman (1998).
Background for Acute Reference Exposure Methods Review
Risk assessment for acute inhalation exposures has been hampered by
the lack of acute toxicity values on which to base an evaluation of
exposure. In an effort to provide toxicity values for acute noncancer
risk assessment for inhalation exposures, the U.S. EPA National Center
for Environmental Assessment has developed a methodology for Agency use
to perform dose-response assessments for noncancer effects due to acute
inhalation exposures. The methodology describes how to derive chemical-
specific acute exposure benchmarks called acute reference exposures
(AREs). These estimates, applicable to single continuous exposures for
up to 24 hours, will have wide applicability in assessing potential
health risks due to short-term exposures to airborne chemicals in the
environment. As they are developed and reviewed, AREs will be available
to the public in chemical-specific files found in U.S. EPA's Integrated
Risk Information System (IRIS) database.
The methodology document, Methods for Exposure-Response Analysis
for Acute Inhalation Exposure to Chemicals, Development of Acute
Reference Exposure, has undergone both internal and external peer
review and was revised accordingly. The supplementary documents, CatReg
Software Documentation and CatReg Software User Manual, were developed
subsequent to the external peer review and have undergone internal peer
review and revision.
For Further Information
Copies of the review document and any background materials for the
review (with the exception of the SAB reports) are not available from
the SAB. Copies of SAB prepared reports mentioned in this FR Notice may
be obtained from the SAB's Committee Evaluation and Support Staff at
(202) 260-4126, or via fax at (202) 260-1889. Please provide the SAB
report number when making a request.
Requests for individual copies of the background material for the
RfC Methods Case Studies review should be directed to Ms. Annie Jarabek
by telephone (919) 541-4847, by fax (919) 541-1818 or via Email at:
[email protected]. Technical questions about the RfC Methods Case
Studies review should also be directed to Ms. Annie Jarabek, National
Center for Environmental Assessment-RTP, Mail Drop 52, U.S. EPA,
Research Triangle Park, NC 27711.
Requests for individual copies of the background material for the
Acute Reference Exposure review should be directed to Dr. Judy
Strickland by telephone (919) 541-4930, by fax (919) 541-0245 or via
Email at: [email protected]. Technical questions about the Acute
Reference Exposure Methods should also be directed to Dr. Judy
Strickland, National Center for Environmental Assessment-RTP, Mail Drop
52, U.S. EPA, Research Triangle Park, NC 27711.
Members of the public desiring additional information about the
meeting, including an agenda, should contact Ms. Mary Winston,
Committee Operations Staff, Science Advisory Board (1400), U.S. EPA,
401 M Street,
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SW, Washington DC 20460, by telephone (202) 260-4126; fax (202) 260-
7118; or via Email at: [email protected]
Anyone wishing to make an oral presentation at the meeting must
contact Ms. Roslyn Edson, Acting Designated Federal Officer for the
EHC, in writing, no later than 5:00 p.m. Eastern Time on June 4, 1998,
by fax (202) 260-7118, or via Email at: [email protected] The
request should identify the name of the individual who will make the
presentation and an outline of the issues to be addressed. At least 35
copies of any written comments to the Committee are to be given to Ms.
Edson no later than the time of the presentation for distribution to
the Committee and the interested public. For questions concerning the
review, Ms. Edson can be contacted at (202) 260-3823.
Providing Oral or Written Comments at SAB Meetings
The Science Advisory Board expects that public statements presented
at its meetings will not repeat previously submitted oral or written
statements. In general, each individual or group making an oral
presentation will be limited to a total time of ten minutes. This time
may be reduced at the discretion of the SAB, depending on meeting
circumstances. Oral presentations at teleconferences will normally be
limited to three minutes per speaker or organization. Written comments
(at least 35 copies) received in the SAB Staff Office sufficiently
prior to a meeting date, may be mailed to the relevant SAB committee or
subcommittee prior to its meeting; comments received too close to the
meeting date will normally be provided to the committee at its meeting.
Written comments, which may be of any length, may be provided to the
relevant committee or subcommittee up until the time of the meeting.
Individuals requiring special accommodation, including wheelchair
access, should contact Ms. Edson at least five business days prior to
the meeting so that appropriate arrangements can be made.
Dated: May 15, 1998.
Donald G. Barnes,
Staff Director, Science Advisory Board.
[FR Doc. 98-13993 Filed 5-26-98; 8:45 am]
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