[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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