United States
Environmental Protection
Agency
Environmental Criteria and
Assessment Office
Cincinnati, OH 45268
Research and Development
EPA/600/S9-85/027 Aug. 1986
SERA Project Summary
Workshops for the
Development of Methodology for
Health Risk Assessment
Jerry Stara and Linda Erdreich
On September 29-30,1982 and July
11-12,1983, fifty environmental scien-
tists from industry, academia, and the
U.S. Environmental Protection Agency
(EPA) met in Cincinnati to explore
methods to assess the risks to human
health from exposure to multiple chem-
ical pollutants. In two workshops spon-
sored by EPA's Cincinnati-based Envi-
ronmental Criteria and Assessment
Office (ECAO), the scientists examined
all relevant routes and durations of
exposure to update and expand the
single-chemical risk assessment meth-
ods developed by ECAO.
The first workshop investigated a
wide range of possible approaches to
assessing risks from exposure to multi-
ple chemicals. The second workshop
was limited to a discussion of five
methods to evaluate risks identified in
the first workshop as having the most
potential for early application, including
interspecies conversions, less-than-life-
time exposure, and role of pharmaco-
kinetic data.
This Project Summary was developed
by EPA's Environmental Criteria and
Assessment Office. Cincinnati, OH, to
announce key findings of the research
pro/act that is fully documented in three
separate reports (see Project Report
ordering information at back).
Introduction
The U.S. EPA's Environmental Criteria
and Assessment Office (ECAO) in Cincin-
nati sponsored two workshops in 1982
and 1983 to bring together scientists
from government, industry, and academia
to review and discuss methods for health
risk assessment of chemical mixtures. An
important secondary purpose of these
meetings was to revise and add to the
previously published health assessment
guidelines (Federal Register, 1980) for
assessing the chronic or lifetime health
risk of single contaminants so that the
more complex questions associated with
exposure to chemical mixtures could be
addressed.
EPA's interest in the development of
risk assessment methodology for multiple
chemicals stems from recognition of the
nature of actual exposures. The Agency
has already regulated public exposure to
several mixtures including coke-oven
emissions and auto and diesel exhaust.
Now, with the implementation of Super-
fund, the Agency must develop methods
for determining the risks posed by thou-
sands of unregulated sites in order to set
priorities and direct cleanup efforts. In
addition, the Agency must respond to
imminent hazards posed by chemical
spills, and toward that goal, ECAO has
developed a rapid response assessment
system. Toxicity data are stored in a
computer and used to make an assess-
ment that can be provided to state or
regional officials within 48 hours. Multi-
chemical assessments also have a role in
other emergency response and remedial
action activities such as determining the
reduction in risk after a cleanup of a
hazardous site. All EPA programs are
often dealing with mixtures rather than
single pollutants.
-------
Approaches to Risk Assessment
for Multiple Chemical
Exposures Workshop,
September 29-30,1982
The developing methodology for assess-
ing risks from exposure to multiple chem-
icals is based on the current methodology
for identifying effects of chronic exposure
to a single chemical from a single route.
The ECAO in Cincinnati developed
original methods for deriving ambient
water quality criteria and for conducting
risk assessments on a specific group of
solvents. The methodology for deriving
ambient water quality criteria focused on
chronic exposure to a single chemical
from a single route of exposure. The
solvent methodology expanded this ap-
proach to consider the effects of a single
chemical by all relevant routes of ex-
posure (oral, dermal, and inhalation) and
for all exposure durations (acute, short-
term, subchronic, and chronic). In both
methodologies, risk assessments for car-
cinogens associated an exposure level
with a particular incidence of cancer
using a nonthreshold model that is linear
at low doses. Risk assessments for sys-
temic toxicants use a threshold model
deriving an estimated acceptable daily
intake (ADI) by dividing the no-observed-
adverse-effect level (NOAEL) by some
uncertainty factors.
The new methodology examined in the
first workshop, when fully developed, will
be used to assess risks in specific haz-
ardous sites. Ideally, the methodology
developed will be used to estimate from
the available exposure data, the types of
health effects that might be expected, the
incidence of these effects, and an est-
imate of the relative hazard of each site.
Thus, some of the major areas for meth-
odology development include a reason-
able approach for multiple chemical ex-
posures, a system for combining weighing
adverse effects, and the selection of a
reasonable extrapolation model for toxic
effects.
These and other relevant issues were
addressed during the first workshop held
on September 29 and 30,1982. As shown
in the listing below, the first day of the
workshop focused on the subject of "Sys-
temic Toxicants" (noncarcinogenic ef-
fects). Presentations were made on seven
aspects of this topic. Each presentation
was followed by prepared critiques from
other attendees and then by a discussion
session. Presentations on the second day
of the workshop addressed four aspects
of the subject of health assessment of
exposures to chemical mixtures.
Systemic Toxicants
(September 29, 1982)
1. Acceptable Daily Intake
2. Interspecies Conversion of Dose
and Duration of Exposure
3. Risk Assessment for Less-Than-
Lifetime Exposure
4. Incidence and/or Severity of Effects
5. Route-to-Route Extrapolation and
the Pharmacokinetic Approach
6. Multiple Route Exposures
7. The Impact of Carcinogens in Risk
Assessment of Chemical Mixtures
Health Assessment of
Exposures to Chemical Mixtures
(September 30, 1982)
1. Outline of Issues and Review of
Present Approaches
2. Assessment of Exposure
3. Subpopulations at Greater Risk
4. Biological Bases of Toxicant Inter-
actions and Mathematical Models
Selected Approaches to
Risk Assessment for Multiple
Chemical Exposures: Progress
Report on Guideline
Development at ECAO-
Cincinnati—Workshop.
July 11-12. 1983
The primary objective of this workshop
was to encourage discussions of the
development and implementation of mul-
tiple chemical assessment methodology.
To provide structure to these discussions,
the meeting was divided into three ses-
sions.
In Session I, specific selected ap-
proaches were proposed for five subjects
discussed in the September 1982 work-
shop. During Session I of the July 1983
meeting, discussion focused on whether
or not the approach was acceptable as
stated. If not, an attempt was made to
amend the approach to achieve consen-
sus or to clearly identify remaining prob-
lems or disagreements.
The following topics were presented for
consensus: interspecies conversion of
dose and duration of exposure; calcula-
tion of risk for partial-lifetime exposure to
carcinogens or toxicants; calculation of
ADIs based on quanta), continuous, or
graded response data; pharmacokinetic
approaches that can be used for conver-
sion among various exposure routes; and
methods for multichemical assessment.
In Session II, several new topics were
presented that had not been previously
discussed or had been only touched upon
in previous meetings. Presentation of
brief outlines of the issues was followed
by discussion to elicit comments from
participants about the direction develop-
ment that these issues should follow. New
topics included the use of structure-activ-
ity relationships, special methods for
reproductive endpoints, and use and
biological justification of mathematical
models.
In Session III, issues introduced at
previous meetings, but needing further
development, were discussed in four
workgroups. Invited scientists and the
ECAO staff discussed the strengths and
limitations of alternative approaches in
order to develop guidelines. The objec-
tives of this session were eventual de-
velopment of scientifically defensible
approaches reflecting current knowledge
and identification of options that reflected
consensus.
The following topics were discussed in
the three sessions of the July 11-12,
1983 workshop:
Consensus Topics (Session I)
1. Interspecies Conversion of Dose
and Duration of Exposure—Noncar-
cinogenic Toxicants
2. Health Risk Assessment for Less-
Than-Lifetime Exposure—Toxi-
cants and Carcinogens
3. ADIs Based on Quanta), Contin-
uous or Graded Data
4. Pharmacokinetic Approach for Route-
to-Route Conversion
5. Multiple Chemical Assessment
Presentation of New Topics
(Session II)
1. Approaches Using Structure-Activ-
ity Relationships
2. Use of Reproductive Effects as
Endpoints in Risk Assessment
3. Use and Biological Justification of
Mathematical Models
Workshops (Session III)
1. Consideration of High Risk (Sensi-
tive) Subgroups in Health Risk
Assessment
2. Assessment of Multiple Route Ex-
posure
3. Ranking the Severity of Effects
4. Use of Exposure Data in Assessing
Health Risk
-------
The EPA authors Jerry F. Stars and Linda S. Erdnich are with the Environmental
Criteria and Assessment Office, Cincinnati. OH 45268.
This Project Summary covers three separate reports, entitled:
"Approaches to Risk A ssessment for Multiple Chemical Exposures," (Order No.
PB 84-182 369; Cost: $22.95, subject to change)
"Selected Approaches to Risk Assessment for Multiple Chemical Exposures:
Progress Report on Guideline Development at ECAO-Cin," (Order No. PB 84-
226 992; Cost: $16.95, subject to change)
"Selected Approaches to Risk Assessment for Multiple Chemical Exposures:
Appendix," (Order No. PB 84-227 008; Cost: $ 16.95, subject to change)
The above reports will be available only from:
National Technical Information Service
5285 Port Royal Road
Springfield. VA 22161
Telephone: 703-487-4650
The EPA authors can be contacted at:
Environmental Criteria and Assessment Office
U.S. Environmental Protection Agency
Cincinnati, OH 45268
United States
Environmental Protection
Agency
Center for Environmental Research
Information
Cincinnati OH 45268
Official Business
Penalty for Private Use $300
EPA/600/S9-85/027
• 0000339 PS
------- |