United States
                    Environmental Protection
 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).

                     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
  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
  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-
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-
  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
  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
  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
  2.  Assessment of Multiple Route Ex-
  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
Center for Environmental Research
Cincinnati OH 45268
Official Business
Penalty for Private Use $300

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