This document is a supplement to the EPA Guidelines for the
Health Risk Assessment of Chemical Mixtures of 1986. The 1986
Guidelines represent the Agency's science policy and are a procedural
guide for evaluating data on the health risks from exposures to
chemical mixtures. The emphasis is on dose response and risk characterization.
The principles and concepts put forth in the Guidelines remain
in effect. However, where the Guidelines describe broad principles
and include few specific procedures, the present guidance is a
supplement that is intended to provide more detail on these principles
and their applications.
After an overview of the background and scope, this supplementary
guidance puts forth the risk assessment paradigm for mixtures.
This paradigm begins with problem formulation, then briefly discusses
hazard identification, dose-response assessment, exposure, and
risk characterization. The document is organized according to the
type of data available. Procedures are described for assessment
using data on the mixture of concern, data on a toxicologically
similar mixture, and data on the mixture component chemicals. The
state of the science varies dramatically for these three approaches.
The whole-mixture procedures are most advanced for assessing carcinogenic
risk, mainly because of the long use of in vitro mutagenicity tests
to indicate carcinogenic potency. In vitro test procedures for
noncancer endpoints are still in the pioneering stage. In contrast,
the component-based procedures, particularly those that incorporate
information on toxicologic interactions, are most advanced for
noncarcinogenic toxicity. No single approach is recommended. Instead,
guidance is given for the use of several approaches depending on
the nature and quality of the data. The appendices contain definitions,
a discussion on toxicologic interactions and pharmacokinetic models,
and a reprint of the 1986 Guidelines.
For more information, please contact Richard Hertzberg via e-mail
(hertzberg.rick@epa.gov),
or the Technical Information Staff by telephone (202-564-3261)
or facsimile (202-565-0050).