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INTRODUCTION
The information available on the potential toxicity of most chemicals
is scanty, and the resources available for toxicity testing do not
suffice to test all chemicals for every possible health effect. Hence, a
priority-setting system is needed for selecting substances to be tested
and selecting tests with which to evaluate them. Because of limitations
in available data and methods, the priority-setting system must be
designed to operate in the presence of considerable uncertainty.
The Committee on Priority Mechanisms has sought to develop a
priority-setting approach applicable to the large number of chemicals of
potential concern with respect to human health. The approach, which is
drawn from systems analysis and decision theory, is based on the thesis
that the rationale of any priority-setting system should be explicit,
open to inspection, and scientifically defensible. In view of the
rapidity with which the art of toxicity testing is evolving, the
committee does not propose a particular priority-setting scheme now, but
rather suggests an approach for designing a system that can keep pace
with advances in the field. The approach is presented in this report
largely in conceptual form, although examples are given to illustrate how
it could be applied to the selection of chemicals for carcinogenicity
testing.
Testing priorities have traditionally been assigned on the basis of
expert judgment, which is now supplemented with a variety of analytic,
data-based techniques, such as scoring systems. The committee believes
that this basic pattern should continue, with further improvement in
techniques that allow expert judgment to be most effective. The
committee recognized that no priority system, scheme, or procedure can be
perfect, because the knowledge needed for unerring selection of the most
important chemicals and tests is the same as the knowledge resulting from
a complete and accurate testing program for all chemicals, which would of
course make priority-setting unnecessary. The priority-setting system
and the testing program form a continuum whose overall objective is to
yield the most information about the overall hazards of chemicals.
Given a goal for the priority-setting system, the committee needed to
decide whether improvements over current procedures for selecting
chemicals for testing were possible. It concluded that improvements were
possible--at least at the margin--by injecting additional systematic
information-gathering and -processing procedures.
Because the total number of chemicals far exceeds the number that can
be evaluated in depth at any one time, the committee's approach seeks to
arrive at the combination of information-gathering procedures that, for a
given investment of resources, will yield the most useful toxicity data
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on the universe of chemicals to be considered. To enable the entire
select universe of chemicals to be scanned for compounds that may warrant
testing, a multistage scheme is presented for consideration; it begins
with automated processing of machine-retrievable data and proceeds
through successive stages to costlier procedures that depend on expert
judgment.
A model is presented to illustrate how the performance of this
four-stage priority-setting system can be optimized by selecting the most
effective set of decisions for a given investment of resources.
Lack of knowledge about the effectiveness of toxicity testing, the
extent and distribution of toxic properties among chemicals, or the
exposure to chemicals hinders the design of an optimal system. However,
the report shows not only how a priority-setting scheme might operate
with incomplete and uncertain information, but also how to determine what
information is most needed to improve the system itself.
The work of the committee is presented as a review of the elements of
systems analysis as applied to priority-setting for toxicity testing in
Chapter 2. These principles are applied to an illustrative system in
Chapter 4. An explanation of the operation of the illustrative system is
presented in Chapter 3, and suggestions for implementation are presented
in Chapter 5.
The committee believes that a fully developed version of the outlined
system not only is a plausible extension of current practice, but also
would provide at least marginal improvements over existing priority-
setting procedures toward the goal defined earlier. Obviously, it might
not provide improvements toward other goals, but it should not impede
them. Even at the margin, the improvements would probably easily justify
the costs of developing, implementing, and operating the system.
However, the implementation of these concepts in the illustrative system
or one of similar scope would require adjustments in the established
patterns of thinking about testing priorities. Specifically, full
application of the proposed analytic techniques will require that each
information-gathering procedure be described quantitatively with respect
to its ability to identify and to characterize potentially toxic
chemicals. This requirement is not readily fulfilled in our present
state of knowledge. Hence, efforts toward further quantification of the
performance characteristics of toxicologic methods would be essential to
full implementation of the priority-setting approach proposed herein.
For this reason, the approach can be pursued initially on a pilot scale,
with further implementation depending on the development and availability
of the necessary data. The committee believes that it should be possible
to institute changes in current procedures gradually, without
irreversibly committing resources to the novel features of its
suggestions.
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Representative terms from entire chapter:
expert judgment
