3 -
EDSTAC Final Report Chapter Three August 1998
themselves.
• To facilitate making decisions within the EDSTAC Conceptual Framework, all screens
and tests should have well-defined endpoints.
• The use of animals should be reduced to the minimum level needed to obtain scientifically
valid results and interpretations.
• The results of screens and tests should support further research on effects of endocrine
disruptors on populations, communities, and ecosystems.
• In interpreting screening and testing results, a “weight-of-evidence” approach should be
used, but should be consistent with a principle of prudence in protecting human health and
the environment. In the case of T1S, this means that the strategy will err on the side of
false positive identifications rather than false negatives.
• Screening and testing results should be reported in a format that facilitates database
development and analysis by a broad array of scientific, regulatory, and management
organizations.
• Decision criteria, such as those for determining statistical significance (e.g., necessary
confidence intervals) and biological plausibility, should be clearly defined.
6. The EDSTAC recommends that T1S provide the minimum, yet valid and reliable, data to
detect interactions with the endocrine system. In contrast to Tier 2 tests, T1S assays should:
• be inexpensive, quick, and easy to perform;
• be validated and standardized as soon as possible, defining characteristics such as
sensitivity and specificity against a “gold standard,” once it is identified;
• be more “sensitive” than they are “specific,” meaning that they should have as their
primary objective the minimization of false negative or (Type II) errors, while permitting
an as-of-yet undetermined, but acceptable, level of false positive or (Type I) errors;
• capture multiple endpoints and reflect as many modes of endocrine action as possible;
• be broadly predictive across species, gender, and age; and
• yield data capable of being interpreted as either positive or negative for the purpose of
determining whether and how to conduct T2T.
7. The EDSTAC recommends that T1S be used to make initial judgments about areas of concern
in order to direct the focus of T2T. The interpretation of T1S results should be consistent with
best scientific judgment, formed on the basis of considerations such as “weight-of-evidence,”
consistency of the data set, and methodological strengths and limitations.
8. The EDSTAC recommends that T2T be based upon T1S results and other relevant
information. An underlying principle of T2T is that it should provide information useful for
human and ecological hazard assessment. The T2T scheme should be flexible enough to allow
for scientific judgment in the selection of the most appropriate tests and endpoints, and costs
should be reasonable. Tests should be aimed at determining whether the chemical substance or
mixture is an endocrine disruptor and whether the effects are a result of primary or secondary
disturbances of endocrine function. In addition, these tests should be designed to establish the
relationship between different exposure levels, timing and duration of exposure, and adverse
16