Human Effects
In order to determine whether atrazine, or any other substance, causes endocrine effects in
humans or wildlife, the tests used to determine those effects must first be validated: i.e., proven
accurate, reliable and reproducible. There are very few if any tests that have been validated for
endocrine effects in humans or wildlife.
EPA is required by the FQPA, 21 U.S.C. § 46(a)(p), to validate tests to determine
whether pesticides cause endocrine effects in humans. To validate these tests, EPA follows the
validation process established by the Interagency Coordinating Committee on the Validation of
Alternative Methods (ICCVAM), of which EPA was a charter member. ICCVAM, on their website, states:
"The Interagency Coordinating Committee on the Validation of Alternative
Methods (ICCVAM) was established in 1997 by the Director of the
National Institute of Environmental Health Sciences (NIEHS) to
implement NIEHS directives in Public Law (P.L.) 103-43 [the 1993 NIH
Revitalization Act]. This law directed NIEHS to develop and validate new
test methods, and to establish criteria and processes for the validation and
regulatory acceptance of toxicological testing methods. P. L. 106-545, the
ICCVAM Authorization Act of 2000, established ICCVAM as a
permanent committee. The Committee is composed of representatives
from 15 Federal regulatory and research agencies; these agencies generate,
use, or provide information from toxicity test methods for risk assessment
purposes. The Committee coordinates cross-agency issues relating to
development, validation, acceptance, and national/international
harmonization of toxicological test methods."
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"The National Toxicology Program (NTP) Interagency Center for the
Evaluation of Alternative Toxicological Methods (NICEATM) was
established in 1998 to provide operational support for ICCVAM, and to
carry out committee-related activities such as peer reviews and workshops
for test methods of interest to Federal agencies. NICEATM and ICCVAM
coordinate the scientific review of the validation status of proposed
methods and provide recommendations regarding their usefulness to
appropriate agencies. NICEATM and ICCVAM seek to promote the
validation and regulatory acceptance of toxicological test methods that will
enhance the agencies' ability to assess risks and make decisions, and
methods that will refine, reduce, and/or replace animal use. The ultimate
goal is the validation and regulatory acceptance of test methods that are
more predictive of adverse human and ecological effects than currently
available methods. Such methods are expected to support improved
protection of human health and the environment."
ICCVAM has established a government-wide standard that requires proper validation of any tests
before those tests can be considered reliable:
"Before a new or revised test method is used to generate information to
support regulatory decisions, it must be (a) validated to determine its
reliability and relevance for its proposed use, and (b) determined to be
acceptable by one or more regulatory agencies to fill a specific need.
Criteria for validation and regulatory acceptance have been prepared and
are described in the report, Validation and Regulatory Acceptance of
Toxicological Test Methods: A Report of the Ad Hoc Interagency
Coordinating Committee on the Validation of Alternative Methods. Prior
to the initiation of any test method development or validation efforts,
sponsors are encouraged to consider the validation and acceptance criteria
developed by the Federal government."
According to EPA and ICCVAM, validation is necessary to ensure reliable tests, and reproducibility
is one of the primary scientific criteria for test validation:
"For a new or revised test method to be considered validated for regulatory
risk assessment purposes, it should generally meet the following criteria.... "
"The extent of within-test variability, and the reproducibility of the test
within and among laboratories must have been demonstrated. Data must
be provided describing the level of intra- and interlaboratory
reproducibility and how it varies over time. The degree to which
biological variability affects this test reproducibility should also be
addressed."
Validation and Regulatory Acceptance of Toxicological Test Methods: A Report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods ("Validation Criteria"), "Executive Summary", p. 2, Prepared by ICCVAM and NICEATM (March1997). Attachment E.
EPA has had difficulty validating endocrine effects tests for humans. EPA’s schedule for
validating these tests has slipped considerably.
CRE's position on validation of tests for Human Endocrine Effects
CRE believes that conclusions regarding human endocrine effects must be based on properly validated tests.
