Overview of Projects
View NICEATM-ICCVAM presentations on endocrine disruptor projects from scientific meetings
NICEATM coordinated an international interlaboratory validation study of the BG1Luc ER TA (LUMI-CELL®)
test method developed by Xenobiotic Detection Systems, Inc. The study included three laboratories sponsored by NICEATM, the
European Centre for the Validation of Alternative Methods, and the Japanese Center for the
Validation of Alternative Methods. The goal of the validation study was to evaluate the usefulness
of the BG1Luc ER TA test method as a screening test to identify substances with in vitro estrogen
receptor (ER) agonist and antagonist activity.
The validation study of the BG1Luc ER TA test method has been completed and was the subject of a
2011 peer review by an ICCVAM-sponsored independent peer review panel.
Following the recommendations of the independent peer review panel, ICCVAM recommends that the
BG1Luc ER TA test method may be used as a screening test to identify substances with in vitro
estrogen receptor agonist and/or antagonist activity. The ICCVAM recommendations to be transmitted to Federal agencies
include recommendations on performance standards for the expedited validation of functionally and
mechanistically similar test methods.
NICEATM is also coordinating an international interlaboratory validation study of a MCF-7 cell
proliferation test method, developed by CertiChem, Inc., for the detection of estrogenic activity.
The study includes three laboratories sponsored by NICEATM, the Japanese Center for the Validation
of Alternative Methods, and the Korean Center for the Validation of Alternative Methods.
This validation study is ongoing and should be completed later in 2011. Results from the study will
be used as the basis for ICCVAM recommendations on usefulness and limitations of the test method.
Prior to initiating the validation studies described above,
ICCVAM evaluated the validation status of four types of in vitro
method proposed as possible components of the U.S. Environmental Protection Agency's
Endocrine Disruptor Screening Program. The ICCVAM interagency Endocrine Disruptor Working Group and
NICEATM prepared four background review
documents (BRDs) that detailed the available data and information needed to evaluate the current
validation status of each of the four types of test methods.
An independent expert panel review of the ICCVAM BRDs concluded that
there were no adequately validated in vitro estrogen receptor (ER)- or androgen receptor (AR)-based test methods.
Based on the expert panel’s
conclusions and recommendations,
along with comments from the public, ICCVAM developed test method recommendations that included minimum procedural standards
and a list of reference substances that should be used to standardize and validate
in vitro ER and AR binding and transcriptional activation (TA) test methods.
NICEATM and ICCVAM actively participate in the development of OECD Guidelines for the testing of
chemicals. OECD Test Guidelines are based on the most relevant internationally agreed-upon test methods
used by government, industry, and independent laboratories. Current NICEATM-ICCVAM activities for
Test Guidelines involving test methods for the detection of endocrine disrupting chemicals can be
found on the "ICCVAM Participation in OECD Test Guidelines for the Detection of Endocrine-Disrupting Substances" page.
A test guideline based on the NICEATM validation study of the BG1Luc ER TA test method (see above) has
been developed and submitted to the OECD for review.
National Toxicology Program High Throughput Screening Project
The National Toxicology Program is
developing a high-throughput screening (HTS) approach to screen for mechanistic targets active within cellular pathways
considered critical to adverse health effects in humans (e.g., carcinogenicity, reproductive and developmental
toxicity, genotoxicity, neurotoxicity, and immunotoxicity). The goals of the HTS program
are to prioritize substances for further in-depth toxicological evaluation, to identify mechanisms
of action for further investigation, and to develop predictive models for in vivo biological
response. NICEATM staff are monitoring the development and testing of the in vitro assays being
evaluated for use in this program for the detection of endocrine-disrupting chemicals.
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