NTP Database Summarization And Evaluation

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The goal of this project is to summarize, evaluate, and interpret data contained in the NTP rodent carcinogenicity database and other large databases. Recently, the NIEHS co-sponsored a meeting to examine data addressing the presence or absence of low-dose effects of endocrine disruptors in specific studies. All invited speakers agreed to provide their raw data in advance of the meeting to a Statistics Subpanel, that was asked to re-evaluate the authors' experimental design, data analysis, and interpretation of experimental results. Dr. Haseman chaired this subpanel, and a paper summarizing their evaluation was recently published. The statistical principles and issues that are discussed in this paper are not unique to endocrine disruptor studies, and should provide important guidelines regarding appropriate experimental design and statistical analysis for other types of laboratory investigations. Evaluations of large databases provide a unique opportunity to examine a series of experiments conducted with similar study protocols. Dr. Peddada is playing a key role in the design and analysis of the second phase of an international (Organization for Economic Co-operation and Development (OECD)) validation program for the uterotrophic bioassay. This bioassay is intended to identify the in vivo activity of compounds that are suspected agonists or antagonists of estrogen, and to assist the prioritization of positive compounds for further testing. Two model systems, the immature female rat and the adult ovariectomized rat, are being tested and compared. Data from nineteen participating laboratories using seven different chemicals ,and both a blinded and unblinded protocol were evaluated. Although the final summarization and interpretation of study results are still ongoing, there seemed to be generally good agreement among laboratories and also within laboratories between blinded and unblinded protocols for most of the chemicals evaluated. In another ongoing project, we have been asked by the Director of the NIEHS to evaluate the available literature on transgenic mouse bioassays and make specific recommendations as to how the NTP should make use of these animal models in the evaluation of potential carcinogens. This compilation is nearing completion and the statistical analysis of the database will soon begin.