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. In addition to publishing updated tumor rates in control Fischer 344 rats and B6C3F1 mice, we identified ten chemicals in the NTP database that increased the incidence of brain tumors in F344 rats. Most of these increases were considered to be equivocal because of the low tumor incidences, and/or the lack of dose response trends. Glycidol was the only chemical evaluated by the NTP for which there was clear evidence of brain tumor induction. Another database evaluation documented the frequency of significant chemically-related decreasing trends in tumor incidence in NTP studies. While the frequency of these decreases exceeds chance expectation, many are related to reduced body weight and/or target organ toxicity in the dosed groups. It was demonstrated that a failure to follow four important scientific principles in a previously published evaluation of the NTP database led to greatly exaggerated frequencies of statistically significant decreasing tumor trends. The factors contributing to these errors included failure to adjust for survival differences, evaluating improper tumor combinations, failure to achieve the reported level of significance (p<0.01), multiply counting the same decreasing tumor effect, and using scientifically inadequate studies. - Rodent carcinogenicity, tumor incidence; brain tumors; transgenic mice, historical control data, decreasing tumor trends