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. One recent database evaluation revealed a 5-fold increase in the incidence of spontaneous hepatoblastoma in B6C3F1 mice over the last eight years. There was also a corresponding increase in the number of chemicals producing hepatoblastoma during this time period. There was no apparent association between a specific chemical structure or biological class of compounds and their capacity to induce hepatoblastoma. Another database evaluation investigated the lobe-specific incidences and degrees of severity of background prostatic, seminal vesicular, and ampullary glandular lesions in 1768 control Fischer 344 rats from 35 recent NTP studies. Inflammation in the dorsolateral lobes of the prostate were significantly associated with the occurrence of pituitary gland adenoma, whose prolactin was suggested to play an important role in the pathogenesis of prostatic inflammation. We also found that the quantity of dorsolateral and ventral lobe tissue was highly variable across laboratories. We recommended an optimal embedment and trimming method in rat prostate and seminal vesicle to ensure adequate and consistent sampling. Dr. Shyamal Peddada and I recently completed our participation in the second phase of an 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, were tested and compared. Data from nineteen participating laboratories using seven different chemicals, and both a blinded and unblinded protocol were evaluated (each leading to papers submitted for publication). The overall conclusions were that both model systems appear robust, reproducible and transferable across laboratories and able to detect weak estrogen agonists.