NTP Database Summarization And Evaluation

Environmental Health Sciences

Investigators

Linked publications & trials

Abstract

The goal of this project is to summarize, evaluate, and interpret data contained in NTP carcinogenicity databases.[unreadable] [unreadable] We contributed to NTP Technical Reports on methylene blue trihydrate and alpha-methylstyrene. These reports were reviewed and approved by the NTP Technical Reports Subcommittee in June, 2006. We contributed to NTP Genetically Modified Mouse Reports on allyl bromide, benzene, dicyclohexylcarbodiimide, phenolphthalein, and glycidol. These reports were reviewed and approved by the NTP Technical Reports Subcommittee in August, 2006.[unreadable] [unreadable] [unreadable] As part of the NTP rodent bioassay, short-term studies are conducted to help identify target organs and dose ranges for long-term studies. If a chemical is suspected to affect the thyroid gland, levels of three thyroid hormones are measured in the short-term studies. Often, these hormones increase or decrease in a dose-related pattern. The effects that changes in hormone levels may have on later development of thyroid tumors remain unclear. We are analyzing data from 16 NTP chemicals in which early thyroid hormone levels were measured to determine if these levels are associated with the development of tumors in the long-term studies.[unreadable] [unreadable] [unreadable] We assisted with the development of a statistical test that formally incorporates historical control data into the trend test of the NTP two-year bioassay. In support of this method, we analyzed the variability of control animal tumor prevalence for animals on the NTP-2000 diet. This information was incorporated into evaluation of the new test through computer simulation of realistic situations encountered in NTP studies.[unreadable] [unreadable] [unreadable] NTP is interested in reducing, replacing and refining the use of rodents in laboratory studies. We provided advice to the NTP on experimental design and statistical methods for evaluating alternative methods for toxicity and carcinogenicity testing. These include:[unreadable] ? advising NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) on statistical methods for validating the use of in vitro cell cultures to predict toxicity in laboratory animals,[unreadable] ? designing a study to estimate false positive and false negative rates of a dog model for testing whether chemicals prolong the QT wave in the heart beat which may ultimately lead to lethal arrhythmias,[unreadable] ? continuing our evaluation of the usefulness of growth, reproduction, feeding, and movement of C. elegans for assessing toxicity,[unreadable] ? evaluating statistical methods for analyzing Salmonella mutagenicity assays, and[unreadable] ? reconsidering existing statistical methods for analyzing micronucleated erythrocyte assays in light of the underdispersion observed in the data