NTP Database Summarization And Evaluation

Environmental Health Sciences

Investigators

Linked publications & trials

Abstract

We contributed to NTP Technical Reports on two-year rodent studies of sodium dichromate dihydrate, formamide, cumene, cresols, and propargyl alcohol. These reports were reviewed and approved by the NTP Technical Reports Subcommittee in May, 2007. We also contributed to NTP Toxicity reports on short-term rodent studies of sodium dichromate dihydrate and dimethylaminopropyl chloride, hydrochloride that were published in 2007. [unreadable] [unreadable] An important approach to evaluating and interpreting NTP data is to make comparisons across multiple studies. This year, we undertook two such investigations. 1) We compared thyroid hormone levels (T3, T4 and TSH) observed at several time points in a series of 8 studies of dioxin and dioxin-like compounds in rats. These compounds are structurally similar to thyroid hormones and, in fact, can cause thyroid tumors in humans exposed to high levels of dioxin or related compounds. NTPs studies in rats, however, found no increased thyroid tumors. We analyzed data on thyroid hormone levels in rats at 14, 31 and 53 weeks to determine whether hormone levels were associated with exposure levels. While exposure to dioxin and dioxin-like compounds initially increased T3 and decreased T4, levels of these hormones returned to normal by one year. Changes in the thyroid tissue were also observed, but these changes did not progress to cancer. 2) We contributed to a summary and characterization of the chemical-induced lung tumors found within the 545 NTP peer-reviewed two-year rodent studies. [unreadable] [unreadable] The 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: 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, evaluating preliminary data from 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, and continuing our evaluation of the usefulness of growth, reproduction, feeding, and movement of C. elegans for assessing toxicity.