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Comparison of Liver Toxicity Potencies of Three Dinitrotoluene Compounds
Yan, J. AND J. Zhao. Comparison of Liver Toxicity Potencies of Three Dinitrotoluene Compounds. To be Presented at SOT, Phoenix, AZ, March 23 - 27, 2014.
Munitions compounds 2,4-dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT) are the two of the six most common isomers of dinitrotoluene (DNT). Technical grade dinitrotoluene (tgDNT) is a mixture of the six DNT isomers and is comprised of 76% 2,4-DNT and 19% 2,6-DNT with the remaining 5% a combination of four other DNT isomers (2,3-, 2,5-, 3,4-, and 3,5-DNT). Toxicity studies and health assessments on 2,4-, 2,6-, and tgDNT have reported distinct liver effects. In order to compare liver toxicity potencies of these three DNTs, we reviewed available studies in dogs, rats, and mice and compared noncancer and cancer liver effects following oral subchronic- and chronic-duration exposure to 2,4-, 2,6- and tgDNT. Potential points of departure for liver effects were identified and used to compare their toxicity potencies. We then examined the potential mechanisms that could account for the differences in hepatotoxicity. Our results indicated that similar pathologic liver lesions were induced after chronic-duration exposure to the three DNTs and their progression can be summarized in four stages: liver degenerative effects and/or cell death, hyperplastic/regenerative effects, neoplastic nodules, and hepatocellular carcinoma. Based on available biotransformation, toxicogenomics and genotoxicity information, imbalanced detoxification due to covalent binding with proteins and DNA, production of reactive oxygen species, and inhibition of oxygen supply may all contribute to DNTs-induced noncancer liver toxicity and carcinogenesis. While their potencies of noncancer liver toxicity are not significantly different, 2,6-DNT is the most potent liver carcinogen followed by tgDNT; 2,4-DNT is the least potent. The differences of liver cancer potencies are consistent with their potencies of DNTs-induced hepatocyte genotoxicity. The views expressed in this abstract are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.
Record Details:Record Type: DOCUMENT (PRESENTATION/POSTER)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL CENTER FOR ENVIRONMENTAL ASSESSMENT
CHEMICAL RISK ASSESSMENT BRANCH