Record Display for the EPA National Library Catalog


Main Title Potentiation of 2,6-Dinitrotoluene Genotoxicity in Fischer-344 Rats by Pretreatment with Aroclor 1254.
Author Chadwick, R. W. ; George, S. E. ; Kohan, M. J. ; Williams, R. W. ; Allison, J. C. ;
CORP Author North Carolina Univ. at Chapel Hill. ;Environmental Health Research and Testing, Inc., Research Triangle Park, NC.;Health Effects Research Lab., Research Triangle Park, NC.;Air Force Office of Scientific Research, Bolling AFB, DC.
Publisher 1993
Year Published 1993
Report Number EPA-68-02-4456; EPA/600/J-93/414;
Stock Number PB93-236677
Additional Subjects Aroclors ; Toxicology ; Drug synergism ; Rats ; DNA adducts ; Metabolic activation ; Salmonella ; Enzymes ; Gastrointestinal system ; Body weight ; Organ weight ; Microbiology ; Reprints ; Dinitrotoluenes
Library Call Number Additional Info Location Last
NTIS  PB93-236677 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 21p
Pretreatment of Fischer 344 rats for 5 weeks with Aroclor 1254, a commercial mixture of polychlorinated biphenyls, potentiated the genotoxicity of 2,6-dinitrotoluene (DNT), a componenet of an industrial chemical used in the production of polyurethane foams. This interaction resulted from Aroclor 1254-mediated bioactivation of DNT to markedly greater levels of the genotoxic metabolites, that were excreted in urine and formed DNA adducts in the liver. A significant increase in the excretion of mutagenic urinary DNT metabolites was observed after the first week of Aroclor 1254 treatment, peaked at week 2 and then declined by nearly 25% at week 4. Nevertheless, by week 5, there was almost a 4-fold increase in the formation of hepatic DNA adducts. Significantly elevated hepatic metabolism and increased beta-glucuronidase in the small intestine and cecum, at 4 weeks, may account for the increased adducts and decreased urinary mutagens. Altered nitroreductase activity, reduced pH, and changes in the microfloral population may also play a role in the effect of Aroclor 1254 on the bioactivation of DNT. Such chemical interactions could be important to predictive risk assessment because the overall cancer risk of the mixture would exceed that determined by the current guidelines for chemical mixtures.