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2,4,5-TRICHLOROPHENOXYACETIC ACID INFLUENCE ON 2,6-DINITROTOLUENE-INDUCED URINE GENOTOXICITY IN FISCHER 344 RATS: EFFECT ON G.I. MICROFLORA AND ENZYME ACTIVITY
Citation:
George, S., R. Chadwick, J. Chang, M. Kohan, J. Allison, J. Dekker, AND Y. Hayes. 2,4,5-TRICHLOROPHENOXYACETIC ACID INFLUENCE ON 2,6-DINITROTOLUENE-INDUCED URINE GENOTOXICITY IN FISCHER 344 RATS: EFFECT ON G.I. MICROFLORA AND ENZYME ACTIVITY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/250 (NTIS PB92206309).
Description:
2,4,5-Trichlorophenoxyacetic acid and 2,6-dinitrotoluene are hazardous chemicals that have potential harmful effects 2,6-DNT is recognized as a hepatoxicant while 2,4,5-T, a component in Agent Orange, is also suspect. ,6-DNT requires both oxidative and reductive metabolism to elicit genotoxic effects. n order to determine what effect 2,4,5-T had on 2,6-DNT metabolism, intestinal enzymes, microbial populations, and urine mutagenicity were examined during 2,4,5-T treatment. eanlin Fischer 344 male ra ere treated daily with 54.4 mg/kg 2,4,5-T by gavage for 4 weeks. , 2, and 4 weeks after the initial dose, rats were administered (p.o.) 2,6-DNT (75 mg/kg) and urine was collected for 24 hours in metabolism cages. zo reductase, nitroreductase, B-glucuronidase, dechlorinase, and dehydrochlorinase activities were examined concurrently. reatment of rats for one week reduced the transformation of 2,6-DNT to mutagenic urinary metabolites. his was accompanied by a decrease in the fecal anaerobic microorganisms. he elimination of Lactobacillus fermentum from the small intestine and cecum of treated animals accompanied a significant increase in oxygen tolerant lactobacilli and other unidentified aerobic microorganisms. owever, there were no significant alterations in the intestinal enzyme activities xamined. y two weeks of 2,4,5-T treatment, microbiota and urine genotoxicity returned to the levels observed in control animals. Alterations in G.I. enzyme activities also occurred.