Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.107 (DAT)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2,6-Diaminotoluene (2,6-DAT) is a major industrial chemical; approximately 100 million pounds are used annually in the synthesis of 2,6-toluene diisocyanate. 2,6-DAT is mutagenic in Salmonella typhimurium TA98 requiring metabolic activation, but has been previously shown to be a noncarcinogen in male and female F344 rats and male and female 86C3F1 mice dosed orally in 2-year bioassays. 2,6-DAT was rapidly and extensively absorbed following oral administration, indicating that its lack of carcinogenicity is not due to poor absorption from the gastrointestinal tract. 2,6-DAT was also rapidly excreted, with 85% of 2,6-DAT-associated radioactivity being recovered in the urine within 24 hr. Resolution of the urine by reverse phase HPLC demonstrated the presence of four metabolites, but none of the parent 2,6-DAT. Therefore, the lack of carcinogenicity of 2,6-DAT is not due to lack of biotransformation in vivo. Following separation by HPLC, the metabolites were analyzed by electron impact and fast atom bombardment mass spectroscopy and by NMR spectroscopy. The metabolites were identified as a) 3-hydroxy-2,6-DAT, b) 4-hydroxy-2-acetylamino-6-aminotoluene, c) 2-acetylamino-6-aminotoluene, and d) 2,6-di(acetylamino)-toluene. Metabolites b and d were found to be mutagenic in Salmonella typhimurium TA98 and then only in the presence of an activation system. Results of this study indicate that 2,6-DAT, which is a mutagen in in vitro tests, is also metabolized by the rat to compounds which are proximate mutagens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolism, disposition, and mutagenicity of 2,6-diaminotoluene, a mutagenic noncarcinogen. 257 96

Bioconcentration curves of 2,4-dinitrotoluene(2,4-DNT) in carps (whole fish, liver, intestine and muscle) were investigated using semistatic system. For whole fish, its curve could be described as a gentle peak which began with a rise in concentration to summit or steady state, then declined and reached lower level followed by another steady state. For liver and intestine, their curves both contained two successive peaks, with the second peak followed by slight fluctuation. Bioconcentration factors of 2,4-DNT in whole fish during the first and second steady state were 9.15 and 4.15,(97.86 and 44.39, based on lipid content), respectively. By logarithmic plotting, two straight-lines with different slopes(3.6 and 0.1 d-1) were measured for elimination. According to peaky curves of 2,4-DNT in whole fish, liver and intestine, smaller BCFs than calculated BCFs based on the regression equations for inert chemicals, and large rate constants of elimination, biotransformation was inferred to have happened in tissues such as liver, intestine, and other tissues. Two metabolites were separated from liver and identified as 4-amino-2-nitrotoluene(4A2NT) and 2,4-diamino-toluene(2,4-DAT) on HPLC, their retention times were 23.1 and 8.8 min, respectively. In bioconcentration test of 2,4-DNT in liver, two metabolites and parent were determined at the same time at intervals, higher concentrations of 4A2NT and 2,4-DAT were found when level of 2,4-DNT declined. Such results demonstrated our inference that metabolism caused the declines in bioconcentration curves. A one-compartment model was set up to simulate the bioconcentration, in which biotransformation adhered to Delayed Enzyme-Catalytic Logarithmic Kinetics. Good fit of model curves with measured values could be observed.
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PMID:Bioconcentration, elimination and metabolism of 2,4-dinitrotoluene in carps(Cyprinus Carpio L.). 935 7