Add time:08/21/2019         Source:sciencedirect.com

Recent studies have demonstrated marked species and strain differences in the toxicity of inhaled nitrobenzene. Since some of these differences could be due to variations in metabolism of nitrobenzene among species and strains, we have compared the metabolism of nitrobenzene in male Fischer-344 rats, CD rats, and B6C3F1 mice. In both strains of rats the urinary metabolites after a po dose of nitrobenzene were p-hydroxyacetanilide, p-nitrophenol, and m-nitrophenol. Fischer-344 rats excreted the metabolites as sulfate esters, but CD rats excreted them both as sulfate esters and glucuronides. In addition to these metabolites Fischer-344 rats excreted one, and CD rats two, very polar unidentified metabolites in the urine. These compounds did not coelute on HPLC with the glutathione conjugate of p-hydroxyacetanilide or further metabolic products of the glutathione conjugates. B6C3F1 mice excreted the same metabolites (except glucuronide of m-nitrophenol) in the urine as did CD rats. In addition mice excreted a substantial percentage of the dose (9.7%) as p-aminophenol sulfate, a compound not found in the urine of either strain of rat. In all three animals urinary excretion of nitrobenzene metabolites peaked 12 to 24 hr after po administration of nitrobenzene. This finding probably reflects slow nitrobenzene metabolism, since similar excretion rates were observed after an ip dose of nitrobenzene. Treatment of Fischer-344 rats with phenobarbital, 3-methylcholanthrene, piperonyl butoxide, or SKF 525-A did not substantially alter the pattern of urinary metabolites or their rates of excretion. Bile was a minor route of excretion of nitrobenzene and its metabolites in both strains of rat; 2–4% of the dose was excreted by this route in 12 hr. There were six metabolites in bile, but the quantities available did not allow conclusive identification. Three of the metabolites coeluted on HPLC with 4-hydroxy-3-methylthioacetanilide, 2-acetamido-3-(5′-acetamido-2′-hydroxyphenylthio)propanoic acid, and 5-(5′-acetamido-2′-hydroxyphenyl)glutathione. The excretion of these metabolites was decreased in rats pretreated with diethyl maleate. The data indicate that differences in metabolism and excretion of nitrobenzene exist in the animals studied, and suggest that experiments designed to correlate nitrobenzene metabolism with toxicity may provide important information concerning the mechanism of toxicity of this compound.

We also recommend Trading Suppliers and Manufacturers of NITROBENZENE, [14C(U)] (cas 100990-47-4). Pls Click Website Link as below: cas 100990-47-4 suppliers