Identification and quantification of urinary metabolites of dinitrotoluenes in occupationally exposed humans |
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Authors: | M J Turner R J Levine D D Nystrom Y S Crume D E Rickert |
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Affiliation: | 1. Department of Biochemical Toxicology and Pathobiology, Chemical Industry Institute of Toxicology, P.O. Box 12137. Research Triangle Park, North Carolina 27709 USA;2. Department of Epidemiology, Chemical Industry Institute of Toxicology, P.O. Box 12137. Research Triangle Park, North Carolina 27709 USA |
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Abstract: | Rats exposed to technical grade dinitrotoluene (DNT) develop hepatocellular carcinomas. Humans may be exposed to DNT during its manufacture and use. To permit comparisons of human excretion patterns of DNT metabolites with those previously observed in rats, urine specimens were collected over a 72-hr period from workers at a DNT manufacturing plant. Samples were analyzed for 2,4- and 2,6-DNT and putative metabolites by gas chromatography-mass spectrometry. Urine from workers exposed to DNT contained 2,4- and 2,6-DNT, 2,4- and 2,6-dinitrobenzoic acid, 2,4- and 2,6-dinitrobenzyl glucuronide, 2-amino-4-nitrobenzoic acid, and 2-(N-acetyl)amino-4-nitrobenzoic acid. Excretion of these metabolites peaked near the end of the workshift, but declined to either very low or undetectable concentrations by the start of work the following day. The calculated half-times for elimination of total DNT-related material detected in urine ranged from 1.0 to 2.7 hr, and those of individual metabolites from 0.8 to 4.5 hr. The most abundant metabolites were 2,4-dinitrobenzoic acid and 2-amino-4-nitrobenzoic acid, collectively accounting for 74 to 86% of the DNT metabolites detected. The data indicate that urinary metabolites of DNT in humans are qualitatively similar to those found in rats, but quantitative differences exist in the relative amounts of each metabolite excreted. |
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Keywords: | To whom correspondence should be addressed at: Department of Investigative Toxicology Smith Kline & Frenh Laboratories Philadelphia Pa. 19101. |
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