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• W1543131408 abstract "The relationship between the relative nephrotoxicity of the mercapturic acids (NAc) of the fluorinated ethylanes tetrafluoroethylene (TFE), chlorotrifluoroethylene (CTFE), 1,1-dichloro-2,2-difluoroethylene (DCDFE) and 1,1-dibromo-2,2-difluoroethylene (DBDFE), and the biotransformation by activating (N-deacetylase and β-lyase) and inactivating (N-acetyltransferase) enzymes was studied in the rat. After intraperitoneal (i.p.) administration of 50 μmol/kg of N-(trideuteroacetyl)-labeled mercapturic acids of DCDFE and DBDFE to rats, significant amounts of the dose were excreted unchanged: with DCDFE-NAc, 17% of the dose, and DBDFE-NAc, 31% of the dose. In contrast, the corresponding deuterium-labeled mercapturic acids of TFE and CTFE were excreted unchanged at less than 1% of the dose. With DCDFE-NAc and DBDFE-NAc, also high amounts of unlabeled mercapturic acids were excreted, respectively 48% and 28% of the dose, indicating extensive N-deacetylation followed by reacetylation in vivo. Only small amounts (< 2%) of unlabeled mercapturic acids were excreted with TFE-NAc and CTFE-NAc. After administration of the cysteine S-conjugates DCDFE-Cys and DBDFE-Cys to rats, high amounts of the corresponding mercapturic acids were detected in urine, respectively 57% of the dose. After administration of TFE-Cys and CTFE-Cys, however, only small amounts were excreted as the corresponding mercapturic acid, approximately 4% of the dose. The strongly different amounts of mercapturic acids in urine may be attributed to the strong differences in N-deacetylation activities which were found in rat renal fractions. The threshold dose of the mercapturic acids to cause nephrotoxicity in male Wistar rats increased in the order: CTFE-NAc (25 μmol/kg) < TFE-NAc (50 μmol/kg) < DCDFE-NAc (75 μmol/kg) < DBDFE-NAc (100 μmol/kg). A higher ratio of N-deacetylation and N-acetyltion activities, resulting in a higher availability of cysteine S-conjugate, in addition to a higher specific activity of cysteine S-conjugate β-lyase, probably explains the higher nephrotoxicity of TFE-NAc and CTFE-NAc and CTFE-NAc when compared to DCDFE_NAc and DBDFENAc. The much lower activities of N-decatylation and β-lyase are observed in hepatic fractions may explain the lack of hepatotoxicity of the mercapturic acids studied." @default.
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• W1543131408 date "1991-06-01" @default.
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• W1543131408 title "Metabolism of l-cysteine S-conjugates and N-(trideuteroacetyl)-l-cysteineS-conjugates of four fluoroethylenes in the rat" @default.
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• W1543131408 doi "https://doi.org/10.1016/0006-2952(91)90677-w" @default.
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