© 1991 Oxford University Press
research-article |
Metabolism of the Flame Retardant Plasticizer Tris(2-chloroethyl)phosphate by HUman and Rat Liver Preparations1
Department of Pharmacology, Mayo Clinic and Foundation 200 First Street Southwest, Rochester, Minnesota 55905
Received September 5, 1990; accepted January 31, 1991
Metabolism of the Flame Retardant Plasticizer Tris(2-chloroethyl)phosphate by Human and Rat Liver Preparations. CHAPMAN, D. E., MICHENER, S. R., AND POWIS, G. (1991) Fundam. Appl Toxrcol. 17, 2 15–224. Previous studies indicate that tris(2-chloroethyl)phosphate (TCP) preferentially produces hippocampal brain lesions in female versus male rats, and the expression of these lesions is inversely related to the in vivo rate of TCP metabolism. In the present studies. TCP (0.17 mM in all incubations) was metabolized in vivo by liver slices and microsomes from human and Fischer 344N rat Liver to bis(2-chloroethy) hydrogen phosphate (BCP), 2-chloroethanol (CE), and three unidentified metabolites. The rate of TCP metabolism by male rat liver microsomes and liver slices was 0.049 nmol/min/mg protein and 2.53 nmol/min/g liver, respectively. TCP metabolism by male rat liver microsomes was inhibited by 10 µM diisopropyl fluorophosphate, 10 µM paraoxon and carbon monoxide. TCP did not appear to be metabolized by female rat liver microsomes, but female rat liver slices metablized TCP at a rate of 1.5 1 nmol/mln/g liver. TCP was metabolized by male and female rat plasma at a rate of 0.156 and 0.169 nmol/ml plasma respectively. TCP was metabolized by male and female human liver microsomes at a rate of 0.027 and 0.031 nmol/mln/mg protein, respectively. TCP was metabolized by male and female human liver slices at a rate of 1.37 and 1.82 nmol/min/g liver, respectively. BCP and CE were the major metabolites formed in all studies, except for liver slices and microsomes from two human male subjects in which an unidentified metabolite constituted 29 to 38% of the total TCP metabolism. TCP was not metabolized by plasma or whole blood from male or female human subjects. These results support the previously reported sex-specific difference in TCP metabolism by male and female Fischer 344N rats. However, no sex-specific difference In rates of TCP metabolism by male and female human liver microsomes or slices was observed.