COMPARATIVE BIOTRANSFORMATION OF HEXACHLOROBENZENE AND HEXAFLUOROBENZENE IN RELATION TO THE INDUCTION OF PORPHYRIA

The porphyrinogenic action of hexafluorobenzene was investigated and c ompared to that of hexachlorobenzene. Metabolite patterns in the urine of exposed rats were determined to quantify the extent of metabolism through cytochrome P450 catalysed oxidation and glutathione conjugatio n, Results obtained demonstrate an almost similar extent of formation of phenolic metabolites. However, in the urine of hexachlorobenzene ex posed rats significantly higher levels of the N-acetyl-S-(pentahalophe nyl)cysteine were ob served than in the urine of hexafluorobenzene exp osed rats. Hexafluorobenzene exposure did not result in induction of p orphyria, whereas exposure to hexachlorobenzene did result in signific antly elevated levels of urinary as well as liver porphyrins. Together these results indicate that if the reactive intermediate is indeed fo rmed in the cytochrome P450 catalysed initial oxidative dehalogenation , the extent of its formation as well as its subsequent reactivity and reaction pathways vary with the type of the halogen substituents. Fur thermore, the results seem to indicate that the extent of metabolism o f hexahalogenated benzenes into urinary metabolites resulting from glu tathione conjugation is a better indication of their porphyrinogenic a ction than their extent of metabolism to phenolic metabolites. Two exp lanations for this observation are presented.