Biodegradation of alpha-hexachlorocyclohexane. V. Characterization of the major urinary metabolites.

1. Free 2,4,5- and 2,4,6-trichlorophenol (TCP) have been identified by co-crystallization with authentic carrier as constituents of the urine of rats given 3-H-labelled alpha-hexachlorocyclohexane (alpha-HCH). The two TCP's constituted 7% and 63%, respectively, of the free phenol fraction which was found to account for less than 5% of all urinary metabolites. 2. 75% of the label contained in the urine of rats collected for four weeks after an i.p. dose of 14-C-alpha-HCH could be extracted into an organic solvent after alkaline and acid hydrolysis. The radioactive material thus extracted was examined by TLC and GLC. It is shown to consist mainly of chlorophenols and chlorothiophenols. 3. The extracts' major constituent was 2,4,6-TCP. Its amount was determined by GLC and was found to account for, on average, 45% of the total urinary metabolites. In conjunction with other evidence, this is considered to establish 2,4,6-TCP as the major product of alpha-HCH-biodegradation in the rat. 4. Chromatographic evidence is presented for 2,3,4,5-tetrachlorophenol and 2,4,5-TCP being other components of the chlorophenol fraction isolated from hydrolysed urine. 5. The amount of label associated with the chlorothiophenol fraction suggests a pathway involving endogenous thiol to be of significance in alpha-HCH-biodegradation in rats. Pretreatment with the drug itself increased the proportion of label associated with the fraction.