1. The oxidative metabolism of [3-36C]chloropropan-1,2-diol (alpha-chlorohydrin, I) was studied in male rats. Two metabolites were isolated and identified as beta-chlorolactic acid (IV) and oxalic acid (V). 2. Neither alpha-chlorohydrin nor beta-chlorolactate was concentrated in any tissue. Traces of an intermediate metabolite, beta-chlorolactaldehyde (III) were detected in the urine within 4 h of administration. Studies in vitro indicated that the metabolic pathway is: alpha-chlorohydrin leads to beta-chlorolactaldehyde leads to beta-chlorolactic acid. 3. A comparative study of the metabolism of 36Cl- and 14C-beta-chlorolactate showed that oxalate was produced slowly and, as calcium oxalate, caused a type of renal glomerular nephritis. This pathological condition is responsible for the diuretic action of both alpha-chlorohydrin and beta-chlorolactate and, in higher doses, for their toxicities. 4. The role of oxalate, as a metabolite of alpha-chlorohydrin and of a number of related compounds, in inducing the formation of spermatocoeles in the male rat reproductive tract is discussed.
alpha-Chlorohydrin (I) is oxidatively metabolized to beta-chlorolactic acid (III) and oxalic acid (IV). Deposition of calcium oxalate within the renal tubules is responsible for the toxic effects of alpha-chlorohydrin and a similar action on the epididymis or epididymal blood vessels could initiate the formation of spermatocoeles from this and other male antifertility agents.
1. The metabolism of 3-amino[36Cl]chloropropan-2-ol (III) was studied in male rats. Three urinary metabolites were isolated and identified as alpha-chlorohydrin (I), beta-chlorolactic acid (V) and oxalic acid (VI). Much of the administered aminochloropropanol was excreted unchanged in the urine; 63% within 72 h, 75% over 250 h. 2. Monoamine oxidase is capable of converting aminochloropropanol to beta-chlorolactaldehyde (IV) which, by processes of either reduction or oxidation, suggests that the metabolic pathway is IV leads to I and IV leads to V leads to VI. 3. As assessed by the diuretic activities of the isomers of aminochloropropanol, oxalate appears to be produced by the (+)-isomer but not by the (-)-isomer. A difference in metabolic rate or route of the isomers may account for their differing physiological activities. 4. (+)- and (-)-aminochloropropanol exhibited identical in vitro inhibitory activities on the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase and triosephosphate isomerase, and were substrates for monoamine oxidase to equivalent extents.
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