Antifertility and toxicological studies with aromatic esters of alpha-chlorohydrin in male rats.
Due to the drawbacks in the potential use of alpha-chlorohydrin itself as a male oral contraceptive, two novel crystalline derivatives, alpha-chlorohydrin-bis-m-nitrobenzoate and alpha-chlorohyrdin-mono-p-acetamidobenzoate, were synthesized and tested for antifertility activity in male rats. In addition, the nephrotoxic effects of alpha-chlorohydrin itself and of the two aromatic esters were investigated by the use of diuretic experiments, plasma biochemical analyses and kidney histology. Both esters were found to be of comparable molar potency to alpha-chlorohydrin in inducing temporary infertility following daily oral administration. The nephrotoxic effects following high oral doses of alpha-chlorohydrin were largely eliminated by the use of either ester. These derivatives have several advantages over alpha-chlorohydrin, being crystalline compounds of definable purity. Although potency was retained, acute oral toxicity was greatly reduced, due to a combination of factors - the esters were poorly absorbed in high dosage whilst relatively slow breakdown permitted effective levels to be attained on epididymal spermatozoa.
D000818:Animals; D002728:Chlorohydrins / Q000494:pharmacology*; D003272:Contraceptive Agents, Male / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D004231:Diuresis / Q000187:drug effects; D005298:Fertility / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008297:Male; D051381:Rats; D013094:Spermatozoa / Q000187:drug effects; D013329:Structure-Activity Relationship; D013997:Time Factors; D014508:Urea / Q000097:blood; D000517:alpha-Chlorohydrin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity
D002728:Chlorohydrins; D003272:Contraceptive Agents, Male; C027307:alpha-chlorohydrin-bis(3-nitrobenzoate); C027308:alpha-chlorohydrin mono-4-acetamidobenzoate; D014508:Urea; D000517:alpha-Chlorohydrin; D003404:Creatinine