Effects of short-term administration of alpha-chlorohydrin on reproductive toxicity parameters in male Sprague-Dawley rats.
alpha-Chlorohydrin (alpha-CH) was administered orally at doses of 0, 2 or 8 mg/kg/day for 2 weeks to Sprague-Dawley male rats. At the end of the administration period or 2 weeks after withdrawal (one group also treated with 8 mg/kg for 4 weeks), males were mated (treatment with alpha-CH was continued throughout the mating period of 2 weeks) with untreated females, and underwent examination, including assessment of sperm, to determine fertility. No significant treatment-associated changes were observed in terms of body weight, food consumption, or weights of the testes, epididymides or prostate in either the 2 or the 8 mg/kg group. Although there were no significant differences in sperm number, viability or maturation rate between either of the treated groups and the control group, sperm motility in the 8 mg/kg group observed after 2 hours incubation and sperm activity in groups treated with 8 mg/kg observed immediately after collection or after 2 hours incubation, as well as in the 2 mg/kg observed after 2 hours of incubation were significantly decreased. Two weeks after withdrawal (8 mg/kg group only), sperm motility and activity were no longer decreased. Histopathological examination of the testes after 4 weeks of alpha-CH administration disclosed no abnormalities on staining with Hematoxylin-Eosin after fixation in Bouin's solution. All treated male rats copulated with untreated females, but no pregnancy resulted from mating in the 8 mg/kg continuous administration case. There were no significant differences between the control and 2 mg/kg groups in numbers of corpora lutea and implantations in animals becoming pregnant. Two weeks after withdrawal, male rats treated with 8 mg/kg copulated and impregnated females. These findings suggest that evaluation of male fertility is possible within or following a 2-week treatment period for compounds like alpha-CH which have no toxicological, histopathological or sperm morphological effects, and that the use of several parameters for sperm examination is important in determining male fertility.
Yamada
T
T
Development Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Inoue
T
T
Sato
A
A
Yamagishi
K
K
Sato
M
M
D000818:Animals; D003272:Contraceptive Agents, Male / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005298:Fertility / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D000517:alpha-Chlorohydrin / Q000008:administration & dosage* / Q000633:toxicity*
D003272:Contraceptive Agents, Male; D000517:alpha-Chlorohydrin