Assessment of procedures for screening agents for effects on male reproduction: effects of dibromochloropropane (DBCP) on the rat.
This study was designed to evaluate new protocols proposed for use as an initial screen or a dose-response test of an agent for adverse effects on male reproduction. Seven groups of adult male rats (15/group) were nongavaged or received orally 0.00, 0.94, 1.88, 3.75, 7.5, or 15.0 mg/kg of 1,2-dibromo-3-chloropropane (DBCP) in corn oil each day for 77 days. From Day 65 to Day 71, each male was caged with 2 untreated female rats. Pregnancy rate and the ratio between the numbers of embryos and corpora lutea were determined. Males were killed on Day 78 and blood was collected and one testis and epididymis were used to determine daily spermatozoal production and epididymal spermatozoal reserves. The contralateral testis was fixed for quantitative histologic evaluation. Considering only data for the 15.0 and 0.00 mg/kg doses, as in an initial screen, DBCP would have been identified as a compound of concern. Body weight, paired testicular weight, parenchymal weight of the left testis, daily spermatozoal production per testis, numbers of sperm in the caput-corpus or cauda epididymidis, mean diameter of seminiferous tubules, and the ratio of leptotene spermatocytes to Sertoli cells were reduced (p less than 0.05). Fertility was normal, but the incidence of dead embryos and the ratio of dead embryos to corpora lutea were increased. Considering all data, as in a dose-response test, discriminant analysis was more sensitive in distinguishing treated rats from those receiving 0.0 mg DBCP/kg than was univariate analysis of variance. Using DBCP as a test compound, it was concluded that use of relatively simple, objective criteria in a test lasting approximately 10 weeks will be useful in identifying agents requiring detailed scrutiny.
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005260:Female; D005298:Fertility / Q000187:drug effects; D005313:Fetal Death / Q000139:chemically induced; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000473:pathology
C007318:1,2-dibromo-3-chloropropane; D011407:Propane