UTILIZATION OF A SHORT-TERM MALE REPRODUCTIVE TOXICITY STUDY DESIGN TO EXAMINE EFFECTS OF ALPHA-CHLOROHYDRIN (3-CHLORO-1,2-PROPANEDIOL)

Alpha-Chlorohydrin (ACH) was administered to rats in a short-term male reproductive toxicity study to examine the usefulness of the method a nd to provide reference data with a substance that is known to elicit adverse effects on both sperm production and sperm quality within or f ollowing a 2-week treatment period. Adult male CD rats (10 per group) were administered ACH orally by gavage at doses of 0, 1, 5, or 25 mg/k g/day for 14 days. Males were killed on Test Day (TD) 15 or 29. A 2-we ek period without treatment was included to distinguish between testic ular and posttesticular effects. At each time point, the reproductive system was evaluated by comparing testes weight, DNA ploidy distributi ons of testicular cell suspensions, testicular and epididymal histopat hology, and epididymal sperm concentration, motility, morphology, and breakage. Beginning on TD 14, males to be killed on TD 29 were cohabit ed with untreated females (1 : 2). Females were killed on Gestation Da y 13 and examined for pregnancy status. During the treatment period, m inor depressions in body weight and relative food consumption occurred in rats administered 25 m2/kg ACH. Testicular and epididymal lesions also occurred at this dose level. DNA ploidy distributions determined by flow cytometry were predictive of testicular damage, with effects m ore pronounced on TD 29 than on TD 15. The preparation methods used se lected for the most motile and vigorous population of epididymal sperm . Sperm motion was altered at the 5- and 25-mg/kg dose levels on TD 15 . The percentage of motile sperm and the percentage of progressively m otile sperm were markedly depressed at both the 5- and 25-mg/kg dose l evels where antifertility effects occurred. Sperm velocities and ampli tude of lateral head displacement were depressed at the 25-mg/kg dose level on both TD 15 and 29. Additionally, decreased epididymal sperm c oncentrations and increased breakage were recorded at this dose level. The findings in this study are consistent with the scientific literat ure for ACH and demonstrate posttesticular effects on epididymal sperm and delayed expression of testicular lesions. They also support the u se of this methodology for an initial assessment of male reproductive effects.