DOMINANT LETHAL STUDY OF SULFUR MUSTARD IN MALE AND FEMALE RATS

Sulfur mustard (HD) (bis(2-chloroethyl)sulfide) is a strong alkylating agent with known mutagenic and suspected carcinogenic properties, but occupational health standards have not been established. The purpose of this study was to determine the dominant lethal effect in male and female rats dosed orally with HD, for which currently available data a re ambiguous. Sprague-Dawley rats of each sex, 6-7 weeks old, were ora lly administered 0, 0.08, 0.20 or 0.50 mg kg-1 HD 5 days a week for 10 weeks, after which dominant lethal studies were conducted during the post-exposure period. The studies were conducted in two phases: a fema le dominant lethal phase in which treated or untreated males were mate d with treated females and their fetuses were evaluated 14 days after copulation; and a male dominant lethal phase in which treated males co habited with untreated females for 5 days and fetuses were evaluated 1 4 days after the mid-point of the week of cohabitation, for each of 10 weeks. In addition, motility, population size and morphology were mea sured in sperm obtained from the cauda epididymis. Parental growth rat es were reduced in both sexes treated with the high level of HD. Femal e dominant lethal effects were not observed, although significant male dominant lethal effects were observed in HD-exposed male rats mated t o untreated females at 2 and 3 weeks' post-exposure. These effects, wh ich included increases of early fetal resorptions and preimplantation losses and decrease in total live embryo implants, were most consisten tly observed at a dose of 0.50 mg kg-1. A significant P(P < 0.05) incr ease in the percentage of abnormal sperm was detected in males exposed to 0.50 mg kg-1 HD. The timing of dominant lethal effects is consiste nt with an effect during the post-meiotic stages of spermatogenesis, p ossibly involving the generally sensitive spermatids.