kg rabbit. Rats were dosed daily from 6 to 15 days with 0, 0.5, 1.0, and 2.0 mg/kg; rabbits received 0, 0.4, 0.6, and 0.8 mg/kg on 6-19 days. In rats, indicators of maternal toxicity were observed at all dose levels, but significant fetal effects (decreased weights, reduced ossification, and skeletal anomalies) occurred only at the highest dose (2.0 mg/kg). In rabbits, maternal toxicity occurred at the highest dose level, body weights of fetuses were reduced, but no other fetal effects were observed.
Finally, Sasser and colleagues (1989c) studied rats to evaluate the effects of sulfur mustards on reproduction. Groups of rats (27 females and 20 males per group per generation) were force-fed with 0, 0.03, 0.1, or 0.4 mg/kg sulfur mustard for 13 weeks prior to mating and throughout gestation, parturition, and lactation in a 42-week two-generation study. There were no significant effects on reproductive function or pregnancy outcome in either generation. Growth of adult F1 rats of both sexes was reduced by the highest exposure, as was the growth of their F1 and F2 offspring during lactation. A dose-related lesion of the squamous epithelial mucosa of the forestomach was observed in both sexes, and benign neoplasms of the forestomach were found in about 10 percent of the intermediate (8/94) and high-dose (10/94) groups. The NOEL in this study was <0.03 mg/kg for toxicity and > 0.4 mg/kg for reproductive effects.
In humans, two studies have attempted to evaluate the potential of sulfur mustard to induce adverse reproductive outcomes. Yamakido and colleagues (1985) used electrophoresis to study blood protein variants in 456 children of 325 workers exposed occupationally to sulfur mustard and Lewisite at the Okuno-jima poison gas factory; children were divided into three exposure groups based upon parental job category within the plant. The blood protein analysis revealed 6 types of protein variants in 11 children, and 11 variant erythrocyte proteins in 25 children. Examination of 32 of the 36 families of interest showed all of the detected variants to be familial and not exposure induced. One protein variant was found in one child that did not differ electrophoretically, but did differ in its enzymatic activity. This variant was not inherited. The female child in question was mentally retarded and had a normal g-banded karyotype but was born with a cleft palate and hypomyotonia (significant decrement in normal muscle tone). The significance of these findings is unclear, as this variant might have been the result of either (1) a germ cell mutation in an intron sequence (a DNA sequence outside of the region coding for the RNA and subsequent protein) that controls expression of the gene of interest, or (2) aberrant