Two-generation reproduction study of lewisite in rats

Lewisite, a potent toxic vesicant and chemical warfare agent, is used in a number of research laboratories, is stored in large quantities at depot sites throughout the USA and is occasionally transported to distant sites. Thus, the potential for environmental or occupational exposure exists where lewisite is present. A 42-week two-generation study was conducted to determine the reproductive consequences of lewisite in parental male and female rats and their offspring. Rats were administered lewisite in sesame oil (0, 0.10, 0.25 or 0.60 mg kg-1 day-1 for 5 days a week) via intragastic intubation before mating, during mating and after mating until the birth of their offspring. The dams continued to receive lewisite during lactation. At weaning, male and female offspring of each group were selected to continue the study, receiving lewisite during adolescence, mating and throughout gestation and lactation. Lewisite had no adverse effect on reproduction performance, fertility or reproductive organ weights of male or female rats through two consecutive generations. No adverse effects to offspring were attributed to lewisite exposure. Minor changes in growth were the only maternal effects observed. Lewisite exposure of parental rats caused no gross or microscopic lesion in testes, epididymis, prostate, seminal vesicles, ovaries, uterus or vagina. The no-observable-effect level (NOEL) for the reproductive effects of Lewisite would be > 0.60 mg kg-1 day-1.