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than those secondary to other conditions related to exposure to mustard agents.

There is insufficient information to link Lewisite with long-term health effects on the hematological, gastrointestinal, and neurological systems.

REPRODUCTIVE RISKS

Sulfur Mustards

Sulfur mustard causes cross-linking of DNA and is known to alkylate DNA at the 0-6 position of guanine. This observation is consistent with the known mutagenic potential of sulfur mustard (see Chapter 6). It is a bacterial and mammalian mutagen. Sulfur mustard causes chromosome breakage and induces sister chromatid exchanges in a wide variety of cells. Epidemiologic studies have also led the International Agency for Research on Cancer to classify sulfur mustard as a human carcinogen. These observations underscore the potential of this compound to induce genetic damage. They also suggest that sulfur mustards could be a reproductive toxin.

Animal Studies

Sulfur mustards induce dominant lethal mutations in Drosophila. Luening (1952) observed gross deletions in chromosomes in Drosophila offspring. Sonbati and Auerbach (1960) also showed that sulfur mustard can cause heritable mutations in germ cells in the offspring of treated Drosophila. Sasser and colleagues (1989c) administered sulfur mustard orally to rats in sesame oil for 5 days per week for 10 weeks at doses of 0, 0.08, 0.2, and 0.5 mg/kg. Treated and untreated males were mated with treated females and untreated females and their fetuses evaluated after 14 days. The observed effects included early fetal resorptions and preimplantation losses, as well as decreases in live embryo implants. A significant increase in abnormal sperm was detected in males exposed to the highest dose. The authors concluded that the timing of these effects was consistent with an effect during the post-meiotic stages of spermatogenesis, possibly involving the generally sensitive spermatids. In an earlier experiment, Rozmiarek and colleagues (1973) exposed pregnant female rats to 0.1 mg/m3 of sulfur mustard by inhalation; exposure during the interval of gestation failed to produce any fetal malformations.

In an extensive study, Hackett and colleagues (1987) studied maternal toxicity, intrauterine mortality, and developmental toxicology in rats and rabbits. Distilled sulfur mustard, diluted in sesame oil, was delivered by intragastric intubation in a volume of 1 ml/300 g rat and 1 ml/4



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