In‐vitro prenatal toxicity of trimethylarsine, trimethylarsine oxide and trimethylarsine sulfide

The embryolethality and the embryotoxicity of trimethylarsine, trimethylarsine oxide and trimethylarsine sulfide were investigated employing Sprague–Dawley rat embryos with intact yolk sacs. The embryos were removed on day 11 of gestation and grown in a culture medium (Way‐mouth's 725/1) spiked with the arsenic compounds to concentrations in the range 4–100 mM in the presence or absence of rat liver (S‐9) homogenate. After 24 h the yolk‐sac circulation and heart beat were monitored (indicator of embryolethality), the crown‐to‐rump lengths were measured, the neural structures (somites) counted, and the development of the limb buds evaluated (indicators of embryotoxicity). At a trimethylarsine concentration of 18.7 mM 78% of the embryos were dead when no S‐9 was present. In the presence of S‐9 all embryos survived but were necrotic and malformed. Signs of embryotoxicity were observed at concentrations of 18.7 and 9.3 mM. At the 4.7 mM concentration the embryos grew as well as the control embryos. Trimethylarsine oxide v as lethal at 100 mM and severely embryotoxic at 50 and 25 mM. At all but the lowest concentration (4.5 mM) the embryos looked sick, and were frequently necrotic, deformed and underdeveloped. Trimethylarsine sulfide exhibited severe embryotoxicity at 50 mM concentration in the absence and in the presence of S‐9. Signs of acute toxicity were observable at 9 mM concentrations of trimethylarsine and trimethylarsine oxide. Compared with other environmental toxicants that show effects at concentrations orders of magnitude smaller, these arsenic compounds cannot be classified as very toxic.