THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF INDIUM IN THE SWISS MOUSE

Indium is increasingly used in a variety of industries, and while ther e are few studies of its developmental toxicity, there are no reports of its potential reproductive toxicity. These studies were undertaken to investigate the possible reproductive toxicity of indium and to det ermine the relative vulnerability of males and females. We used, initi ally, a 21-day combined developmental/reproductive toxicity protocol. Oral exposures to InCl3 (less than or equal to 250 mg/kg) were without effect on the male reproductive system or liver. A kidney effect was demonstrated in males by a decrease in urinary N-acetyl glucosaminidas e. The ability of females to become pregnant was unaffected. However, fetal development was adversely affected, manifested as increased intr auterine deaths in the presence of reduced maternal weight gain. A dev elopmental toxicity study identified no increase in fetal malformation s, but verified the increased fetal deaths, in the absence of effects on adjusted maternal body weight. In vitro toxicity studies showed tha t the embryolethality was at least in part a result of direct toxicity to the conceptus, with effective doses in the low micromolar range. A limited disposition study showed that fetuses contained low micromola r concentrations of indium, more indium than maternal liver, and compa rable to levels that were toxic in vitro. Although studies of greater exposure duration are required for risk assessment, these data indicat e that fetal development is likely to be more affected by indium than female or male reproduction, with adverse effects occurring at low mic romolar levels in vivo and at exposures that may or may not affect bod y weight. (C) 1995 Society of Toxicology.