The Reproductive and Developmental Toxicity of Indium in the Swiss Mouse

Indium is increasingly used in a variety of industries, andwhile there are few studies of its developmental toxicity, thereare no reports of its potential reproductive toxicity. Thesestudies were undertaken to investigate the possible reproductivetoxicity of indium and to determine the relative vulnerabilityof males and females. We used, initially, a 21-day combineddevelopmental/reproductive toxicity protocol. Oral exposuresto InCl₃ (250 mg/kg) were without effect on the male reproductivesystem or liver. A kidney effect was demonstrated in males bya decrease in urinary N-acetyl glucosaminidase. The abilityof females to become pregnant was unaffected. However, fetaldevelopment was adversely affected, manifested as increasedintrauterine deaths in the presence of reduced maternal weightgain. A developmental toxicity study identified no increasein fetal malformations, but verified the increased fetal deaths,in the absence of effects on adjusted maternal body weight.In vitro toxicity studies showed that the embryolethality wasat least in part a result of direct toxicity to the conceptus,with effective doses in the low micromolar range. A limiteddisposition study showed that fetuses contained low micromolarconcentrations of indium, more indium than maternal liver, andcomparable to levels that were toxic in vitro. Although studiesof greater exposure duration are required for risk assessment,these data indicate that fetal development is likely to be moreaffected by indium than female or male reproduction, with adverseeffects occurring at low micromolar levels in vivo and at exposuresthat may or may not affect body weight.