The reproductive and developmental toxicity of indium in the Swiss mouse.
Indium is increasingly used in a variety of industries, and while there are few studies of its developmental toxicity, ther are no reports of its potential reproductive toxicity. These studies were undertaken to investigate the possible reproductive toxicity of indium and to determine the relative vulnerability of males and females. We used, initially, a 21-day combined developmental/reproductive toxicity protocol. Oral exposures to InCl3 ( < or = 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 glucosaminidase. The ability of females to become pregnant was unaffected. However, fetal development was adversely affected, manifested as increased intrauterine deaths in the presence of reduced maternal weight gain. A developmental toxicity study identified no increase in 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 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 micromolar concentrations of indium, more indium than maternal liver, and comparable to levels that were toxic in vitro. Although studies of greater exposure duration are required for risk assessment, these data indicate that fetal development is likely to be more affected by indium than female or male reproduction, with adverse effects occurring at low micromolar levels in vivo and at exposures that may or may not affect body weight.
Chapin
R E
RE
Reproductive Toxicology Group, National Toxicology Program/NIEHS, Research Triangle Park, North Carolina 27709, USA.
Harris
M W
MW
Hunter
E S
ES
Davis
B J
BJ
Collins
B J
BJ
Lockhart
A C
AC
D000014:Abnormalities, Drug-Induced; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D046508:Culture Techniques; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D007204:Indium / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D012098:Reproduction / Q000187:drug effects*; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens; D007204:Indium; C020758:indium trichloride