Interactions in developmental toxicology: effects of concurrent exposure to lead, organic mercury, and arsenic in pregnant mice.
The development toxicity of lead nitrate (25 mg/kg, SC), methylmercury chloride (12.5 mg/kg, PO), and sodium arsenite (6 mg/kg, SC) was assessed in CD1 mice following administration on gestation day 10 of these chemicals separately or in their binary and ternary combinations. Cesarean sections were performed on day 18 of gestation, and fetuses were examined for malformations and variations. Three fetuses from each dam were used for whole-body analyses of Pb, Hg, and As. Maternal toxic effects were more remarkable in the group concurrently exposed to Pb, Hg, and As than in those given binary combinations of the elements. In turn, maternal toxicity was more notable in these groups than in those given separately the test compounds. With regard to developmental toxicity, the most relevant effects (decreased fetal weight, cleft palate) corresponded to the Hg-treated groups. It is in agreement with the finding that in all experimental groups the levels of Pb and As in whole fetuses were under their respective detection limits. In general terms, the present data suggests that at the current doses, the interactive effects of Pb and As on Hg-induced developmental toxicity were not greater than additive. In contrast, exposure of pregnant mice to Pb and As at doses that were practically nontoxic to dams, concurrently with organic Hg at a toxic dose, caused supra-additive interactions in maternal toxicity.
Bellés
M
M
Laboratory of Toxicology and Environmental Health, School of Medicine, Rovira i Virgili University, San Lorenzo 21, 43201-Reus, Spain.
Albina
M L
ML
Sánchez
D J
DJ
Corbella
J
J
Domingo
J L
JL
D000284:Administration, Oral; D000818:Animals; D001151:Arsenic / Q000009:adverse effects* / Q000494:pharmacology; D001724:Birth Weight; D002972:Cleft Palate / Q000139:chemically induced* / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D007279:Injections, Subcutaneous; D007854:Lead / Q000009:adverse effects* / Q000494:pharmacology; D007928:Lethal Dose 50; D008431:Maternal-Fetal Exchange; D008628:Mercury / Q000009:adverse effects* / Q000494:pharmacology; D051379:Mice; D011247:Pregnancy; D014018:Tissue Distribution
D007854:Lead; D008628:Mercury; D001151:Arsenic