Maternal and Developmental Toxicity of Chronic Aluminum Exposure in Mice

Maternal and Developmental Toxicity of Chronic Aluminum Exposurein Mice. GOLUB, M. S., GERSHWIN, M. E., DONALD, J. M., NEGRI,S., AND KEEN, C. L. (1987). Fundam. Appl. Toxicol. 8, 346–357.The present study demonstrated aluminum-induced neurotoxicityin mouse dams and developmental retardation in their offspringfollowing oral exposure to several dose levels during gestationand lactation. Female mice fed aluminum lactate (AL) at levelsof 500 or 1000 ppm in their diet from Day 0 gestation to Day21 postpartum were compared to mice which received a 100 ppmaluminum diet either ad libitum or pair-fed to the 1000 ppmAL group. Dams receiving the 500 and 1000 ppm AL diets showedsigns of neurotoxicity beginning at Days 12–15 postpartumand showed significant weight loss. Offspring showed dose-dependentdecreases in body weight (F = 6.47, p < 0.001), crown-rumplength (F = 1.11, p < 0.0001), and ponderal index (F = 6.90,p < 0.0002), at birth and preweaning. Absolute and relativeliver and spleen weights were lower in pups from the high ALgroups compared to controls (F = 3.34, p < 0.025 and F =15.54, p < 0.001, respectively). Neurobehavioral developmentwas somewhat delayed in aluminum-treated pups, but not in theirpair-fed controls (F = 5.52, p < 0.005). In addition to showingoral toxicity of excess AL during development dose-dependenttoxic effects of parenteral aluminum exposure were demonstratedin pregnant mice which were injected subcutaneously with aluminumlactate solution at 10, 20, or 40 mg Al/kg body wt on Days 3,5, 7, 9, 12, 13, and 15 of gestation. Maternal spleen and liverweights were significantly increased in aluminum treated animals(p < 0.001 and p < 0.05, respectively). Fetal crown-rumplengths were significantly reduced in the 20 mg/kg aluminumgroup (F = 9.79, p < 0.001).