Maternal and developmental toxicity of chronic aluminum exposure in mice.
The present study demonstrated aluminum-induced neurotoxicity in mouse dams and developmental retardation in their offspring following oral exposure to several dose levels during gestation and lactation. Female mice fed aluminum lactate (AL) at levels of 500 or 1000 ppm in their diet from Day 0 gestation to Day 21 postpartum were compared to mice which received a 100 ppm aluminum diet either ad libitum or pair-fed to the 1000 ppm AL group. Dams receiving the 500 and 1000 ppm AL diets showed signs of neurotoxicity beginning at Days 12-15 postpartum and showed significant weight loss. Offspring showed dose-dependent decreases in body weight (F = 6.47, p less than 0.001), crown-rump length (F = 7.37, p less than 0.0001), and ponderal index (F = 6.90, p less than 0.0002), at birth and preweaning. Absolute and relative liver and spleen weights were lower in pups from the high AL groups compared to controls (F = 3.34, p less than 0.025 and F = 15.54, p less than 0.001, respectively). Neurobehavioral development was somewhat delayed in aluminum-treated pups, but not in their pair-fed controls (F = 5.52, p less than 0.005). In addition to showing oral toxicity of excess AL during development dose-dependent toxic effects of parenteral aluminum exposure were demonstrated in pregnant mice which were injected subcutaneously with aluminum lactate 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 liver weights were significantly increased in aluminum treated animals (p less than 0.001 and p less than 0.05, respectively). Fetal crown-rump lengths were significantly reduced in the 20 mg/kg aluminum group (F = 9.79, p less than 0.001).
D000284:Administration, Oral; D000535:Aluminum / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001724:Birth Weight; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D008098:Litter Size; D008431:Maternal-Fetal Exchange; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D000535:Aluminum