Developmental toxicity evaluation of oral aluminum in rats: influence of citrate

To evaluate the influence of citrate on the potential developmental toxicity of high doses of aluminum (133 mg/kg/day), three groups of pregnant Sprague-Dawley rats were given by gavage aluminum hydroxide (384 mg/kg/day), aluminum citrate (1064 mg/kg/day), or aluminum hydroxide (384 mg/kg/day) concurrent with citric acid (62 mg/kg/day) on gestational days 6 through 15. Control animals received distilled water. At termination on gestation day 20, live fetuses were examined for external, visceral, and skeletal alterations. There were no significant differences between controls and Al-treated rats on pre- or postimplantation loss, number of live fetuses per litter, or sex ratio. Fetal body weight was significantly reduced in the group treated with Al(OH)3 and citric acid. Although no increases in the incidence of malformations were observed, the incidence of skeletal variations was significantly increased in the group given Al(OH)3 concurrent with citric acid. In summary, although the administration of citric acid did not modify the lack of embryotoxicity and teratogenicity of Al(OH)3 in rats, some signs of maternal toxicity and fetotoxicity could be observed in this group.