DEVELOPMENTAL TOXICITY OF CYCLOHEXANEDIAMINETETRAACETIC ACID (CDTA) IN MICE

Cyclohexanediaminetetraacetic acid (CDTA), an effective antagonist for the treatment of zinc, lead, and manganese poisoning was evaluated fo r maternal and developmental toxicity in pregnant Swiss mice. CDTA was given intraperitoneally on gestation days 6-15 at doses of 0, 270, 54 0, and 1080 mg/kg/day. On gestational day 18, the fetuses were examine d for external, visceral, and skeletal malformations and variations. T reatment with CDTA at 1080 mg/kg/day resulted in a high level of mater nal deaths, as well as less severe clinical signs (significant reducti on in weight gain and food consumption). Increased resorptions, fetal deaths, and decreased number of live fetuses per litter were observed at 1080 mg/kg/day. Mean fetal body weights were also significantly dec reased in this group. At 1080 mg/kg/day, CDTA caused external malforma tions, while the development of skeletal tissues was less affected. Th e no observable adverse effect level (NOAEL) for maternal and developm ental toxicity of CDTA in mice was 540 mg/kg/day. Analyses of maternal and fetal tissues revealed only slight effects of CDTA on concentrati ons of calcium, magnesium, zinc, copper and iron. According to these r esults, the alterations in mineral metabolism should not be the major reason for CDTA-induced developmental toxicity.