Cyclohexanediaminetetraacetic acid (
CDTA), an effective antagonist for the treatment of
zinc, lead, and
manganese poisoning was evaluated for maternal and developmental toxicity in pregnant Swiss mice.
CDTA was given intraperitoneally on gestation days 6-15 at doses of 0, 270, 540, and 1080 mg/kg/day. On gestational day 18, the fetuses were examined for external, visceral, and skeletal malformations and variations. Treatment with
CDTA at 1080 mg/kg/day resulted in a high level of
maternal deaths, as well as less severe clinical signs (significant reduction 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 decreased in this group. At 1080 mg/kg/day,
CDTA caused external malformations, while the development of skeletal tissues was less affected. The no observable adverse effect level (NOAEL) for maternal and developmental toxicity of
CDTA in mice was 540 mg/kg/day. Analyses of maternal and fetal tissues revealed only slight effects of
CDTA on concentrations of
calcium,
magnesium,
zinc,
copper and
iron. According to these results, the alterations in
mineral metabolism should not be the major reason for
CDTA-induced developmental toxicity.