Effect of route of administration on the toxicity and teratogenicity of EDTA in the rat.

The toxic and teratogenic effects of EDTA were studied in the rat following administration of the compound in the diet (EDTA/do), by gastric intubation (EDTA/po), or subcutaneously (EDTA/sc). EDTA was administered on Days 7 through 14 of gestation at the following dosages: EDTA/do, 3% in the diet (954 mg/kg/day); EDTA/po, 625 mg/kg twice daily (1250 mg/kg/day) or 750 mg/kg twice daily (1500 mg/kg/day); EDTA/sc, 375 mg/kg. Appropriate controls were run for each route of exposure. EDTA/do resulted in no maternal deaths but did produce severe maternal toxicity and malformations in 71% of the offspring. EDTA/po was much more toxic to the dams (87.5% maternal death at 750 mg/kg twice daily, and 36% at 625 mg/kg twice daily) but produced fewer malformed young (20.5% at 625 mg/kg twice daily) than did the slightly lower dose of EDTA administered in the diet. EDTA/sc was lethal to 24% of the dams at a much lower dose than that given by either oral route but did not produce a significant number of malformations in the offspring. Possible factors involved in these differences in toxicity and teratogenicity are absorption into the circulation, interaction with essential metals, and the stress associated with administration of the compound.