Ethylenediamine is a major industrial chemical with an estimated U.S. production of 64 million pounds in 1985. Based upon its widespread solvent applications and the potential for exposure in pregnant women, EDA was evaluated for maternal and developmental toxicity using a laboratory animal model.
Artificially-inseminated New Zealand White rabbits (26/group) were administered ethylenediamine (0, 10, 40 or 80 mg/kg/day) by gavage on gestational days 6 through 19. In order to avoid the irritant/corrosive properties of the EDA base, the test chemical was administered as the dihydrochloride salt. The doses administered were equivalent to 0, 22, 89 or 178 of EDA 2HCI. Maternal clinical signs, body weight, and food consumption were monitored at regular intervals throughout gestation. At termination (gd 30), the uterus was removed and examined to determine pregnancy status and to evaluate the number of resorptions, and dead or live fetuses. Dead or live fetuses were weighed, and live fetuses examined for external, visceral and skeletal defects.
There were no treatment-related maternal deaths in this study, and no characteristic clinical signs of toxicity in EDA-treated does. At scheduled necropsy, 19-22 pregnancies per group were confirmed. There were no statistically significant effects of EDA on maternal food intake, body weight, weight gain, liver or kidney weight (absolute or relative), or gravid uterine weight. Uterine examination on gd 30 revealed no adverse effects of EDA upon prenatal viability, litter size, fetal weight or fetal morphology.
In conclusion, the maternal and developmental no observed adverse effect level for EDA in the New Zealand White rabbit exposed during major organogenesis is greater than or equal to 80 mg/kg/day. Higher doses were not evaluated in this study due to the observation of greater than or equal to 20% maternal mortality at greater than or equal to 100 mg/kg/day in a preliminary investigation (NTP, 1991).