This study investigated DEA-induced postnatal toxicity in Sprague-Dawley rats. In the study, timed-mated Sprague-Dawley rats were dosed (0, 50, 125, 200, 250, or 300 mg DEA/kg/day, p.o.) on gestational days (GD) 6–19. Dams and pups were monitored for body weight, feed/water intake, clinical signs, litter size, and sex ratio. At necropsy (PND 21), maternal liver and kidney weights and number of uterine implantation sites were recorded.
The high-dose group was terminated early due to excessive toxicity. The estimated maternal LD10 was 218 mg/kg/day. Maternal effects included decreased body weight and relative feed intake (≥200 mg/kg/day), transiently reduced relative water intake (125 and 250 mg/kg/day), and increased absolute kidney weight (≥125 mg/kg/day). Postimplantation loss (PND 0) and pup mortality (PND 0–4) were increased (≥200 and≥125 mg/kg/day, respectively). Pup body weight was reduced (≥200 mg/kg/day) as late as PND 21.
In conclusion, this study demonstrates reduced postnatal growth and survival after gestational exposure to DEA, persistence of toxic effects through the end of lactation, possibly due to long elimination half-life. The maternal and developmental toxicity no-observed-adverse-effect level (NOAEL) is 50 mg/kg/day and the lowest-observed-adverse-effect level (LOAEL) is 125 mg/kg/day for oral DEA exposure during embryo/fetal development in the rat.