Diethanolamine is a surfactant used in industrial processing and as a constituent of consumer products. In this screening study, DEA was administered orally to rats throughout the embryo/fetal period. Maternal and developmental endpoints were monitored through the end of lactation.
Female Sprague-Dawley-derived (CD) rats were dosed by gavage with DEA (50, 125, 200, 250 or 300 mg/kg body weight/day) or vehicle (Pico water) on gestational days 6 through 19. The dose volume was 5ml/kg. Dose selection was based upon a previous developmental toxicity screening study in mice and general toxicity studies in mice and rats (Melnick et al., 1994a,b; NTP, 1990).
In this study, 12 timed-mated rats were assigned per group. Dams were monitored at regular intervals throughout gestation and lactation for clinical signs, food and water intake, and body weight. At scheduled termination on postnatal day 21, the following were recorded: maternal clinical condition; body, liver and paired kidney weights; and number of uterine implantation sites. Naturally delivered offspring were monitored for clinical condition on pnd 0, 4, 7, 14 and 21. Numbers of live or dead pups per litter and individual live pup body weights were recorded on pnd 0, 4, 7, 14 and 21. Gross (external) morphology was examined on pnd 0, and major organs were examined for gross pathology at scheduled necropsy on pnd 7 (culling) or pnd 21 (termination).
The calculated LD10 was 218 mg/kg/day under the conditions of this study. At 200 mg/kg/day, one pregnant female was euthanized moribund on gd 22. One pregnant female at 250 mg/kg/day was euthanized moribund on gd 21 and another pregnant female in the same group was found dead on gd 15. At 300 mg/kg/day, excessive toxicity included a 26% reduction in maternal body weight (gd 12), tremors, lethargy and piloerection. Two females were sacrificed moribund on gd 11, and the remaining females in this group were terminated by gd 15. The following description of results therefore excludes the 300 mg/kg/day group.
Maternal relative feed intake was decreased at greater than or equal to 200 mg/kg/day from gd 6 to 9, 9 to 12 and 12 to 15. At 250 mg/kg/day, feed intake was transiently decreased from pnd 0 to 4. Maternal relative water intake was reduced at 125 and 250 mg/kg/day from gd 9 to 12. Otherwise, maternal relative feed and water intakes were comparable to or greater than controls.
Maternal body weight was decreased on gd 12 and pnd 4 at 200 mg/kg/day, and on gd 12, 15, 18, 20 and pnd 4 at 250 mg/kg/day. Maternal liver weight (absolute or relative) was unaffected on pnd 21. Maternal kidney weight (absolute or relative) showed an increasing trend, and absolute kidney weight was significantly elevated at greater than or equal to 125 mg/kg/day.
On pnd 0, postimplantation loss was noted for 2, 6, 3, 17 and 51% of implantation sites per litter in the control through 250 mg/kg/day groups, respectively, and this increase was statistically significant at greater than or equal to 200 mg/kg/day. From pnd 0 to 4, postnatal mortality occurred in 0, 0.6, 1.8, 2.8 and 13.4% of pups per live litter in the control through 250 mg/kg/day groups, respectively, and this increase was statistically significant at greater than or equal to 125mg/kg/day. There were no statistically significant effects on the incidence of postnatal mortality for pnd 4 to 7, 7 to 14 or 14 to 21.
Pup body weight per litter was reduced at greater than or equal to 200 mg/kg/day for one or more timepoints. No treatment-related morphological anomalies were detected upon external examination and no treatment-related gross pathology was detected at necropsy.
In summary, CD rats were dosed by gavage with DEA (0, 50, 125, 200, 250 or 300mg/kg/day) from gd 6-19. Maternal effects included reduced body weight or weight gain (greater than or equal to 200 mg/kg/day), increased absolute kidney weight (greater than or equal to 125 mg/kg/day), altered feed intake (greater than or equal to 200 mg/kg/day) and water intake (greater than or equal to 125 mg/kg/day). Postimplantation mortality (pnd 0) was elevated at greater than or equal to 200 mg/kg/day, and early postnatal mortality (pnd 0 to 4) was increased at greater than or equal to 125 mg/kg/day. Pup body weight was reduced at greater than or equal to 200 mg/kg/day. Thus, maternal and developmental toxicity no observed adverse effect levels were 50 mg/kg/day and the lowest observed adverse effect levels were 125 mg/kg/day.