The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Acrylamide. a cumulative neurotoxicant. was evaluated for developmental toxicity in timed-pregnant Sprague-Dawley (CD) rats. ACRL was dissolved in distilled water to yield doses of 0. 2.5, 7.5. and 15 mg/kg and administered once daily by gavage on gestational days 6 through 20.
Maternal toxicity during ACRL exposure was expressed primarily by decreased weight gain at the high dose. Maternal weight gain during treatment and gestation as well as weight gain corrected for gravid uterine weight exhibited decreasing trends. Maternal weight gain during treatment was reduced below control values in the high dose group, and corrected weight gain was reduced in the 7.5 and 15 mg/kg dose groups. Gravid uterine and liver weights were not measurably affected by ACRL treatment. In addition, other clinical signs were observed infrequently and exhibited no clear-cut relationship to ACRL dose.
ACRL treatment during gestation did not alter measured endpoints of embryo/fetal viability, growth or development. The percentages of resorptions. dead fetuses or malformed fetuses per litter, as well as fetal body weights, were statistically similar among the dose groups. ACRL treatment had no effect on the incidence of skeletal. visceral or external malformations. There was a dose-related trend toward an increased incidence of variations, but there were no statistically significant pairwise comparisons.
In conclusion, development of the CD rat was not sensitive to ACRL administered by gavage at doses which depressed maternal weight gain. The lowest ACRL dose administered, 2.5 mg/kg/day , represented a no observed adverse effect level for ACRL-induced maternal toxicity. Embryo/fetal toxicity was not observed across the doses of ACRL administered in this study.
Consequently, 15 mg/kg/day , the highest dose tested, represented a no-observed-adverse-effect-level for developmental toxicity under the conditions of this study.