Developmental toxicity assessment of C8 iso acid in CD rats: relevance to embryotoxic aliphatic carboxylic acids.

Cekanoic® C8 acid (CAS RN 25103-52-0) is a complex isomeric substance containing several aliphatic carboxylic acids, primarily dimethyl hexanoic acid. Because Cekanoic® C8 acid is a structural isomer of octanoic acid, its potential for developmental toxicity was investigated in CD (Sprague-Dawley) rats. Cekanoic® C8 acid was administered by oral gavage to 25 confirmed-mated females at doses of 0, 200, 400, and 800 mg/kg/day on gestation days (GD) 6-15, based on a range-finding experiment. Maternal body weights, food consumption, and clinical observations were recorded throughout gestation. On GD 21, cesarean sections were performed and the uterine contents removed and subjected to conventional teratological evaluation. At 800 mg/kg/day, maternal body weight gain and food consumption were reduced during the exposure period, and clinical signs were evident. There were no significant differences in fetal weight, malformation incidence, or fetal viability in any of the experimental groups. There was a statistically significant increase in the incidence of total variations in the 800-mg/kg/day group, which was within the historical control range of this laboratory and not considered biologically significant. These results indicate that, unlike related compounds, Cekanoic® C8 acid was not teratogenic or a selective developmental toxicant in rats. This is the first report of a dimethyl substituted aliphatic acid being evaluated for developmental toxicity in a definitive study. The results are consistent with a structure-teratogenicity relationship for aliphatic acids, indicating that side-chain branching larger than a methyl group is required to elicit teratogenic effects. This study established a maternal no-observable-adverse-effect level (NOAEL) for Cekanoic® C8 acid at 400 mg/ kg/day and a developmental NOAEL at 800 mg/kg/day.