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

Cekanoic(R) C8 acid (CAS RN 25103-52-0) is a complex isomeric substance con taining several aliphatic carboxylic acids, primarily dimethyl hexanoic aci d. Because Cekanoic(R) C8 acid is a structural isomer of octanoic acid, its potential for developmental toxicity was investigated in CD (Sprague-Dawle y) rats. Cekanoic(R) C8 acid was administered by oral gavage to 25 confirme d-mated females at doses of 0, 200, 400, and 800 mg/kg/day on gestation day s (GD) 6-15, based on a range-finding experiment. Maternal body weights, fo od consumption, and clinical observations were recorded throughout gestatio n. On GD 21, cesarean sections were performed and the uterine contents remo ved and subjected to conventional teratological evaluation. At 800 mg/kg/da y, maternal body weight gain and food consumption were reduced during the e xposure 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 incre ase 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 consider ed biologically significant. These results indicate that, unlike related co mpounds, Cekanoic(R) C8 acid was not teratogenic or a selective development al toxicant in rats. This is the first report of a dimethyl substituted ali phatic acid being evaluated for developmental toxicity in a definitive stud y. The results are consistent with a structure-teratogenicity relationship for aliphatic acids, indicating that side-chain branching larger than a met hyl group is required to elicit teratogenic effects. This study established a maternal no-observable-adverse-effect level (NOAEL) for Cekanoic(R) C8 a cid at 400 mg/kg/day and a developmental NOAEL at 800 mg/kg/day.