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Administrative data

Key value for chemical safety assessment

Effects on developmental toxicity

Description of key information
Developmental toxicity screening and a Segment II-type study are available for valeric acid.
Effect on developmental toxicity: via oral route
Dose descriptor:
50 mg/kg bw/day
Additional information
The U.S. EPA examined the toxicity of valeric acid and reviewed the developmental toxicity studies conducted with valeric acid and concluded that there were no significant developmental effects. The assessment report states that although delayed ossification of several bone structures and an increase in the incidence of fetuses with dilated renal pelvises/ureters were observed, these effects were at most only borderline statistically significant when compared to controls, and were observed at maternally toxic doses. As part of an investigation of the developmental effects and structure-activity relationships of aliphatic acids, valeric acid was evaluated using an in vivo developmental toxicity screen as well as a conventional Segment II-type protocol. In both assays valeric acid was administered by gavage to Sprague-Dawley rats on gestation days 6-15. In the screen, the rats received 0, 75, or 1000 mg/kg/day; the dams were allowed to deliver and their litters were examined through postnatal day 6 . In the Segment II study, animals received 0, 50, 100, or 200 mg/kg/day and cesarean sections were performed on gestation day 20. Maternal respiratory toxicity (e.g. rales, dyspnea) was present at all doses tested. Causticity to the gastric mucosa and high mortality were also present at 200 mg/kg. In addition, reduced weight gains indicated maternal toxicity at 75 mg/kg and greater. In the in vivo screen, no developmental delays were suggested by reduce fetal weights at 100 and 200 mg/kg and by sternebral variations at 50, 100, and 200 mg/kg.

A further re-analysis of the data generated by the Environmental Protection Agency on the developmental toxicity potential of valeric acid (pentanoic acid) in Sprague- Dawley rats following repeated gavage administration came to the conclusion, that despite overt maternal toxicity at 50 mg/kg/day and exceeding the maximally tolerated dose at 100 and 200 mg/kg/day, the fetal examination findings were limited to equivocal alterations in sternebrae ossification and offset sternebrae. These findings are considered spurious due to: 1) the lack of dose response; 2) the limited biological significance and nonadverse nature of these variations; 3) the fact that delayed sternebrae ossification was limited to sternebrae #5 and #6, which show limited ossification even in control animals; and, 4) the transient nature of these observations. Taken together, these effects are considered spurious and not related to treatment. Thus, the no-observed-effect-level (NOEL) for developmental toxicity was 50 mg/kg/day of valeric acid, due to decreased fetal body weights in the 100 and 200 mg/kg/day dose groups. The no-observed-effect-level (NOEL) for maternal toxicity was not determined due to maternal toxicity at all tested doses.

In conclusion, Valeric acid produced siginficant maternal toxicity at all dose levels tested. The only fetal effect observed was reduced fetal body weight at the 2 highest dose levels in the presence of severe maternal toxicity (including mortality). This effect however is transient, reversible, respectively and clearly a secondary effect of maternal toxicity. No teratogenicity was observed

Justification for classification or non-classification

Valeric acid did not produce any developmental effects in the absence of maternal toxicity. Hence, no classification for reproductive toxicity is required for valeric acid.

Additional information