Screening of toxicological properties of 4-methylbenzoic acid by oral administration to rats

摘要

Oral toxicity of 4-methylbenzoic acid in male and female Sprague-Dawley rats was profiled through a twenty-eight-day repeated dose toxicity study (the 28-day study) and a screening test for reproductive/developmental toxicities (the reproduction/developmental study) conducted under Organisation for Economic Co-operation and Development (OECD) test guidelines. Daily administration of 4-methylbenzoic acid, at a dose level of 0, 100, 300 or 1,000 mg/kg, did not show any adverse effect on reproductive organs of animals in the 28-day study. In the reproductive/developmental study, however, 1,000 mg/kg/day of the compound reduced epididymal weights and increased incidence of cauda epididy-mal oligo/azoospermia. While the compound did not affect estrous cycle or mating performances, 1,000 mg/kg of the compound reduced fertility. Furthermore, 300 mg/kg or more of the compound increased pre-implantation loss, which resulted in a decrease in the number of offspring, and reduced body weight gain of the dams during the latter period of gestation. From these results, the no-observed-effect-level (NOEL) for reproductive/developmental toxicities is considered to be 100 mg/kg, whereas 1,000 mg/kg did not show any effect on neonates. In the 28-day study, NOEL is considered to be 300 mg/kg for male and female rats, since 1,000 mg/kg of the compound caused, in both sexes, a few minor changes, such as temporal salivation, a slight increase in food consumption and a moderate increase in blood aspartate ami-notransferase (AST) activity. Thus, 4-methylbenzoic acid has the potential for reproductive toxicity, with diverse adverse effects on the epididymis, after repeated administration, observed in the two studies.