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

Abstract

-Oral toxicity of 4-methylbenzoic acid in male and female Sprague-Dawley rats was proreproductive/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 epididymal 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 aminotransferase (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.Key words: 4-methylbenzoic acid, Epididymis, OECD test guideline, Reproductive toxicant, Repeated dose toxicity, RatsCorrespondence: Mariko Shirota (E-mail: shirota.m@fdsc.or.jp) Original ArticleThe Journal of Toxicological Sciences (J. Toxicol. Sci.) Vol.33, No.4, 431-445, 2008 Vol. 33 No. 4 431 MATERIALS AND METHODS Test substance4-Methylbenzoic acid (CAS No. 99-94-5, purity 98.95%) was supplied by Toray (Tokyo, Japan), and was kept at room temperature until use. To prepare dosing -pended in a 0.5% sodium carboxymethylcellulose solution, and each dose was adjusted to a constant volume of 5 ml/kg. The stability of the suspended compound in the vehicle and the content and uniformity of the compound -tute.The doses used in the studies were determined based on a preliminary, 7-day, repeated dose, oral toxicity study of the compound, in which a dose level of 1,000 mg/kg did not show any toxic effects. This was considered sufficient for the highest dose, and the doses used in the present studies were set at 0, 100, 300 and 1,000 mg/kg. AnimalsMale and female rats of the Sprague-Dawley (Crj: CD(SD)) strain were purchased from Charles River Japan (Atsugi Breeding Center, Atsugi, Kanagawa, Japan). For the 28-day study, the animals were purchased at 4 weeks of age, and after an 8-day quarantine period, the animals were divided into 4 groups of each sex according to a the day before initial dosing. For the reproduction/develo...

A Comparative Study of Electrochemical Treatment of Para-Toluic Acid (p-TA) from Aqueous Solution: Process Optimization and Sludge Analysis

“…Although p-TA has wide applications, intake in high amount is very dangerous for the human body due to its hazardous and toxic nature [13]. It can be a reason for the abatement in epididymal oligozoospermia [14]. Because of the highly toxic nature of BA, p-TA, and TPA, the US Environmental Protection Agency (USEPA) included these compounds in the list of priority pollutants [14][15][16].…”

“…It can be a reason for the abatement in epididymal oligozoospermia [14]. Because of the highly toxic nature of BA, p-TA, and TPA, the US Environmental Protection Agency (USEPA) included these compounds in the list of priority pollutants [14][15][16]. No specific discharge limit for p-Toluic acid has been proposed by the pollution regulating agencies in India.…”

Experimental and modeling study of pure terephthalic acid (PTA) wastewater transport in the vadose zone

“…8 PA can induce reproductive and developmental toxicity, as well as disrupt endocrine function. 13 The literature suggests that PTA wastewater is toxic to living organisms, 14,15 and the US Environmental Protection Agency recently added this class of chemicals to the list of priority pollutants. 10,11 Generally, BA reveals that the compound could affect the growth and reproduction of freshwater organisms, sperm viability, though it is not clinically considered as a reproductive or developmental toxicant.…”

“…12 According to the information available, p-Tol will cause a decrease in epididymal weight and an increase of incidence in cauda epididymal oligo/azoospermia. 13 The literature suggests that PTA wastewater is toxic to living organisms, 14,15 and the US Environmental Protection Agency recently added this class of chemicals to the list of priority pollutants. There are at least ve kinds of benzoate pollutants existing in PTA wastewater.…”

Toxicity of purified terephthalic acid manufacturing wastewater on reproductive system of male mice (Mus musculus)

“…Information is unavailable about the reproductive toxicity induced by p-CBA, but the compound p-Tol was found to cause the decrease of epididymal weight and the increase of incidence in cauda epididymal oligo/azoospermia [9]. It is well-known that PA can disrupt endocrine function and induce reproductive and developmental toxicity in laboratory animals [10].…”