Estrogenic Effects ofp-Hydroxybenzoic Acid in CD1 Mice

Lemini, Cristina; Silva, G.; Timossi, Carlos; Luque, D.; Valverde, Aránzazu; González-Martı́nez, Marco T.; Hernández, Alfredo Ortega; Rubio-Poo, C.; Lara, Baldomero; Valenzuela, F

doi:10.1006/enrs.1997.3782

Cited by 82 publications

(63 citation statements)

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“…Another biological activity of 4-hydroxybenzoic acid is its oestrogenic activity, which was demonstrated within human and animal models (62)(63)(64)). An assay using human breast cells was used to provide evidence of its oestrogenic effect (64).…”

Section: Hydroxybenzoic Acids From Lignin Hydrolysismentioning

confidence: 99%

Biological activities of lignin hydrolysate-related compounds

Lee¹,

Monnappa²,

Mitchell³

2012

BMB Reports

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Section: Hydroxybenzoic Acids From Lignin Hydrolysismentioning

confidence: 99%

Biological activities of lignin hydrolysate-related compounds

Lee¹,

Monnappa²,

Mitchell³

2012

BMB Reports

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“…Because mating was done within the same dose groups (Nagao et al, 1997;Yamamoto et al, 1999), although estrogenic potency of 4-hydroxybenzoic acid was observed in a uterotrophic assay (Lemini et al, 1997). Detailed investigation, such as crossover matelucidate the characteristics of the reproductive toxicity of 4-methylbenzoic acid.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2008

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-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...

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“…The experiments of Lemini et al (1995Lemini et al ( , 1997 reported uterotrophic activity for benzoic acid (BA) and p-hydroxybenzoic acid (HBA) in immature mice. These data are unique in two respects, the percentage increase over controls was 60-70% for both chemicals, and the mean weights of blotted uteri for the vehicle controls were ~30 mg (BA) and 38 ± 2.2 mg (HBA).…”

mentioning

confidence: 99%

“…This suggests that that preliminary range-finding experiments, or other procedures to select suitable test doses, and procedures for addressing suspect data, are necessary. Third, the data of Lemini et al (1995Lemini et al ( , 1997) also suggest the need to consider and to define data acceptance criteria, such as a maximum uterine control weight of 45-50 mg in the immature rat, and 16-18 mg in the immature mouse.…”

mentioning

confidence: 99%

Detailed Background Review of the Uterotrophic Bioassay

2004

OECD Series on Testing and Assessment

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Estrogenic Effects ofp-Hydroxybenzoic Acid in CD1 Mice

Cited by 82 publications

References 19 publications

Biological activities of lignin hydrolysate-related compounds

Biological activities of lignin hydrolysate-related compounds

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

Detailed Background Review of the Uterotrophic Bioassay

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