Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 4,4′-butylidenebis(2-tert-butyl-5-methylphenol) and 3-(dibutylamino)phenol, based on the OECD draft protocols

Yamasaki, Kanji; Miyata, Katusi; Shiraishi, Keiji; Muroi, Takako; Higashihara, Nobuhiko; Oda, Hiroshi; Minobe, Yasushi

doi:10.1007/s00204-007-0250-1

Cited by 6 publications

(1 citation statement)

References 27 publications

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“…For the in vivo assay, OECD Test Guideline 407, a repeated dose 28-day oral toxicity study in rodents, is a screening assay conducted to detect endocrine disrupters acting through various toxicity mechanisms. Several chemicals have been evaluated with this assay. − In our study, IAA treatment increased the weights of the hypothalamus and reduced the weights of the ovaries of the female rats. The previous in vitro study reported that treatment with IAA inhibits antral follicle growth and decreases estradiol levels in mouse ovarian follicles .…”

Section: Discussionmentioning

confidence: 72%

Iodoacetic Acid Disrupting the Thyroid Endocrine System in Vitro and in Vivo

Xia

Yan

Yang

et al. 2018

Environ. Sci. Technol.

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Exposure to drinking water disinfection byproducts (DBPs) is potentially associated with adverse developmental effects. Iodoacetic acid (IAA), an unregulated DBP, has been shown to be cytotoxic, mutagenic, genotoxic, and tumorigenic. However, its endocrine-disrupting effects remain unknown. This study evaluated the IAA-induced disruption of the thyroid endocrine system using in vitro and in vivo assays. Rat pituitary tumor GH3 cells were treated with IAA in the presence and absence of triiodothyronine (T3). IAA exposure significantly reduced T3-activated GH3 cell proliferation, indicating the antagonistic activity of IAA in vitro. Sprague-Dawley rats were also subjected to IAA treatment through oral gavage for 28 consecutive days. IAA exposure significantly down-regulated the mRNA expression levels of the thyrotropin receptor (TSHR), the sodium/iodide symporter (NIS), and type I deiodinase and simultaneously reduced the protein expression levels of TSHR and NIS. IAA exposure decreased T3 levels but increased the weights of hypothalamus and the levels of thyrotropin releasing hormone and thyrotropin. In addition, IAA induced the formation of smaller and more depleted follicles or even vacuolization in the thyroid. These results suggested that IAA potentially disrupts the thyroid endocrine system both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 72%

Iodoacetic Acid Disrupting the Thyroid Endocrine System in Vitro and in Vivo

Xia

Yan

Yang

et al. 2018

Environ. Sci. Technol.

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Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 3-amino-1,2,4-triazole based on the Organization for Economic Co-operation and Development draft protocols

et al. 2008

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We performed a uterotrophic assay, the Hershberger assay, and the 28-day repeated-dose toxicity study (enhanced OECD test guideline no. 407) of 3-amino-1,2,4-triazole based on the OECD draft protocols. In the uterotrophic assay, female SD rats were subcutaneously injected with the chemical at doses of 0, 100, 300, and 1,000 mg/kg on each of 3 days from postnatal day 20 to day 22, and no changes were observed. In the Hershberger assay, the test chemical was orally administered at doses of 0, 40, 200, and 1,000 mg/kg/day to castrated male Wistar rats for 10 consecutive days beginning on postnatal day 56, and no androgen agonistic and antagonistic changes were observed. Alternatively, when the test chemical was orally administered at doses 0, 5, 25, and 125 mg/kg/day for at least 28 days in the subacute oral toxicity study, thyroid follicular epithelial cell hypertrophy with increased thyroid weights was detected in the male and female rats in 25 and/or 125 mg/kg groups, and hypertrophy of the anterior pituitary cells with increased pituitary weights in male and female rats was also observed in the 125 mg/kg group. Furthermore, serum T3 and T4 values decreased and serum TSH values increased in male and female rats in the 125 mg/kg group. Therefore, 3-amino-1,2,4-triazole was concluded to have anti-thyroid acting as endocrine-mediated effects, but no estrogenic or androgenic effects. In addition, decreased body weight, and abnormal biochemical parameters attributed to thyroid, liver or kidney dysfunction were observed in male and female rats in the 25 and/or 125 mg/kg groups.

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Pharmacokinetics and toxicity evaluation following oral exposure to bisphenol F

Lee

Kim

et al. 2022

Arch Toxicol

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Bisphenol F is a substitute material for bisphenol A and is widely used in household products as a raw material for polycarbonate resin, epoxy resin, and plastic reinforcement. It is known to be mainly used in food containers, thermal paper for receipts, and coatings for water pipes. In some countries, bisphenol F has been detected in drinking water and human urine samples. However, due to the lack of safety evaluation data on bisphenol F, it is difficult to establish appropriate guidelines for the proper use of the substance, and social anxiety is increasing accordingly. This study investigated the use, exposure route, and distribution flow of bisphenol F, a household chemical. To determine the no-observed-adverse-effect level (NOAEL) and target organ of bisphenol F after exposure, a single-dose oral toxicity, dose-range finding (28 day oral), repeated dose toxicity (90 day oral), and genotoxicity (reverse mutation, chromosomal abnormality, in vivo micronucleus test) tests were performed. The pharmacokinetic profile was also obtained. The test results are as follows: in the pharmacokinetic study, it was confirmed that single oral exposure to BPF resulted in systemic exposure; in single oral dose toxicity test, the approximate lethal dose was found to be 4000 mg/kg and confusion and convulsion was shown in the test animals; NOAEL was determined to be 2 mg/kg/day for male and 5 mg/kg/day for female, and the no-observed-effect level (NOEL) was determined to be 2 mg/kg/day for males and 1 mg/kg/day for females, and the target organ was the small intestine; genotoxicity tests confirmed that BPF does not induce genotoxicity.

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Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 4,4′-butylidenebis(2-tert-butyl-5-methylphenol) and 3-(dibutylamino)phenol, based on the OECD draft protocols

Cited by 6 publications

References 27 publications

Iodoacetic Acid Disrupting the Thyroid Endocrine System in Vitro and in Vivo

Iodoacetic Acid Disrupting the Thyroid Endocrine System in Vitro and in Vivo

Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 3-amino-1,2,4-triazole based on the Organization for Economic Co-operation and Development draft protocols

Pharmacokinetics and toxicity evaluation following oral exposure to bisphenol F

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