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Enhanced OECD TG 407 in detection of endocrine-mediated effects of 4,4′-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol

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Abstract

The purpose of this study was to investigate whether the estrogenic effects were detected in the enhanced TG 407 if the estrogenic property was not so strong in the uterotrophic assay. The estrogenic property of 4,4′-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol in the uterotrophic assay was slightly stronger than that of genistein or nonylphenol, but weaker than that of ethinyl estradiol. We performed a 28-day repeated-dose toxicity study (enhanced OECD test guideline No. 407) on 4,4′-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol based on the OECD draft protocol. The test chemical, administered orally at doses of 0, 10, 50, and 250 mg/kg per day for at least 28 days, caused such estrogenic effects as abnormal estrous cycle, increased ovarian follicles, increased uterine epithelial height, and vaginal mucification in the 50 and/or 250 mg/kg groups. Moreover, follicular epithelial cell hyperplasia of the thyroid was detected in all male rats given the test chemical and in female rats in the 250 mg/kg group. It was concluded that the estrogenic effects were detected in growing rats given 4,4′-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol, and thyroid dysfunction was also observed as the endocrine-mediated effects.

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References

  • Andrews P, Freyberger A, Hartmann E, Eiben R, Loof I, Schmidt U, Temerowski M, Folkerts A, Stahl B, Kayser M (2002) Sensitive detection of the endocrine effects of the estrogen analogue ethinylestradiol using a modified enhanced subacute rat study protocol (OECD test guideline no. 407). Arch Toxicol 76:194–202

    Article  CAS  PubMed  Google Scholar 

  • Odum J, Lefevre PA, Tittensor S, Paton D, Routledge EJ, Beresford NA, Sumpter JP, Ashby J (1997) The rodent uterotrophic bioassay: critical protocol features, studies with nonylphenol, and comparison with a yeast estrogenicity assay. Reg Toxicol Pharmacol 25:176–188

    Article  CAS  Google Scholar 

  • OECD (1999) EMSG OECD draft proposal for testing of adequacy of an enhanced OECD protocol, repeated dose (28 days) toxicity (oral) study, based on OECD 407. OECD, Paris

    Google Scholar 

  • OECD (2003) OECD 4th meeting of the validation management group for mammalian effects testing (VMG-Mammalian) of the task force on endocrine disrupters testing and assessment. OECD, Paris

    Google Scholar 

  • OECD (2006) OECD 5th meeting of the validation management group for mammalian effects testing (VMG-Mammalian) of the task force on endocrine disrupters testing and assessment. OECD, Washington

    Google Scholar 

  • OECD (2007a) OECD 6th meeting of the validation management group for mammalian effects testing (VMG-Mammalian) of the task force on endocrine disrupters testing and assessment. OECD, Ljubljana

    Google Scholar 

  • OECD (2007b) OECD 7th meeting of the validation management group for mammalian effects testing (VMG-Mammalian) of the task force on endocrine disrupters testing and assessment. OECD, Paris

    Google Scholar 

  • Yamasaki K, Sawaki M, Noda S, Imatanaka M, Takatsuki M (2002a) Subacute oral toxicity study of ethynyl estradiol and bisphenol A based on the draft protocol for the “Enhanced OECD Test Guideline no. 407”. Arch Toxicol 76:65–74

    Article  CAS  PubMed  Google Scholar 

  • Yamasaki K, Takeyoshi M, Yakabe Y, Sawaki M, Imatanaka M, Takatsuki M (2002b) Comparison of reporter gene assay and immature rat uterotrophic assay of twenty-three chemicals. Toxicology 170:21–30

    Article  CAS  PubMed  Google Scholar 

  • Yamasaki K, Takeyoshi M, Yakabe Y, Sawaki M, Imatanaka M, Shinoda K, Takatsuki M (2003) Immature rat uterotrophic assay of 18 chemicals and hershberger assay of 30 chemicals. Toxicology 183:95–115

    Article  Google Scholar 

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Acknowledgments

This work was supported by a grant from Ministry of Economical Trade and Industry.

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Correspondence to Kanji Yamasaki.

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Umano, T., Miyata, K., Minobe, Y. et al. Enhanced OECD TG 407 in detection of endocrine-mediated effects of 4,4′-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol. Arch Toxicol 84, 175–182 (2010). https://doi.org/10.1007/s00204-009-0483-2

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  • DOI: https://doi.org/10.1007/s00204-009-0483-2

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