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Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 4,4´-[1-[4-[1-(4-hydroxyphenyl)-1-methylethyl]phenyl]ethylidene]bis[phenol] based on the OECD draft protocols

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Abstract

We performed an uterotrophic assay, the Hershberger assay, and a 28-day repeated-dose toxicity study (enhanced OECD test guideline No. 407) of 4,4´-[1-[4-[1-(4-hydroxyphenyl)-1-methylethyl]phenyl]ethylidene]bis[phenol] 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 the uterine weight of rats given the 1,000 mg/kg dose of the test chemical plus ethinyl estradiol decreased. In the Hershberger assay, the test chemical was orally administered at doses of 0, 100, 300, and 1,000 mg/kg day to castrated male SD rats for ten consecutive days beginning on postnatal day 56, and no changes were observed. On the other hand, when the test chemical was orally administered at doses 0, 100, 300, and 1,000 mg/kg day for at least 28 days, a decrease in LH values in rats of both sexes and a decrease in FSH and estradiol values in female rats were detected in the 1,000 mg/kg group, and abnormal estrous cycles, uterine glandular atrophy, persistence of ovarian corpora lutea, vaginal epithelial mucification, and mammary glandular hyperplasia were also observed in one female rat in the 1,000 mg/kg group. Therefore, the uterotrophic assay used in this study showed that the chemical has the estrogen–antagonist properties, and some potentially endocrine-mediated effects were detected in growing rats based on the results of the enhanced OECD test guideline No. 407. However, the changes were observed in rats given a high dose of the chemical, 1,000 mg/kg day.

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References

  • Andrews P, Freyberger A, Hartmann E, Eiben R, Loof I, Schmidt U, Temerowski M, Becka M (2001) Feasibility and potential gains of enhancing the subacute rat study protocol (OECD test guideline no. 407) by additional parameters selected to determine endocrine modulation. A pre-validation study to determine endocrine-mediated effects of the antiandrogenic drug flutamide. Arch Toxicol 75:65–73

    Article  PubMed  CAS  Google Scholar 

  • Cho SD, Kim JH, Kim DY, Lee YS, Kang KS (2003) Pre-validation study for OECD enhanced test guideline 407 protocol by gavage for 4 weeks using propylthiouracil and tamoxifen. Toxicol Lett 144:195–204

    Article  PubMed  CAS  Google Scholar 

  • Kennel P, Pallen C, Barale-Thomas E, Espuna G, Bars R (2003) Tamoxifen: 28-day oral toxicity study in the rat based on the enhanced OECD test guideline 407 to detect endocrine effects. Arch Toxicol 77:487–499

    Article  PubMed  CAS  Google Scholar 

  • Kunimatsu T, Yamada T, Miyata K, Yabushita S, Seki T, Okuno Y, Matsuo M (2004) Evaluation for reliability and feasibility of the draft protocol for the enhanced rat 28-day subacute study (OECD guideline 407) using androgen antagonist flutamide. Toxicology 2000:77–89

    Article  Google Scholar 

  • Mellert W, Deckardt K, Walter J, Gfatter S, van Ravenzwaay B (2003) Detection of endocrine-modulating effects of the antithyroid acting drug 6-propyl-2-thiouracil in rats, based on the “enhanced OECD test guideline 407”. Regul Toxicol Pharmacol 38:368–377

    Article  PubMed  CAS  Google Scholar 

  • Miyata K, Shiraishi S, Houshuyama S, Imatanaka N, Umano T, Minobe Y, Yamasaki K (2006) Subacute oral toxicity study of di(2-ethylhexyl)adipate based on the draft protocol for the “enhanced OECD test guideline no. 407”. Arch Toxicol 80:181–186

    Article  PubMed  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

  • OECD (2000) OECD protocol for investigating the efficacy of the enhanced TG407 test guideline (phase 2), rationale for the investigation, and description of the protocol. OECD, Paris

  • OECD (2001) Third meeting of the validation management group for the screening and testing of endocrine disrupters (mammalian effects). OECD, Paris

  • 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

  • Okazaki K, Imazawa T, Nakamura H, Furukawa F, Nishikawa A, Hirose M (2002a) A repeated 28-day oral dose toxicity study of 17α-methyltestosterone in rats, based on the ‘enhanced OECD test guideline 407’ for screening endocrine-disrupting chemicals. Arch Toxicol 75:635–642

    Article  PubMed  CAS  Google Scholar 

  • Okazaki K, Okazaki S, Nakamura H, Kitamura Y, Hatayama K, Wakabayashi S, Tsuda T, Katsumata T, Nishikawa A, Hirose M (2002b) A repeated 28-day oral dose toxicity study of genisein in rats, based on the ‘enhanced OECD test guideline 407’ for screening endocrine-disrupting chemicals. Arch Toxicol 76:553–559

    Article  PubMed  CAS  Google Scholar 

  • Okazaki K, Okazaki S, Nishimura S, Nakamura H, Kitamura Y, Hatayama K, Nakamura A, Tsuda T, Katsumata T, Nishikawa A, Hirose M (2001) A repeated 28-day oral dose toxicity study of methoxychlor in rats, based on the ‘enhanced OECD test guideline 407’ for screening endocrine-disrupting chemicals. Arch Toxicol 75:513–521

    Article  PubMed  CAS  Google Scholar 

  • Shin JH, Moon HJ, Kim TS, Kang IH, Ki HY, Choi KS, Han SY (2006) Repeated 28-day oral toxicity study of vinclozolin in rats based on the draft protocol for the “enhanced OECD test guideline no. 407” to detect endocrine effects. Arch Toxicol 80:547–554

    Article  PubMed  CAS  Google Scholar 

  • Shiraishi K, Miyata K, Houshuyama S, Imatanaka N, Umano T, Minobe Y, Yamasaki K (2006) Subacute oral toxicity study of diethylphthalate based on the draft protocol for “Enhanced OECD Test Guideline no. 407”. Arch Toxicol 80:10–16

    Article  PubMed  CAS  Google Scholar 

  • Toyoda K, Shibuntani M, Tamaru T, Koujitani T, Uneyama C, Hirose M (2000) Repeated dose (28 days) oral toxicity study of flutamide in rats, based on the draft protocol for the ‘enhanced OECD test guideline 407’ for screening for endocrine-disrupting chemicals. Arch Toxicol 74:127–132

    Article  PubMed  CAS  Google Scholar 

  • Wason S, Pohlmeyer-Esch G, Pallen C, Palazzi X, Espina G, Bars R (2003) 17α-methyltestosterone: 28-day oral toxicity study in the rat based on the “enhanced OECD test guideline 407” to detect endocrine effects. Toxicology 192:119–137

    Article  PubMed  CAS  Google Scholar 

  • Yamasaki K, Noda N, Imatanaka N, Yakabe Y (2004) Comparative study of the uterotrophic potency of fourteen chemicals in a uterotrophic assay and their receptor-binding affinity. Toxicol Lett 146:111–120

    Article  PubMed  CAS  Google Scholar 

  • Yamasaki K, Tago Y, Nagai K, Sawaki M, Noda S, Takatsuki M (2002a) Comparison of toxicity studies based on the draft protocol for the “enhanced OECD test guideline no. 407” and the research protocol of “pubertal development and thyroid function in immature male rats” with 6-n-propyl-2-thiouracil. Arch Toxicol 76:495–501

    Article  PubMed  CAS  Google Scholar 

  • Yamasaki K, Sawaki M, Noda S, Imatanaka M, Takatsuki M (2002b) 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  PubMed  CAS  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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Authors and Affiliations

  1. Chemicals Evaluation and Research Institute, 3-822 Ishii, Hita, Oita, 877-0061, Japan

    Kanji Yamasaki, Katumi Miyata, Takako Muroi, Hatsune Ehara, Nobuhiko Higashihara, Satsuki Houshuyama, Hiroshi Oshima & Yasushi Minobe

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  1. Kanji Yamasaki
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  2. Katumi Miyata
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  3. Takako Muroi
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  4. Hatsune Ehara
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  5. Nobuhiko Higashihara
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  6. Satsuki Houshuyama
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  7. Hiroshi Oshima
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  8. Yasushi Minobe
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Correspondence to Kanji Yamasaki.

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Yamasaki, K., Miyata, K., Muroi, T. et al. Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 4,4´-[1-[4-[1-(4-hydroxyphenyl)-1-methylethyl]phenyl]ethylidene]bis[phenol] based on the OECD draft protocols. Arch Toxicol 81, 749–757 (2007). https://doi.org/10.1007/s00204-007-0211-8

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  • DOI: https://doi.org/10.1007/s00204-007-0211-8

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