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Subacute oral toxicity study of ethynylestradiol and bisphenol A, based on the draft protocol for the "Enhanced OECD Test Guideline no. 407".
Arch Toxicol. 2002 Mar; 76(2):65-74.AT

Abstract

We performed a 28-day repeated-dose toxicity study of ethynylestradiol (EE) and bisphenol A (BPA) based on the draft protocol of the "Enhanced OECD Test Guideline no. 407", and assessed the sensitivity of a list of parameters for detecting endocrine-related effects of endocrine disruption. Doses of EE at 0, 10, 50 or 200 microg/kg per day, or BPA at 0, 40, 200 or 1000 mg/kg per day were orally administered to Sprague-Dawley rats. The highest dose of BPA was decreased to 600 mg/kg per day from the second week of administration because a male rat given 1000 mg/kg BPA had died within 1 week with toxic clinical signs. In the assay using EE, the decrease of prostate, seminal vesicle and pituitary weights, increase of the testis weight, atrophic changes of the prostate, seminal vesicle and mammary gland, and degenerative changes in the testes were detected in male rats in the 50 and/or 200 microg/kg groups. In females of the 200 microg/kg group, decrease of the ovary weight, increase of the uterine weight, atrophy of the ovary, hypertrophy or squamous metaplasia of the uterine epithelial cells and mucification in the vagina were observed. Furthermore, diestrous, estrous or the unknown stage was prolonged in the 50 and 200 microg/kg groups of rats. Endocrine-mediated effects of EE were not detected in general observations, hematology, serum biochemistry, or hormonal or spermatological examinations. In the assay using BPA, the diestrous stages were prolonged at the highest dose, but changes related to endocrine effects were not detected in other examinations. Thus, among the parameters tested, the weight of endocrine-linked organs and their histopathological assessment and estrous cycle stage allowed the detection of the endocrine-related effect of EE, whereas the estrous cycle stage was only a useful parameter to detect the effect of BPA.

Authors+Show Affiliations

Chemicals Assessment Center, Chemicals Evaluation and Research Institute, 3-822 Ishii, Hita, Oita 877-0061, Japan. yamasaki-kanji@ceri.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11914775

Citation

Yamasaki, Kanji, et al. "Subacute Oral Toxicity Study of Ethynylestradiol and Bisphenol A, Based On the Draft Protocol for the "Enhanced OECD Test Guideline No. 407"." Archives of Toxicology, vol. 76, no. 2, 2002, pp. 65-74.
Yamasaki K, Sawaki M, Noda S, et al. Subacute oral toxicity study of ethynylestradiol and bisphenol A, based on the draft protocol for the "Enhanced OECD Test Guideline no. 407". Arch Toxicol. 2002;76(2):65-74.
Yamasaki, K., Sawaki, M., Noda, S., Imatanaka, N., & Takatsuki, M. (2002). Subacute oral toxicity study of ethynylestradiol and bisphenol A, based on the draft protocol for the "Enhanced OECD Test Guideline no. 407". Archives of Toxicology, 76(2), 65-74.
Yamasaki K, et al. Subacute Oral Toxicity Study of Ethynylestradiol and Bisphenol A, Based On the Draft Protocol for the "Enhanced OECD Test Guideline No. 407". Arch Toxicol. 2002;76(2):65-74. PubMed PMID: 11914775.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subacute oral toxicity study of ethynylestradiol and bisphenol A, based on the draft protocol for the "Enhanced OECD Test Guideline no. 407". AU - Yamasaki,Kanji, AU - Sawaki,Masakuni, AU - Noda,Shuji, AU - Imatanaka,Nobuya, AU - Takatsuki,Mineo, Y1 - 2002/02/06/ PY - 2001/10/08/received PY - 2001/12/13/accepted PY - 2002/3/27/pubmed PY - 2002/8/3/medline PY - 2002/3/27/entrez SP - 65 EP - 74 JF - Archives of toxicology JO - Arch Toxicol VL - 76 IS - 2 N2 - We performed a 28-day repeated-dose toxicity study of ethynylestradiol (EE) and bisphenol A (BPA) based on the draft protocol of the "Enhanced OECD Test Guideline no. 407", and assessed the sensitivity of a list of parameters for detecting endocrine-related effects of endocrine disruption. Doses of EE at 0, 10, 50 or 200 microg/kg per day, or BPA at 0, 40, 200 or 1000 mg/kg per day were orally administered to Sprague-Dawley rats. The highest dose of BPA was decreased to 600 mg/kg per day from the second week of administration because a male rat given 1000 mg/kg BPA had died within 1 week with toxic clinical signs. In the assay using EE, the decrease of prostate, seminal vesicle and pituitary weights, increase of the testis weight, atrophic changes of the prostate, seminal vesicle and mammary gland, and degenerative changes in the testes were detected in male rats in the 50 and/or 200 microg/kg groups. In females of the 200 microg/kg group, decrease of the ovary weight, increase of the uterine weight, atrophy of the ovary, hypertrophy or squamous metaplasia of the uterine epithelial cells and mucification in the vagina were observed. Furthermore, diestrous, estrous or the unknown stage was prolonged in the 50 and 200 microg/kg groups of rats. Endocrine-mediated effects of EE were not detected in general observations, hematology, serum biochemistry, or hormonal or spermatological examinations. In the assay using BPA, the diestrous stages were prolonged at the highest dose, but changes related to endocrine effects were not detected in other examinations. Thus, among the parameters tested, the weight of endocrine-linked organs and their histopathological assessment and estrous cycle stage allowed the detection of the endocrine-related effect of EE, whereas the estrous cycle stage was only a useful parameter to detect the effect of BPA. SN - 0340-5761 UR - https://www.unboundmedicine.com/medline/citation/11914775/Subacute_oral_toxicity_study_of_ethynylestradiol_and_bisphenol_A_based_on_the_draft_protocol_for_the_"Enhanced_OECD_Test_Guideline_no__407"_ L2 - https://doi.org/10.1007/s00204-001-0319-1 DB - PRIME DP - Unbound Medicine ER -