Changes of serum alpha 2u-globulin in the subacute oral toxicity study of ethynyl estradiol and bisphenol A based on the draft protocol for the 'Enhanced OECD Test Guideline No. 407'.
To investigate the usefulness of serum alpha 2u-globulin changes as a new parameter for detecting endocrine-mediated effects, we performed a 28-day repeated-dose toxicity study using the administration of bisphenol A (BPA) or ethynyl estradiol (EE) in male rats, based on the draft protocol of the 'Enhanced OECD Test Guideline 407 (enhanced TG 407)'. BPA at doses of 0, 40, 200 and 1000 mg/kg per day or EE at doses of 0, 15, 75 and 375 microg/kg per day were orally administered to SD rats. The highest dose of BPA was reduced to 600 mg/kg per day from the second week of the study onwards because a male rat given 1000 mg/kg per day of BPA died within the first week, showing toxic clinical signs. In the assay using BPA, a reduction in the level of alpha 2u-globulin was detected in the group receiving a dose of 600 mg/kg per day. Reductions in the absolute and relative ventral prostate weights were only observed in the 600 mg/kg per day group. In the assay using EE, the alpha 2u-globulin level decreased significantly in the 375 microg/kg per day group. A reduction in the absolute and relative dorsolateral prostate weights was also observed in the 75 and 375 microg/kg per day groups, morphologically abnormal sperm were observed in the 375 microg/kg per day group. Furthermore, atrophic changes in the prostate and seminal vesicle and degenerative changes in the testis were observed in the 375 microg/kg per day group. Although the alpha 2u-globulin level was reduced in this assay using BPA and EE, further studies are necessary before this assay becomes a useful method for detecting endocrine-mediated effects.
Yamasaki
Kanji
K
Chemicals Evaluation and Research Institute, Chemicals Assessment Center, 3-822 Ishii, Hita, Oita 877-0061, Japan. yamasaki-kanji@ceri.jp
Takeyoshi
Masahiro
M
Noda
Shuji
S
Takatsuki
Mineo
M
D000284:Administration, Oral; D000510:Alpha-Globulins / Q000032:analysis*; D000818:Animals; D001559:Benzhydryl Compounds; D015415:Biomarkers / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D045166:Estradiol Congeners / Q000008:administration & dosage / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000633:toxicity*; D005062:European Union; D005837:Genitalia, Male / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D011517:Prothrombin Time; D051381:Rats; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology; D018675:Toxicity Tests; D000098826:Bisphenol A Compounds
D000510:Alpha-Globulins; D001559:Benzhydryl Compounds; D015415:Biomarkers; D045166:Estradiol Congeners; D004968:Estrogens, Non-Steroidal; D004997:Ethinyl Estradiol; D010636:Phenols; C013803:alpha 2u globulin; C006780:bisphenol A; D000098826:Bisphenol A Compounds