Subchronic toxicity study on soy isoflavones in rats.
OBJECTIVE
To investigate the subchronic toxicity of soy isoflavones (SIF) in male rats.


METHODS
Fifty Sprague-Dawley rats were randomly divided into 5 groups, 10 rats per group. SIF were given to rats in different groups by gavage at dose of 0, 0.2, 0.5, 1.5, and 4.5 g/kg bw, respectively for 13 weeks. Clinical manifestations, body weight, and food consumption were observed weekly. At the end of the study, urinalysis, hematology, clinical chemistry, total testosterone, and follicle-stimulating hormone were tested, and histopathological examinations were performed.


RESULTS
No mortality, ophthalmic abnormalities or treatment-related clinical signs were identified during the study. As compared with the control group, significantly lower body weights and food consumption were observed in 1.5 and 4.5 g/kg bw groups. In clinical chemistry tests, triglyceride was significantly decreased and high-density lipoprotein cholesterol was significantly increased in all SIF-treated groups. Total testosterone levels were significantly lower in 0.50, 1.50, and 4.5 g/kg bw dose groups than in the control group. Microscopic examination showed that the mammary glands exhibited hyperplasia and excreted latex in rats of the 4.5 g/kg bw group. No changes attributable to treatment of SIF in other parameters were found.


CONCLUSIONS
SIF at high dosages caused significant endocrine disruption in male rats. The no observed adverse effect level (NOAEL) of SIF to male rats in this study is considered to be 0.20 g/kg bw.
Zhang
Wen-Zhong
WZ
Institute of Nutrition and Food Safety, Chinese Center for Disease Control and Prevention, Beijing 100021, China.
Cui
Wen-Ming
WM
Zhang
Xin
X
Wang
Wei
W
Jia
Xu-Dong
XD
Zhang
Xiao-Peng
XP
Li
Ning
N
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005640:Follicle Stimulating Hormone / Q000097:blood; D007529:Isoflavones / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013025:Glycine max / Q000737:chemistry*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D007529:Isoflavones; D014284:Triiodothyronine; D005640:Follicle Stimulating Hormone; D013974:Thyroxine