Combined subchronic toxicity of bisphenol A and dibutyl phthalate on male rats.

Zhang, Wen Zhong; Yong, Ling; Jia, Xu Dong; Li, Ning; Fan, Yong Xiang

OBJECTIVE To evaluate the combined subchronic toxicity of bisphenol A (BPA) and dibutyl phthalate (DBP) in male Sprague Dawley (SD) rats. METHODS Forty 4-week-old male rats weighing 115-125 g were randomly divided into BPA-treated, DBP-treated group, BPA+DBP-treated and control groups and fed with a soy- and alfalfa-free diet containing 285.4 ppm BPA, 285.4 ppm DBP, 285.4 ppm BPA plus 285.4 ppm DBP, and a control diet, respectively, for 90 consecutive days. At the end of the study, the animals were sacrificed by exsanguination via the carotid artery under diethyl etherane aesthesia and weighed. Organs, including liver, kidneys, spleen, thymus, heart, brain, and testis underwent pathological examination. The androgen receptor (AR), gonadotropin-releasing hormone receptor (GNRHR), and progesterone hormone receptor (PR) genes from the hypothalamus were detected by real-time PCR. The biomedical parameters were analyzed. RESULTS No significant difference was found in food intake, body weight, tissue weight, organ/brain weight ratio, and biomedical parameters among the four groups (P>0.05). However, BPA and DBP up-regulated AR, PR and GNRHR expression levels in rats and showed a synergistic or an additive effect in the BPA+DBP group. CONCLUSION The combined subchronic toxicity of BPA and DBP is synergistic or additive in male SD rats.