Toxicology Letters 135 (2002) 111 – 123 No androgenic/anti-androgenic effects of bisphenol-A in Hershberger assay using immature castrated rats Hyung Sik Kim a , Soon Young Han a , Tae Sung Kim a , Seung Jun Kwack a , Rhee Da Lee a , In Young Kim a , Ji-Hyun Seok a , Byung Mu Lee b , Sun Dong Yoo b , Kui Lea Park a, * a Reproductie and Deelopmental Toxicology Diision, Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration, 5 Nokbun -dong, Eunpyung -ku, 122 -704 Seoul, South Korea b College of Pharmacy, Sungkyunkwan Uniersity, Kyunggi -do, 440 -746 Suwon, South Korea Received 15 October 2001; received in revised form 6 March 2002; accepted 7 March 2002 Abstract Several studies have demonstrated that bisphenol A (BPA) exhibited weak estrogenic activity in the 3-day uterotrophic assay using ovariectomized (OVX) and immature rats (Toxicol. Lett. 115 (2000) 231; Regul. Toxicol. Pharmacol. 32 (2000) 118; J. Toxicol. Sci. 26 (2001) 111) and BPA also possessed anti-androgenic activity in in vitro yeast based assays (J. Endocrinol. 158 (1998) 327). To investigate anti-androgenic effects of BPA. a rodent Hershberger assay was carried out using immature Sprague – Dawley male rats. An androgen agonist, testosterone (0.4 mg/kg per day), was administered for 7 consecutive days by subcutaneous (s.c.) injection as a positive control. Additionally, a pure androgen antagonist, flutamide (1, 5. 10 mg/kg per day. oral) was co-administered with testosterone (0.4 mg/kg per day s.c.). BPA was also administered orally with or without testosterone (0.4 mg/kg per day, s.c.) for 7 consecutive days. In the testosterone treated groups, glans penis, seminal vesicles, ventral prostate, and leator ani plus bulbocaernosus muscles (LABC) weights were significantly increased compared with control. However. flulamide dose-dependently inhibited the testosterone-induced re-growth of seminal vesicles, ventral prostate, and LABC, with a significant decrease at flutamide 1.0 mg/kg and above (P 0.05). Serum LH levels were also significantly increased (5 mg/kg and above, P 0.05), but no changes in serum testosterone levels. In contrast, BPA had no effects on the re-growth of seminal vesicles, ventral prostate and LABC induced by testosterone, and no significant differences were observed in serum LH and testosterone levels. In summary, the Hershberger assay could be a sensitive method for detecting androgenic or anti-androgenic chemicals, but BPA did not exhibit any androgenic or anti-androgenic activities in Hershberger assay. © 2002 Published by Elsevier Science Ireland Ltd. Keywords: Bisphenol A; Uterotrophic assay; Hershberger assay; Flutamide; Testosterone www.elsevier.com/locate/toxlet 1. Introduction The endocrine-disrupting effects of many xeno- biotics may result from interference with sex * Corresponding author. Tel.: +82-2-380-1878; fax: +82- 2-388-6395 E-mail address: parkkl@kfda.go.kr (K.L. Park). 0378-4274/02/$ - see front matter © 2002 Published by Elsevier Science Ireland Ltd. PII:S0378-4274(02)00130-3