Toxicology 192 (2003) 119–137 17-Methyltestosterone: 28-day oral toxicity study in the rat based on the “Enhanced OECD Test Guideline 407” to detect endocrine effects Sheila Wason ∗ , Gabriele Pohlmeyer-Esch, Catherine Pallen, Xavier Palazzi, Gemma Espuña, Remi Bars Bayer CropScience, Centre de Recherche de Sophia-Antipolis, BP153, F-06903 Sophia-Antipolis, France Received 11 April 2003; accepted 16 June 2003 Abstract A 28-day oral gavage toxicity study in the rat with 17-methyltestosterone was conducted as part of the international validation exercise on the modified Enhanced OECD Test Guideline 407 (Organisation for Economic Co-operation and Development, Paris). Special emphasis was placed on the endocrine mediated effects exerted by 17-methyltestosterone, a potent androgen agonist. The test compound was administered daily by oral gavage for at least 28 days to groups of 7-week-old-Wistar rats. Dose levels were 0, 10, 40 and 200 mg/kg body weight per day for males and 0, 10, 100 and 600 mg/kg body weight per day for females. In addition, and outside the remit of the enhanced protocol, testosterone levels in males, oestradiol levels in females and luteinizing hormone (LH) levels in both sexes were measured, to provide a broader profile on the hormonally mediated effects of 17-methyltestosterone. Furthermore, stage-specific quantification of Terminal deoxynucleotidyl transferase-mediated dUTP Nick-End Labeling (TUNEL)-labeled germ cells (apoptotic germ cells) in the seminiferous tubules was also performed, in an effort to demonstrate the precise stages in the spermatogenic cycle 17-methyltestosterone exerts its effect. In this study, the most critical additional parameters contained in the Enhanced OECD Test Guideline 407 for the detection of endocrine disruption were considered to be the histopathological assessment and organ weight data of endocrine-related tissues. Beyond the scope of this validation exercise, an increase in apoptosis in specific germ cell types was detected using the TUNEL assay in male rats treated at 200 and 40 mg/kg. © 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Enhanced OECD Test Guideline 407; Rat; Endocrine disruptors; 17-Methyltestosterone; Androgen agonist; Apoptosis ∗ Corresponding author. Tel.: +33-492-943-460; fax: +33-493-958-454. E-mail address: sheila.wason@bayercropscience.com (S. Wason). 1. Introduction In recent years, there has been growing concern amongst both the general public and scientific com- munity regarding the adverse effects on man and the environment caused by chemicals with an en- docrine disruptive potential. In response to these 0300-483X/$ – see front matter © 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0300-483X(03)00265-8