TESTICULAR CYTOTOXICITY OF INTRAVENOUS METHOTREXATE IN RATS

Although the testicular cytotoxicity of methotrexate has been evaluate d in the rat, previous models have utilized routes other than the intr avenous one, and have generally employed multiple-dose regimens. In th is report, we describe testicular toxicity in the Sprague-Dawley rat f ollowing a single intravenous bolus of methotrexate (0-700 mg/kg body weight [BW]), with necropsy 56 days later. Testicular toxicity was eva luated qualitatively by histology and quantitatively by testicular wei ght, sperm head count, modified Johnsen score, repopulation index, and epididymal index. Effects of methotrexate on heart, lung, liver, and kidney histology were evaluated qualitatively. Oligospermia occurred a t low and intermediate dosages of methotrexate, but testicular atrophy was not observed. LD50 at day five for methotrexate appears to be app roximately 300 mg/kg BW using this regimen. This model will facilitate the study of techniques to avoid drug-induced testicular damage. (C) 1994 Wiley-Liss, Inc.