Testicular cytotoxicity of intravenous methotrexate in rats.

Although the testicular cytotoxicity of methotrexate has been evaluated in the rat, previous models have utilized routes other than the intravenous one, and have generally employed multiple-dose regimens. In this report, we describe testicular toxicity in the Sprague-Dawley rat following a single intravenous bolus of methotrexate (0-700 mg/kg body weight [BW]), with necropsy 56 days later. Testicular toxicity was evaluated qualitatively by histology and quantitatively by testicular weight, 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 at low and intermediate dosages of methotrexate, but testicular atrophy was not observed. LD50 at day five for methotrexate appears to be approximately 300 mg/kg BW using this regimen. This model will facilitate the study of techniques to avoid drug-induced testicular damage.