Comparative testicular toxicity of bis(2-methoxyethyl) ether and 2-methoxyethanol in rats

Male rats were exposed to 0, 110, 370, or 1100 ppm bis(2-methoxyethyl)ether (diglyme) 6 h/day, 5 days/week for 2 weeks. One group of male rats was exposed to 300 ppm 2-methoxyethanol (2-ME) for 2 weeks as a positive control. Exposed rats were killed after 10 days of exposure and 14, 42, or 84 days post-exposure (PE), respectively. At 110 ppm diglyme, spermatocytes in pachytene and meiotic division at spermatogenic stages XII-XIV were mainly affected. At 370 ppm diglyme, affected germ cells were similar to those seen at 110 ppm diglyme, but round spermatids at spermatogenic stages I-VII were also affected. The testes regained normal spermatogenesis by 84 days PE. At 1100 ppm diglyme or 300 ppm 2-ME, marked testicular atrophy was found affecting all spermatogenic stages. Damaged seminiferous tubules were lined with regenerating pachytene spermatocytes at 14 days PE and with spermatocytes and round spermatids after 42 days PE. Most but not all testes in rats exposed to 300 ppm 2-ME or 1100 ppm diglyme had normal morphology after 84 days PE. Based on the observation of germ cell damage, spermatozoa population in the epidymal tubules, reversibility of spermatogenesis after various PE periods, testicular toxicity induced by 300 ppm 2-ME was more severe than that seen at 370 ppm diglyme but was slightly less remarkable than that of 1100 ppm diglyme.