COMPARISON OF THE TESTICULAR EFFECTS OF 2-METHOXYETHANOL (ME) IN RATSAND GUINEA-PIGS

Glycol ethers produce both hemato- and testicular toxicity in animals, which is dependent on both the alkyl chain length and animal species used. Ethylene glycol monobutyl ether (2-butoxyethanol, BE) causes hem olytic anemia in rats but not in guinea pigs, and red blood cells from both guinea pigs and humans are minimally affected in vitro by the ac tive metabolite 2-butoxyacetic acid. This demonstrates the importance of animal species selection for assessing human risk to BE exposure. 2 -Methoxyethanol (ME) produces testicular lesions in rats characterized primarily by the degeneration of spermatocytes undergoing meiotic div ision with minimal or no hemolytic changes. Because of the differentia l hemolytic response to BE between rats and guinea pigs, the present s tudy addressed whether the testicular response to ME was similarly dic hotomous. Adult rats or guinea pigs were given a single dose of either 200 or 300 mg ME/kg by gavage, and testicular and hemolytic changes w ere assessed 24 hr after treatment. Testis histology in rats showed do se-dependent degeneration of dividing spermatocytes in stage XIV tubul es as expected, with only minimal hemolytic changes, also as expected. In contrast, no testicular or hemolytic effects were observed in guin ea pigs 24 hr after either single ME dose. In a subsequent study, a si ngle dose or multiple (3 daily) doses of 200 mg MEikg were given, and animals were examined at 4 days after the start of treatment. Testes f rom rats given both single and multiple ME doses showed, as expected, tubules depleted of spermatocytes and early spermatids. In guinea pigs , spermatocyte degeneration was observed in stage III/IV tubules for b oth dosing schemes, but was much less severe and widespread and differ ed from rats in morphological characteristics, specifically in the app earance of nuclear chromatin degeneration. In the rat, degenerating sp ermatocytes showed uniformly condensed and dispersed chromatin, while in the guinea pig they showed marked chromatin condensation at the nuc lear periphery. No hemolytic changes were observed in either species o r dosing scheme. In summary, although ME-associated testicular lesions were observed in both species, they differed significantly in onset, characteristics, and severity. Both the nature of the differential tes ticular response to ME and a comparison to the in vitro human testicul ar response to the active metabolite 2-methoxyacetic acid are subjects of future study. (C) 1991 Academic Press, Inc.