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Studies on the toxicity of some glycol ethers and alkoxyacetic acids in primary testicular cell cultures

Studies on the toxicity of some glycol ethers and alkoxyacetic acids in primary testicular cell cultures

Toxicology & Applied Pharmacology 79(3): 490-501

Primary mixed cultures of Sertoli and germ cells were prepared from testes of immature rats and their response to the known testicular toxicants ethylene glycol monomethyl ether (EGM) and ethylene glycol monoethyl ether (EGE) was studied. EGM nor EGE did not produce any morphological evidence of toxicity when added to the culture medium at up to 50 mM for 72 h. Their metabolites methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) at 2-10 mM for 24-72 h caused degeneration of the pachytene and dividing spermatocytes, the target cells of the parent ethers in vivo. As in vivo, earlier spermatocytes, spermatogonia and Sertoli cells apepared unaffected. EAA was less potent than MAA; n-propoxy- and n-butoxyacetic acid, and methoxyacetylglycine, a further metabolite of MAA, produced no morphological changes under these conditions. The same order of toxicity was observed in concurrent studies with the 4 acids in rats. In culture, the severity of the morphological changes was paralleled by decreases in the activity of carnitine acetyltransferase and lactate dehydrogenase-X in the attached germ cell fraction. Analysis of culture medium provided no evidence for the conversion of EGM to MAA or other metabolities or for the further metabolism of MAA. The close correspondence between the testicular toxicity of alkoxyacetic acids in culture and in vivo suggested a similar mode of action in both cases and pointed to the potential value of these cultures for mechanistic studies and for screening purposes. The results emphasized the role of metabolism in the testicular toxicity of glycol ethers and indicated that MAA was an active metabolite of EGM.

Accession: 006522588

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PMID: 4035690

DOI: 10.1016/0041-008x(85)90146-2

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