Testicular toxicity produced by ethylene glycol monomethyl and monoethyl ethers in the rat.

• DOI: 10.1289/ehp.8457207
• Publication Date: 2011-05-02T15:18:09Z
• Authors: P M Foster; D M Creasy; J R Foster; T J Gray
• Keywords: Male; 0301 basic medicine; Time Factors; Organ Size; Acetates; Seminiferous Tubules; Testicular Diseases; Rats; 3. Good health; 03 medical and health sciences; Pargyline; Disulfiram; Testis; Animals; Pyrazoles; Ethylene Glycols; Tissue Distribution; Biotransformation; Cells, Cultured

Ethylene glycol monomethyl ether (EGME) and ethylene monoethyl (EGEE) were administered orally to young male rats at doses varying from 50 500 mg/kg/day 250 1000 for EGME EGEE, respectively, 11 days. At sequential times animals killed testicular histology examined. The initial major site of damage following treatment was restricted the primary spermatocytes undergoing postzygotene meiotic maturation division. EGEE produced an identical nature, but a larger dose required elicit equivalent severity (500 mg EGEE/kg being approximately 100 EGME/kg). Additionally, within spermatocyte population, differential sensitivity observed depending on precise stage maturation: dividing (stage XIV) early pachytene (stages I-II) greater than late VIII-XIII) mid-pachytene III-VII). Equivalent methoxyacetic acid (MAA) ethoxyacetic (EAA) gave injury similar corresponding ether. When pretreated with inhibitors alcohol metabolism followed by toxic mg/kg), inhibitor dehydrogenase (pyrazole) offered complete protection. Pretreatment aldehyde disulfiram or pargyline did not ameliorate toxicity EGME. In mixed cultures Sertoli-germ cells, MAA effects analogous that seen in vivo, concentrations steady-state plasma levels after single oral mg/kg). It would seem likely metabolite (MAA possibly methoxyacetaldehyde) is responsible production damage.