Testicular toxicity of ethylene glycol monomethyl and monoethyl ethers in the rat

Ethylene glycol monomethyl (EGM) and monoethyl (EGE) ethers were administered po to rats at dosages varying from 50 to 500 mg/kg body weight/day for EGM and 250 to 1000 mg/kg body weight/day EGE for 11 days. First evidence of testicular damage following EGM treatment was observed 24 hr after a single dose of 100 mg/kg body weight when the lesion appeared localized in the primary spermatocyte. At 16 hr after a single dose of 500 mg/kg, mitochondrial damage was one of the first subcellular changes to be demonstrated. Treatment of animals with EGE resulted in a similar lesion; however, to obtain damage of equivalent severity, a larger dosage for a longer period was required. In limited studies with 2-methoxy- and 2-ethoxyacetic acids (putative metabolites of EGM and EGE, respectively), using equimolar doses to their parent compounds (500 mg EGM or EGE/kg for 4 or 11 days, respectively) gave damage of equivalent severity to the corresponding glycol ether. After dosing animals with 500 mg EGM/kg body weight for 4 days, the testes recovered weight, and the majority of tubules recovered their spermatogenic potential within one full maturation cycle. The recovery study also indicated a possible effect on the spermatogonia in a small number of tubules although no morphological abnormalities to this cell type could be observed. No effect levels over the 11-day treatment period were 50 and 250 mg/kg body weight/day for EGM and EGE, respectively.