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Metabolism of bis(2-methoxyethyl) ether in the adult male rat: evaluation of the principal metabolite as a testicular toxicant.
Cheever KL; Richards DE; Weigel WW; Lal JB; Dinsmore AM; Daniel FB
Toxicol Appl Pharmacol 1988 Jun; 94(1):150-159
The testicular toxicity of bis(2-methoxyethyl)ether (111966) (diglyme) was studied in rats. Male Sprague-Dawley-rats were given labeled diglyme orally. Expired air, feces, and urine were collected for 96 hours and analyzed for C-14 and diglyme metabolites by high performance liquid chromatography. Approximately 86 to 90 percent of each dose was excreted in the urine over 96 hours. Less than 5 percent of the doses was excreted in the feces. Only trace amounts of radiolabel were found in the expired air as volatile organic compounds. The principal urinary metabolites were (2- methoxyethoxy)acetic-acid (16024569) (MEAA) and methoxyacetic-acid (625456) (MAA) which accounted for around 70 and 6 percent of the doses, respectively. Smaller amounts of N-(methoxyacetyl)glycine, diglycolic-acid (110996 ), 2-methoxyethanol (109864), and 2-(2- methoxyethoxy)ethanol (111773) (MEE) were found. Only unchanged diglyme was found in the volatile organic fraction of the expired air. Additionally, rats were given up to 20 daily doses of 5.1mmol/kg MEE or MEAA. Selected animals were killed at 2 day intervals on days 3 through 21, the testes were removed, and examined for gross and histopathological changes. MEE and MEAA induced no gross or histopathological testicular changes. The authors conclude that diglyme metabolism proceeds primarily through an O-demethylation pathway, followed by oxidation to MEAA. The lack of toxicity of MEE and MEAA suggests that the testicular toxicity of diglyme may be due to MAA, a minor metabolite.
NIOSH-Author; In-vivo-studies; Laboratory-animals; Ethers; Histopathology; Organic-solvents; Biotransformation; Urinalysis; Reproductive-hazards
111-96-6; 16024-56-9; 625-45-6; 109-86-4; 111-77-3
Issue of Publication
Toxicology and Applied Pharmacology
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