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

Journal Article · Wed Aug 01 00:00:00 EDT 1984 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.1289/ehp.8457207· OSTI ID:5829754

Foster, P M.D.; Creasy, D M; Foster, J R; Gray, T J.B.

Ethylene glycol monomethyl ether (EGME) and ethylene glycol monoethyl ether (EGEE) were administered orally to young male rats at doses varying from 50 to 500 mg/kg/day and 250 to 1000 mg/kg/day EGME and EGEE, respectively, for 11 days. At sequential times animals were killed and testicular histology examined. The initial and major site of damage following EGME treatment was restricted to the primary spermatocytes undergoing post-zygotene meiotic maturation and division. EGEE produced damage of an identical nature, but a larger dose was required to elicit equivalent severity (500 mg EGEE/kg/being approximately equivalent to 100 mg EGME/kg). Additionally, within the spermatocyte population, differential sensitivity was observed depending on the precise stage of meiotic maturation: dividing (stage XIV) and early pachytene (stages I-II) > late pachytene (stages VIII-XIII) > mid-pachytene (stages III-VII). Equivalent doses of methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) gave injury similar to the corresponding glycol ether. When animals were pretreated with inhibitors of alcohol metabolism followed by a testicular toxic dose of EGME (500 mg/kg), an inhibitor of alcohol dehydrogenase (pyrzaole) offered complete protection. Pretreatment with the aldehyde dehydrogenase inhibitors disulfiram or pargyline did not ameliorate the testicular toxicity of EGME. In mixed cultures of Sertoli-germ cells, MAA and not EGME produced effects on spermatocytes analogous to that seen in vivo, at concentrations approximately equivalent to steady-state plasma levels after a single oral dose of EGME (500 mg/kg). It would seem likely that a metabolite and not EGME is responsible for the production of testicular damage. 16 references, 10 figures, 4 tables.

• Research Organization: British Industrial Biological Research Association, Surrey, England
• OSTI ID: 5829754
• Journal Information: Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 57; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETIC ACID
ALCOHOLS
ANIMALS
BODY
CARBOXYLIC ACIDS
CELL DIVISION
DOSE-RESPONSE RELATIONSHIPS
ENZYME INHIBITORS
ENZYMES
ETHERS
ETHYL ETHER
GERM CELLS
GLYCOLS
GONADS
HYDROXY COMPOUNDS
INJURIES
MALE GENITALS
MAMMALS
METABOLITES
METHYL ETHER
MONOCARBOXYLIC ACIDS
ORAL ADMINISTRATION
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
RATS
RODENTS
SENSITIVITY
SPERMATOCYTES
TESTES
TOXICITY
VERTEBRATES