Metabolism of bis(2-methoxyethyl) ether in the adult male rat: evaluation of the principal metabolite as a testicular toxicant

Journal Article · Wed Jun 15 00:00:00 EDT 1988 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(88)90345-6· OSTI ID:6922248

Cheever, K L; Richards, D E; Weigel, W W; Lal, J B; Dinsmore, A M; Daniel, F B

The metabolism of the reproductive toxicant bis(2-methoxyethyl) ether was studied in male Sprague-Dawley rats, and the principal metabolite (2-methoxyethoxy)acetic acid and its metabolic precursor 2-(2-methoxyethoxy)ethanol were evaluated separately as testicular toxicants. For the metabolism study, rats were given single po doses of (1,2-ethylene-/sup 14/C)bis(2-methoxyethyl) ether at 5.1 or 0.051 mmol/kg body wt. Within 96 hr, approximately 86 to 90% of the radioactivity was excreted in the urine. Urinary metabolites were separated by high-performance liquid chromatography and isolated for characterization by gas chromatography-mass spectrometry. The principal urinary metabolite, accounting for 67.9 +/- 3.3% of the administered high dose and 70.3 +/- 1.3% of the low dose, was identified as (2-methoxyethoxy)acetic acid. A second metabolite, representing 6.2 +/- 0.8% of the high dose and 5.8 +/- 0.8% of the low dose, was identified as methoxyacetic acid, a previously recognized testicular toxicant. In the toxicity study, (2-methoxyethoxy)acetic acid and 2-(2-methoxyethoxy)ethanol were administered to rats at 5.1 mmol/kg body wt by gavage as single daily doses for as many as 20 consecutive days. The testes of rats killed 24 hr after the administration of even numbered doses showed no gross or microscopic abnormalities. These results are in contrast to the previously reported testicular atrophy evoked after as few as 8 daily doses of the parent compound, bis(2-methoxyethyl) ether, tested under the same experimental conditions. Thus, the testicular toxicity reported for bis(2-methoxyethyl) ether could be explained by the presence of a minor metabolite, methoxyacetic acid.

• Research Organization: Centers for Disease Control, Cincinnati, OH (USA)
• OSTI ID: 6922248
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 94:1; ISSN TXAPA
• Country of Publication: United States
• Language: English

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560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETIC ACID
ALCOHOLS
ANIMALS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHROMATOGRAPHY
DEALKYLATION
ETHANOL
GAS CHROMATOGRAPHY
GONADS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MALE GENITALS
MAMMALS
MASS SPECTROSCOPY
METABOLISM
METABOLITES
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PRECURSOR
RATS
RODENTS
SENSITIVITY
SEPARATION PROCESSES
SPECTROSCOPY
TESTES
TOXICITY
TRACER TECHNIQUES
VERTEBRATES