Bis(2-methoxyethyl) ether: metabolism and embryonic disposition of a developmental toxicant in the pregnant cd-1 mouse.
Daniel-FB; Cheever-KL; Begley-KB; Richards-DE; Weigel-WW; Eisenmann-CJ
Fundam Appl Toxicol 1991 Apr; 16(3):567-575
An investigation was conducted to determine whether developmental toxicity in the pregnant CD-1 mouse, reported to occur after the oral administration of bis(2-methoxyethyl)-ether (111966) (DGDME), can be explained by the metabolism or fetal distribution of DGDME in the mouse. Elimination of DGDME was primarily by the urine, with 97% of the administered dose excreted within 48 hours. The percentage of the various urinary metabolites in the pregnant CD-1 mouse was dependent on the time interval of urine collected after administration of DGDME. The major urinary metabolite present at each of the times tested was identified as (2-methoxyethoxy)acetic- acid (MEAA) and the second most abundant metabolite was methoxyacetic-acid (MA). In the 6 and 24 hour urine samples, these two acids accounted for 71 and 24% of the total urinary radioactivity, respectively. High pressure liquid chromatographic analysis of the radioactivity present in embryonic tissue collected at termination revealed a profile of metabolites similar to that noted for the blood. The major peak demonstrated an elution time consistent with that of MA after 3 hours. The highest level of carbon-14 present in embryos taken at each time point after the administration of DGDME was detected 6 hours after dosing. The ratio of residual MA present in the embryo to that of the maternal blood was 1.6. MA was the only radiolabeled peak detected in either maternal blood or embryonic tissue 6 hours after dosing. The authors conclude that DGDME is rapidly metabolized in the pregnant CD-1 mouse and is excreted principally by the urine.
NIOSH-Author; Laboratory-animals; Excretion; Metabolic-study; Ethers; Tissue-distribution; Urinalysis; Blood-analysis; Organic-solvents; Solvents; Developmental-disorders
Fundamental and Applied Toxicology