GENDER DIFFERENCE IN THE ELIMINATION OF 2-METHOXYETHANOL, METHOXYACETIC ACID AND ETHOXYACETIC ACID IN RAT

1. The elimination of 2-methoxyethanol (2-ME) and its toxic metabolite methoxyacetic acid (MAA) was studied in the male and female rat We al so studied the elimination of ethoxyacetic acid (EAA), the toxic metab olite formed by 2-ethoxyethanol (2-EE). 2. The rate of 2-ME eliminatio n after i.p. injection of 2-ME (150 mg/kg) was significantly higher in the female compared with male. The elimination half-life was estimate d to 49 +/- 10 min in the male and 28 +/- 5 min in the female. There w as, however, no gender difference in the elimination of MAA after i.p. injection of 2-ME (100 mg/kg), and the elimination of MAA was markedl y slower compared with 2-ME. The elimination half-life for MAA was est imated to 12.6 +/- 1.3 h in the male and 14.1 +/- 1.4 h in the female. 3. The elimination half-life of EAA after i.p. injections of 100 mg/k g 2-EE was estimated to 7.6 +/- 1.1 h and 7.6 +/- 0.75 h in the male a nd female rat respectively. There was no gender difference in the elim ination of EAA, but the rate of elimination of EAA was significantly h igher compared with MAA. 4. Accumulation of the toxic metabolites MAA and EAA following frequent exposures to 2-ME and 2-EE respectively can then occur, and it remains to be determined whether there is a sex-di fference in the susceptibility to toxic effects following exposure to 2-ME and 2-EE.