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 also studied the elimination of ethoxyacetic acid (EAA), the toxic metabolite formed by 2-ethoxyethanol (2-EE). 2. The rate of 2-ME elimination after i.p. injection of 2-ME (150 mg/kg) was significantly higher in the female compared with male. The elimination half-life was estimated to 49 +/- 10 min in the male and 28 +/- 5 min in the female. There was, 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 markedly slower compared with 2-ME. The elimination half-life for MAA was estimated to 12.6 +/- 1.3 h in the male and 14.1 +/- 1.4 in the female. 3. The elimination half-life of EAA after i.p. injections of 100 mg/kg 2-EE was estimated to 7.6 +/- 1.1 h and 7.6 +/- 0.75 h in the male and female rat respectively. There was no gender difference in the elimination of EAA, but the rate of elimination of EAA was significantly higher 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-difference in the susceptibility to toxic effects following exposure to 2-ME and 2-EE.