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METHOXYACETALDEHYDE, AN INTERMEDIATE METABOLITE OF 2-METHOXYETHANOL, IS IMMUNOSUPPRESSIVE IN THE RAT
Citation:
Smialowicz, R., M. Riddle, AND W. Williams. METHOXYACETALDEHYDE, AN INTERMEDIATE METABOLITE OF 2-METHOXYETHANOL, IS IMMUNOSUPPRESSIVE IN THE RAT. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/037 (NTIS PB94137171).
Description:
2-Methoxyethanol (ME) is metabolized to 2-methoxyacetic acid (MAA) via the intermediate metabolite methoxyacetaldehyde (MAAD). oth ME and MAA have been shown in this laboratory to be immunosuppressive in rats following oral dosing. n this study, the plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP-LPS) was used to determine if MAAD is immunosuppressive in rats. ats pretreated with the aldehyde dehydrogenase inhibitors disulfiram (2 mol/kg) or cyanamide (0.48 mmol/kg) followed by oral dosing with ME (2.64 mol/kg) resulted in suppressed PFC responses equivalent to the suppressed responses of rats dosed with ME alone. ats pretreated with disulfiram and then dosed with 2.64 mmol/kg 2-methoxyethyl acetate (MEA), also resulted in suppressed PFC responses similar to that of MEA alone. in contrast, co-administration of the alcohol dehydrogenase inhibitor 4methylpyrazole (1.2 mmol/kg) with ME or MEA blocked suppression of the PFC response following exposure to ME or MEA alone. ral dosing with equimolar (2.64 mmol/kg) concentrations of ME, MAA or MAAD resulted in equivalent suppression of the TNP-LPS PFC response. ats exposed to either disulfiram or cyanamide and MAAD also resulted in suppression of the PFC response. hese results indicate that metabolism of ME to either MAAD or MAA is required for immunosuppression, and that these two metabolites are equipotent immunosuppressants in the rat.