title: Comparative immunosuppression of various glycol ethers orally administered to Fischer 344 rats.
abstract: Oral dosing of adult male F344 rats with the glycol ether 2-methoxyethanol (ME) or its principal metabolite 2-methoxyacetic acid (MAA) results in the suppression of the primary plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP-LPS). In the present study, the PFC response to TNP-LPS was used to evaluate the immunotoxic potential of ethylene glycol (EG) as well as the glycol ethers 2-methoxyethyl acetate (MEA), 2-(2-methoxyethoxy) ethanol, bis(2-methoxyethyl) ether, 2-ethoxyethanol and its principal metabolite 2-ethoxyacetic acid, 2-ethoxyethyl acetate, and 2-butoxyethanol relative to ME and MAA. Rats were immunized with TNP-LPS and then exposed 4 and 28 hr later to 50, 100, 200, or 400 mg/kg of glycol ether or EG. Three days following immunization, the PFC response to TNP-LPS was determined. In addition to ME and MAA, only MEA, which was as effective as ME, suppressed the PFC response to TNP-LPS. Concomitant administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole with ME or MEA prevented suppression of the PFC response by these glycol ethers. These results indicate that of the chemicals tested only ME, MEA, and MAA are immunosuppressive, and that oxidative metabolism via alcohol dehydrogenase is necessary for ME- and MEA-suppression of the response to TNP-LPS.
authors.affiliation: Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: R J
authors.initials: RJ
authors.lastname: Smialowicz
authors.forename: W C
authors.initials: WC
authors.lastname: Williams
authors.forename: M M
authors.initials: MM
authors.lastname: Riddle
authors.forename: D L
authors.initials: DL
authors.lastname: Andrews
authors.forename: R W
authors.initials: RW
authors.lastname: Luebke
authors.forename: C B
authors.initials: CB
authors.lastname: Copeland
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005026:Ethylene Glycols / Q000494:pharmacology / Q000633:toxicity*; D006462:Hemolytic Plaque Technique; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008070:Lipopolysaccharides; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D005026:Ethylene Glycols; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; C048761:trinitrophenyl-lipopolysaccharide; C005219:methyl cellosolve; C045156:2-methoxyethanol acetate