Suppression of the contact hypersensitivity response following topical exposure to 2-butoxyethanol in female BALB/c mice.
The effects of route of exposure, time of exposure and metabolism of 2-butoxyethanol (BE) on the contact hypersensitivity response (CHR) were evaluated in female BALB/c mice. Mice were either orally exposed to 50, 150 or 400 mg BE/kg or topically exposed to 0.25, 1.0, 4.0 or 16.0 mg BE on the ear and the oxazolone (OXA)-induced CHR evaluated by measuring ear thickness before and after OXA challenge. While no modulation was observed following oral exposure to BE, topical exposure resulted in a significant decrease in the CHR. Application of 4.0 mg BE in 4:1 acetone and olive oil (AOO) vehicle at the time of sensitization, challenge or both, decreased the CHR by 18%, 18% and 22%, respectively. A time course study of the effects of topical exposure to 4.0 mg BE/ear during the challenge phase of the CHR revealed that BE must be applied at the time of OXA challenge to significantly reduce the ear swelling response. In order to determine if metabolism of topically applied BE was required for suppression of the CHR, butoxyacetic acid (BAA), the primary metabolite of BE, was applied to the ear immediately following OXA challenge. No topical dose of BAA (2.0,4.0 and 8.0 mg BAA/ear) administered in this study altered the CHR. Blocking the metabolism of BE by oral administration of 4-methylpyrazole (MP), further reduced OXA-induced ear swelling when compared to mice exposed to BE without MP treatment. Taken together, these studies indicated that suppression of the CHR in mice following topical exposure to this glycol ether was due to the activity of BE itself and was not dependent on metabolic activation of the compound. Further studies were undertaken to identify a potential mechanism of BE-induced reduction of the CHR. Epidermal cells from untreated BALB/c mice were isolated and exposed to BE in vitro (10(-12), 10(-10), 10(-8), 10(-6) and l0(-4) M BE). In vitro exposure to BE at these concentrations did not significantly affect expression of MHC class II surface protein or protein synthesis in epidermal Langerhans cells, failing to provide in vitro evidence that BE-associated suppression of the CHR is associated with a reduction in MHC class II expression.
Singh
P
P
Division of Toxicology, College of Pharmacy and Health Sciences, The University of Louisiana at Monroe, 71209-0470, USA.
Morris
B
B
Zhao
S
S
Blaylock
B L
BL
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D004431:Ear, External / Q000187:drug effects / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D005026:Ethylene Glycols / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D005260:Female; D000077604:Fomepizole; D006016:Glycolates; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014176:Protein Biosynthesis; D011720:Pyrazoles / Q000494:pharmacology; D012997:Solvents
D000276:Adjuvants, Immunologic; D005026:Ethylene Glycols; D006016:Glycolates; D000949:Histocompatibility Antigens Class II; D011720:Pyrazoles; D012997:Solvents; C017095:n-butoxyacetic acid; D000077604:Fomepizole; C017096:n-butoxyethanol