Reduced sensitizing capacity of epoxy resin systems: a structure-activity relationship study.
Epoxy resins can be prepared from numerous chemical compositions. Until recently, alternatives to epoxy resins based on diglycidyl ethers of bisphenol A (DGEBA) or bisphenol F (DGEBF) monomers have not received commercial interest, but are presently doing so, as epoxy resins with various properties are desired. Epoxy resin systems are known to cause allergic contact dermatitis because of contents of uncured monomers, reactive diluents, and hardeners. Reactive diluents, for example, glycidyl ethers, which also contain epoxide moieties, are added to reduce viscosity and improve polymerization. We have investigated the contact allergenic properties of a series of six analogues to phenyl glycidyl ether (PGE), all with similar basic structures but with varying carbon chain lengths and degrees of saturation. The chemical reactivity of the compounds in the test series toward the hexapeptide H-Pro-His-Cys-Lys-Arg-Met-OH was investigated. All epoxides were shown to bind covalently to both cysteine and proline residues. The percent depletion of nonreacted peptide was also studied resulting in 88% depletion when using PGE and 46% when using butyl glycidyl ether (5) at the same time point, thus revealing a large difference between the fastest and the slowest reacting epoxide. The skin sensitization potencies of the epoxides using the murine local lymph node assay (LLNA) were evaluated in relation to the observed physicochemical and reactivity properties. To enable determination of statistical significance between structurally closely related compounds, a nonpooled LLNA was performed. It was found that the compounds investigated ranged from strong to weak sensitizers, congruent with the reactivity data, indicating that even small changes in chemical structure result in significant differences in sensitizing capacity.
Niklasson
Ida B
IB
Department of Chemistry, Dermatochemistry and Skin Allergy, University of Gothenburg, SE-412 96 Gothenburg, Sweden.
Broo
Kerstin
K
Jonsson
Charlotte
C
Luthman
Kristina
K
Karlberg
Ann-Therese
AT
D000818:Animals; D001559:Benzhydryl Compounds; D002851:Chromatography, High Pressure Liquid; D017449:Dermatitis, Allergic Contact / Q000209:etiology; D004852:Epoxy Compounds / Q000737:chemistry / Q000633:toxicity; D004853:Epoxy Resins / Q000737:chemistry* / Q000633:toxicity; D005260:Female; D023441:Local Lymph Node Assay; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry; D010647:Phenyl Ethers / Q000737:chemistry / Q000633:toxicity; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004852:Epoxy Compounds; D004853:Epoxy Resins; D009842:Oligopeptides; D010647:Phenyl Ethers; C477247:H-Pro-His-Cys-Lys-Arg-Met-OH; C016050:phenylglycidyl ether; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds; C423722:bisphenol F diglycidyl ether