title: Structure elucidation, synthesis, and contact allergenic activity of a major hydroperoxide formed at autoxidation of the ethoxylated surfactant C12E5.
abstract: Ethoxylated alcohols, widely used as surfactants, are known to be susceptible to oxidation when exposed to air. At autoxidation, a complex mixture is formed, in which alkyl poly(ethylene glycol) aldehydes, alkyl poly(ethylene glycol) formates, hydroxyaldehydes, and formaldehyde have previously been identified. These compounds are all secondary oxidation products, some of which have been shown to be skin sensitizers and irritants. The primary oxidation products from ethoxylated alcohols are described in the literature as peroxides and hydroperoxides, but their structures have not been elucidated more closely. Peroxides and hydroperoxides are usually reactive species and can be suspected to be biologically active as skin sensitizers and irritants. In the present investigation, we studied the autoxidation of the pure ethoxylated alcohol pentaethylene glycol mono-n-dodecyl ether (C(12)E(5)), using NMR and HPLC-MS. On the basis of experience from previous studies on a small model compound, diethyleneglycol monoethyl ether (C(2)E(2)), the hydroperoxide expected to be found in the highest amount in autoxidized C(12)E(5) was synthesized and used as a reference substance in the analyses. This same hydroperoxide, 16-hydroperoxy-3,6,9,12,15-pentaoxaheptacosan-1-ol, was identified in the autoxidation mixture of C(12)E(5), and its sensitizing capacity was determined. It was found to be a moderate allergen in experimental sensitization studies in guinea pigs. Our data further indicate the presence of at least three additional hydroperoxides in the autoxidation mixture of C(12)E(5), one of which was identified as 1-hydroperoxy-3,6,9,12,15-pentaoxaheptacosan-1-ol. The results accentuate the importance of controlling the storage, transportation, and handling conditions of ethoxylated surfactants, to avoid the formation of allergenic and skin irritant oxidation products.
authors.affiliation: Department of Chemistry, Medicinal Chemistry, Dermatochemistry and Skin Allergy, Göteborg University, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Bodin
authors.forename: Malin
authors.initials: M
authors.lastname: Linnerborg
authors.forename: J Lars G
authors.initials: JL
authors.lastname: Nilsson
authors.forename: Ann-Therese
authors.initials: AT
authors.lastname: Karlberg
mesh_terms: D000485:Allergens / Q000737:chemistry* / Q000633:toxicity; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D017449:Dermatitis, Allergic Contact / Q000209:etiology; D004987:Ethers / Q000737:chemistry*; D005026:Ethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D005260:Female; D006168:Guinea Pigs; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010545:Peroxides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000485:Allergens; D004987:Ethers; D005026:Ethylene Glycols; D010545:Peroxides; D013501:Surface-Active Agents; C077053:pentaethylene glycol monododecyl ether; D011092:Polyethylene Glycols; C010111:carbitol