Dosimetry of glycidyl ethers in mice by quantification of haemoglobin adducts

Abstract

Glycidyl ethers are used in epoxy resins. Epoxy resins are widely used in adhesives and coatings, as well as in electronics and structural composites, thus there is a potential of human exposure to glycidyl ethers. The aim of the present investigation was to explore the utility of haemoglobin adducts for biomonitoring of these types of compounds. Adducts to N-terminal valine were analysed by a modified Edman method with gas chromatographymass spectrometry (or tandem mass spectrometry) for adduct detection and quantification. Groups of three male mice (C 3H/Hej) were administered 4 mg/mouse of allyl, butyl, phenyl or cresyl glycidyl ether (AGE, BGE, PGE or CGE) by i.p. injection. Blood samples were collected 24 h after treatment and assayed for haemoglobin adducts using the N-alkyl Edman method. Additional groups of AGE-treated mice were used to study dose response and adduct stability. The experiments with AGE indicate a linear dose response for adduct formation in the dose range studied (0, 2 and 4 mg/mouse). As expected for stable haemoglobin adducts, about 50% of the initial adduct level remained 21 days after exposure. The haemoglobin binding indices (HBI), 1.1–1.2 pmol/g globin for AGE and BGE and 1.3 pmol/g globin for PGE and CGE per μmol glycidyl ether per kg body weight, are similar to that of propylene oxide (ca. 1.4 pmol/g globin) and about five- to six-fold lower than that of ethylene oxide (about 7 pmol/g). The background adduct levels of glycidyl ethers in globin samples from three unexposed human subjects were below the detection limit for quantification by GC and tandem mass spectrometry (0. l pmol/g globin). Because of the low background and the high analytical sensitivity that can be achieved, haemoglobin adduct measurements would be useful for monitoring low level exposures in humans.