DOSIMETRY OF GLYCIDYL ETHERS IN MICE BY QUANTIFICATION OF HEMOGLOBIN ADDUCTS

Glycidyl ethers are used in epoxy resins. Epoxy resins are widely used in adhesives and coatings, as well as in electronics and structural c omposites, thus there is a potential of human exposure to glycidyl eth ers. The aim of the present investigation was to explore the utility o f haemoglobin adducts for biomonitoring of these types of compounds. A dducts to N-terminal valine were analysed by a modified Edman method w ith gas chromatography-mass 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 sample s were collected 24 h after treatment and assayed for haemoglobin addu cts using the N-alkyl Edman method. Additional groups of AGE-treated m ice were used to study dose response and adduct stability. The experim ents 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 h aemoglobin adducts, about 50% of the initial adduct level remained 21 days after exposure. The haemoglobin binding indices (HBI), 1.1-1.2 pm ol/g globin for AGE and BGE and 1.3 pmol/g globin for PGE and CGE per mu mol glycidyl ether per kg body weight, are similar to that of propy lene oxide (ca. 1.4 pmol/g globin) and about five- to six-fold lower t han that of ethylene oxide (about 7 pmol/g). The background adduct lev els of glycidyl ethers in globin samples from three unexposed human su bjects were below the detection limit for quantification by GC and tan dem mass spectrometry (0.1 pmol/g globin). Because of the low backgrou nd and the high analytical sensitivity that can be achieved, haemoglob in adduct measurements would be useful for monitoring low level exposu res in humans. (C) 1997 Elsevier Science Ireland Ltd.