DNA adducts in granulocytes of hospital workers exposed to ethylene oxide

Abstract

This study has demonstrated for the first time, detectable levels of N7-HEG adducts in granulocytes of hospital workers with EtO exposures at levels less than the current U.S. standard of 1 ppm (8-hr TWA). A nonsignificant increase in adduct levels with increasing EtO exposure indicates that further studies of EtO-exposed workers are needed to clarify the relationship between EtO exposure and N7-HEG adduct formation.

Dose-Response Relationships for N7-(2-Hydroxyethyl)Guanine Induced by Low-Dose [14C]Ethylene Oxide: Evidence for a Novel Mechanism of Endogenous Adduct Formation

“…Using our established LC-MS/MS assay for N7-HEG, it was possible to accurately quantify the background (unlabeled) adduct level in rat tissues, distinct from those formed as a consequence of [ ]N7-HEG formation in rat tissues was around 10 to 20 adducts/10 9 nucleotides; this is 5-to 100-fold lower than the endogenous level of these adducts reported in WBCs isolated from unexposed humans (16)(17)(18).…”

“…After incubation (15 min, 37jC), the supernatant was concentrated to dryness and reconstituted in mobile phase (100 AL). Chromatographic separations were carried out on a Waters Atlantis C 18 3 Am column (2.1 Â 150 mm) with isocratic elution using 1.8 mmol/L nonafluoropentanoic acid in water/methanol (90:10) at a flow rate of 0.19 mL/min. The column was coupled to a Micromass Quattro Ultima mass spectrometer (Waters) equipped with an electrospray interface operated in positive ion mode.…”

“…A confounding factor in evaluating the risks associated with EO inhalation is the fact that ethylene is also generated in vivo during normal physiologic processes and can be converted to the epoxide by cytochrome P450 2E1 (15). Humans are therefore continually exposed to EO, as illustrated by detectable N7-HEG at levels of f1 to 10/10 7 nucleotides in lymphocytes isolated from people not knowingly in contact with EO (16)(17)(18). Physiologic sources of ethylene are believed to include methionine oxidation, lipid peroxidation, and the metabolizing activity of intestinal bacteria (19)(20)(21); however, the mechanisms of formation in mammalian systems have not been defined in any of these cases and the origins of endogenous N7-HEG adducts have never been directly shown.…”

Synthesis and Characterization of Novel Amphiphilic Block Copolymer poly(4-vinyl benzene chloride)-b-poly(ethylene oxide)

“…Extensive investigations have been conducted on amphiphilic cellulose 6 , PEG 7 , poly(acrylic acid) 8 , and others 9 ,aswellason polyacrylamide based copolymers 10 . The former polymers were mainly prepared by chemical modiûcation of a preformed polymer, and the latter were obtained by copolymerization of the appropriate monomers.. Generally, the hydrophilic block is made of poly(ethylene oxide)(PEO), because of its availability, high solubility in water, and high biocompatibility [11][12][13][14][15] .…”

The application of mass spectrometry in molecular dosimetry: Ethylene oxide as an example

“…Short-term EO exposures were reported at a time-weighed average of 7.35 and 27.6 ppm during unloading of medical devices in medical-supply manufacturing industries (Chien et al, 2007). EO exposures for sterilization workers in hospitals were much less than 1 ppm, and were estimated to vary from 0.03 to 0.36 ppm or from 0.009 to 0.18 ppm (Yong et al, 2007;Haufroid et al, 2007). Smokers were exposed to EO in tobacco smoke at 5 mg/cigarette (IARC, 1994).…”