N-(2-Hydroxyethyl)-l-valyl-l-leucine: a novel urinary biomarker of ethylene oxide exposure in humans

• Published in: Toxicology letters Vol. 326; pp. 18 - 22
• Main Authors: Mráz, Jaroslav, Hanzlíková, Iveta, Dušková, Šárka, Tvrdíková, Monika, Linhart, Igor
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2020
• Subjects: Adult; Biological monitoring; Biological Monitoring - methods; Biomarkers - urine; Carcinogens - toxicity; Ethylene oxide; Ethylene Oxide - urine; Female; Globin adducts; Humans; Male; Middle Aged; Occupational exposure; Occupational Exposure - adverse effects; Urinary dipeptidic adducts; Valine - urine; Urinary dipeptidic adducts; Globin adducts; Ethylene oxide; Occupational exposure; Biological monitoring
• ISSN: 0378-4274; 1879-3169; 1879-3169
• DOI: 10.1016/j.toxlet.2020.03.004

•Novel urinary metabolite of ethylene oxide in occupationally exposed workers.•Non-invasive biomonitoring strategy to assess long-term exposures to ethylene oxide.•In vivo cleavage of ethylene oxide adduct in globin to a specific urinary dipeptide. Ethylene oxide (EO), a carcinogenic chemical used as an industrial intermediate and sterilant, forms covalent adducts with DNA and proteins. The adduct with N-terminal valine [N-(2-hydroxyethyl)-l-valine, HEV] in blood protein globin has been employed as a principal biomarker of cumulative exposures to EO. However, as sampling of blood is inconvenient in routine occupational health practice, a non-invasive alternative to globin analysis has been investigated. Following identification of N-(2-hydroxyethyl)-l-valyl-l-leucine (HEVL) as ultimate cleavage product of EO-adducted globin excreted in the rat urine, here we report for the first time on the presence of HEVL in the urine of humans. In 18 sterilization workers, urinary HEVL ranged from 0.67 to 11.98 μg/g creatinine (mean ± SD: 5.04 ± 3.14 μg/g creat) and correlated with HEV: HEVL (μg/g creat) = 0.833 HEV (nmol/g globin) + 1.19 (R2 = 0.45). As unexpectedly high levels of urinary HEVL were found also in controls (mean ± SD: 0.97 ± 0.37 μg/g creat, n = 32), HEVL is not proposed for the accurate assessment of sub-ppm exposures to EO. On the other hand, non-invasive sampling and facile work-up procedure predetermine HEVL for screening purposes to identify subjects approaching to or exceeding occupational exposure limit for EO (1.8 mg/m3) to be re-examined by the more sensitive reference analysis for HEV.