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.

中文翻译：

---

N-（2-羟乙基）-L-缬氨酰-L-亮氨酸：一种新型的人类环氧乙烷暴露的尿液生物标志物

环氧乙烷 (EO) 是一种用作工业中间体和消毒剂的致癌化学物质，可与 DNA 和蛋白质形成共价加合物。血液蛋白珠蛋白中 N 端缬氨酸 [N-(2-羟乙基)-L-缬氨酸，HEV] 的加合物已被用作 EO 累积暴露的主要生物标志物。然而，由于血液采样在常规职业健康实践中不方便，因此研究了一种非侵入性的珠蛋白分析替代方法。在将 N-(2-羟乙基)-L-缬氨酰-L-亮氨酸 (HEVL) 鉴定为大鼠尿液中排泄的 EO 加成珠蛋白的最终裂解产物后，我们首次报告了 HEVL 在大鼠尿液中的存在人类的尿液。在 18 名绝育工人中，尿液 HEVL 的范围为 0.67 至 11.98 µg/g 肌酐（平均值 ± SD：5.04 ± 3.14 µg/g 肌酐）并且与 HEV 相关：HEVL (µg/g creat) = 0.833 HEV (nmol/g 球蛋白) + 1.19 (R2 = 0.45)。由于在对照组中也发现了出乎意料的高水平尿液 HEVL（平均值 ± SD：0.97 ± 0.37 µg/g creat，n = 32），因此不建议将 HEVL 用于准确评估亚 ppm 暴露于 EO 的情况。另一方面，非侵入性采样和简便的检查程序预先确定了 HEVL 以进行筛查，以识别接近或超过 EO (1.8 mg/m3) 职业暴露限值的受试者，以便通过更敏感的参考分析进行重新检查混合动力汽车。