Analysis of protein adducts as biomarkers of short-term exposure to ethylene oxide and results of follow-up biomonitoring.

An accidental exposure of six workers to ethylene oxide (EO) provided the rationale for a biomonitoring and follow-up study, whose aim was to analyse protein adduct kinetics and examine the differentiation between accidental and environmental exposure, e.g., from tobacco smoke. For this purpose, the decrease in the concentration of the haemoglobin adduct N-2-hydroxyethylvaline (HEV) was followed during a five-month period after the accident, together with N-2-cyanoethylvaline (CEV) and urinary cotinine, two well-established biomarkers for smoking. The follow-up study showed that EO adduct concentrations significantly increased after a short but presumably high exposure. Initial biomonitoring revealed HEV levels above 500 pmol g(-1) globin in all cases, with a maximum of about 2,400 pmol g(-1) globin. This compares to a German EKA value (exposure equivalent for carcinogenic substances) for a daily 8-h-exposure to 1 ppm EO of 90 μg L(-1) blood (~3,900 pmol g(-1) globin). The adduct levels dropped in accordance with the expected zero-order kinetics for a single exposure. After the five-month observation interval, the HEV concentrations in blood reflected the individual background from tobacco smoking. The results of this study show that even a short exposure to ethylene oxide may result in a significant rise in haemoglobin adduct levels. Although protein adducts and their occupational-medical assessment values are considered for long-term exposure surveillance, they can also be used for monitoring accidental exposures. In these cases, the calculation of daily 'ppm-equivalents' may provide a means for a comparison with the existing assessment values.