The measured CEV concentrations could be extrapolated to the CEV concentrations expected on the day of the accident, based on the well-known toxicokinetics of the CEV adducts. For emergency responders, the time between accident and blood sampling was generally longer than for residents. Accordingly, difference between

measured and extrapolated CEV concentrations was more pronounced for emergency responders than for residents. The extrapolation method is adequate when the CEV background in the blood is negligible, i.e. in the case of non-smokers. For smokers, we cannot use this formula as such because we need to take into account the background CEV concentrations due to tobacco smoking. Indeed, acrylonitrile from Ibrutinib tobacco smoke has a CYC202 chemical structure significant influence on the CEV levels in globin ( Lewalter, 1996 and Schettgen et al., 2002). While CEV is usually close to the detection limit in the blood of non-smokers, a background value between 50 pmol/g globin and 300 pmol/g globin is typically found in smokers, depending on their tobacco consumption ( Bader and

Wrbitzky, 2006). In this study, the background CEV level of the smokers is unknown. Without this value, a correct extrapolation of the exposure to the time of the accident is not possible. And without extrapolation we cannot take into account the decrease in CEV concentrations due to elimination of CEV adducts between accident and sampling date. A precise evaluation D-malate dehydrogenase of the ACN exposure from the accident was therefore only possible for non-smoker emergency responders. This human biomonitoring study is among

the first published examples of large-scale investigations carried out promptly after a crisis, in this case a severe train accident with leakage of ACN. An increased exposure to ACN was found in emergency responders involved in the on-site management of the train accident with more than a quarter of the non-smokers exceeding the reference value of the non-exposed and non-smoking general population. The extent of the exposure remained, however, relatively moderate as it corresponded to what may be observed as background levels in smokers. In addition to smoking, ACN exposure was influenced by the distance to the accident, the number of days spent on-site, and the occupational function of the participants. The exposure in the emergency responders was less pronounced than the exposure in the local population. Thus, the present study demonstrates that human biomonitoring is an efficient tool in the exposure assessment of certain chemicals released following accidents and disasters. The authors declare no conflict of interest. Transparency Document. This study has been financed by the FPS Health, Food Chain Safety and Environment, following an advice of the Belgian Minister of Social Affairs and Public Health.