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Biomarkers for occupational diesel exhaust exposure monitoring


Brief description: %
Four underground mining operations in Italy, Ireland, Czech Republic and Estonia will be investigated for their suitability to validate a large set of environmental and biological markers (biomarkers). Environmental monitoring of the working conditions will be conducted using real-time monitoring of airborne polycyclic aromatic hydrocarbons (PAH), personal exposure monitoring of particle-associated nitrated PAH and of elemental carbon originating from inhalable particles. The monitoring methods will be introduced in pilot studies in two (of the four) selected mines after an extensive information and informed consent procedure. Workers will be asked to complete questionnaires related to job history, life style, nonoccupational exposures to diesel exhaust etc. Important biomarkers will be hemoglobin adducts of nitro-substituted PAH, bulky DNA adducts, oxidative DNA-damage and DNA-repair and urinary 1-hydroxypyrene. In addition, biomarkers for interindividual differences in susceptibility will be studied through genotyping of cytochromes P450 (CYP lA1, 2E1 and 2D6), glutathione transferases GSTM1 and GSTT1, N-acetyltransferases NAT1 and NAT2 and DNA-repair. Samples from the work environment and biological samples (blood and urine) will be prepared, divided in portions and randomly coded (double blind) and shipped to ten different laboratories throughout Europe for analysis. Based on results obtained from these studies a final study will be planned, comprising a complete environmental and biological monitoring programme in a population of high diesel exhaust exposed miners and a matching reference population. If possible the final study will be linked to an on-going epidemiological study.

Biological monitoring, diesel exhaust, underground mining, lung cancer, occupational hygiene, toxicology, hemoglobin adducts, DNA adducts, genotyping

Summary The general purpose of this Reinforced Concerted Action is to establish a European Network on Diesel Exhaust, which aims to assemble a group of scientists in the area of research on the effects of exposure to diesel engine emissions. This type of exposure is known to have various short-term and long-term effects on the health of workers in a variety of occupational situations. Acute effects may involve those induced by the interaction of fine dust and the adsorbed chemical substances with the respiratory tract, whereas long-term effects may include the development of respiratory cancer. Within this Network, experts from different disciplines will be brought together, e.g. from the fields of general toxicology, occupational hygiene, genetic toxicology, and epidemiology. At regular Meetings, the participants in the Network will exchange information and expertise in their specific research areas, and seek opportunities for further collaborative work. An important activity within the Network will be to investigate, in a multidisciplinary study, the presence, extent and biological effects of exposure to diesel-engine emissions in specific high exposure situations, in underground mining operations in central-Europe, where diesel-powered vehicles are widely used for transport and haulage.

This collaborative work will be designed and carried out as a (molecular) epidemiological study focused on assessment of exposure to diesel exhaust through environmental monitoring and by use of various biomarkers of internal exposure (urinary hydroxypyrene) and its biological and biochemical effects related to or predictive of cancer (protein adducts, DNA adducts, oxidative DNA damage). In addition, biomarkers of susceptibility towards these effects (DNA repair capacity, activity of bioactivating and detoxifying enzymes) will be determined. Through this activity, the Network will provide opportunities for targeted training and mobility of researchers and technical staff to/from the central-European areas where the field studies are conducted. In this way, one of the aims of the Network, i.e. the transfer of technology to central-European laboratories, can be realized. It is expected that this study, in a well-defined situation of relatively high occupational exposure, will lead to validation of the various methods used for (bio)monitoring and to establishment of dose/effect relationships. The techniques will then be applicable to investigate other occupational and environmental exposures. In addition, it is expected that the methods will be used in further epidemiological studies for risk assessment. Keywords (max 10): diesel exhaust, biomonitoring, biomarkers, DNA adducts, susceptibility markers, genotoxic exposure, underground mining, risk assessment, molecular epidemiology.


Katholieke Universiteit Nijmegen - Stichting Katholieke Universiteit
9,Geert Grooteplein
6500 HB Nijmegen