Cancer Risk due to Diesel Emissions? New Toxicological Approaches in Assessing the Risk of Diesel Particles

Authors

Prof. Dr.med. J. Bruch (a,b), Dipl.-Biol. Dr.rer.nat. B. Rehn (b), Dipl.-Biol. F. Seiler (b,c) a: Institute for Hygiene and Occupational Medicine, University Essen - b: IBE – Institute for Biological Emission Assessment GmbH, Marl - c: Squarix GmbH, Marl

Year

2003

Print Info

Fortschritt-Berichte VDI, Reihe 12, Nr. 539

Summary

In the hygienic evaluation of Diesel particles different experience levels led to the appraisal of a potential cancer effect of Diesel soot, so the content of PAH and other organic substances, which are carcinogenic both toxicologically (i) as well as with humans (coking plant worker) (ii). In the rat model the particle character proved to be the prominent cancer cause (iii). Finally there are epidemiological data at Diesel soot exposed cohortes, which are regarded as indications or proofs of a cancer effect (iv). One of the Federal Environmental Agency Berlin compelled risk assessment for cancers of the respiratory tract in the population, caused by Diesel soot, is based on an extrapolation of the particle effect in the rat (see iii), whereby a linear, stochastic risk model was used. Other critical considerations refer to the small diameter of primary soot particles; from the toxicological view isolated ultrafine particles and aggregated particles should be carefully differentiated. A quantitative risk assessment for humans must evaluate the actual very low exposure range in the environment in connection with that the Diesel soot peculiar mode of action. The toxicological examination should identify the mechanisms (illness path), leading to the potential tumor risk and quantify in the further the critical steps for the tumor manifestation. A condition for the tumor development is the persistent damage of the hereditary substance of proliferation competent cells by the tumorigenic agent (a). The further indispensable condition is the stimulation of the proliferation under the exposure; this stimulation could be caused by genotoxic agent (b1) or by other circumstances (b2), dominant with the exposure. For the carcinogenic effects released by particles in high dosage the chronic inflammation is regarded as a cause. Here radical molecule species (O and NO radicals) are generated, which lead to the oxidative DNA damage and to mutation. The proliferation is stimulated by proinflammatory mediators. In new studies the appearance of specific DNA damage as well as the proliferation in individual cells can be quantitatively determined in the intact lung tissue by the application of immunological markers. The procedures evaluate sensitively the critical conditions in an early stage of the tumor path, necessary for the tumor emergence. The test substances are administered in a multi-dose approach in low realistic dosages. In recent investigations threshold values for particle (exact: poorly soluble particles PSP) released genotoxicty could be identified; these thresholds lie clearly above other lung-toxic effects of the examined substances (hard particles such as fine types of dust of quartz, titandioxid, soot and others). In connection with further investigations (in vitro genotoxicty, morphology of the processing of the fine particles in the lung) the data argue for a secondary genotoxicity mechanism by PSP. The toxicity of the particles varies within a very large range. In principle the harmful effect of PSP are generated at the surface of the particles. Here the size of the biologically accessible surface is critical as well as the specific conformation of the chemico-physical parameters of the only 2-3 molecule thick layer on the surface. At the model substance quartz fine dust (> 98% SiO2) with different species from different deposits toxicity differences (including threshold for genotoxicity) over 4 dose doubling steps were determined; some samples had an activity close to an inert dust (am. nuisance dust). This corresponds to the range, which is given by different dust limit values as for quartz fine dust and the limit value for respirable dust (nuisance dust). The chemico-physical causes are scarcely clarified and are due to subtle differences of the molecular structure of the surface (e.g. dotation by added ions). For Diesel soot and a technical soot we recently could find indications for the existence of a threshold value for oxidative DNA damage and for mutagenicity. It is to be assumed that the toxicological effects of species of Diesel soot are similarly strongly spread as a function of different parameters such as burn and exhaust treatment. The question of a carcinogenic effect of organic components adhering at the soot is open in principle, since the bioavailability and the genotoxicity in critical target cells of the lung tissue must be analyzed. For this likewise specific antibodies are available. Also the analysis of the threshold value would be important for organic carcinogenic effects regarding environmental typical loads. The current technical developments of engine management and the exhaust treatment could lead to a drastic depletion of organic portions of the Diesel soot. Since particle effects are presumably associated with thresholds the expected reduction of organic compounds would influence also updated risk assessment.

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