An exposure towards dusts that are well known to be the cause of lung injuries (fibrosis, cancer) have been discussed during the past decades for several work places (e.g. building and construction industry, mental industry). Tumours of the lung were observed following inhalative uptake mainly for ultra fine materials (soot, titanium dioxide) where as larger material was carcinogenic following intratracheal instillation only (see Project 1843). The underlying mechanism is yet not fully understood. Besides a direct genotoxic mechanism of the particles themselves an indirect mechanism based on inflamatory processess is discussed too (Knaapen et al. 2004). Based on suitable experimental systems (epithelial cells of the lung as target cells of carcinogenicity, in vitro or in vivo) the induction of genotoxic effects has to be investigated for particular materials. In addition, the influence of present inflamatory cells on the genotoxic response of the target cells has to be investigated (Johnson, 2000). Actually, the genotoxic mechanism of granular, biopersistant particles is under discussion in the Commisio for the Investigation of Health Harzards of Chemical Compounds in the Work Area (MAK) and the Advisory Commity on Hazardous Substances. The results are expected to give a deeper understanding on the mechanism of the carcinogenicity of particles, e.g. is there a treshold. Furthermore, the assessment of an Exposure towards individual dusts as well as the derivation of work place measures (e.g. an Occupational Exposure Limit, OEL) could be improved.
Unit 4.3 "Toxicology"