Risk Assessment for Biopersistent Granular Particles

In 1997 the German MAK-Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area established a “general threshold value” of 4 mg/m3 for the inhalable fraction and 1.5 mg/m3 for the respirable fraction of poorly soluble dusts. The “general threshold value” is to apply for dusts for which no specific MAK value exists. This value is based on data from epidemiological studies with the target criterion being the impairment of lung function as well as on data from long-term experimental studies with rats with the target criterion being the reduction in the rate of alveolar clearance. Thereby, the deposition of 1 μl dust/g lung is seen as the threshold value. In recent years several studies have shown tumorigenic responses of rats after exposure to poorly soluble low-toxicity particles. The MAK Commission together with members of the subcommittee III of the Committee on Hazardous Substances (AGS) is currently reevaluating the toxic effects of granular dusts, known as poorly soluble low-toxicity particles (PSP). The target is to evaluate the mode of action for tumor induction and to determine the most sensitive parameters that trigger these effects. Since induction of inflammation is seen as the underlying mechanism, the commission is presently evaluating the parameters that indicate an inflammatory response of the airway system in order to identify a no-observed-adverse-exposure level (NOAEL), which can then be used to establish an MAK value. In this case biopersistent granular particles would be classified in Category 4, for carcinogenic substances for which genotoxic effects play no or at most a minor part. Provided the MAK value is observed, no significant contribution to human cancer is expected.