Translational toxicology in setting occupational exposure limits for dusts and hazard classification - a critical evaluation of a recent approach to translate dust overload findings from rats to humans.

BACKGROUND: We analyze the scientific basis and methodology used by the German MAK Commission in their recommendations for exposure limits and carcinogen classification of "granular biopersistent particles without known specific toxicity" (GBS). These recommendations are under review at the European Union level. We examine the scientific assumptions in an attempt to reproduce the results. MAK's human equivalent concentrations (HECs) are based on a particle mass and on a volumetric model in which results from rat inhalation studies are translated to derive occupational exposure limits (OELs) and a carcinogen classification. METHODS: We followed the methods as proposed by the MAK Commission and Pauluhn 2011. We also examined key assumptions in the metrics, such as surface area of the human lung, deposition fractions of inhaled dusts, human clearance rates; and risk of lung cancer among workers, presumed to have some potential for lung overload, the physiological condition in rats associated with an increase in lung cancer risk. RESULTS: The MAK recommendations on exposure limits for GBS have numerous incorrect assumptions that adversely affect the final results. The procedures to derive the respirable occupational exposure limit (OEL) could not be reproduced, a finding raising considerable scientific uncertainty about the reliability of the recommendations. Moreover, the scientific basis of using the rat model is confounded by the fact that rats and humans show different cellular responses to inhaled particles as demonstrated by bronchoalveolar lavage (BAL) studies in both species. CONCLUSION: Classifying all GBS as carcinogenic to humans based on rat inhalation studies in which lung overload leads to chronic inflammation and cancer is inappropriate. Studies of workers, who have been exposed to relevant levels of dust, have not indicated an increase in lung cancer risk. Using the methods proposed by the MAK, we were unable to reproduce the OEL for GBS recommended by the Commission, but identified substantial errors in the models. Considerable shortcomings in the use of lung surface area, clearance rates, deposition fractions; as well as using the mass and volumetric metrics as opposed to the particle surface area metric limit the scientific reliability of the proposed GBS OEL and carcinogen classification.

Personal sampling for inhalable aerosol exposures of carbon black manufacturing industry workers.

The study was concerned with the measurement of inhalable aerosol exposures in the carbon black production industry. The primary goal of the study was to determine the extent to which inhalable aerosol exposure, as measured by the Institute of Occupational Medicine (IOM) personal inhalable sampling head, compared to "total" aerosol exposure, as measured by traditional methodology. A secondary objective was the evaluation of another inhalable aerosol sampler for carbon black aerosol measurement. In addition, an exploratory evaluation of the applicability of the National Institute for Occupational Safety and Health (NIOSH) analytical method (Method 5040) for the determination of carbon black, measured as elemental carbon, was conducted. A field study was carried out in a number of North American carbon black production plants using three samplers: the 2 Lpm IOM sampler as a reference sampler for the inhalable fraction, the 2 Lpm closed-face 37-mm plastic cassette that has been used for many years for total aerosol, and the 3.5 Lpm GSP sampler that has recently been identified by some as a possible candidate for inhalable aerosol. No such studies have previously been reported for the carbon black industry. Further, there have been no reports of the GSP performance in direct comparison to a reference instrument like the IOM sampler. The results showed that inhalable aerosol exposures for workers in carbon black production and packing areas were higher than the corresponding total aerosol exposures by a factor of nearly three, implying the presence of significantly coarser aerosol than previously thought based simply on knowledge of the carbon black production process. The fact that the aerosols collected in portions of the process comprised high proportions of non-elemental carbon particulate was thought likely to be responsible, underlining the need to consider whether gravimetric assessment for such exposure is the most appropriate metric. In addition, and somewhat surprisingly, the GSP sampler emerged clearly as a good alternative to the IOM sampler for collecting inhalable aerosol in carbon black industry workplaces like those studied (although this conclusion cannot yet be extended to other workplaces).