Limits...
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.

Morfeld P, Bruch J, Levy L, Ngiewih Y, Chaudhuri I, Muranko HJ, Myerson R, McCunney RJ - Part Fibre Toxicol (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Occupational Epidemiology and Risk Assessment of Evonik Industries, AG Rellinghauser Straße 1-11, Essen, 45128, Germany. peter.morfeld@evonik.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Inhalable carbon black concentration, geometric mean (GM) exposures for production, maintenance, and materials handling (warehousing), highest exposure job classes in carbon black manufacturing operations, 1979–2014.
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Fig1: Inhalable carbon black concentration, geometric mean (GM) exposures for production, maintenance, and materials handling (warehousing), highest exposure job classes in carbon black manufacturing operations, 1979–2014.

Mentions: The CB producing industry has conducted industry-wide exposure assessments at approximately 40 CB manufacturing plants in North America and Europe in support of epidemiology studies, internal and external occupational exposure level (OEL) development, and other industrial hygiene applications. Between 1979 and 2014 more than 13,500 inhalable TWA personal samples have been collected, and in the period up to 2001 nearly 9,400 respirable TWA personal dust samples were collected. These samples documented worker exposures by major job class and job title [162-172]. Figure 1 presents inhalable dust exposure trends over the past 35 years for three of the major job classes associated with CB production in Europe and North America. Two comprehensive respiratory morbidity studies were completed in Europe and North America in the mid-1990s and early 2000s, respectively [163-168,171,172]. One of the outcomes of these studies was that the inhalable dust fraction was affirmed as the most appropriate metric for assessing health risks in the CB producing industry based on reported findings of bronchitis and small, but statistically significant, decrements in one aspect of lung function over a 40 year period.Figure 1


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.

Morfeld P, Bruch J, Levy L, Ngiewih Y, Chaudhuri I, Muranko HJ, Myerson R, McCunney RJ - Part Fibre Toxicol (2015)

Inhalable carbon black concentration, geometric mean (GM) exposures for production, maintenance, and materials handling (warehousing), highest exposure job classes in carbon black manufacturing operations, 1979–2014.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4443602&req=5

Fig1: Inhalable carbon black concentration, geometric mean (GM) exposures for production, maintenance, and materials handling (warehousing), highest exposure job classes in carbon black manufacturing operations, 1979–2014.
Mentions: The CB producing industry has conducted industry-wide exposure assessments at approximately 40 CB manufacturing plants in North America and Europe in support of epidemiology studies, internal and external occupational exposure level (OEL) development, and other industrial hygiene applications. Between 1979 and 2014 more than 13,500 inhalable TWA personal samples have been collected, and in the period up to 2001 nearly 9,400 respirable TWA personal dust samples were collected. These samples documented worker exposures by major job class and job title [162-172]. Figure 1 presents inhalable dust exposure trends over the past 35 years for three of the major job classes associated with CB production in Europe and North America. Two comprehensive respiratory morbidity studies were completed in Europe and North America in the mid-1990s and early 2000s, respectively [163-168,171,172]. One of the outcomes of these studies was that the inhalable dust fraction was affirmed as the most appropriate metric for assessing health risks in the CB producing industry based on reported findings of bronchitis and small, but statistically significant, decrements in one aspect of lung function over a 40 year period.Figure 1

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Occupational Epidemiology and Risk Assessment of Evonik Industries, AG Rellinghauser Straße 1-11, Essen, 45128, Germany. peter.morfeld@evonik.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus