7 research outputs found
Translational toxicology in setting occupational exposure limits for dusts and hazard classification â 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 âgranular biopersistent particles without known specific toxicityâ (GBS). These recommendations are under review at the European Union level. We examine the scientific assumptions in an attempt to reproduce the results. MAKâs 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.International Carbon Black Associatio
The Reference Site Collaborative Network of the European Innovation Partnership on Active and Healthy Ageing
The reference site collaborative network of the european innovation partnership on active and healthy ageing
Seventy four Reference Sites of the European Innovation
Partnership on Active and Healthy Ageing (EIP on AHA)
have been recognised by the European Commission in
2016 for their commitment to excellence in investing and
scaling up innovative solutions for active and healthy
ageing. The Reference Site Collaborative Network
(RSCN) brings together the EIP on AHA Reference Sites
awarded by the European Commission, and Candidate
Reference Sites into a single forum. The overarching goals
are to promote cooperation, share and transfer good
practice and solutions in the development and scaling up
of health and care strategies, policies and service delivery
models, while at the same time supporting the action
groups in their work. The RSCN aspires to be recognized
by the EU Commission as the principal forum and
authority representing all EIP on AHA Reference Sites.
The RSCN will contribute to achieve the goals of the EIP
on AHA by improving health and care outcomes for
citizens across Europe, and the development of sustainable
economic growth and the creation of jobs
Response to the Reply on behalf of the âPermanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Areaâ (MAK Commission) by Andrea Hartwig Karlsruhe Institute of Technology (KIT)
The Reference Site Collaborative Network of the European Innovation Partnership on Active and Healthy Ageing.
International audienc
The reference site collaborative network of the european innovation partnership on active and healthy ageing
Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, and the development of sustainable economic growth and the creation of jobs
The Reference Site Collaborative Network of the European Innovation Partnership on Active and Healthy Ageing.
International audienceSeventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, and the development of sustainable economic growth and the creation of jobs