42 research outputs found
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.International Carbon Black Associatio
“Pesticides Protect the Fruit, but Not the People”: Using Community-Based Ethnography to Understand Farmworker Pesticide-Exposure Risks
Objectives. We used community-based ethnography and public health risk assessment to assess beliefs about pesticide exposure risks among farmworkers in the Lower Yakima Valley of Washington State
Recommended from our members
Children and Adults With Frequent Hospitalizations for Asthma Exacerbation, 2012-2013: A Multicenter Observational Study
© 2015 American Academy of Allergy, Asthma & Immunology. Background: Earlier studies reported that many patients were frequently hospitalized for asthma exacerbation. However, there have been no recent multicenter studies to characterize this patient population with high morbidity and health care utilization. Objective: To examine the proportion and characteristics of children and adults with frequent hospitalizations for asthma exacerbation. Methods: A multicenter chart review study of patients aged 2 to 54 years who were hospitalized for asthma exacerbation at 1 of 25 hospitals across 18 US states during the period 2012 to 2013 was carried out. The primary outcome was frequency of hospitalizations for asthma exacerbation in the past year (including the index hospitalization). Results: The cohort included 369 children (aged 2-17 years) and 555 adults (aged 18-54 years) hospitalized for asthma exacerbation. Over the 12-month period, 36% of the children and 42% of the adults had 2 or more (frequent) hospitalizations for asthma exacerbation. Among patients with frequent hospitalizations, guideline-recommended outpatient management was suboptimal. For example, among adults, 32% were not on inhaled corticosteroids at the time of index hospitalization and 75% had no evidence of a previous evaluation by an asthma specialist. At hospital discharge, among adults with frequent hospitalizations who had used no controller medications previously, 37% were not prescribed inhaled corticosteroids. Likewise, during a 3-month postdischarge period, 64% of the adults with frequent hospitalizations were not referred to an asthma specialist. Although the proportion of patients who did not receive these guideline-recommended outpatient care appeared higher in adults, these preventive measures were still underutilized in children; for example, 38% of the children with frequent hospitalizations were not referred to asthma specialist after the index hospitalization. Conclusions: This multicenter study of US patients hospitalized with asthma exacerbation demonstrated a disturbingly high proportion of patients with frequent hospitalizations and ongoing evidence of suboptimal longitudinal asthma care
Recommended from our members
Children and Adults With Frequent Hospitalizations for Asthma Exacerbation, 2012-2013: A Multicenter Observational Study
© 2015 American Academy of Allergy, Asthma & Immunology. Background: Earlier studies reported that many patients were frequently hospitalized for asthma exacerbation. However, there have been no recent multicenter studies to characterize this patient population with high morbidity and health care utilization. Objective: To examine the proportion and characteristics of children and adults with frequent hospitalizations for asthma exacerbation. Methods: A multicenter chart review study of patients aged 2 to 54 years who were hospitalized for asthma exacerbation at 1 of 25 hospitals across 18 US states during the period 2012 to 2013 was carried out. The primary outcome was frequency of hospitalizations for asthma exacerbation in the past year (including the index hospitalization). Results: The cohort included 369 children (aged 2-17 years) and 555 adults (aged 18-54 years) hospitalized for asthma exacerbation. Over the 12-month period, 36% of the children and 42% of the adults had 2 or more (frequent) hospitalizations for asthma exacerbation. Among patients with frequent hospitalizations, guideline-recommended outpatient management was suboptimal. For example, among adults, 32% were not on inhaled corticosteroids at the time of index hospitalization and 75% had no evidence of a previous evaluation by an asthma specialist. At hospital discharge, among adults with frequent hospitalizations who had used no controller medications previously, 37% were not prescribed inhaled corticosteroids. Likewise, during a 3-month postdischarge period, 64% of the adults with frequent hospitalizations were not referred to an asthma specialist. Although the proportion of patients who did not receive these guideline-recommended outpatient care appeared higher in adults, these preventive measures were still underutilized in children; for example, 38% of the children with frequent hospitalizations were not referred to asthma specialist after the index hospitalization. Conclusions: This multicenter study of US patients hospitalized with asthma exacerbation demonstrated a disturbingly high proportion of patients with frequent hospitalizations and ongoing evidence of suboptimal longitudinal asthma care