Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-24 (of 24 Records) |
Query Trace: Kuempel ED[original query] |
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Utilizing literature-based rodent toxicology data to derive potency estimates for quantitative risk assessment
Boots TE , Kogel AM , Drew NM , Kuempel ED . Nanotoxicology 2021 15 (6) 1-21 Evaluating the potential occupational health risk of engineered nanomaterials is an ongoing need. The objective of this meta-analysis, which consisted of 36 studies containing 86 materials, was to assess the availability of published in vivo rodent pulmonary toxicity data for a variety of nanoscale and microscale materials and to derive potency estimates via benchmark dose modeling. Additionally, the potency estimates based on particle mass lung dose associated with acute pulmonary inflammation were used to group materials based on toxicity. The commonalities among the physicochemical properties of the materials in each group were also explored. This exploration found that a material's potency tended to be associated primarily with the material class based on chemical composition and form (e.g. carbon nanotubes, TiO(2), ZnO) rather than with particular physicochemical properties. Limitations in the data available precluded a more extensive analysis of these associations. Issues such as data reporting and appropriate experimental design for use in quantitative risk assessment are the main reasons publications were excluded from these analyses and are discussed. |
A methodology for developing key events to advance nanomaterial-relevant adverse outcome pathways to inform risk assessment
Halappanavar S , Ede JD , Mahapatra I , Krug HF , Kuempel ED , Lynch I , Vandebriel RJ , Shatkin JA . Nanotoxicology 2020 15 (3) 1-24 Significant advances have been made in the development of Adverse Outcome Pathways (AOPs) over the last decade, mainly focused on the toxicity mechanisms of chemicals. These AOPs, although relevant to manufactured nanomaterials (MNs), do not currently capture the reported roles of size-associated properties of MNs on toxicity. Moreover, some AOs of relevance to airborne exposures to MNs such as lung inflammation and fibrosis shown in animal studies may not be targeted in routine regulatory decision making. The primary objective of the present study was to establish an approach to advance the development of AOPs of relevance to MNs using existing, publicly available, nanotoxicology literature. A systematic methodology was created for curating, organizing and applying the available literature for identifying key events (KEs). Using a case study approach, the study applied the available literature to build the biological plausibility for 'tissue injury', a KE of regulatory relevance to MNs. The results of the analysis reveal the various endpoints, assays and specific biological markers used for assessing and reporting tissue injury. The study elaborates on the limitations and opportunities of the current nanotoxicology literature and provides recommendations for the future reporting of nanotoxicology results that will expedite not only the development of AOPs for MNs but also aid in application of existing data for decision making. |
Dosimetry of inhaled elongate mineral particles in the respiratory tract: The impact of shape factor
Asgharian B , Owen TP , Kuempel ED , Jarabek AM . Toxicol Appl Pharmacol 2018 361 27-35 Inhalation exposure to some types of fibers (e.g., asbestos) is well known to be associated with respiratory diseases and conditions such as pleural plaques, fibrosis, asbestosis, lung cancer, and mesothelioma. In recent years, attention has expanded to other types of elongate mineral particles (EMPs) that may share similar geometry with asbestos fibers but which may differ in mineralogy. Inhalability, dimensions and orientation, and density are major determinants of the aerodynamic behavior for fibers and other EMPs; and the resultant internal dose is recognized as being the critical link between exposure and pathogenesis. Insufficient data are available to fully understand the role of specific physicochemical properties on the potential toxicity across various types of fiber materials. While additional information is required to assess the potential health hazards of EMPs, dosimetry models are currently available to estimate the initially deposited internal dose, which is an essential step in linking airborne exposures to potential health risks. Based on dosimetry model simulations, the inhalability and internal dose of EMPs were found to be greater than that of spherical particles having the same mass or volume. However, the complexity of the dependence of internal dose on EMPs dimensions prevented a straightforward formulation of the deposition-dimension (length or diameter) relationship. Because health outcome is generally related to internal dose, consideration of the factors that influence internal dose is important in assessing the potential health hazards of airborne EMPs. |
Characterizing risk assessments for the development of occupational exposure limits for engineered nanomaterials
Schulte PA , Kuempel ED , Drew NM . Regul Toxicol Pharmacol 2018 95 207-219 The commercialization of engineered nanomaterials (ENMs) began in the early 2000's. Since then the number of commercial products and the number of workers potentially exposed to ENMs is growing, as is the need to evaluate and manage the potential health risks. Occupational exposure limits (OELs) have been developed for some of the first generation of ENMs. These OELs have been based on risk assessments that progressed from qualitative to quantitative as nanotoxicology data became available. In this paper, that progression is characterized. It traces OEL development through the qualitative approach of general groups of ENMs based primarily on read-across with other materials to quantitative risk assessments for nanoscale particles including titanium dioxide, carbon nanotubes and nanofibers, silver nanoparticles, and cellulose nanocrystals. These represent prototypic approaches to risk assessment and OEL development for ENMs. Such substance-by-substance efforts are not practical given the insufficient data for many ENMs that are currently being used or potentially entering commerce. Consequently, categorical approaches are emerging to group and rank ENMs by hazard and potential health risk. The strengths and limitations of these approaches are described, and future derivations and research needs are discussed. Critical needs in moving forward with understanding the health effects of the numerous EMNs include more standardized and accessible quantitative data on the toxicity and physicochemical properties of ENMs. |
Control banding tools for engineered nanoparticles: What the practitioner needs to know
Dunn KH , Eastlake AC , Story M , Kuempel ED . Ann Work Expo Health 2018 wxy002-wxy002 Control banding (CB) has been widely recommended for the selection of exposure controls for engineered nanomaterials (ENMs) in the absence of ENM-specific occupational exposure limits (OELs). Several ENM-specific CB strategies have been developed but have not been systematically evaluated. In this article, we identify the data inputs and compare the guidance provided by eight CB tools, evaluated on six ENMs, and assuming a constant handling/use scenario. The ENMs evaluated include nanoscale silica, titanium dioxide, silver, carbon nanotubes, graphene, and cellulose. Several of the tools recommended the highest level of exposure control for each of the ENMs in the evaluation, which was driven largely by the hazard banding. Dustiness was a factor in determining the exposure band in many tools, although most tools did not provide explicit guidance on how to classify the dustiness (high, medium, low), and published data are limited on this topic. The CB tools that recommended more diverse control options based on ENM hazard and dustiness data appear to be better equipped to utilize the available information, although further validation is needed by comparison to exposure measurements and OELs for a variety of ENMs. In all CB tools, local exhaust ventilation was recommended at a minimum to control exposures to ENMs in the workplace. Generally, the same or more stringent control levels were recommended by these tools compared with the OELs proposed for these ENMs, suggesting that these CB tools would generally provide prudent exposure control guidance, including when data are limited. |
A quantitative framework to group nanoscale and microscale particles by hazard potency to derive occupational exposure limits: Proof of concept evaluation.
Drew NM , Kuempel ED , Pei Y , Yang F . Regul Toxicol Pharmacol 2017 89 253-267 The large and rapidly growing number of engineered nanomaterials (ENMs) presents a challenge to assessing the potential occupational health risks. An initial database of 25 rodent studies including 1929 animals across various experimental designs and material types was constructed to identify materials that are similar with respect to their potency in eliciting neutrophilic pulmonary inflammation, a response relevant to workers. Doses were normalized across rodent species, strain, and sex as the estimated deposited particle mass dose per gram of lung. Doses associated with specific measures of pulmonary inflammation were estimated by modeling the continuous dose-response relationships using benchmark dose modeling. Hierarchical clustering was used to identify similar materials. The 18 nanoscale and microscale particles were classified into four potency groups, which varied by factors of approximately two to 100. Benchmark particles microscale TiO2 and crystalline silica were in the lowest and highest potency groups, respectively. Random forest methods were used to identify the important physicochemical predictors of pulmonary toxicity, and group assignments were correctly predicted for five of six new ENMs. Proof-of-concept was demonstrated for this framework. More comprehensive data are needed for further development and validation for use in deriving categorical occupational exposure limits. |
Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans
Kuempel ED , Jaurand MC , Moller P , Morimoto Y , Kobayashi N , Pinkerton KE , Sargent LM , Vermeulen RC , Fubini B , Kane AB . Crit Rev Toxicol 2016 47 (1) 1-58 In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials. The findings of this review, in general, affirm those of the original evaluation on the inadequate or limited evidence of carcinogenicity for most types of CNTs and CNFs at this time, and possible carcinogenicity of one type of CNT (MWCNT-7). The key evidence gaps to be filled by research include: investigation of possible associations between in vitro and early-stage in vivo events that may be predictive of lung cancer or mesothelioma, and systematic analysis of dose-response relationships across materials, including evaluation of the influence of physico-chemical properties and experimental factors on the observation of nonmalignant and malignant endpoints. |
Taking stock of the occupational safety and health challenges of nanotechnology: 2000–2015
Schulte PA , Roth G , Hodson LL , Murashov V , Hoover MD , Zumwalde R , Kuempel ED , Geraci CL , Stefaniak AB , Castranova V , Howard J . J Nanopart Res 2016 18 159 Engineered nanomaterials significantly entered commerce at the beginning of the 21st century. Concerns about serious potential health effects of nanomaterials were widespread. Now, approximately 15 years later, it is worthwhile to take stock of research and efforts to protect nanomaterial workers from potential risks of adverse health effects. This article provides and examines timelines for major functional areas (toxicology, metrology, exposure assessment, engineering controls and personal protective equipment, risk assessment, risk management, medical surveillance, and epidemiology) to identify significant contributions to worker safety and health. The occupational safety and health field has responded effectively to identify gaps in knowledge and practice, but further research is warranted and is described. There is now a greater, if imperfect, understanding of the mechanisms underlying nanoparticle toxicology, hazards to workers, and appropriate controls for nanomaterials, but unified analytical standards and exposure characterization methods are still lacking. The development of control-banding and similar strategies has compensated for incomplete data on exposure and risk, but it is unknown how widely such approaches are being adopted. Although the importance of epidemiologic studies and medical surveillance is recognized, implementation has been slowed by logistical issues. Responsible development of nanotechnology requires protection of workers at all stages of the technological life cycle. In each of the functional areas assessed, progress has been made, but more is required. |
Advances in inhalation dosimetry models and methods for occupational risk assessment and exposure limit derivation
Kuempel ED , Sweeney LM , Morris JB , Jarabek AM . J Occup Environ Hyg 2015 12 Suppl 1 S18-40 The purpose of this article is to provide an overview and practical guide to occupational health professionals concerning the derivation and use of dose estimates in risk assessment for development of occupational exposure limits (OELs) for inhaled substances. Dosimetry is the study and practice of measuring or estimating the internal dose of a substance in individuals or a population. Dosimetry thus provides an essential link to understanding the relationship between an external exposure and a biological response. Use of dosimetry principles and tools can improve the accuracy of risk assessment, and reduce the uncertainty, by providing reliable estimates of the internal dose at the target tissue. This is accomplished through specific measurement data or predictive models, when available, or the use of basic dosimetry principles for broad classes of materials. Accurate dose estimation is essential not only for dose-response assessment, but also for interspecies extrapolation and for risk characterization at given exposures. Inhalation dosimetry is the focus of this paper since it is a major route of exposure in the workplace. Practical examples of dose estimation and OEL derivation are provided for inhaled gases and particulates. |
Bayesian evaluation of a physiologically-based pharmacokinetic (PBPK) model of long-term kinetics of metal nanoparticles in rats
Sweeney LM , MacCalman L , Haber LT , Kuempel ED , Tran CL . Regul Toxicol Pharmacol 2015 73 (1) 151-63 Biomathematical modeling quantitatively describes the disposition of metal nanoparticles in lungs and other organs of rats. In a preliminary model, adjustable parameters were calibrated to each of three data sets using a deterministic approach, with optimal values varying among the different data sets. In the current effort, Bayesian population analysis using Markov chain Monte Carlo (MCMC) simulation was used to recalibrate the model while improving assessments of parameter variability and uncertainty. The previously-developed model structure and some physiological parameter values were modified to improve physiological realism. The data from one of the three previously-identified studies and from two other studies were used for model calibration. The data from the one study that adequately characterized mass balance were used to generate parameter distributions. When data from a second study of the same nanomaterial (iridium) were added, the level of agreement was still acceptable. Addition of another data set (for silver nanoparticles) led to substantially lower precision in parameter estimates and large discrepancies between the model predictions and experimental data for silver nanoparticles. Additional toxicokinetic data are needed to further evaluate the model structure and performance and to reduce uncertainty in the kinetic processes governing in vivo disposition of metal nanoparticles. |
Airborne fiber size characterization in exposure estimation: evaluation of a modified transmission electron microcopy protocol for asbestos and potential use for carbon nanotubes and nanofibers
Dement JM , Kuempel ED , Zumwalde RD , Ristich AM , Fernback JE , Smith RJ . Am J Ind Med 2015 58 (5) 494-508 BACKGROUND: Airborne fiber size has been shown to be an important factor relative to adverse lung effects of asbestos and suggested in animal studies of carbon nanotubes and nanofibers (CNT/CNF). MATERIALS AND METHODS: The International Standards Organization (ISO) transmission electron microscopy (TEM) method for asbestos was modified to increase the statistical precision of fiber size determinations, improve efficiency, and reduce analysis costs. Comparisons of the fiber size distributions and exposure indices by laboratory and counting method were performed. RESULTS: No significant differences in size distributions by the ISO and modified ISO methods were observed. Small but statistically-significant inter-lab differences in the proportion of fibers in some size bins were found, but these differences had little impact on the summary exposure indices. The modified ISO method produced slightly more precise estimates of the long fiber fraction (>15 mum). CONCLUSIONS: The modified ISO method may be useful for estimating size-specific structure exposures, including CNT/CNF, for risk assessment research. |
Carcinogenicity of fluoro-edenite, silicon carbide fibres and whiskers, and carbon nanotubes
Grosse Y , Loomis D , Guyton KZ , Lauby-Secretan B , El Ghissassi F , Bouvard V , Benbrahim-Tallaa L , Guha N , Scoccianti C , Mattock H , Straif K , Kane AB , Debia M , Dion C , Moller P , Savolainen K , Canu IG , Jaurand MC , Comba P , Kobayashi N , Morimoto Y , Tsuda H , Yu IJ , Vermeulen R , Bugge MD , Bateson TF , Kuempel ED , Morgan DL , Pinkerton KE , Sargent LM , Stayner L . Lancet Oncol 2014 15 (13) 1427-8 In October, 2014, 21 experts from ten countries met at the International Agency for Research on Cancer (IARC; Lyon, France) to assess the carcinogenicity of fluoro-edenite, silicon carbide (SiC) fibres and whiskers, and carbon nanotubes (CNTs) including single-walled (SWCNTs) and multi-walled (MWCNTs) types. These assessments will be published as Volume 111 of the IARC Monographs.1 | Fluoro-edenite was first identified around the Etna volcano near Biancavilla, Italy; a similar mineral was also reported from the Kimpo volcano in Japan. Fluoro-edenite can occur as asbestiform fibres. Unpaved roads made from local quarry products from Biancavilla, used since the 1950s, are a source for airborne fluoro-edenite fibres; additionally indoor air was also contaminated from the use of the quarry's products in building materials. Several surveillance studies reported an excess of mesothelioma incidence and mortality in the regional population of Biancavilla.2 Since the rate ratios for mesothelioma were large and stable, chance was unlikely to explain these findings. The excess was similar in men and women, and most prominent in young adults, suggesting an environmental rather than occupational cause. Moreover, most of the cases had no history of occupational exposure to asbestos. Fluoro-edenite fibrous amphibole was classified as carcinogenic to humans (Group 1) on the basis of sufficient evidence in humans that exposure to fluoro-edenite causes mesothelioma. Sufficient evidence of carcinogenicity was also reported in experimental animals, with increased incidences of mesotheliomas observed in one study in male and female rats given fibrous fluoro-edenite by intraperitoneal or intrapleural injection.3 The results of the few available mechanistic studies were consistent with proposed mechanisms of fibre carcinogenicity.4 |
Human and animal evidence supports lower occupational exposure limits for poorly-soluble respirable particles: letter to the editor re: 'low-toxicity dusts: current exposure guidelines are not sufficiently protective' by Cherrie, Brosseau, Hay and Donaldson
Kuempel ED , Attfield MD , Stayner LT , Castranova V . Ann Occup Hyg 2014 58 (9) 1205-8 We commend the overall evaluation by Cherrie et al. (2013) of the current occupational exposure limits (OELs) for respirable poorly-soluble low toxicity (PSLT) particles. As described in that paper, the epidemiological studies provide compelling evidence that exposure to PSLT at the current OELs has been associated with adverse health effects, including pulmonary fibrosis and lung function deficits. In contrast to Cherrie et al. (2013), we discuss here that the chronic inhalation studies in animals also provide evidence of the adverse pulmonary effects of PSLT. | For example, we would like to clarify or correct the following statements (p. 688, 2nd column): | (1) …the phenomenon of rat lung overload has little relevance for human lung response at high lung burden of low-toxicity dust. | This statement is not entirely supported by the scientific evidence. While it is correct that differences have been observed in the rat and human lung clearance and retention kinetics for respirable particles, these differences have been well described, and can be accounted for, using lung dosimetry models in humans (Kuempel et al., 2001a,b; Gregoratto et al., 2010, 2011) and rats (Tran et al., 1999, 2000; Anjilvel and Asgharian, 1995). Because of the slower pulmonary clearance in humans, particles can build up in the lungs at exposures below those that would cause overloading in rats (Snipes, 1989; Kuempel et al., 2000; Kuempel and Tran, 2002). This build up is associated with the movement of particles into the alveolar interstitium of the mammalian lungs (Nikula et al., 1997, 2001). Only at overloading do the particle lung burdens in rats reach the higher levels that have been reported in coal miners, i.e., up to 10 mg g−1 lungs or more in rats (Morrow, 1988; Muhle et al., 1990; Bellmann et al., 1991; Oberdörster et al., 1992) and in humans (Attfield et al., 1994; Kuempel et al., 1997; Tran and Buchanan, 2000). |
Occupational safety and health criteria for responsible development of nanotechnology
Schulte PA , Geraci CL , Murashov V , Kuempel ED , Zumwalde RD , Castranova V , Hoover MD , Hodson L , Martinez KF . J Nanopart Res 2013 16 2153 Organizations around the world have called for the responsible development of nanotechnology. The goals of this approach are to emphasize the importance of considering and controlling the potential adverse impacts of nanotechnology in order to develop its capabilities and benefits. A primary area of concern is the potential adverse impact on workers, since they are the first people in society who are exposed to the potential hazards of nanotechnology. Occupational safety and health criteria for defining what constitutes responsible development of nanotechnology are needed. This article presents five criterion actions that should be practiced by decision-makers at the business and societal levels-if nanotechnology is to be developed responsibly. These include (1) anticipate, identify, and track potentially hazardous nanomaterials in the workplace; (2) assess workers' exposures to nanomaterials; (3) assess and communicate hazards and risks to workers; (4) manage occupational safety and health risks; and (5) foster the safe development of nanotechnology and realization of its societal and commercial benefits. All these criteria are necessary for responsible development to occur. Since it is early in the commercialization of nanotechnology, there are still many unknowns and concerns about nanomaterials. Therefore, it is prudent to treat them as potentially hazardous until sufficient toxicology, and exposure data are gathered for nanomaterial-specific hazard and risk assessments. In this emergent period, it is necessary to be clear about the extent of uncertainty and the need for prudent actions. |
Overview of risk management for engineered nanomaterials
Schulte PA , Geraci CL , Hodson LL , Zumwalde RD , Kuempel ED , Murashov V , Martinez KF , Heidel DS . J Phys Conf Ser 2013 429 (1) 012062 Occupational exposure to engineered nanomaterials (ENMs) is considered a new and challenging occurrence. Preliminary information from laboratory studies indicates that workers exposed to some kinds of ENMs could be at risk of adverse health effects. To protect the nanomaterial workforce, a precautionary risk management approach is warranted and given the newness of ENMs and emergence of nanotechnology, a naturalistic view of risk management is useful. Employers have the primary responsibility for providing a safe and healthy workplace. This is achieved by identifying and managing risks which include recognition of hazards, assessing exposures, characterizing actual risk, and implementing measures to control those risks. Following traditional risk management models for nanomaterials is challenging because of uncertainties about the nature of hazards, issues in exposure assessment, questions about appropriate control methods, and lack of occupational exposure limits (OELs) or nano-specific regulations. In the absence of OELs specific for nanomaterials, a precautionary approach has been recommended in many countries. The precautionary approach entails minimizing exposures by using engineering controls and personal protective equipment (PPE). Generally, risk management utilizes the hierarchy of controls. Ideally, risk management for nanomaterials should be part of an enterprise-wide risk management program or system and this should include both risk control and a medical surveillance program that assesses the frequency of adverse effects among groups of workers exposed to nanomaterials. In some cases, the medical surveillance could include medical screening of individual workers to detect early signs of work-related illnesses. All medical surveillance should be used to assess the effectiveness of risk management; however, medical surveillance should be considered as a second line of defense to ensure that implemented risk management practices are effective. |
Application of Markov chain Monte Carlo analysis to biomathematical modeling of respirable dust in US and UK coal miners
Sweeney LM , Parker A , Haber LT , Tran CL , Kuempel ED . Regul Toxicol Pharmacol 2013 66 (1) 47-58 A biomathematical model was previously developed to describe the long-term clearance and retention of particles in the lungs of coal miners. The model structure was evaluated and parameters were estimated in two data sets, one from the United States and one from the United Kingdom. The three-compartment model structure consists of deposition of inhaled particles in the alveolar region, competing processes of either clearance from the alveolar region or translocation to the lung interstitial region, and very slow, irreversible sequestration of interstitialized material in the lung-associated lymph nodes. Point estimates of model parameter values were estimated separately for the two data sets. In the current effort, Bayesian population analysis using Markov chain Monte Carlo simulation was used to recalibrate the model while improving assessments of parameter variability and uncertainty. When model parameters were calibrated simultaneously to the two data sets, agreement between the derived parameters for the two groups was very good, and the central tendency values were similar to those derived from the deterministic approach. These findings are relevant to the proposed update of the ICRP human respiratory tract model with revisions to the alveolar-interstitial region based on this long-term particle clearance and retention model. |
Development of risk-based nanomaterial groups for occupational exposure control
Kuempel ED , Castranova V , Geraci CL , Schulte PA . J Nanopart Res 2012 14 1029 Given the almost limitless variety of nanomaterials, it will be virtually impossible to assess the possible occupational health hazard of each nanomaterial individually. The development of science-based hazard and risk categories for nanomaterials is needed for decision-making about exposure control practices in the workplace. A possible strategy would be to select representative (benchmark) materials from various mode of action (MOA) classes, evaluate the hazard and develop risk estimates, and then apply a systematic comparison of new nanomaterials with the benchmark materials in the same MOA class. Poorly soluble particles are used here as an example to illustrate quantitative risk assessment methods for possible benchmark particles and occupational exposure control groups, given mode of action and relative toxicity. Linking such benchmark particles to specific exposure control bands would facilitate the translation of health hazard and quantitative risk information to the development of effective exposure control practices in the workplace. A key challenge is obtaining sufficient dose-response data, based on standard testing, to systematically evaluate the nanomaterials' physical-chemical factors influencing their biological activity. Categorization processes involve both science-based analyses and default assumptions in the absence of substance-specific information. Utilizing data and information from related materials may facilitate initial determinations of exposure control systems for nanomaterials. (2012 Springer Science+Business Media B.V. (outside the USA).) |
Risk assessment and risk management of nanomaterials in the workplace: translating research to practice
Kuempel ED , Geraci CL , Schulte PA . Ann Occup Hyg 2012 56 (5) 491-505 In the last decade since the rise in occupational safety and health (OSH) research focusing on nanomaterials, some progress has been made in generating the health effects and exposure data needed to perform risk assessment and develop risk management guidance. Yet, substantial research gaps remain, as do challenges in the translation of these research findings to OSH guidance and workplace practice. Risk assessment is a process that integrates the hazard, exposure, and dose-response data to characterize risk in a population (e.g. workers), in order to provide health information needed for risk management decision-making. Thus, the research priorities for risk assessment are those studies that will reduce the uncertainty in the key factors that influence the estimates. Current knowledge of OSH in nanotechnology includes the following: (i) nanomaterials can be measured using standard measurement methods (respirable mass or number concentration), (ii) workplace exposures to nanomaterials can be reduced using engineering controls and personal protective equipment, and (iii) current toxicity testing and risk assessment methods are applicable to nanomaterials. Yet, to ensure protection of workers' health, research is still needed to develop (i) sensitive and quantitative measures of workers' exposure to nanomaterials, (ii) validation methods for exposure controls, and (iii) standardized criteria to categorize hazard data, including better prediction of chronic effects. This article provides a state-of-the-art overview on translating current hazard research data and risk assessment methods for nanomaterials to the development and implementation of effective risk management guidance. |
Increased lung cancer mortality among chrysotile asbestos textile workers is more strongly associated with exposure to long thin fibres
Loomis D , Dement JM , Elliott L , Richardson D , Kuempel ED , Stayner L . Occup Environ Med 2012 69 (8) 564-8 BACKGROUND: Animal data and physical models suggest that the carcinogenicity of asbestos fibres is related to their size and shape. OBJECTIVES: To investigate the influence of fibre length and diameter on lung cancer risk in workers at asbestos textile mills in North Carolina and South Carolina, USA.METHODS: Men and women (n=6136) who worked ≥30 days in production and were employed between 1940 and 1973 were enumerated and followed for vital status through 2003. A matrix of fibre size-specific exposure estimates was constructed using determinations of fibre numbers and dimensions through analysis of 160 historical dust samples by transmission electron microscopy. Associations of lung cancer mortality with metrics of fibre exposure were estimated by Poisson regression with adjustment for age, sex, race and calendar year. RESULTS: Exposure to fibres throughout the range of length and diameter was significantly associated with increased risk of lung cancer. Models for fibres >5 mum long and <0.25 mum in diameter provided the best fit to the data, while fibres 5-10 mum long and <0.25 mum in diameter were associated most strongly with lung cancer mortality (log rate about 4% per IQR, p<0.001). When indicators of mean fibre length and diameter were modelled simultaneously, lung cancer risk increased as fibre length increased and diameter decreased. CONCLUSIONS: The findings support the hypothesis that the occurrence of lung cancer is associated most strongly with exposure to long thin asbestos fibres. The relationship of cancer risk and fibre dimensions should be examined in cohorts exposed to other types of fibres. |
Focused actions to protect carbon nanotube workers
Schulte PA , Kuempel ED , Zumwalde RD , Geraci CL , Schubauer-Berigan MK , Castranova V , Hodson L , Murashov V , Dahm MM , Ellenbecker M . Am J Ind Med 2012 55 (5) 395-411 There is still uncertainty about the potential health hazards of carbon nanotubes (CNTs) particularly involving carcinogenicity. However, the evidence is growing that some types of CNTs and nanofibers may have carcinogenic properties. The critical question is that while the carcinogenic potential of CNTs is being further investigated, what steps should be taken to protect workers who face exposure to CNTs, current and future, if CNTs are ultimately found to be carcinogenic? This paper addresses five areas to help focus action to protect workers: (i) review of the current evidence on the carcinogenic potential of CNTs; (ii) role of physical and chemical properties related to cancer development; (iii) CNT doses associated with genotoxicity in vitro and in vivo; (iv) workplace exposures to CNT; and (v) specific risk management actions needed to protect workers. (Am. J. Ind. Med. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.) |
Carbon black: Kuempel et al. respond
Kuempel ED , Schulte PA , Sorahan T , Caldwell J , Straif K , Ward E . Environ Health Perspect 2011 119 (8) a333-4 In “Research Recommendations for Selected IARC-Classified Agents,” Ward et al. (2010) identified research gaps for 20 occupational agents “based on evidence of widespread human exposures and potential carcinogenicity in animals or humans.” (Ward et al. 2010) For carbon black, the authors suggested that Research needs include updating epidemiology cohorts with data on work histories and exposures in relation to particle size and surface area, and recruitment of additional carbon black facilities. The relationship between occupational exposure to carbon black and validated biomarkers of oxidative stress should be examined and exposure–response relationships in humans and rodents quantified, including the role of particle size. Ward et al. (2010) referred to a study of British carbon black workers in which carbon black was suggested as a possible “late stage carcinogen” (Sorahan and Harrington 2007). In that study, Sorahan and Harrington (2007) called for similar analyses of other carbon black cohorts (i.e., evaluating the possibility of carbon black acting as a late stage carcinogen via the concept of “lugging,” which considers only recent exposures and not historical exposures). In response to suggestions made by Sorahan and Harrington, we conducted such analyses on a large German carbon black cohort (Morfeld and McCunney 2007, 2009). We were unable to reproduce the results of the British analysis, despite the elevation noted in lung cancer among German cohort workers, thus providing no support for the late stage-lugging hypothesis. Results of a detailed analysis of the German cohort using Bayesian methodology showed smoking and exposure to occupational carcinogens prior to work at the carbon black plant as confounders probably responsible for the lung cancer excess (Morfeld and McCunney 2010). Ward et al. (2010) called for enhanced exposure–response assessments in humans. Currently, a dose–response exposure analysis is under way on the U.S. carbon black cohort (> 5,000 production workers). An earlier evaluation of this cohort showed no increase in any type of cancer (Dell et al. 2006). |
Estimates of historical exposures by phase contrast and transmission electron microscopy for pooled exposure-response analyses of North Carolina and South Carolina, USA asbestos textile cohorts
Dement JM , Loomis D , Richardson D , Wolf SH , Kuempel ED . Occup Environ Med 2011 68 (8) 593-8 OBJECTIVES: To develop pooled size-specific asbestos fiber exposure estimates for North Carolina and South Carolina asbestos textile plants. METHODS: Airborne sample data and prior exposure estimates by phase-contrast microscopy (PCM) for the two cohorts were reviewed and compared. Estimates by transmission electron microscopy (TEM) for 160 membrane filter samples from all plant were pooled. Poisson regression models were developed to predict bivariate diameter/length airborne fiber size distributions based on independent categorical variables for fiber diameter, fiber length, plant, and exposure zone. The model predicted bivariate diameter/length distributions were expressed as the proportion of fibers in 28 size-specific cells and these data were used to calculate PCM to TEM adjustment factors in order to estimate fiber size-specific exposures for the pooled cohort. RESULTS: Exposure levels in the North Carolina plants were in excess of 50 f/cc for many operations through about 1955 owing to lack of dust control measures in early years whereas levels in the South Carolina plant were generally less than 10 f/cc by about 1950. The Poisson regression models found covariates for plant department to be a stronger predictor of bivariate size proportions than plant; however, a plant effect was observed. The final Poisson models demonstrated good fit to the observed data. CONCLUSIONS: Consistent with early studies, fiber exposures in the North Carolina plants were much higher than in South Carolina plant. Use of the predicted size-specific TEM exposures by plant and department based on the Poisson model predictions should reduce exposure. |
Carbon nanotube risk assessment: implications for exposure and medical monitoring
Kuempel ED . J Occup Environ Med 2011 53 S91-7 OBJECTIVE: Quantitative risk estimates using toxicology data provide information for risk management to protect workers with potential exposure to carbon nanotubes (CNTs). METHODS: Dose-response data from subchronic inhalation studies in rats were used in benchmark dose modeling. Dose was airborne mass concentration of multiwalled CNTs. Responses included pulmonary inflammation, lipoproteinosis, and fibrosis. RESULTS: Estimated human-equivalent concentrations to the rat lowest observed adverse effect levels were similar to some workplace airborne concentrations of CNTs. Working lifetime risk estimates of early-stage adverse lung effects were more than 10% at the limit of quantification (7 mcg/m(3)) of the National Institute for Occupational Safety and Health analytical method for measuring CNT airborne concentrations. CONCLUSIONS: Exposure monitoring and control are the primary occupational health measures to protect workers from potential exposure to CNT. Medical monitoring for early detection of occupational respiratory diseases may also be warranted. |
Contributions of dust exposure and cigarette smoking to emphysema severity in coal miners in the United States
Kuempel ED , Wheeler MW , Smith RJ , Vallyathan V , Green FH . Am J Respir Crit Care Med 2009 180 (3) 257-64 RATIONALE: Previous studies have shown associations between dust exposure or lung burden and emphysema in coal miners, although the separate contributions of various predictors have not been clearly demonstrated. OBJECTIVES: To quantitatively evaluate the relationship between cumulative exposure to respirable coal mine dust, cigarette smoking, and other factors on emphysema severity. METHODS: The study group included 722 autopsied coal miners and nonminers in the United States. Data on work history, smoking, race, and age at death were obtained from medical records and questionnaire completed by next-of-kin. Emphysema was classified and graded using a standardized schema. Job-specific mean concentrations of respirable coal mine dust were matched with work histories to estimate cumulative exposure. Relationships between various metrics of dust exposure (including cumulative exposure and lung dust burden) and emphysema severity were investigated in weighted least squares regression models. MEASUREMENTS AND MAIN RESULTS: Emphysema severity was significantly elevated in coal miners compared with nonminers among ever- and never-smokers (P < 0.0001). Cumulative exposure to respirable coal mine dust or coal dust retained in the lungs were significant predictors of emphysema severity (P < 0.0001) after accounting for cigarette smoking, age at death, and race. The contributions of coal mine dust exposure and cigarette smoking were similar in predicting emphysema severity averaged over this cohort. CONCLUSIONS: Coal dust exposure, cigarette smoking, age, and race are significant and additive predictors of emphysema severity in this study. |
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