In accordance with its mandate to protect worker health and safety, the National Institute for Occupational Safety and Health (NIOSH) carries out research projects with NTP through an interagency agreement with NIEHS to assess the effects of exposure to substances. Setting priorities in occupational toxicological research is based on several sources of information NIOSH develops and maintains. Sources include health hazard evaluations, industry-wide studies, gaps in knowledge identified while developing criteria for recommended standards or criteria documents, current intelligence bulletins, hazard reviews and alerts, other technical reports, and information profiles on chemical hazards. NIOSH research projects with NTP are funded by voluntary allocations and an interagency agreement focused on comprehensive assessment of occupationally relevant exposures and immunotoxicology research.
NIOSH Staff: Health Effects Laboratory Division; Education and Information Division; Division of Applied Research and Technology and the Division of Surveillance, Hazard Evaluations, and Field Studies
NIOSH/NTP projects in FY 2017 funded through voluntary allocations are listed below. Click the project title for a brief summary.
Study Scientist: John Snawder
Support of multiple branch and interdivisional projects through (1) managing and planning field sample collection, (2) developing new classical and immunochemical biomonitoring methods, and (3) validating and adapting existing methods. Biological monitoring can assess exposure by analyzing acute and latent metabolites in various biological media. This project will develop low-cost, rapid immunochemical and analytical chemistry biomonitoring methods to be used to identify exposures and evaluate potential interventions. Concurrent with development of exposure assessment methods, this project will identify and develop new multiplex immunochemical methods to evaluate biomarkers of occupational illness or subclinical signs of occupational illness.
Study Scientist: John Snawder
Development and evaluation of a readily adaptable, next-generation, direct-reading personal monitor for use in measuring worker exposure to a wide variety of chemicals, including naphthalene and components of asphalt fume. The development of personal monitors for volatile and semivolatile workplace chemicals will be helpful in rapidly assessing chemical exposure and will result in more realistic occupational exposure assessments. These assessments will allow for rapid interventions leading to reduced worker exposures and helping prevent occupational illness and disease.
Study Scientist: Patti Erdely
Investigation of both carcinogenic metal-containing and non-carcinogenic metal-containing welding fumes as lung carcinogens using a two-stage initiation-promotion mouse model. The findings will establish if welding fume inhalation at relevant occupational exposure levels increases lung tumorigenesis. The project also is generating valuable data regarding the carcinogenic potential of fumes from different types of welding processes that contain or do not contain carcinogenic metals. In addition, the project is providing information on which metal oxide components of the welding fume have the greatest carcinogenic potency. Thus far, the results of this project have contributed to the reevaluation of welding fumes by the International Agency for Research on Cancer in March 2017.
Study Scientist: Yong Qian
Investigation of cobalt oxide and lanthanum oxide nanoparticle-induced pulmonary injury in vivo and cellular toxicity in vitro. This project will reveal the toxicological modes of action for cobalt oxide and lanthanum oxide nanoparticles. Metal oxide nanoparticles are an important class of engineered nanomaterials with broad application in many industrial products. Concerns over potential metal oxide nanoparticle-induced toxicity have emerged, particularly due to the propensity of these nanoparticles to induce oxygen radicals and oxidative stress. Results obtained from this study will lead to development of methods for early detection and interventions of cobalt oxide and lanthanum oxide-induced pulmonary diseases, particularly fibrosis, in humans.
Study Scientist: Mary Schubauer-Berigan
Collection of exposure data and exposure factors from participating pilot-scale or full-scale manufacturers or users of single-walled carbon nanotubes (SWCNTs) or multiwalled carbon nanotubes and carbon nanofibers. A study of biomarkers for early pulmonary, cardiovascular, and carcinogenic effects was carried out among workers at these facilities. The creation of a predictive model using the collected exposure factors will allow for the estimation of exposure for future registry and cohort studies.
Study Scientist: James Yiin
Elucidation of exposure-outcome associations, especially dose-response relationships, for risk assessment and to examine relationships between biomarkers of exposure, susceptibility, and oncogene expression and determine health effects.
Study Scientist: Robert Streicher
Support of administrative needs and analytical instrumentation repair and maintenance for Chemical Exposure and Monitoring Branch chemists conducting research on sampling and developing analytical methods for workplace chemicals. Development, evaluation, validation, and use of methods for evaluating bisphenol A, manganese speciation, flame retardants, and other chemicals are part of the NIOSH/NTP exposure assessment interagency agreement.
Study Scientist: Robert Streicher
Development and evaluation of sampling and analytical methods for diacetyl and other higher molecular-weight alpha dicarbonyl flavoring compounds to enable accurate exposure assessment and evaluation of the effectiveness of control technology. Two sampling and analysis methods are being investigated for measurement of specific flavoring compounds, most notably diacetyl and 2,3-pentanedione. One method measures alpha dicarbonyl compounds present as vapor; the other measures the compounds in airborne particles and bulk powders. A modification to improve a recently developed Occupational Safety and Health Administration method for flavorings by gas chromatography-mass spectrometry using a different extraction solvent has been investigated in FY 2017. In addition, a new sampler that can distinguish flavorings present in air as vapors, particle-bound flavorings, and vapors off-gassing from collected particles has undergone evaluation with diacetyl and has performed well.
Study Scientist: Eileen Birch
Development and application of measurement methods for hazardous aerosols. Globally, exposure to hazardous aerosols remains a serious health concern, with growing attention on fine, ultrafine, and nanosized aerosol particles. New nanomaterials are being developed and used in multiple commercial products, but their health and environmental impacts are little known. Multiple analytical tools are being used because the properties most responsible for nanoaerosol toxicity are unclear and exposures to complex mixtures often occur. This research is providing critical exposure data and information on the widely differing physical and chemical properties of nanoscale aerosols and materials, properties which might influence particle toxicity. The methods have general application to exposure monitoring and control studies.
Metal content was determined by inductively coupled plasma atomic emission spectroscopy after microwave digestion in concentrated nitric acid. All materials were analyzed by thermogravimetric analysis, which gives the onset of oxidation (a measure related to stability) and residual ash content (a measure of purity). Most sample contained high concentrations, and the residual ash contents of the materials ranged from about 1 to 10%. Previously (FY 2016), polycyclic aromatic hydrocarbons and transmission electron microscopy analyses were completed.
Study Scientist: Brian Curwin
Characterization of workplace exposures to chemicals of toxicological concern as identified by NTP and NIOSH. Current studies evaluate welding fumes with emphasis on manganese, occupational exposure to carbon nanotubes and nanofibers, flame retardants, and polycyclic aromatic hydrocarbons in coal tar sealants. Goals of these studies include: (1) identifying industries, workplaces, uses, and users; (2) determining occupational health relevance; (3) estimating the number of workers exposed; and (4) conducting exposure sampling.
Study Scientist: Elizabeth Whelan
Support of strategic planning and feasibility studies of high-priority issues and emerging problems in occupational health.
Study Scientist: Charles Geraci
Collection of information from as many different facilities in the field as possible regarding the (1) nature of engineered nanomaterials, (2) processes involved in the manufacture and use of nanomaterials, (3) potential worker exposures to nanomaterials, and (4) practices and control procedures in the workplace where nanomaterials are produced or used. As toxicology studies identify the biological hazards of nanomaterials, gaining a better understanding of actual workplace exposures is essential.
Study Scientist: Stacey Anderson
Identification of occupational and environmental chemical hazards and evaluation of immune function and mechanisms associated with exposure. This research is contributing to better risk assessment and increased identification of immunological hazards encountered in the workplace, which ultimately will establish occupational exposure limits.
Study Scientist: John Noti
(1) Identification of exposures to substances that can cause inflammatory or immune reactions in certain work environments. These exposures are important causes of occupational lung diseases, such as asthma and allergic alveolitis.
(2) Development of improved techniques for detecting such immune reactions before adverse clinical outcomes occur.
(3) Development of improved techniques for detecting and identifying inciting occupational agents.
This project is analyzing clinical samples, environmental bulk samples, and environmental aerosol samples. Successful completion of these investigations should lead to the development of effective prevention strategies for occupational allergies and asthma.
Study Scientist: Justin Hettick
Determination of the molecular targets of inhaled diisocyanate particulates and better understanding of the pathogenic mechanism of isocyanate-induced allergic disease. The project enhances the overall understanding of the fate of diisocyanate in vivo following occupational exposure by increasing our understanding of disease and identifying potential biomarkers of exposure.
Study Scientist: Justin Hettick
Definition of mechanisms of occupational asthma associated with exposure to methylene diphenyldiisocyanate (MDI) by identifying biomarkers of MDI exposure and immune regulatory factors that influence the progression and severity of MDI-associated occupational asthma. Exposure to MDI, used in the manufacturing of glues and polyurethanes, results in occupational asthma in approximately 5–15% of workers. Currently, sensitive and reliable markers for MDI exposure and sensitization do not exist, partially due to the lack of specificity of markers commonly associated with asthma. Furthermore, the factors influencing susceptibility and severity of MDI-associated occupational asthma have not been elucidated. This project is identifying response and legacy biomarkers found in exosomes secreted into the bloodstream that would indicate isocyanate exposure and sensitization. Attempts are being made to distinguish chemically induced biomarkers from high-molecular-weight allergen-induced biomarkers and determine how exosome genetic content can influence asthma progression. The biomarkers identified in this study can be incorporated into a human exposome database and be used in future studies to distinguish MDI-associated occupational asthma from general environmental asthmas.
Study Scientist: Brett Green
Determination of the pulmonary immunopathological outcomes of subchronic exposures to fungi nominated to NTP. Subchronic exposure studies with mycotoxin-producing strains of Stachybotrys chartarum and Aspergillus versicolor have been completed. Future subchronic exposure studies will focus on an atranone-producing strain of S. chartarum, A. versicolor, A. alternate, and fungi identified in NIOSH Health Hazard Evaluations and collaborative exposure assessment studies. Proposed studies will provide further insight into the mechanisms of pulmonary toxicity to fungi encountered in the workplace.
Study Scientist: Nikki Marshall
Identification of the cellular and molecular mechanisms behind the immune-modulating effects of the antibacterial chemical, triclosan. This information is providing the basis for evaluating other nonsensitizing antimicrobial chemicals and helps identify potentially conserved mechanisms that contribute to allergic disease. Results of this project will help assess the need to evaluate these types of workplace chemicals, leading to better risk assessment and establishment of occupational exposure limits.
Study Scientist: Pius Josephweb
Development, validation, and testing (using a rat model) of highly sensitive and minimally invasive biomarkers for early detection of pulmonary toxicity potentially associated with exposure to toxic nanomaterials. Techniques are being employed to develop transcriptomic signatures in blood as surrogate biomarkers for the pulmonary toxicity induced by inhalation exposure to specific nanomaterials. Bioinformatic analysis of the global transcriptomics data is being conducted to gain insights into the molecular mechanisms underlying the pulmonary toxicity of nanomaterials. Determining the molecular mechanisms of pulmonary toxicity and developing highly sensitive and minimally invasive biomarkers for nanotoxicity have implications in monitoring workers for their risk of developing adverse health effects potentially associated with exposure to toxic nanomaterials.
Results obtained from preliminary studies demonstrated that rats exposed to multiwalled carbon nanotubes (MWCNTs) can be distinguished from those exposed to crystalline nanocellulose using blood gene expression profiles.
Study Scientist: Dale Porter
Examination of the potential effect of altering the chemical composition of MWCNTs on their bioactivity in vivo. Knowledge of doping modification could allow for the development and use of MWCNTs with reduced bioactivity, which might help reduce the hazard from workplace exposures. Such information might enable material scientists to incorporate a prevention-through-design philosophy into the development of new nanoparticle-based technologies using nanomaterials that pose lower risks to human health. These data contribute to NIOSH’s effort to develop and implement an evidence-based strategy for recommending occupational exposure limits or occupational exposure bands for carbon nanotubes. These studies are comparing two MWCNTs with different chemical compositions: MWCNTs and nitrogen-doped MWCNTs. These studies should increase our understanding of the toxicological mechanisms responsible for MWCNT-induced pathologies and could help identify extrapulmonary sites of toxicity resulting from systemic transport of MWCNTs after pulmonary exposure.
Study Scientist: Krishnan Sriram
Evaluation of potential neurotoxicological effects associated with exposure to chemical agents, incidental nanoparticles, and engineered nanomaterials in experimental models. This study includes identifying hazards, evaluating molecular mechanisms of neurotoxicity, and identifying potential biomarkers of neurotoxicity. Findings from this study could contribute to the development of novel biomarkers for monitoring exposures and health effects, pre-job planning protocols, hazard and risk assessment paradigms, and occupational safety standards for neurotoxic exposures.
Study Scientist: Linda Sargent
Investigation of the relationship between carbon nanotube diameter and mechanism of carcinogenesis and aneuploidy. In vitro exposure of human cells to 1- to 4-nm-diameter single-walled carbon nanotubes disrupts the mitotic apparatus, resulting in errors of chromosome number. Data comparisons with 10- to 20-nm-diameter MWCNTs suggest the diameter of the nanotube is important in the genotoxic response and that carbon nanotubes are potentially carcinogenic. In a study in which MWCNTs were inhaled using a two-stage initiation and promotion model, 49-nm-diameter MWCNT not only disrupted the mitotic spindle pole but also disrupted the center of the chromosome. Previous work has demonstrated that MWCNTs are strong promoters of mouse lung adenocarcinoma. Ongoing research investigates the dose-response relationship of lung tumor promotion in a mouse model.
Study Scientist: Min Ding
Investigation of potential pulmonary carcinogenesis in response to tungsten carbide-cobalt (WC-Co) particle exposure using cell culture and animal models. Mechanistic investigations, including gene mutation, activation of transcription factors, and reactive oxygen species generation, are being conducted to explain the events of WC-Co-induced tumor initiation, promotion, and progression. Determining the mechanisms involved in WC-Co-induced carcinogenesis and elucidating target-signaling pathways could provide insights for the development of biomarkers and possible prevention strategies for WC-Co-induced diseases.
Study Scientist: Liying Rojanasakul
Investigation of the properties of nano-metal oxides that affect their fibrogenicity or carcinogenicity. Metal oxide nanoparticles are increasingly used in a variety of applications having the potential to release particles into the workplace air. Limited published studies using animal models have shown lung inflammation and fibrosis with pulmonary exposure to metal oxide nanoparticles at human exposure-relevant doses. This project is determining the effects of physicochemical properties (size and coating) on metal oxide nanoparticles toxicity and the underlying mechanisms. Results thus far have shown that cerium oxide nanoparticles in mice cause lung inflammation that is particle-size dependent. In addition, consistent fibrogenic effects from cerium oxide nanoparticles are observed in vitro and in an animal model. These results support the development of an economical in vitro tool for predicting the potential toxicity of metal oxide nanoparticles in vivo. Low-dose/long-term in vitro exposure models have been continually tested using several well-characterized metal oxide nanoparticles and human lung cells to determine metal oxide nanoparticle-type-dependent neoplastic transformation induction and mechanism, including ferric oxide nanoparticle-disrupted iron homeostasis. Silicon dioxide coating of the ferric oxide nanoparticle partially ablated such effects and could support potential safe-by-design strategies.
Study Scientist: Jeffrey Fedan
Study of toxicological effects associated with hydraulic fracturing silica exposure and diesel exhaust exposure. The toxicities of inhaled hydraulic fracturing sand dust—alone and in combination with inhaled diesel exhaust to mimic worker exposures during hydraulic fracturing operations—are being studied. Effects of exposure on the lung, cardiovascular system, immune system, brain, skin, and blood are being examined using a battery of in vivo and in vitro experiments. The initial exposures to hydraulic fracturing sand dust, using two exposure doses, are completed. Exposures to diesel exhaust from a type II diesel engine are underway. Inhalation exposures to fracturing sand dust in combination with diesel exhaust also will be assessed.
Study Scientist: Jeffrey Fedan
Characterization of MWCNT effects on critical aspects of lung function in vivo and airway function in vitro and provision of metrics to enable risk assessment strategies. In vivo experiments have demonstrated changes in pulmonary function and airway reactivity in animals exposed to MWCNTs. A comparison of the relative pulmonary toxicities of pristine and nitrogen-doped MWCNTs is underway.
Study Scientist: Jeffrey Fedan
Design and building of an inhalation exposure system that delivers crude oil vapor to rats. This system is being used to study the effects of crude oil vapor inhalation on the lung, cardiovascular system, immune system, brain, skin, and blood. Surrogate oil for the Macondo well in the Gulf of Mexico is being used. Acute inhalation exposures have been completed, and subchronic exposures are in progress.
Study Scientist: Aaron Erdely
Evaluation of the toxicity of carbon nanotubes and carbon nanofibers obtained from U.S. facilities. To date, few studies have examined the toxicity of such a broad range of materials collected from manufacturing facilities with direct relevance to U.S. worker health. This study is assessing general pulmonary and systemic toxicity, pathology, biodistribution, and genotoxicity.
Study Scientist: Aaron Erdely
Investigation of carbon nanotube toxicity at different stages of production. In vivo and in vitro data suggest that exposure to carbon nanotubes has significant adverse health effects. Few data are available to define the toxicity of carbon nanotubes at each stage of the production life cycle (as produced, post-production modification, and incorporation into composites), although the numbers of potentially exposed workers increases with each stage. This project is evaluating the pulmonary response and genotoxicity of carbon nanotubes at different stages of production.
Study Scientist: Aaron Erdely
Development of an in vitro model to assess cardiovascular risk from particulates. Respiratory exposure to particulates has been associated with increased mortality from cardiovascular diseases. This project is developing and testing an in vitro model to assess cardiovascular risk following pulmonary exposure to engineered nanomaterials.