Occupational and Inhalation Exposures Research Program

National Institute Of Environmental Health Sciences

Investigators

Linked publications & trials

Abstract

According to National Institute for Occupational Safety and Health (NIOSH), fatalities from respiratory diseases and cancers caused by inhalation exposures account for approximately 70% of all occupational disease deaths. Respiratory diseases caused by occupational inhalation exposures include those affecting the large and small airways (such as allergy/asthma and fibrosis), interstitial (fibrotic) lung diseases (such as silicosis/asbestosis), pleural disease, and lung cancers. These adverse respiratory tract effects can be linked to acute or chronic (high- or low-dose) inhalation exposures in a wide variety of workplace settings and range from mild, reversible conditions to progressive, irreversible fatal disorders. Inhalation exposures can also cause adverse health effects in other (non-respiratory) organ systems. Inhalation exposures to toxic compounds tend to be weighted to occupational settings, although the general public may also be exposed to similar hazards via inhalation in the environment. However, inhalation exposures in the workplace tend to be at relatively higher doses compared with chronic, low-dose exposures to the general public. Other potential (non-inhalation) routes of exposure exist in the workplace (e.g., dermal sensitization) and for the general public (e.g., radiation) that can also cause adverse health effects to the respiratory tract and other organ systems. In alignment with NTP goals, the OIE Program provides trusted science to support decision-making. Results from hazard characterization studies are utilized to ensure risks related to exposures are mitigated. In addition, this program actively engages stakeholders and subject matter experts, in coordination across the Division of Translational Toxicology (DTT) and the National Institute of Environmental Health Sciences (NIEHS), to enhance the goal of developing and applying innovative tools and strategies for addressing occupational/inhalation toxicology. This program also examines current in-house approaches and processes to enhance our ability to detect translatable toxicological responses more effectively and efficiently. Progress has been made on several projects this past year, including those related to characterizing the toxicological hazards from in vivo inhalation exposures to natural mineral fibers (e.g., Libby Amphibole), multiwall carbon nanotubes, alkylbenzene compounds (gasoline components), and radio-frequency radiation. Several publications and reports are publicly available while others are in development for review in the next fiscal year. Projects to assess respiratory hazards following inhalation exposure to tremolite as well as per- and polyfluoroalkyl substances (PFAS) have also been initiated. Method development/validation, protocol optimization, and model application continued for in vitro studies evaluating the inhalation toxicity of 2,3-pentanedione using human- and rat-derived air-liquid interface (ALI) airway cultures combined with a Vitrocell exposure system. This work was presented at an international conference this year and is currently being drafted for publication. A steering committee was also formed which will generate a working protocol (SOPs) for the conduct of an inter-laboratory reproducibility study using PD vapor-exposed human ALI airway cultures. Additionally, the OIE Program generated a summary report of the feedback from the Spring 2024 “Request for Information (RFI) on the Use of In Vitro Lung Models in Inhalation Toxicology Research with Potential Application to Regulatory Decision-Making" which we intend to post to the OIE webpage for viewing by interested stakeholders and collaborators. Through an Interagency Agreement (IAA) between DTT and NIOSH, exposure assessments and the development of technologies to quantify indoor and occupational fungal aerosols have progressed this year. Specifically, an in vivo assessment to characterize toxicological hazards associated with Stachybotrys Chartarum exposure in mice was published this year while reporting is ongoing for Aspergillus Versicolor. Additional research under this IAA is supported to assess occupational exposures in various industries including those that work with per- and polyfluoroalkyl substances (PFAS), monoterpenes including alpha-pinene, volatile organic compounds in nail salon workers, and graphene. This work, as well as additional ongoing efforts, are focused on understanding the health hazard potential of current/emerging agents of concern to the general public and in the workplace using guideline and alternative/novel in vivo studies, complemented by in vitro approaches, with designs tailored to address specific key questions and data needs.