Carcinogenicity of Poorly Soluble Low Toxicity Particles: Commentary on Epidemiology as a Risk Assessment "Reality Check".

Inhaled particles that are poorly soluble or insoluble and of low toxicity ("poorly soluble low toxicity" or "PSLT" particles), can accumulate in the lung and at lung overload levels induce lung cancers in rats. The question of whether PSLT particles increase lung cancer risk in humans is complicated by large differences between rats and humans and the relatively large particle doses administered in animal studies even when compared with heavy human occupational exposures. We review the findings of epidemiological studies on occupational exposure to each of three different PSLT particles (carbon black, talc and taconite). The epidemiological evidence indicates that at even very high occupational exposure levels at which non-malignant respiratory diseases including pneumoconiosis and even talcosis are observed, lung cancer risks appear not to be elevated. Although positive human cancer risks might be predicted based on extrapolation from overload doses in rats to relevant exposures in humans, the epidemiological "reality check" based on the three examples indicates that these PSLT particles are unlikely to increase lung cancer risk in humans even at high occupational levels of exposure. Therefore, we propose that careful evaluation of the epidemiological evidence can serve as a "reality check" for human risk assessment and help balance the risk evaluation process.

Multi-route exposure sampling of quaternary ammonium compounds and ethanol surface disinfectants in a K-8 school.

The frequency of surface disinfectant use has increased over the last several years in public settings such as schools, especially during the COVID-19 pandemic. Although these products are important for infection control and prevention, their increased use may intensify the exposure to both persons applying the disinfection product as well as bystanders. Safety assessments have demonstrated that these products, when used as intended, are considered safe for use and effective; however, point-of-contact effects (such as respiratory or dermal irritation) may still occur. Additionally, relative exposures may vary significantly due to the wide variation in disinfectant formulation and application methods. Quantitative estimations of exposures to two commonly used active ingredients, quaternary ammonium compounds (QACs) and ethanol, are not well characterized during product use and application scenarios. To assess the potential for health risks attributable to increased use in classroom settings, as well as to quantitatively evaluate the potential exposure to both ethanol and QACs, student and adult bystander surface and air measurements were collected in a K-8 school setting in Ohio, United States, over a three-day period. Direct-reading instruments were utilized to collect real-time air samples that characterized mass fraction concentrations following the use of the QAC- and ethanol-based disinfectants. Furthermore, surface and air sampling of microbial species were conducted to establish the overall bioburden and effectiveness of each disinfectant to inform the comparative risk and health effect impacts from the tested products use scenario. Both tested products were approximately equally effective at reducing bioburdens on desk surfaces. In some classrooms, concentrations of QAC congeners were significantly increased on desk surfaces following the application of the disinfectant spray; however, the magnitude of the change in concentration was small. Ethanol was not measured on surfaces due to its volatility. Airborne concentrations increased immediately following spray of each disinfectant product but rapidly returned to baseline. Each of the QAC congeners listed in the product safety data sheets were detected and measurable on desk surfaces; however, air concentrations were generally below the limit of detection. The 15-min time-weighted averages (TWAs) of both QACs and ethanol in the air were below respective health effects benchmarks, and therefore, the negative impact on health outcomes is considered to be minimal from short-term, repeated use of ethanol- or QAC-based spray products in a school setting when the products are used as directed.

Determination of murine norovirus aerosol concentration during toilet flushing.

Murine norovirus (MNV) was used as a surrogate for human viral pathogens (e.g., norovirus) to determine if toilet flushing resulted in the aerosolization of virus. A flushometer type toilet was seeded with a viral solution of 105 and 106 PFU mL-1 of MNV and then flushed. Upon flushing, two bioaerosol samplers were activated to collect aerosolized MNV. Prior to the experiment, two optical particle counters monitored particle size and number distribution of aerosol produced from flushing a toilet across height, position, and side. The location with the highest mean particle concentration, was behind the toilet and 0.15 m above the toilet bowl rim, which is where bioaerosol sampling occurred. Bioaerosol and toilet water samples were collected, extracted and then quantified using RT-ddPCR. The concentration of MNV collected after seeding the toilet water ranged from 2.18 × 105 to 9.65 × 106 total copies of MNV. Positive samples of airborne MNV were detected with collected concentrations ranging from 383 to 684 RNA copies/m3 of air. This study provides evidence that viral pathogens may be aerosolized when a toilet is flushed. Furthermore, the MNV used in this study is a model organism for human norovirus and may be generalizable to other viral pathogens (e.g., coronavirus). This study suggests that virus is aerosolized from toilet flushing and may contribute to human exposure to viral pathogens.

Derivation of an occupational exposure limit for ß-glucans.

ß-Glucans are abundant bacterial, yeast, and fungal cell wall polysaccharides that have been shown to activate the immune system. Establishment of an occupational exposure limit (OEL) for ß-glucan exposure is critical to the protection of worker health, as these exposures have been linked to immunosuppressive and inflammatory reactions and possibly the development of respiratory diseases. Detectable concentrations of ß-glucans have been identified in common occupational inhalation exposure scenarios, such as in the agricultural and waste management sectors. However, no published exposure benchmarks for inhalation of ß-glucans are available for workers or the general population. Thus, a health-based OEL for inhalation exposure of workers to ß-glucans was derived based on consideration of human and non-human effect data for this class of compounds and contemporary risk assessment methods. The weight of the evidence indicated that the available data in humans showed significant methodological limitations, such as lack of a representative study size, appropriate control population, and clear dose-response relationship. Thus, an OEL of 150 ng/m3 was derived for ß-glucans based on the most relevant nonclinical study. This OEL provides an input to the occupational risk assessment process, allows for comparisons to worker exposure, and can guide risk management and exposure control decisions.

Lessons learned for COVID-19 in the cruise ship industry.

The coronavirus disease 2019 (COVID-19) pandemic has created widespread disruption in individuals' personal and occupational lives all around the world. Vacationers and tourism, recreation, and leisure employees were among those who experienced substantial disruption. Cruise ships, especially, faced turmoil on a global scale for both their customers and workers. COVID-19 outbreaks were reported on cruise ships beginning in February 2020, presenting new and unique challenges for the industry. Conditions on cruise ships, including close and frequent contact between passengers and crew members, use of common areas, the confined nature of the vessels, and gathering of passengers from different countries, aided in transmitting the disease both onboard and in the community. As the pandemic evolved, federal and state governments and industries worldwide, including cruise ship companies, developed response plans. In this article, we provide a high-level overview of the US government and cruise ship industry's response to the COVID-19 pandemic, as well as a brief commentary on lessons learned, and recommendations for the cruise ship sector going forward. The outlined suggestions may be used as a starting point to increase emergency preparedness and to inform outbreak response plans in the event of future infectious disease outbreaks.

Advancing toward normal operations for arenas and stadiums.

The reopening of arenas and stadiums following closures due to the 2019 coronavirus disease (COVID-19) pandemic presents unique challenges related to large crowds and close contact between players, vendors, and spectators. While each venue should be assessed individually for development and implementation of reopening plans, the general guidance presented in this document can serve as a minimum baseline for considerations to reduce the risk of COVID-19 transmission in these venues. The intention of these guidelines is to provide a layered approach to risk mitigation for various aspects of particular concern in arenas and stadiums, including crowd management, tailgating and parking, restrooms, high-contact surfaces, face masks, food and merchandising, communications, athletes and support staff, press and third parties, intermissions/breaks, and downtime. The implementation of these multifaceted approaches in each area of concern, along with the integration of regulations and requirements from local, state, and federal government bodies and agencies, will reduce the risk of a single point of failure and offer some protection to those at arenas and stadiums from COVID-19 transmission. The approaches outlined are dynamic and should be regularly reviewed and revised as new information becomes available regarding the transmission of COVID-19.

Current understanding and future directions for an occupational infectious disease standard.

The coronavirus disease 2019 pandemic has demonstrated a need for an infectious disease standard that will promote a safe and healthy work environment and assure business continuity. The current pandemic has revealed gaps in workplace preparedness and employee protections to microbial exposures. Federal and state government agencies have responded by providing interim guidelines and stop-gap measures that continue to evolve and vary in approach and required controls. This interim and inconsistent approach has resulted in confusion on the part of businesses as they work toward reopening during the pandemic and uncertainty as to the efficacy of required or suggested controls. Moving forward, the US Occupational Safety and Health Administration, with guidance from the US National Institute for Occupational Safety and Health, should establish consistent and effective strategies through a nationwide standard to address the potential microbial exposures in the workplace. Such a standard will require effective worker protections from infectious diseases and assure business continuity.

Return to normal operations: COVID-19 mitigation strategies for workplaces.

As spikes and resurgences of COVID-19 cases continue to increase in different geographical regions across the United States, more and more companies are left with numerous questions about reopening or restarting their operations. The current pandemic in the United States poses unique challenges unlike any other for businesses and employers as they begin to reopen. Businesses and employers are forced to ensure that they are not only in compliance with federal guidances but also with state and local guidances. In addition to the complex and ever evolving guidances, we are still learning about and adapting best practices during these reopening phases. Therefore, it is crucial for businesses to stay up-to-date not only with the released guidances but also with the latest understanding and information about SARS-CoV-2. As part of reopening, it is crucial for businesses to have comprehensive reopening plans prior to restart of operation. These plans must be clear, concise, and flexible enough to include updated guidances and information. In this publication, we describe reopening frameworks, considerations, and strategies that can be used as a starting point for businesses to further optimize and tailor to their unique operations.

The Optimization of Methods for the Collection of Aerosolized Murine Norovirus.

Globally, norovirus is the most common gastroenteritis causing pathogen. Annually, norovirus causes 685 million cases of acute gastroenteritis and 200,000 deaths, worldwide. Recent evidence has suggested that norovirus can also be spread via aerosolization; however, an indoor generation source has yet to be determined. We optimized a sampling method for the collection of aerosolized norovirus using murine norovirus (MNV) as a surrogate. Optimization of the sampling method was performed using two bioaerosol samplers (SKC BioSampler and the NIOSH Bioaerosol Cyclone Sampler 251) and two sampling media (Hanks Balanced Salt Solution [HBSS] and Phosphate Buffered Saline [PBS]). Murine norovirus was aerosolized in a bioaerosol chamber and later collected using each sampler/media combination. Collected MNV was quantified using quantitative polymerase chain reaction (qPCR). Intact capsids of MNV were assessed using propidium monoazide dye in combination with qPCR and confirmed with transmission electron microscopy. Ten trials were conducted, with each trial lasting for 30 min. The SKC BioSampler collected a significantly higher concentration of MNV than the NIOSH-251 sampler did (p-value < 0.0001). However, there were no significant differences in the relative percent of MNV that remained viable between both samplers (p-value = 0.2215). The use of HBSS sampling media yielded a higher concentration of MNV than PBS media (p-value = 0.0125). However, PBS media maintained viability at a significantly higher percentage than HBSS media (p-value < 0.0001). The results support the optimization of a sampling method for the collection of aerosolized MNV and possibly norovirus in different sampling environments.

Bioaerosol concentrations generated from toilet flushing in a hospital-based patient care setting.

Background: In the United States, 1.7 million immunocompromised patients contract a healthcare-associated infection, annually. These infections increase morbidity, mortality and costs of care. A relatively unexplored route of transmission is the generation of bioaerosols during patient care. Transmission of pathogenic microorganisms may result from inhalation or surface contamination of bioaerosols. The toilet flushing of patient fecal waste may be a source of bioaerosols. To date, no study has investigated bioaerosol concentrations from flushing fecal wastes during patient care. Methods: Particle and bioaerosol concentrations were measured in hospital bathrooms across three sampling conditions; no waste no flush, no waste with flush, and fecal waste with flush. Particle and bioaerosol concentrations were measured with a particle counter bioaerosol sampler both before after a toilet flushing event at distances of 0.15, 0.5, and 1 m from the toilet for 5, 10, 15 min. Results: Particle concentrations measured before and after the flush were found to be significantly different (0.3-10 µm). Bioaerosol concentrations when flushing fecal waste were found to be significantly greater than background concentrations (p-value = 0.005). However, the bioaerosol concentrations were not different across time (p-value = 0.977) or distance (p-value = 0.911) from the toilet, suggesting that aerosols generated may remain for longer than 30 min post flush. Toilets produce aerosol particles when flushed, with the majority of the particles being 0.3 µm in diameter. The particles aerosolized include microorganisms remaining from previous use or from fecal wastes. Differences in bioaerosol concentrations across conditions also suggest that toilet flushing is a source of bioaerosols that may result in transmission of pathogenic microorganisms. Conclusions: This study is the first to quantify particles and bioaerosols produced from flushing a hospital toilet during routine patient care. Future studies are needed targeting pathogens associated with gastrointestinal illness and evaluating aerosol exposure reduction interventions.

Raccoonpoxvirus safety in immunocompromised and pregnant mouse models.

Numerous poxviruses infect humans and animal hosts, and a poxvirus vaccine with an improved safety profile is needed as the current vaccinia virus vaccine is contraindicated in individuals that have a history of eczema or heart disease, or are immunocompromised or pregnant. In addition, poxviruses make excellent vaccine vectors for other infectious diseases and cancer. Raccoonpoxvirus is a naturally occurring attenuated North American poxvirus, and thus it is of interest as a vaccine vector platform. This study explores the effects of raccoonpoxvirus in SCID and Nude immunocompromised and pregnant mouse models to assess its virulence and probable safety for human and animal populations. We also analyzed the safety of recombinant raccoonpox carrying a gene expressing a foreign antigen, rabies virus glycoprotein, designed for heterologous vaccine protection. Our data show that recombinant raccoonpoxviruses are avirulent in many cases and are much safer than vaccinia virus (strain WR). Raccoonpoxviruses also have the advantage of being able to replicate in mammalian cells. This allows increased immunogenicity and production efficiency, giving an advantage over non replicating vectors such as Modified Vaccinia Ankara MVA or canarypoxvirus.