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The intercellular communications mediating radiation-induced bystander effects and their relevance to environmental, occupational, and therapeutic exposures
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Impact of phenanthrene co-administration on the toxicokinetics of benzo[a]pyrene in humans. UPLC-accelerator mass spectrometry following oral microdosing
Current risk assessments for environmental carcinogens rely on animal studies utilizing doses orders of magnitude higher than actual human exposures. Epidemiological studies of people with high exposures (e.g., occupational) are of value, but rely on uncertain exposure data. In addition, exposures are typically not to a single chemical but to mixtures, such as polycyclic aromatic hydrocarbons (PAHs). The extremely high sensitivity of accelerator mass spectrometry (AMS) allows for dosing humans with known carcinogens with de minimus risk. In this study UPLC-AMS was used to assess the toxicokinetics of [ 14 C]-benzo[a]pyrene ([ 14 C]-BaP) when dosed alone or in a binary mixture with phenanthrene (Phe). Plasma was collected for 48 h following a dose of [ 14 C]-BaP (50 ng, 5.4 nCi) or the same dose of [ 14 C]-BaP plus Phe (1250 ng). Following the binary mixture, C max of [ 14 C]-BaP significantly decreased (4.4-fold) whereas the volume of distribution (V d ) increased (2-fold). Further, the toxicokinetics of twelve [ 14 C]-BaP metabolites provided evidence of little change in the metabolite profile of [ 14 C]-BaP and the pattern was overall reduction consistent with reduced absorption (decrease in C max ). Although Phe was shown to be a competitive inhibitor of the major hepatic cytochrome P-450 (CYP) responsible for metabolism of [ 14 C]-BaP, CYP1A2, the high inhibition constant (K i ) and lack of any increase in unmetabolized [ 14 C]-BaP in plasma makes this mechanism unlikely to be responsible. Rather, co-administration of Phe reduces the absorption of [ 14 C]-BaP through a mechanism yet to be determined. Furthermore, this is the first study to provide evidence that, at actual environmental levels of exposure, the toxicokinetics of [ 14 C]-BaP in humans is markedly altered by the presence of a second PAH, Phe, a common component of environmental PAH mixtures.
New Approach Methodology for Assessing Inhalation Risks of a Contact Respiratory Cytotoxicant: Computational Fluid Dynamics-Based Aerosol Dosimetry Modeling for Cross-Species and In Vitro Comparisons
Regulatory agencies are considering alternative approaches to assessing inhalation toxicity that utilizes in vitro studies with human cells and in silico modeling in lieu of additional animal studies. In support of this goal, computational fluid-particle dynamics models were developed to estimate site-specific deposition of inhaled aerosols containing the fungicide, chlorothalonil, in the rat and human for comparisons to prior rat inhalation studies and new human in vitro studies. Under bioassay conditions, the deposition was predicted to be greatest at the front of the rat nose followed by the anterior transitional epithelium and larynx corresponding to regions most sensitive to local contact irritation and cytotoxicity. For humans, simulations of aerosol deposition covering potential occupational or residential exposures (1–50 µm diameter) were conducted using nasal and oral breathing. Aerosols in the 1–5 µm range readily penetrated the deep region of the human lung following both oral and nasal breathing. Under actual use conditions (aerosol formulations >10 µm), the majority of deposited doses were in the upper conducting airways. Beyond the nose or mouth, the greatest deposition in the pharynx, larynx, trachea, and bronchi was predicted for aerosols in the 10–20 µm size range. Only small amounts of aerosols >20 µm penetrated past the pharyngeal region. Using the ICRP clearance model, local retained tissue dose metrics including maximal concentrations and areas under the curve were calculated for each airway region following repeated occupational exposures. These results are directly comparable with benchmark doses from in vitro toxicity studies in human cells leading to estimated human equivalent concentrations that reduce the reliance on animals for risk assessments.
Mortality among workers at the Rocky Flats Plant, 1951–2017
The Rocky Flats (RFs) Plant operated from 1951–1989 as part of the U.S. Department of Energy (DOE) nuclear complex. Its primary mission was weapons component fabrication, whereby workers were potentially exposed to radioactive and non-radioactive hazards. RF worker mortality was compared to the general population, and dose-response relationships between mortality and radiation organ doses were examined. RF workers first employed between 1951 and 1979 for ⩾30 d were identified (n = 9397). Vital status was determined using national and state death records up to 2017. Organ doses from external photons and neutrons irritation and internalised plutonium (Pu), americium (Am), and uranium (U) were modelled as cumulative lagged total doses per year. Beryllium exposure was evaluated as an effect modifier using data from the DOE Nationwide Beryllium Medical Program. Statistical analyses included standardised mortality ratios (SMRs), Cox proportional hazard models, and excess relative risk (ERR) models. Approximately 53.2% of workers were deceased by the end of the study. Nearly 90% were monitored for radiation exposure, with a mean weighted absorbed dose of 59.0 mGy for the lungs. Nearly 45% of workers had intakes of alpha-particle emitting radionuclides, and 46.7% were monitored for neutrons. Leading causes of death included ischemic heart disease (n = 999) and lung cancer (n = 361). The highest SMRs were observed for berylliosis (SMR: 176.9; 95% CI: 76.2, 348.7; n < 10) and asbestosis (SMR: 4.65; 95% CI: 2.23, 8.55; n = 10). Dose-response analyses showed no statistical increase in risk from low-dose radiation including lung cancer (ERR per 100 mGy: −0.02; 95% CI: −0.11, 0.08; n = 361) and Parkinson’s disease (ERR per 100 mGy: 0.13; 95% CI: −0.26, 0.31; n = 57). Approximately 45% of workers were monitored for beryllium, with a weak non-significant indication of effect modification for lung cancer risk. The RF cohort showed no evidence of a statistically significant increase in mortality from occupational radiation exposure. However, this study was limited by low statistical power, which inhibits the ability to detect effects. Future pooling of Million Person Study (MPS) cohorts will provide further insights, particularly regarding Pu as a carcinogen.
Regional difference and related cooling electricity savings of air pollutant affected natural ventilation in commercial buildings across the US
Maintaining indoor air pollutants under acceptable levels is significant to protect occupants from exposure to excessive air pollutants in natural ventilation. In this paper, using the representative air pollutant concentration data, we present the natural ventilation usability with associated cooling energy saving potentials in different location settings (urban and city center, suburban and rural) of the US under the influence of local weather conditions and major outdoor air pollutants, i.e. PM2.5, PM10 and ozone. It is found that the impacts of air pollutants on natural ventilation are usually higher in urban/suburban areas than rural areas (up to 25% difference) with the PM2.5 being the most significant outdoor air pollutant affecting natural ventilation usage. Furthermore, ozone could become increasingly influential on natural ventilation as moving from urban to suburban/rural areas. As to the cooling energy saving considering the impacts of outdoor air pollutants, natural ventilation is estimated to save approximately 10%–40% cooling energy (800–2600 kWh per small commercial building) annually in different location settings of investigated areas across the US. The following economic analysis demonstrates that these electricity savings lead to approximately 80–540 dollars annual savings of building operation cost per building. If the time of use rate is adopted, these cost savings could further increase by approximately 20% (Los Angeles) to more than 50% (Albuquerque) depending on different rate structures, which further demonstrates the potential of adopting natural ventilation as a sustainability measurement with benefits for building owners without compromising occupants health.
Reconstructing Hanford worker external doses from photons for epidemiology
The accurate reconstruction of external photon doses is essential for credible radiation epidemiology. This article presents the methodology used to derive dose estimates for 37 012 Hanford Site workers included in the Million Person Study. The approach employs historical dose records from the Hanford Radiation Exposure database and a previous epidemiology study. Bias correction factors specific to dosimeter type and period of use were applied and missing annual doses were estimated using a hierarchical nearby method to estimate deep dose equivalent for each worker. For early years with limited detection sensitivity, missed doses were quantified based on expected time-period-specific, low-dose statistical distributions. The revised dose estimates resulted in lower median and mean career doses than unadjusted data, while increasing the number of person-years with nonzero dose. Sensitivity analyses assessed the influence of bias in dosimetry measurements, missed doses and gap years on dose estimates. Differences in cumulative dose estimates between unadjusted and revised annual estimates are most prominent in the early operational years due to the highest bias during that time period.
Designing a boron nitride polyethylene composite for shielding neutrons
Neutrons are encountered in many different fields, including condensed matter physics, space exploration, nuclear power, and healthcare. Neutrons interacting with a biological target produce secondary charged particles that are damaging to human health. The most effective way to shield neutrons is to slow them to thermal energies and then capture the thermalized neutrons. These factors lead us to consider potential materials solutions for neutron shields that maximize the protection of humans while minimizing the shield mass and adapt well to modern additive manufacturing techniques. Using hexagonal boron nitride (hBN) as a capture medium and high-density polyethylene (HDPE) as a thermalization medium, we aim to design the optimal internal structure of h 10 BN/HDPE composites by minimizing the effective dose, which is a measure of the estimated radiation damage exposure for a human. Through Monte Carlo simulations in Geant4, we find that the optimal structure reduces the effective dose up to a factor of 72 over aluminum (Al) and up to a factor of 4 over HDPE; this is a significant improvement in shielding effectiveness that could dramatically reduce the radiation exposure of occupational workers.
RCT Continuing Training (Q3, 2021) [Slides]
Radiological Control Technicians (RCTs) serve an important part in the mission of Los Alamos National Laboratory by monitoring the diverse radiological conditions at the Lab. The role of RCTs is critical in maintaining personnel safety from radiological hazards and in keeping occupational radiation exposure As low As Reasonably Achievable (ALARA). This training content consists of two parts: viewing an online lecture and completing the associated exercise guide. The online lecture, presented here, will review performing job coverage and all of the necessary steps associated with it.
RCT Continuing Training Presentation Transcript (Q3, 2021)
Radiological Control Technicians (RCTs) serve an important part in the mission of Los Alamos National Laboratory by monitoring the diverse radiological conditions at the Lab. This role is critical in maintaining personnel safety from radiological hazards, and in keeping occupational radiation exposure As Low As Reasonably Achievable (ALARA). This training presentation will review performing job coverage and all of the necessary steps associated with it.
Studying Response to Light in Offices: A Literature Review and Pilot Study
Researchers have been exploring the influence of light on health in office settings for over two decades; however, a greater understanding of physiological responses and technology advancements are shifting the way researchers study the influence of light in realistic environments. New technologies paired with Ecological Momentary Assessments (EMAs) administered via smartphones provide ways to collect information about individual light exposure and occupant response throughout the day. The study aims to document occupant response to tunable lighting in a real office environment, including potential beneficial or adverse health and well-being effects. Twenty-three office employees agreed to participate in a twelve-week study examining occupant response to two lighting conditions (static vs. dynamic). No significant differences were observed for any of the measures, highlighting the importance and complexity of in-situ studies conducted in realistic environments. While prior office studies have shown a significant influence on daytime sleepiness and sleep quality, research has not shown mood or stress to be significantly impacted by lighting conditions. Correlation analyses regarding lighting satisfaction, environmental satisfaction, and visual comfort demonstrate a significant relationship between certain items that may inform future studies. Further, the high correlation means it is reasonable to assume that many environmental factors in offices can influence occupant behavior and well-being.
Chronic obstructive pulmonary disease among former United States Department of Energy workers: comorbidities and lung function changes
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality in the United States and is frequently associated with multiple comorbidities which lead to poor COPD outcomes in the general population. However, little is known regarding COPD comorbidities in occupational cohorts whose exposure experiences could result in differences in comorbidities compared to the general population. These differences may also be important for assessing COPD outcomes such as lung function changes or decline. Therefore, the objectives of this study were to: (1) identify and describe clusters of COPD comorbidities among Department of Energy (DOE) former workers; (2) assess if the attributes of the identified clusters differ from those identified among the general population based on the published literature, and (3) identify predictors of lung function changes and decline among DOE former workers.
High-performance windows improve thermal survivability of occupants during cold snaps
Exposure to low indoor air temperature is a major contributor to temperature-related mortality during extreme cold events, especially when power outages disrupt operation of space heating systems. This study explores the impact of high-performance windows on the thermal resilience of residential buildings during extreme cold weather and grid power outages, as well as their long-term benefits through energy efficiency and reduced risk of property damage. Building performance simulations were conducted for reference residential buildings in three construction vintages and two major U.S. cities located in cold climate zones, considering two types of extreme cold events: short and severe, and long and milder. Our research found that even houses compliant with current energy codes struggle to maintain safe indoor temperatures for more than a few hours during power outages, necessitating rapid evacuations. High-performance windows can extend the thermal survivability time by up to 3.8 days within a 7-day cold snap and significantly reduce risk of bursting frozen water pipes, depending on the building’s insulation and infiltration level, cold event severity, and occupant vulnerability. This extended thermal safety time is crucial in scenarios where reduced mobility complicates emergency responses in senior housing. In addition to boosting thermal resilience, upgrading older homes with high-performance windows can reduce heating energy consumption by over 18% and cooling energy by 15%. Our findings highlight the need to incorporate thermal resilience assessments into new designs or major retrofits, including the use of typical and extreme weather scenarios and advanced technologies like high-performance windows.
Unraveling the Hsp70-ROS-autophagy axis in pentachlorophenol-challenged lung and liver epithelial cells
Pentachlorophenol (PCP) was extensively utilized as an organochlorine pesticide and wood preservative in the United States from the 1930s until the Environmental Protection Agency (EPA) imposed restrictions due to concerns about its toxicity and potential carcinogenic properties. Although it is no longer widely used, PCP remains a concern due to its environmental persistence and potential for long-term health effects. Significant occupational and environmental exposures have likely occurred, with the health and economic costs of PCP exposure potentially being substantial given its known toxicity. Notably, PCP exhibits rapid absorption through both the skin and respiratory system and has been shown to cause hepatotoxicity, developmental toxicity, immunotoxicity, irritation, and carcinogenicity in laboratory animal studies. PCP exposure induces oxidative stress, a key mechanism underlying its inflammatory and toxic effects, which can activate cellular stress responses including upregulation of heat shock protein 70 (Hsp70). Previous studies in lung and liver epithelial cells have shown that Hsp70 and oxidative stress play pivotal roles in triggering autophagy. This study establishes the critical role of the Hsp70-reactive oxygen species (ROS)-autophagy axis in regulating cellular responses to PCP exposure in human alveolar (A549) and liver carcinoma (HepG2) epithelial cells. Our research elucidated the molecular mechanisms underlying PCP's cellular effects, demonstrating that its exposure resulted in increased expression of autophagy-related proteins (Beclin-1, LC3B, ATG12, and ATG16), subunits of NADPH oxidase (NCF-1, NCF-2, NOX2, and Rac), and antioxidant proteins (SOD and GPx) in both lung and liver cell types. Notably, PCP augmented the interaction between Hsp70 and the autophagy regulator Beclin-1. Pretreatment with the ROS inhibitor N-acetylcysteine or Hsp70 knockdown markedly reversed PCP-induced responses. Our in-silico protein–protein docking analysis and molecular dynamics simulation studies revealed enhanced interactions and/or stable confirmations maintained throughout the simulations for TLR4-Hsp70 and Hsp70-Beclin-1 complexes in the presence of PCP. These findings provide a strong foundation for future studies, employing in vivo experimental models and human populations to identify promising targets for PCP-induced toxicity and cellular injury. As a result, these findings may have far-reaching implications for public health and environmental policy, ultimately leading to the identification of biomarkers and the development of more effective interventions for environmentally induced toxicity and diseases.
Investigation of inter-subject variation in ultrafine particle deposition across human nasal airways: A study involving children, adults, and the elderly
Occupational and environmental exposure to toxic nanoparticles, driven by the rapid expansion of nanotechnology, raises significant respiratory health concern. Numerous studies have explored airflow and particle dynamics in adult nasal airways, but understanding the impact of age-related anatomical changes in children and the elderly remains limited. This study systematically investigates age-related anatomical variations and associated influence on nasal airflow dynamics and ultrafine particle deposition characteristics. Using Computational Fluid-Particle Dynamics (CFPD) method, simulation was conducted under diverse inhalation conditions spanning a wide age range, including: two children (5 years old), two young adults (in their twenties), and two elderly (over 77 years old). Our results reveal distinctive variations across age groups in anatomical dimensions, which affect distribution of wall shear stress where the elderly and children display unique patterns distinct from the young adults. While total deposition efficiency differs significantly between children and adults, filtration efficiency in the subregion with most deposition, main respiratory, remains consistent. However, inter-subject differences are observed in the vestibular and olfactory regions,emphasizing nuanced impact of age-related anatomical variations. Overall and subregional empirical equations for deposition efficiency were developed by incorporating the combined diffusion parameter, Sc a Δ b , corroborating the use of geometrical characteristic parameters for each specific subject in predicting nasal deposition efficiency across age groups. Our findings contribute to predictive nanoparticle exposure analysis in nasal airways across different age groups, thereby enhancing respiratory healthcare for individuals across the life span.
Influence of overhead HVAC and aerosol control strategies on coarse mode particle dispersion and exposure in a full-scale room experiment
Coarse mode respiratory aerosols can carry viral loads over long distances and have very different dynamics than submicron particles, but experimental studies under realistic conditions remain limited. Here, to study the differential impacts on exposure under different mixing conditions, we co-released 7–10 µm particles and carbon dioxide (CO 2 )—which served as an indicator of gas and submicron particle dynamics—in a 158 m 3 room at LBNL's FLEXLAB facility with an overhead heating, ventilation, and air conditioning (HVAC) system. The room was arranged as a distanced meeting then a classroom with eight heated manikins and a researcher. Spatial variability was measured using 16 particle counters and 22–26 CO 2 sensors throughout the space. Conditions included: HVAC off or supply air at 1000-1060 m 3 h -1 at neutral, cooling, or heating temperatures; with and without 20% outdoor air; and added HVAC filtration, portable air cleaners (PACs), or a physical barrier between the speaker and occupants. We found that good mixing via neutral or cooling supply air or use of PACs under heating lowered coarse particle exposure at some locations, but increased exposure for one-quarter to two-thirds of manikins compared to poor mixing under heating. A physical barrier reduced direct transfer of coarse particles during heating, but less during cooling. High spatial variability shows that a single measurement cannot represent occupant exposure. Instantaneous air mixing assumptions overstate the effectiveness of ventilation, HVAC filtration, and upper-room germicidal ultraviolet disinfection for coarse particles, as relatively few particles reach the return grille or upper room under most conditions.
Natural gas odorants: A scoping review of health effects
Organosulfur compounds are intentionally added to natural gas as malodorants with the intent of short-term nasal inhalation to aid in leak detection. Regulatory exposure limits have not been established for all commonly used natural gas odorants, and recent community-level exposure events and growing evidence of indoor natural gas leakage have raised concerns associated with natural gas odorant exposures. We conducted a scoping review of peer-reviewed scientific publications on human exposures and animal toxicological studies of natural gas odorants to assess toxicological profiles, exposure potential, health effects and regulatory guidelines associated with commonly used natural gas odorants. We identified only 22 studies which met inclusion criteria for full review. Overall, there is limited evidence of both transient nonspecific health symptoms and clinically diagnosed causative neurotoxic effects associated with prolonged odorant exposures. Across seven community-level exposure events and two occupational case reports, consistent symptom patterns included: headache, ocular irritation, nose and throat irritation, respiratory complaints such as shortness of breath and asthma attacks, and skin irritation and rash. Of these, respiratory inflammation and asthma exacerbations are the most debilitating, whereas the high prevalence of ocular and dermatologic symptoms suggest a non-inhalation route of exposure. The limited evidence available raises the possibility that organosulfur odorants may pose health risks at exposures much lower than presently understood, though additional dose-response studies are needed to disentangle specific toxicologic effects from nonspecific responses to noxious organosulfur odors. Numerous recommendations are provided including more transparent and prescriptive natural gas odorant use practices.
IDAC-Bio, A Software for Internal Dosimetry Based on the New ICRP Biokinetic Models and Specific Absorbed Fractions
Radiation dosimetry is central to virtually all radiation safety applications, optimization, and research. It relates to various individuals and population groups and to miscellaneous exposure situations—including planned, existing, and emergency situations. The International Commission on Radiological Protection (ICRP) has developed a new computational framework for internal dose estimations. Important components are more detailed and improved anatomical models and more realistic biokinetic models than before. The ICRP is currently producing new organ dose and effective dose coefficients for occupational intakes of radionuclides (OIR) and environmental intakes of radionuclides (EIR), which supersede the earlier dose coefficients in Publication 68 and the Publication 72 series, respectively. However, the ICRP only publishes dose coefficients for a single acute intake of a radionuclide and for an integration period of 50 years for intake by adults and to age 70 years for intakes by pre-adults. The new software, IDAC-Bio, performs committed absorbed dose and effective dose calculations for a selectable intake scenario, e.g., for a continuous intake or an intake during x hours per day and y days per week, and for any selected integration time. The software uses the primary data and models of the ICRP biokinetic models and numerically solves the biokinetic model and calculates the absorbed doses to organs and tissues in the ICRP reference human phantoms. The software calculates absorbed dose using the nuclear decay data in ICRP publication 107. IDAC-Bio is a further development and an important addition to the internal dosimetry program IDAC-Dose2.1. Here, the results generated by the software were validated against published ICRP dose coefficients. The potential of the software is illustrated by dose calculations for a nuclear power plant worker who had been exposed to varying levels of 60 Co and who had undergone repeated whole-body measurements, and for a hypothetical member of the public subject to future releases of 148 Gd from neutron spallation in tungsten at the European Spallation Source.