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DOE OSTI2020

Health co-benefits and mitigation costs as per the Paris Agreement under different technological pathways for energy supply

This study assesses the reductions in air pollution emissions and subsequent beneficial health effects from different global mitigation pathways consistent with the 2 °C stabilization objective of the Paris Agreement. We use an integrated modelling framework, demonstrating the need for models with an appropriate level of technology detail for an accurate co-benefit assessment. The framework combines an integrated assessment model (GCAM) with an air quality model (TM5-FASST) to obtain estimates of premature mortality and then assesses their economic cost. The results show that significant co-benefits can be found for a range of technological options, such as introducing a limitation on bioenergy, carbon capture and storage (CCS) or nuclear power. Cumulative premature mortality may be reduced by 17–23% by 2020–2050 compared to the baseline, depending on the scenarios. However, the ratio of health co-benefits to mitigation costs varies substantially, ranging from 1.45 when a bioenergy limitation is set to 2.19 when all technologies are available. As for regional disaggregation, some regions, such as India and China, obtain far greater co-benefits than others.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2020

Using Low-Cost Measurement Systems to Investigate Air Quality: A Case Study in Palapye, Botswana

Exposure to particulate air pollution is a major cause of mortality and morbidity worldwide. In developing countries, the combustion of solid fuels is widely used as a source of energy, and this process can produce exposure to harmful levels of particulate matter with diameters smaller than 2.5 microns (PM 2.5 ). However, as countries develop, solid fuel may be replaced by centralized coal combustion, and vehicles burning diesel and gasoline may become common, changing the concentration and composition of PM 2.5 , which ultimately changes the population health effects. Therefore, there is a continuous need for in-situ monitoring of air pollution in developing nations, both to estimate human exposure and to monitor changes in air quality. In this study, we present measurements from a 5-week field experiment in Palapye, Botswana. We used a low-cost, highly portable instrument package to measure surface-based aerosol optical depth (AOD), real-time surface PM 2.5 concentrations using a third-party optical sensor, and time-integrated PM 2.5 concentration and composition by collecting PM 2.5 onto Teflon filters. Furthermore, we employed other low-cost measurements of real-time black carbon and time-integrated ammonia to help interpret the observed PM 2.5 composition and concentration information during the field experiment. We found that the average PM 2.5 concentration (9.5 μg∙m –3 ) was below the World Health Organization (WHO) annual limit, and this concentration closely agrees with estimates from the Global Burden of Disease (GBD) report estimates for this region. Sulfate aerosol and carbonaceous aerosol, likely from coal combustion and biomass burning, respectively, were the main contributors to PM 2.5 by mass (33% and 27% of total PM 2.5 mass, respectively). While these observed concentrations were on average below WHO guidelines, we found that the measurement site experienced higher concentrations of aerosol during first half our measurement period (14.5 μg∙m –3 ), which is classified as "moderately unhealthy" according to the WHO standard.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2022

A Review: PFAS Adsorption, Sensing, and Remediation with Engineered Nanoporous Materials

Per- and polyfluoroalkyl substances (PFAS) are among the most abundant environmental contaminant species. They are widespread due to uncontrolled industrial and commercial use and have been linked to health risks such as cancer. With rising global concerns about the public health effects of PFAS, there is an incentive to develop strategies for reliable monitoring and effective PFAS removal, particularly in drinking water. Traditional PFAS sensing techniques are inefficient due to long measurement times, high labor input, high costs, and limitations to ex situ analysis. Current commercially available sorbents for PFAS removal generally lack the ability to capture PFAS components rapidly and quantitatively. Furthermore, existing sorbents are notably inefficient in removing the more toxic, smaller PFAS chemical chains. Large-scale applications of these methods tend to be costly and resource-intensive. Pacific Northwest National Laboratory has developed unique strategies for PFAS sensing and removal with capture probe technology that has an affinity for fluorocarbons, including PFAS. For both sensing and removal, the customizable capture probes can target specific PFAS compounds since they used a metal-organic framework (MOF)-based technology that can be fine-tuned and molecularly tailored. This tailoring of the materials enables high PFAS sensitivity, selectivity, and faster uptake. PNNL’s capture probe materials have been developed into a sensing technique based on the interactions of the capture probes with PFAS at the molecular level and further transduced that to a quantifiable electrochemical response. The materials have been integrated into a sensor platform developed by New Jersey Institute of Technology (NJIT). Tunable capture probes with a range of detection sensitivities allow for faster and more sensitive PFAS detection limits as low as what appears to be 0.5 ng/L (compared to the U.S. Environmental Protection Agency health advisory level of 70 ng/L). Customization of the capture probe results in improved sorption capacities (fast kinetics and high capacities) compared to commercial granular activated carbons. This research applied various experimental and modeling tools to improve understanding the molecular level interactions between the sorbents towards PFAS adsorption properties.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2024

Distribution of plutonium and radium in the human heart

Since 1968, the United States Transuranium and Uranium Registries (USTUR) has studied the biokinetics and tissue dosimetry of uranium and transuranium elements in nuclear workers. As part of the USTUR collaboration with the Million Person Study of Low-Dose Health Effects, radiation dose to different parts of the human heart is being estimated for workers with documented intakes of 239 Pu or 226 Ra. The study may be expanded for workers with intakes of 238 U and other radionuclides. The distribution of radionuclides, expressed in terms of concentration (Bq per kg of tissue) serves as an important parameter for estimating radiation dose. Based on available organs from workers who donated their bodies or tissues for research, nine undissected hearts were selected: seven from USTUR registrants with plutonium exposure (males) and two individuals with radium intakes (female and male). For the plutonium workers, estimated 239 Pu systemic deposition ranged from <74 Bq to 1765 Bq. Estimated 226 Ra ‘initial systemic intakes’ were 10.1 MBq and 14.8 kBq for the female patient and male worker, respectively. Organ dissection was based on a heart model published by Borrego et al (2019 J. Radiol. Prot. 39 950–65). This model includes nine cardiac substructures: aorta, left main coronary artery, left atrium, left anterior descending artery, left circumflex artery, left ventricle, right atrium, right coronary artery, and right ventricle. In addition, heart valves, fat attached to epicardium, fluids, and a coronary bypass graft were collected resulting in 111 samples that are currently undergoing radiochemical analyses and mass-spectrometric measurements. The 239 Pu and 226 Ra evaluations are not completed. The results of this study are intended to support radiation worker health studies by improving associated dosimetric and epidemiological models.

USTUR↗

DOE OSTI2025

Sulfoquinovose is exclusively metabolized by the gut microbiota and degraded differently in mice and humans

Abstract Background Sulfoquinovose (SQ) is a green-diet-derived sulfonated glucose and a selective substrate for a limited number of human gut bacteria. Complete anaerobic SQ degradation via interspecies metabolite transfer to sulfonate-respiring bacteria produces hydrogen sulfide, which has dose- and context-dependent health effects. Here, we studied potential SQ degradation by the mammalian host and the impact of SQ supplementation on human and murine gut microbiota diversity and metabolism. Results 13 CO 2 breath tests with germ-free C57BL/6 mice gavaged with 13 C-SQ were negative. Also, SQ was not degraded by human intestinal cells in vitro, indicating that SQ is not directly metabolized by mice and humans. Addition of increasing SQ concentrations to human fecal microcosms revealed dose-dependent responses of the microbiota and corroborated the relevance ofAgathobacter rectalisandBilophila wadsworthiain cooperative degradation of SQ to hydrogen sulfide via interspecies transfer of 2,3-dihydroxy-1-propanesulfonate (DHPS). Similar to the human gut microbiome, the genetic capacity for SQ or DHPS degradation is sparsely distributed among bacterial species in the gut of conventional laboratory mice.Escherichia coliandEnterocloster clostridioformiswere identified as primary SQ degraders in the mouse gut. SQ and DHPS supplementation experiments with conventional laboratory mice and their intestinal contents showed that SQ was incompletely catabolized to DHPS. Although someE. clostridioformisgenomes encode an extended sulfoglycolytic pathway for both SQ and DHPS fermentation, SQ was only degraded to DHPS by a mouse-derivedE. clostridioformisstrain. Conclusions Our findings suggest that SQ is solely a nutrient for the gut microbiota and not for mice and humans, emphasizing its potential as a prebiotic. SQ degradation by the microbiota of conventional laboratory mice differs from the human gut microbiota by absence of DHPS degradation activity. Hence, the microbiota of conventional laboratory mice does not fully represent the SQ metabolism in humans, indicating the need for alternative model systems to assess the impact of SQ on human health. This study advances our understanding of how individual dietary compounds shape the microbial community structure and metabolism in the gut and thereby potentially influence host health.

Microbiology↗

DOE OSTI2021

Lifetime risk of suicide among survivors of the atomic bombings of Japan

Abstract Aims The long-term physical health effects of the atomic bombings of Hiroshima and Nagasaki are well characterised, but the psychological effects remain unclear. Therefore, we sought to determine whether measures of exposure severity, as indirect measures of psychological trauma arising from exposure to the atomic bombings, are associated with suicide mortality among atomic bomb survivors. Methods The Life Span Study is a prospective cohort study of 93 741 Japanese atomic bomb survivors who were located within 10 km of the hypocentre in Hiroshima or Nagasaki at the time of the bombings in 1945, and 26 579 residents of Hiroshima and Nagasaki who were not in either city at the time of the bombings, matched to survivors on city, sex and age. Measures of exposure severity included: proximity to the hypocentre, type of shielding between the survivor and the blast and self-reported occurrence of acute radiation and thermal injuries. Date of death was obtained from the Japanese National Family Registry system. Cause of death was obtained from death certificates. Adjusted hazard ratios (HRs) were estimated from Cox regression models overall and stratified by sex and age. Results During the 60-year follow-up period (1950–2009), 1150 suicide deaths were recorded among 120 231 participants (23.6 per 100 000 person-years): 510 among 70 092 women (17.2 per 100 000 person-years) and 640 among 50 139 men (33.6 per 100 000 person-years). Overall, there was no association of proximity, type of shielding or the occurrence of acute injuries with suicide mortality. Among those <25 years of age at the time of the bombings, increased suicide risk was observed for survivors outside v . shielded inside any structure (HR: 1.24; 95% confidence interval (CI): 1.03, 1.48; interaction p = 0.054) and for those who reported flash burns (HR: 1.32; 95% CI: 1.00, 1.73; interaction p = 0.025). Sex-stratified analyses indicated that these associations were limited to men. Among women, closer proximity to the hypocentre was associated with a non-significant increase in suicide risk, with a positive association between proximity and suicide risk observed among women <15 years of age (HR: 1.09 per km; 95% CI: 1.00, 1.18; interaction p = 0.067). Conclusions Proximity to the hypocentre, shielding and acute injury presence do not generally appear to influence suicide mortality among atomic bomb survivors. However, heterogeneity may exist by age and sex, with younger survivors potentially more sensitive to psychological trauma. Coupled with other studies, our results suggest the importance of long-term monitoring of mental health among young populations exposed to catastrophic events or mass trauma.

Psychiatry↗

DOE OSTI2022

Impact of acute temperature and air pollution exposures on adult lung function: A panel study of asthmatics

Background Individuals with respiratory conditions, such as asthma, are particularly susceptible to adverse health effects associated with higher levels of ambient air pollution and temperature. This study evaluates whether hourly levels of fine particulate matter (PM 2.5 ) and dry bulb globe temperature (DBGT) are associated with the lung function of adult participants with asthma. Methods and findings Global positioning system (GPS) location, respiratory function (measured as forced expiratory volume at 1 second (FEV 1 )), and self-reports of asthma medication usage and symptoms were collected as part of the Exposure, Location, and Lung Function (ELF) study. Hourly ambient PM 2.5 and DBGT exposures were estimated by integrating air quality and temperature public records with time-activity patterns using GPS coordinates for each participant (n = 35). The relationships between acute PM 2.5 , DBGT, rescue bronchodilator use, and lung function collected in one week periods and over two seasons (summer/winter) were analyzed by multivariate regression, using different exposure time frames. In separate models, increasing levels in PM 2.5 , but not DBGT, were associated with rescue bronchodilator use. Conversely DBGT, but not PM 2.5 , had a significant association with FEV 1 . When DBGT and PM 2.5 exposures were placed in the same model, the strongest association between cumulative PM 2.5 exposures and the use of rescue bronchodilator was identified at the 0–24 hours (OR = 1.030; 95% CI = 1.012–1.049; p-value = 0.001) and 0–48 hours (OR = 1.030; 95% CI = 1.013–1.057; p-value = 0.001) prior to lung function measure. Conversely, DBGT exposure at 0 hours (β = 3.257; SE = 0.879; p-value>0.001) and 0–6 hours (β = 2.885; SE = 0.903; p-value = 0.001) hours before a reading were associated with FEV 1 . No significant interactions between DBGT and PM 2.5 were observed for rescue bronchodilator use or FEV 1 . Conclusions Short-term increases in PM 2.5 were associated with increased rescue bronchodilator use, while DBGT was associated with higher lung function (i.e. FEV 1 ). Further studies are needed to continue to elucidate the mechanisms of acute exposure to PM 2.5 and DBGT on lung function in asthmatics.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2020

Unveiling 3D Morphology of Multiscale Micro-Nanosilver Sintering for Advanced Electronics Manufacturing by Ptychographic X-ray Nanotomography

The sintering processing–structure–property relationship of a multiscale silver materials is investigated: microparticles with nanofeatures, particularly on their three-dimensional (3D) morphology. The target application is to replace conventional lead-based solders in advanced electronic manufacturing. Unlike lead-based solders, silver powders are suited to satisfy increasingly demanding mechanical, electrical, and thermal requirements, meanwhile being free of health effect. Sintering the material at a low temperature and without applied pressure are desirable conditions, which results in a preferred use of silver nanoparticles, as nanofeatures have higher driving force to sinter with the decrease in particle size. However, nanosized powders present potential health/environmental effects. To address the trade-off between the benefits and shortcomings of nano-versus microparticles, this work studies a novel multiscale silver paste, namely micron-sized powders with nanosized features. To get quantitative 3D visualization of micro- and nanoscale features, ptychographic X-ray computed nanotomography is applied. The correlations between conditions (thermal aging, pressure, and substrate metallization), mechanical properties, and morphological parameters are established. Finally, using novel 3D X-ray nanoimaging technique, it is demonstrated that one can design multiscale materials while balancing complex demands required in advanced electronics manufacturing and research directions in materials design and characterization.

36 MATERIALS SCIENCE↗

DOE OSTI2024

Atomically Precise Hexanuclear Ce(IV) Clusters as Functional Fluorescent Nanosensors for Rapid One-Step Detection of PFAS

Here, the presence of poly- and perfluoroalkyl substances (PFAS) in the environment is associated with adverse health effects but measuring PFAS is challenging due to the associated high cost and technical complexities of the analysis. Here, the reactivity of atomically precise metal-oxo clusters is reported and the foundation for their use is provided as fluorescent nanosensors for PFAS detection. The material comprises crystalline, water soluble, hexanuclear cerium-oxo clusters [Ce 6 (µ 3 -O) 4 (µ 3 -OH) 4 ] 12+ decorated with glycine molecules (Ce-Gly) characterized by fluorescence emission at 353 nm. The Ce-Gly fluorescence is found sensitive to long chain carboxylated PFAS of CF 3 –(CF 2 ) n –, where n ≥ 6, such as perfluorooctanoic, perfluorononanoic and perfluorodecanoic acids. This unique reactivity leads to a change in the emission spectra in a concentration dependent manner, enabling PFAS detection through ligand exchange and aggregation-induced emission (AIE) enhancement. No significant cross-reactivity from potentially co-existing species, including sulfonated PFAS, octanoic and dodecanoic acids, humic acid, and inorganic ions is observed. With an optimal concentration of 3.3 µg mL -1 Ce-Gly, the method demonstrated detection limits of 0.24 ppb for PFOA and 0.4 ppb for PFNA. These findings highlight the potential of fluorescence-based detection strategies utilizing nanoscale probes such as Ce-Gly as fluorescent probes and nanosensors for PFAS.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

DOE OSTI2020

Temperature dependence of nickel ion release from nitinol medical devices

Abstract Nitinol exhibits unique (thermo)mechanical properties that make it central to the design of many medical devices. However, nitinol nominally contains 50 atomic percent nickel, which if released in sufficient quantities, can lead to adverse health effects. While nickel release from nitinol devices is typically characterized using in vitro immersion tests, these evaluations require lengthy time periods. We have explored elevated temperature as a potential method to expedite this testing. Nickel release was characterized in nitinol materials with surface oxide thickness ranging from 12 to 1564 nm at four different temperatures from 310 to 360 K. We found that for three of the materials with relatively thin oxide layers, ≤ 87 nm nickel release exhibited Arrhenius behavior over the entire temperature range with activation energies of 80 to 85 kJ/mol. Conversely, the fourth ''black–oxide'' material, with a much thicker, complex oxide layer, was not well characterized by an Arrhenius relationship. Power law release profiles were observed in all four materials; however, the exponent from the thin oxide materials was approximately 1/4 compared with 3/4 for the black–oxide material. To illustrate the potential benefit of using elevated temperature to abbreviate nickel release testing, we demonstrated that a > 50 day 310 K release profile could be accurately recovered by testing for less than 1 week at 340 K. However, because the materials explored in this study were limited, additional testing and mechanistic insight are needed to establish a protective temperature scaling that can be applied to all nitinol medical device components.

Saylor, David M.↗

DOE OSTI2023

A review of emerging photoinduced degradation methods for per- and polyfluoroalkyl substances in water

The remediation of per- and polyfluoroalkyl substances (PFAS) in water continues to garner significant attention due to their environmental persistence and adverse health effects. Among the various PFAS remediation methods, photoinduced approaches have recently emerged as promising techniques for the degradation of these persistent contaminants. However, many questions remain unanswered regarding the detailed mechanisms in these photoinduced methods as well as the best ways to leverage these approaches for PFAS degradation. In this review, we provide an update on recent experimental and theoretical developments in photoinduced PFAS degradation techniques over the past 2–5 years. We conclude with a perspective of promising research directions in this vibrant area and give recommendations on future experimental and computational approaches needed to further advance these photoinduced remediation capabilities.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2024

Electrochemical reduction of per- and polyfluorinated alkyl substances (PFAS): is it possible? Applying experimental and quantum mechanical insights from the reductive defluorination literature

Remediation of per- and polyfluorinated alkyl substances (PFAS) in global water systems is a critical human and environmental health challenge facing society. PFAS consumption is associated with a litany of adverse health effects, and our knowledge of these dangers is still evolving. Current techniques to remove PFAS from water include adsorption to media (e.g. granular activated carbon, ion-exchange resin), nanofiltration, and reverse osmosis. However, these processes create a concentrated PFAS residual that requires further management. Destructive techniques are therefore needed to detoxify these residuals. Oxidative techniques have garnered the most attention (e.g. supercritical water oxidation, electrochemical oxidation) but are energy intensive and potentially form toxic by-products. As an alternative, several groups have researched advanced reduction processes that form aqueous electrons, but these processes are still chemical and energy intensive (e.g. ultraviolet/SO 3 2− , electron beam). This concise review therefore focuses on whether electrochemical reduction — a chemical-free, modular process — could be technically feasible for PFAS destruction.

King, Jacob F.↗

DOE OSTI2026

Lethality is Local, but Survival is Systemic: Temporal and Multi-Organ Responses to Chlorine Gas Exposure in a Murine Model

Chlorine gas (Cl2) is a highly toxic chemical associated with both localized lung injury and systemic health effects. While pulmonary damage has been well characterized, the systemic inflammatory and metabolic responses remain poorly understood. We aimed to define the temporal and multi-organ responses to Cl2 exposure in a murine model, with a focus on identifying spatiotemporal inflammation and its impact on survival and lethality. SKH1 mice were exposed for 10 min to varying concentrations of Cl2 (94.4–810 ppm, representative of non-lethal, LD10, and LD50 doses) and monitored for respiratory function, perfusion, and acidosis using organ-specific imaging. At multiple time points (40 min, 6 h, 24 h, and 7 d), we measured phosphoproteins, cytokines, chemokines, growth factors, and metabolic hormones in the lungs, heart, cortex, and plasma. Statistical modeling and logistic regression were used to identify biomarkers associated with lethality and survival. We found that lung injury was the primary cause of potential lethality, particularly via early phosphoprotein signaling disruptions. However, survival correlated with early systemic coordination of inflammatory and metabolic signals across organs. Perfusion and acidosis imaging were strongly associated with chemokine and hormone responses. Key survival-associated plasma biomarkers included decreased insulin, increased ghrelin, and decreased eotaxin. While potential lethality from Cl2 exposure is locally driven by pulmonary injury, survival depends on systemic, multi-organ responses that occur rapidly post-exposure. Within this model, our findings identify a potential therapeutic window to enhance survival and suggest candidate biomarkers that may be explored translationally for both triage and treatment of chlorine-related incidents.

chlorine gas↗

DOE OSTI2022

Microcystin-LR aerosol induces inflammatory responses in healthy human primary airway epithelium

Harmful algal blooms plague bodies of freshwater globally. These blooms are often composed of outgrowths of cyanobacteria capable of producing the heptapeptide Microcystin-LR (MC-LR) which is a well-known hepatotoxin. Recently, MC-LR has been detected in aerosols generated from lake water. However, the risk for human health effects due to MC-LR inhalation exposure have not been extensively investigated. In this study, we exposed a fully differentiated 3D human airway epithelium derived from 14 healthy donors to MC-LR-containing aerosol for 3 minutes per day for 3 days. Concentrations of MC-LR ranged from 100 pM to 1 µM. Although there were little to no detrimental alterations in measures of the airway epithelial function (i.e. cell survival, tissue integrity, mucociliary clearance, or cilia beating frequency), a distinct shift in the transcriptional activity was found. Genes related to inflammation were found to be upregulated such as C-C motif chemokine 5 (CCL5; log2FC = 0.56 , p = 0.02) and C-C chemokine receptor type 7 (CCR7; log2FC = 0.83, p = 0.03). Functionally, conditioned media from MC-LR exposed airway epithelium was also found to have significant chemo-attractive properties for primary human neutrophils. Additionally, increases were found in the concentration of secreted chemokine proteins in the conditioned media such as CCL1 (log2FC = 5.07 , p = 0.0001) and CCL5 (log2FC = 1.02, p = 0.046). These results suggest that MC-LR exposure to the human airway epithelium is capable of inducing an inflammatory response that may potentiate acute or chronic disease.

3D human airway epithelium↗

DOE OSTI2023

Thirdhand tobacco smoke exposure increases the genetic background-dependent risk of pan-tumor development in Collaborative Cross mice

Increasing evidence has shown that thirdhand smoke (THS) exposure is likely to induce adverse health effects. An important knowledge gap remains in our understanding of THS exposure related to cancer risk in the human population. Population-based animal models are useful and powerful in investigating the interplay between host genetics and THS exposure on cancer risk. Here, we used the Collaborative Cross (CC) mouse population-based model system, which recapitulates the genetic and phenotypic diversity observed in the human population, to assess cancer risk after a short period of exposure, between 4 and 9 weeks of age. Eight CC strains (CC001, CC019, CC026, CC036, CC037, CC041, CC042 and CC051) were included in our study. We quantified pan-tumor incidence, tumor burden per mouse, organ tumor spectrum and tumor-free survival until 18 months of age. At the population level, we observed a significantly increased pan-tumor incidence and tumor burden per mouse in THS-treated mice as compared to the control (p = 3.04E-06). Lung and liver tissues exhibited the largest risk of undergoing tumorigenesis after THS exposure. Tumor-free survival was significantly reduced in THS-treated mice compared to control (p = 0.044). At the individual strain level, we observed a large variation in tumor incidence across the 8 CC strains. CC036 and CC041 exhibited a significant increase in pan-tumor incidence (p = 0.0084 and p = 0.000066, respectively) after THS exposure compared to control. We conclude that early-life THS exposure increases tumor development in CC mice and that host genetic background plays an important role in individual susceptibility to THS-induced tumorigenesis. Genetic background is an important factor that should be taken into account when determining human cancer risk of THS exposure.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2026

Genetic variations and their interaction with thirdhand smoke exposure on anxiety and memory in Collaborative Cross mice

Thirdhand smoke (THS) is linked to adverse health effects, but the effect of genetic variations on behavioral outcomes is poorly understood. To investigate this, we assessed anxiety- and memory-related behaviors in 820 mice from 21 strains of the genetically diverse Collaborative Cross (CC) mouse that were exposed to THS from 4 through 10 weeks of age. Anxiety was evaluated with a light/dark box assay with a previously established risk score system. Females were generally more sensitive: THS reduced anxiety risk in strains CC013, CC019, and CC051, but increased risk in CC036 and CC061, while males showed no significant effects. Memory was tested using passive avoidance: impairments were observed in both sexes in CC016 and CC019, with sex-dependent effects in CC002 and CC051. A genome-wide association study identified 2,347 SNPs associated with anxiety and 1,568 SNPs with memory, with 32 and 85 SNPs, respectively, interacting with THS exposure. Enrichment analyses revealed distinct biological processes underlying susceptibility, including axonogenesis, synapse organization, cognition, and learning and memory. KEGG pathway analysis identified distinct genetic pathways, including GTPase binding and GTPase regulatory activity, that act as critical molecular switches in the brain that regulate synaptic plasticity, dendritic spine structure, and neuronal signaling, directly influencing anxiety-like behaviors and memory formation. These findings show that THS exposure affects neurobehavioral outcomes in a sex- and genotype-dependent manner, highlighting critical gene-environment interactions and providing a foundation for mechanistic insights into THS neurotoxicity

Anxiety↗

DOE OSTI2022

Particle emissions from mobile sources: Discussion of ultrafine particle emissions and definition

There is no universally agreed upon definition for ultrafine particles (UFP). Commonly used definitions for UFP are either particle number below 100 nm or total particle number, but without an agreed upon lower cut point. For example, a lower cut point of 3 nm compared to 10 nm could result in a substantially higher count. Another definition for UFP is total particle mass but without a commonly agreed upon aerodynamic diameter upper cut point, e.g., below 100 nm, 200 nm, 300 nm, etc. Yet another definition is lung deposited surface area weighted by lung deposition fraction, found mainly in the particle mobility diameter range from 20 to 400 nm. It is clear from these definitions that there are inconsistencies in the way UFP is used and defined in the literature. Sometimes these metrics are well correlated, sometimes not. In this paper we suggest three exposure metrics: UFP-N, UFP-M, and UFP-S, that we believe will add clarity. These metrics represent total number, mass, and surface area below 500 nm, respectively. For surface area and mass, the 500 nm cut point can be either aerodynamic or mobility diameter depending upon measurement methodology. For all metrics, this cut point captures nearly all of the primary particle emissions from mobile sources. Furthermore, UFP-N would include a lower cut point of 3–6 nm and would not require an upper size cut point because there is very little particle number above 500 nm or even above 100 nm. Thus, our definition of UFP-N is consistent with the current definition of ultrafine number except for, importantly, the specification of a lower cut point. These exposure metrics can help facilitate consistency in the characterization of both short- and long-term UFP ambient exposures and associated health effects in epidemiological studies.

42 ENGINEERING↗

DOE OSTI2022

Influence of alveolar mixing and multiple breaths of aerosol intake on particle deposition in the human lungs

Predictive dosimetry models play an important role in assessing health effect of inhaled particulate matter and in optimizing delivery of inhaled pharmaceutical aerosols. Here, in this study, the commonly used 1D Multiple-Path Particle Dosimetry model (MPPD) was improved by including a mechanistically based model component for alveolar mixing of particles and by extending the model capabilities to account for multiple breaths of aerosol intake. These modifications increased the retained fraction of particles and consequently particle deposition predictions in the deep lung during tidal breathing. Comparison with an existing dataset (J. Aerosol Sci., 99:27-39, 2016) obtained under two breathing conditions referred to as slow and fast breathing showed significant differences in 1 µm particle deposition between predictions (slow: 30±1%, fast: 21±1%) and measurements (slow: 43±9%, fast: 30±5%) when the prior version of MPPD (single breath and no mixing, J. Aerosol Sci., 151:105647, 2021) was used. Adding a mixing model and multiple breaths moved the predictions (slow: 34±2%, fast:25±2%) closer to the range of deposition measurements. For 2.9 µm particles, predictions from both the original (slow: 70±2%, fast: 57±2%) and the revised MPPD model (slow: 71±2%, fast: 59±3%) compared well with experiments (slow: 67±8%, fast: 58±10%). This was expected as suspended fraction of 2.9 µm particles was small and thus the addition of alveolar mixing and multi breath capability only slightly increased the retained fraction for particles of this size and greater. The revised 1D model improves dose predictions in the deep lung and support human risk assessment from exposure to airborne particles.

60 APPLIED LIFE SCIENCES↗