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A data engineering approach for sustainable chemical end-of-life management

The presence of chemicals causing significant adverse human health and environmental effects during end-of-life (EoL) stages is a challenge for implementing sustainable management efforts and transitioning towards a safer circular life cycle. Conducting chemical risk evaluation and exposure assessment of potential EoL scenarios can help understand the chemical EoL management chain for its safer utilization in a circular life-cycle environment. However, the first step is to track the chemical flows, estimate releases, and potential exposure pathways. Hence, this work proposes an EoL data engineering approach to perform chemical flow analysis and screening to support risk evaluation and exposure assessment for designing a safer circular life cycle of chemicals. This work uses publicly-available data to identify potential post-recycling scenarios (e.g., industrial processing/use operations), estimate inter-industry chemical transfers, and exposure pathways to chemicals of interest. Furthermore, a case study demonstration shows how the data engineering framework identifies, estimates, and tracks chemical flow transfers from EoL stage facilities (e.g., recycling and recovery) to upstream chemical life cycle stage facilities (e.g., manufacturing). Also, the proposed framework considers current regulatory constraints on closing the recycling loop operations and provides a range of values for the flow allocated to post-recycling uses associated with occupational exposure and fugitive air releases from EoL operations.

54 ENVIRONMENTAL SCIENCES↗

Metagenomic Alterations in Gut Microbiota Precede and Predict Onset of Colitis in the IL10 Gene-Deficient Murine Model

SUMMARY. Currently, predictive markers for the development andcourse of inflammatory bowel diseases (IBD) are not available. This study supports the notion that gut microbiome metagenomic profiles could be developed into a useful tool to assess risk and manage human IBD. BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are chronic inflammatory disorders where predictive bio-markers for the disease development and clinical course are sorely needed for development of prevention and early intervention strategies that can be implemented to improve clinical outcomes. Since gut microbiome alterations can reflect and/or contribute to impending host health changes, we examined whether gut microbiota metagenomic profiles would provide more robust measures for predicting disease outcomes in colitis-prone hosts. METHODS: Using the interleukin (IL) 10 gene-deficient (IL10KO) murine model where early life dysbiosis from antibiotic (cefoperozone [CPZ]) treated dams vertically transferred to pups increases risk for colitis later in life, we investigated temporal metagenomic profiles in the gut microbiota of post-weaning offspring and determined their relationship to even-tual clinical outcomes. RESULTS: Compared to controls, offspring acquiring maternalCPZ-induced dysbiosis exhibited a restructuring of intestinal microbial membership in both bacteriome and mycobiome that was associated with alterations in specific functional subsystems. Furthermore, among IL10 KO offspring fromCPZ-treated dams, several functional subsystems, particularly nitrogen metabolism, diverged between mice that developed spontaneous colitis (CPZ-colitis) versus those that did not (CPZ-no-colitis) at a time point prior to eventual clinical outcome. CONCLUSIONS: Our findings provide support that functional metagenomic profiling of gut microbes has potential and promise meriting further study for development of tools to assess risk and manage human IBD.

59 BASIC BIOLOGICAL SCIENCES↗

Estimates of Lake Nitrogen, Phosphorus, and Chlorophyll‐ a Concentrations to Characterize Harmful Algal Bloom Risk Across the United States

Abstract Excess nutrient pollution contributes to the formation of harmful algal blooms (HABs) that compromise fisheries and recreation and that can directly endanger human and animal health via cyanotoxins. Efforts to quantify the occurrence, drivers, and severity of HABs across large areas is difficult due to the resource intensive nature of field monitoring of lake nutrient and chlorophyll‐aconcentrations. To better characterize how nutrients interact with other environmental factors to produce algal blooms in freshwater systems, we used spatially explicit and temporally matched climate, landscape, in‐lake characteristic, and nutrient inventory data sets to predict nutrients and chlorophyll‐aacross the conterminous US (CONUS). Using a nested modeling approach, three random forest (RF) models were trained to explain the spatiotemporal variation in total nitrogen (TN), total phosphorus (TP), and chlorophyll‐aconcentrations across US EPA's National Lakes Assessment (n = 2,062). Concentrations of TN and TP were the most important predictors and, with other variables, the RF model accounted for 68% of variation in chlorophyll‐a. We then used these RF models to extrapolate lake TN and TP predictions to lakes without nutrient observations and predict chlorophyll‐afor ∼112,000 lakes across the CONUS. Risk for high chlorophyll‐aconcentrations is highest in the agriculturally dominated Midwest, but other areas of risk emerge in nutrient pollution hot spots across the country. These catchment and lake‐specific results can help managers identify potential nutrient pollution and chlorophyll‐ahot spots that may fuel blooms, prioritize at‐risk lakes for additional monitoring, and optimize management to protect human health and other environmental end goals.

Environmental Sciences & Ecology↗

Evaluation and calibration of MERRA-2 and CAMS reanalysis for PM 2.5 in a semi-urbanized area in the south of the Amazon

Air pollution has significant implications for the climate and poses irreversible risks to human health. The Amazon region of Brazil is severely affected by biomass burning (BB) emissions, yet air quality monitoring remains highly inadequate. Given the scarcity of surface-based observations, reanalysis models have become essential tools for assessing air pollution. Although MERRA-2 and CAMS PM 2.5 products are widely utilized, their validation and comprehensive evaluation for the Amazon Basin remain limited. Here, this study assesses the performance of these products in a semi-urbanized region in the southern Amazon. The calibrated time series was employed to analyze PM 2.5 concentrations from 2003 to 2023. Our results showed satisfactory performance of both products for the 24-h averages of PM 2.5 , with linear correlations above 0.76. However, it was found that both products overestimate surface concentrations. MERRA-2 performed better, with approximately 30% lower bias than CAMS. Time series analysis showed that the study area is strongly impacted by emissions BB in the dry period, mainly in August and September. Furthermore, our findings indicate a positive trend in increasing PM 2.5 concentrations, with a notable rise observed since 2014. The average PM 2.5 levels frequently exceed the daily air quality guidelines established by the WHO in 2021. It has been estimated that the population of this region is exposed to concentrations above 15 μg.m -3 , on average, more than 30 days per year. Our results contribute to the evaluation of MERRA-2 and CAMS products for Amazon and provide a corrected estimate for surface PM 2.5 . Recent concerns about air quality and the implementation of new surface monitoring networks may improve the evaluation of reanalysis products. In the short term, the need for this information makes our assessments indispensable.

54 ENVIRONMENTAL SCIENCES↗

Translating nanoparticle dosimetry from conventional in vitro systems to occupational inhalation exposures

As encouraged by Toxicity Testing in the 21st Century, researchers increasingly apply high-throughput in vitro approaches to identify and characterize nanoparticle hazards, including conventional aqueous cell culture systems to assess respiratory hazards. Translating nanoparticle dose from conventional toxicity testing systems to relevant human exposures remains a major challenge for assessing occupational risk of nanoparticle exposures. Here, we explored existing computational tools and data available to translate nanoparticle dose metrics from cellular test systems to inhalation exposures of silver nanoparticles in humans. We used the Multiple-Path Particle Dosimetry (MPPD) Model to predict deposition of humans exposed to 20 and 110 nm silver nanoparticles at 0.9 µg/m3 over an 8 hr period, the proposed a National Institute of Occupational Safety and Health (NIOSH) recommended exposure limit (REL). MPPD predicts 1.88 and 0.98 µg of silver deposited in an 8 hr period for 20 and 110 nm nanoparticles, respectively, with 20 nm particles displaying nearly 11-fold higher total surface area deposited. Peak nanoparticle concentrations occurred more proximal in the pulmonary tract compared to mass deposition patterns (generation 5 vs. generations 20-21, respectively) due to regional differences in lung lining fluid volumes. Assuming 0.4% nanoparticle dissolution by mass as previously measured, we predict peak concentrations of silver ions in cells of 0.24 and 0.17 µg/mL for 20 and 110 nm particles, respectively. Both predicted concentrations are below the measured toxic threshold of 1.7 µg/mL of silver ions in cells from in vitro assessments. Assuming 4% dissolution by mass, we predict 10-fold higher silver concentrations in tissues, peaking at 2.4 and 1.7 µg/mL, for 20 and 110 nm nanoparticles respectively, exceeding the observed in vitro toxic threshold and highlighting the importance and sensitivity of dissolution rates. Overall, this approach offers a framework for extrapolating nanotoxicity results from in vitro cell culture systems to human exposures. Aligning appropriate dose metrics from in vitro and in vivo hazard characterizations and human pulmonary doses from occupational exposures are critical components for successful nanoparticle risk assessment and worker protection and provide guidance for designing future in vitro studies aimed at relevant human exposures.

Smith, Jordan N.↗

Enhanced Iodine Capture Using a Postsynthetically Modified Thione–Silver Zeolitic Imidazole Framework

Efficient management of radionuclides that are released from various processes in the nuclear fuel cycle is of significant importance. Among these nuclides, radioactive iodine (mainly 129 I and 131 I) is a major concern due to the risk it poses to the environment and to human health; thus, the development of materials that can capture and safely store radioactive iodine is crucial. Herein, a novel silver-thione-functionalized zeolitic imidazole framework (ZIF) was synthesized via post-synthetic modification and assessed for its iodine uptake capabilities alongside the parent ZIF-8 and intermediate materials. A solvent-assisted ligand exchange procedure was used to replace the 2-methylimidazole linkers in ZIF-8 with 2-mercaptoimidazole, forming the intermediate compound ZIF-8=S, which was reacted with AgNO 3 to yield the ZIF-8=S-Ag + composite for iodine uptake. Despite possessing the lowest BET surface area of the derivatives, the Ag-functionalized material demonstrated superior I 2 adsorption in terms of both maximum capacity (550 g I 2 /mol) and rapid kinetics (50% loading achieved in 5 hrs, saturation in 50 hrs) compared to our pristine ZIF-8, which reached 450 g I 2 /mol after 150 hours and 50% loading in 25 hours. This improvement is attributed to the presence of the Ag + ions, which provide a strong chemical driving force to form stable Ag-I species. In conclusion, the results of this study contribute to a broader understanding of the strategies that can be employed to engineer adsorbents with robust iodine uptake behavior.

36 MATERIALS SCIENCE↗

Assessment of Potential Dose and Environmental Impacts from Proposed Testing at the INL Radiological Response Training Range

This assessment uses screening-level models to calculate potential environmental impacts from proposed tests at the Idaho National Laboratory (INL) Radiological Response Training Range (RRTR) site. Proposed tests could be conducted using 11 different radioactive material types that include K2O, LaBr3, KBr, Cu, Zr, F, Ga, Ga2O3, NaNO2, Ga-68, and Tc-99m. The tests could potentially release radioactive material to the atmosphere and radionuclides and other contaminants to the soil, which could leach into the unsaturated zone and migrate to the aquifer. Atmospheric transport of radionuclides to potential human receptors and time-integrated air concentrations were calculated with a Gaussian plume model and three years of hourly meteorological data. Potential surface-soil impacts were calculated with the computer program mixing-cell model (MCM). Groundwater impacts were calculated with the computer programs MCM and GWSCREEN. Radiological doses from potential atmospheric releases were calculated for public receptors off the INL Site and for workers at nearby INL facilities. Results were compared to regulatory dose limits. Maximum potential groundwater concentrations were estimated in the aquifer below the NSTR site and compared to drinking water standards or risk-based screening levels for resident tap water. Soil concentrations were calculated and compared to risk-based screening levels for workers and potential future residents. All impacts were estimated assuming 12 tests are conducted annually using all 11 material types for a period of 15 years. This document provides the resources to enable a subject matter expert in the field of environmental assessments to replicate the modeling and calculations. The methodology and parameters are presented in the text. All electronic files, including computer-code input, output, executable files, batch files, scripts, and spreadsheet files are contained in a zip file that can be accessed by selecting “Additional Information” (select Native File) in the INL Electronic Document Management System (EDMS). It is highly unlikely the test scenarios evaluated in this ECAR will adversely impact human health based on comparisons of calculated dose and concentration against regulatory standards and risk-based screening levels. Conservative estimates of dose to workers and the public from atmospheric transport of possible radionuclide releases are far below federal radiation protection standards. Conservative estimates of potential contaminant concentrations in groundwater are less than federal drinking water standards or screening levels. Predicted radionuclide concentrations in surface soils are below risk-based screening levels, except for Ge-68 (material Ga-68) for the worker. The Ge-68 soil concentration can be made less than the worker PRG, if the number of annual tests using Ga-68 is reduced from 12 to 6. However, the sum of ratios still exceeds one because of the high K-40 ratio. If the EF of the worker (number of days the worker is in the contaminated testing area) is reduced from 225 days/yr (default value for full time worker) to 112 days/yr, the Ge-68 ratio is less than one and the sum of ratios is less than one. Actual radiation doses and groundwater and surface-soil concentrations are likely to be much less than those calculated because of the conservative assumptions and parameters employed in the modeling. For example, atmospheric-transport calculations assume the entire inventory of each material type is readily released to the atmosphere and no plume deposition, depletion, or radioactive decay occurs during transport. The calculations also assume the same meteorological conditions (e.g., wind velocity, wind direction, stability class) that produce the maximum 95th percentile concentration (i.e., concentration representing the 95th percentile of a distribution of concentrations derived from 3 years of hourly meteorological data) at each receptor location are the same for all 12 tests during the year, and each receptor is assumed to be present during all 12 tests. The surface-soil assessment assumes the entire inventory of each test is deposited in the top 5 cm of soil. No atmospheric dispersal is assumed, and the radionuclides are subject only to leaching and radioactive decay. The groundwater-pathway modeling is conservative in that it is one-dimensional in the unsaturated zone (no lateral spreading/dilution) and assumes the entire inventory of contaminants infiltrates into the ground at the same location for every test. This is especially conservative for particulate radionuclides because they would have to dissolve or corrode first and some would be dispersed into the atmosphere. The groundwater receptor is also assumed to consume water directly from a hypothetical well positioned in the location of maximum concentration. In addition, conservative degradation rates were used, and volatilization was not considered for the nonradioactive chemical

54 ENVIRONMENTAL SCIENCES↗

Assessment of Potential Dose and Environmental Impacts from Proposed Testing at the INL National Security Test Range

This assessment uses screening-level models to calculate potential environmental impacts from proposed tests at two locations at the Idaho National Laboratory (INL) National Security Test Range (NSTR) site. Proposed tests could be conducted using 11 different radioactive material types that include K 2 O, LaBr 3 , KBr, Cu, Zr, F, Ga, Ga 2 O 3 , NaNO 2 , Ga-68, and Tc-99m. The tests could potentially release radioactive material to the atmosphere and radionuclides and other contaminants to the soil, which could leach into the unsaturated zone and migrate to the aquifer. Atmospheric transport of radionuclides to potential human receptors and time-integrated air concentrations were calculated with a Gaussian plume model and three years of hourly meteorological data. Potential surface-soil impacts were calculated with the computer program mixing-cell model (MCM). Groundwater impacts were calculated with the computer programs MCM and GWSCREEN. Radiological doses from potential atmospheric releases were calculated for public receptors off the INL Site and for workers at nearby INL facilities. Results were compared to regulatory dose limits. Maximum potential groundwater concentrations were estimated in the aquifer below the NSTR site and compared to drinking water standards or risk-based screening levels for resident tap water. Soil concentrations were calculated and compared to risk-based screening levels for workers and potential future residents. All impacts were estimated based on the assumption that 12 tests are conducted annually using all 11 material types for 15 years. This document provides the resources to enable a subject matter expert in the field of environmental assessments to replicate the modeling and calculations. The methodology and parameters are presented in the text. All electronic files, including computer-code input, output, executable files, batch files, scripts, and spreadsheet files, are contained in a zip file that can be accessed by selecting “Additional Information” (select Native File) in the INL Electronic Document Management System (EDMS). It is highly unlikely the test scenarios evaluated in this ECAR will adversely impact human health based on comparisons of calculated dose and concentration against regulatory standards and risk-based screening levels. Conservative estimates of dose to workers and the public from atmospheric transport of possible radionuclide releases are far below federal radiation protection standards. Conservative estimates of potential contaminant concentrations in groundwater are less than federal drinking water standards or screening levels. Predicted radionuclide concentrations in surface soils are below risk-based screening levels, except for Ge-68 (material Ga-68) for the worker. The Ge-68 soil concentration can be made less than the worker PRG, if the number of annual tests using Ga-68 is reduced from 12 to 6. However, the sum of ratios still exceeds one because of the high K-40 ratio. If the EF of the worker (number of days the worker is in the contaminated testing area) is reduced from 225 days/yr (default value for full time worker) to 112 days/yr, the Ge-68 ratio is less than one and the sum of ratios is less than one. Actual radiation doses and groundwater and surface-soil concentrations are likely to be much less than those calculated because of the conservative assumptions and parameters employed in the modeling. For example, atmospheric-transport calculations assume the entire inventory of each material type is readily released to the atmosphere and no plume deposition, depletion, or radioactive decay occurs during transport. The calculations also assume the same meteorological conditions (e.g., wind velocity, wind direction, stability class) that produce the maximum 95th percentile concentration (i.e., concentration representing the 95th percentile of a distribution of concentrations derived from 3 years of hourly meteorological data) at each receptor location are the same for all 12 tests during the year, and each receptor is assumed to be present during all 12 tests. The surface-soil assessment assumes the entire inventory of each test is deposited in the top 5 cm of soil. No atmospheric dispersal is assumed, and the radionuclides are subject only to leaching and radioactive decay. The groundwater-pathway modeling is conservative in that it is one-dimensional in the unsaturated zone (no lateral spreading/dilution) and assumes the entire inventory of contaminants infiltrates into the ground at the same location for every test. This is especially conservative for particulate radionuclides because they would have to dissolve or corrode first and some would be dispersed into the atmosphere. The groundwater receptor is also assumed to consume water directly from a hypothetical well positioned in the location of maximum concentration. In addition, conservative degradation rates were used, and volatilization was not considered for the nonradradioactive chemicals modeled. And finally, the calculations assume all 12 tests will be performed at the same place at both locations, and all 11 radioactive material types will be used for each test. This is conservative because it is anticipated that no more than two material types will be used per test.

99 GENERAL AND MISCELLANEOUS↗

National Renewable Energy Laboratory Wildland Fire Management Plan (August 2022-August 2025): February-August 2022

The National Renewable Energy Laboratory (NREL) is located in a moderate wildfire risk region. The region has a history of damaging wildland fire activity and is also susceptible to changing environmental conditions (drought, elevated temperatures) that may lead to an increase in wildfire frequency and consequence over time. An integrated, site-wide wildland fire management plan is required by the Department of Energy and is to be consistent with the Federal Wildland Fire Management Policy. The NREL Wildland Fire Management Plan (WFMP) provides an integrated approach to reducing risk to wildland fire at NREL. The goals of the WFMP are to protect human health and safety, protect NREL facilities and research, enhance community protection, diminish risk and consequences of wildland fires, and maintain the health of the ecosystem. The WFMP accomplishes these goals through the use of tools such as fire behavior modeling, fire growth modeling, a structure ignition risk assessment, and through the application of robust fire prevention, emergency management, and environmental programs. The NREL WFMP was developed in a collaborative manner with input from regional stakeholders including cities, counties, local fire departments, and other governmental agencies. The WFMP provides for recommendations to reduce overall wildland fire risk to life safety and property at NREL.

54 ENVIRONMENTAL SCIENCES↗

Native Microalgae-Bacteria Consortia: A Sustainable Approach for Effective Urban Wastewater Bioremediation and Disinfection

Urban wastewater is a significant by-product of human activities. Conventional urban wastewater treatment plants have limitations in their treatment, mainly concerning the low removal efficiency of conventional and emerging contaminants. Discharged wastewater also contains harmful microorganisms, posing risks to public health, especially by spreading antibiotic-resistant bacteria and genes. Therefore, this study assesses the potential of a native microalgae-bacteria system (MBS) for urban wastewater bioremediation and disinfection, targeting NH4+-N and PO43−-P removal, coliform reduction, and antibiotic resistance gene mitigation. The MBS showed promising results, including a high specific growth rate (0.651 ± 0.155 d−1) and a significant average removal rate of NH4+-N and PO43−-P (9.05 ± 1.24 mg L−1 d−1 and 0.79 ± 0.06 mg L−1 d−1, respectively). Microalgae-induced pH increase rapidly reduces coliforms (r > 0.9), including Escherichia coli, within 3 to 6 days. Notably, the prevalence of intI1 and the antibiotic resistance genes sul1 and blaTEM are significantly diminished, presenting the MBS as a sustainable approach for tertiary wastewater treatment to combat eutrophication and reduce waterborne disease risks and antibiotic resistance spread.

Sousa, Joana F.↗

Galactic cosmic ray simulation at the NASA space radiation laboratory – Progress, challenges and recommendations on mixed-field effects

For missions beyond low Earth orbit to the moon or Mars, space explorers will encounter a complex radiation field composed of various ion species with a broad range of energies. Such missions pose significant radiation protection challenges that need to be solved in order to minimize exposures and associated health risks. An innovative galactic cosmic ray simulator (GCRsim) was recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The GCRsim technology is intended to represent major components of the space radiation environment in a ground analog laboratory setting where it can be used to improve understanding of biological risks and serve as a testbed for countermeasure development and validation. The current GCRsim consists of 33 energetic ion beams that collectively simulate the primary and secondary GCR field encountered by humans in space over the broad range of particle types, energies, and linear energy transfer (LET) of interest to health effects. A virtual workshop was held in December 2020 to assess the status of the NASA baseline GCRsim. Workshop attendees examined various aspects of simulator design, with a particular emphasis on beam selection strategies. Experimental results, modeling approaches, areas of consensus, and questions of concern were also discussed in detail. This report includes a summary of the GCRsim workshop and a description of the current status of the GCRsim. This information is important for future advancements and applications in space radiobiology.

79 ASTRONOMY AND ASTROPHYSICS↗

Competing Interests and Creating Value - Balancing Durable and Enforceable Institutional Controls with Beneficial Reuse - 20320

US DOE LM has various real property interests at the 100 sites within its current portfolio, with an anticipated total of 127 sites within the next 5 years. Each site has its own narrative with respect to the real property assets. Since the regulatory time frame for long-term surveillance and maintenance activities at some sites can be in perpetuity, durable and effective instruments and documentation are necessary to support LM's unique mission as a federal land manager and steward. More than half of the sites currently in LM's inventory do not allow unrestricted use, and institutional controls (ICs) are required to limit human and environmental exposures to residual contamination. LM's Asset Management program balances protection of human health and the environment with a goal of optimizing its land portfolio through mitigation of risk, limiting liability, and creating value, whether tangible or intangible, in these types of assets. The IC layering strategy utilizes multiple types, restrictions, and legal authorities to protect human health and the environment. This layering strategy influences the transition of these properties into LM's portfolio to assess potential beneficial reuses. The LM's beneficial reuse program aims to repurpose former contaminated sites to restore the environment, protect the public health, revitalize communities, and spur economic growth. LM strives to create value in a perceived valueless asset and reevaluates and revisits the potential opportunities for these sites as long-term surveillance and maintenance activities are performed and objectives are achieved. Beneficial reuse also promotes protectiveness by ensuring activities are compatible with long-term maintenance and protection of public health and the environment as well as ensuring activities are environmentally sound by retaining good stewardship of natural resources. LM has recently revised both the Institutional Control Program Guidance and its Beneficial Reuse Management Plan to integrate the issues of land use with ICs, creating value in these impaired assets. This paper presents the following topics: (1) a general overview of LM's IC and beneficial reuse programs; (2) the unique aspects of each of these programs as a result of the multiple regulatory requirements and programs that affect LM sites; (3) case studies of LM sites to show examples of how LM created value while complying with the ICs and layering strategies; and (4) the most common challenges to beneficial reuses at LM sites and potential options for value creation in impaired assets. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

From Qualitative to Quantitative AOP: A Case Study of Neurodegeneration

Adverse outcome pathways (AOPs) include a sequence of events that connect a molecular-level initiating event with an adverse outcome at the cellular level for human health endpoints, or at the population level for ecological endpoints. When there is enough quantitative understanding of the relationships between key events in an AOP, a mathematical model may be developed to connect key events in a quantitative AOP (qAOP). Ideally, a qAOP will reduce the time and resources spent for chemical toxicity testing and risk assessment and enable the extrapolation of data collected at the molecular-level by in vitro assays, for example, to predict whether an adverse outcome may occur. Here, we review AOPs in the AOPWiki, an AOP repository, to determine best practices that would facilitate conversion from AOP to qAOP. Then, focusing on a particular case study, acetylcholinesterase inhibition leading to neurodegeneration, we describe specific methods and challenges. Examples of challenges include the availability and collection of quantitative data amenable to model development, the lack of studies that measure multiple key events, and model accessibility or transferability across platforms. We conclude with recommendations for improving key event and key event relationship descriptions in the AOPWiki that facilitate the transition of qualitative AOPs to qAOPs.

Sinitsyn, Dennis↗

Seroprevalence and risk factors for brucellosis amongst livestock and humans in a multi-herd ranch system in Kagera, Tanzania

Background Brucellosis remains a significant health and economic challenge for livestock and humans globally. Despite its public health implications, the factors driving the endemic persistence ofBrucellaat the human-livestock interface in Tanzania remain poorly elucidated. This study aimed to identify the seroprevalence ofBrucellainfection in livestock and humans within a ranching system and determine associated risk factors for disease endemicity. Methods A cross-sectional sero-epidemiological study was conducted in 2023 in Tanzania’s Karagwe District, involving 725 livestock (cattle, goats, sheep) from 10 herds and 112 humans from associated camps. Seroprevalence was assessed using competitive ELISA while epidemiological data were collected via questionnaires. Generalized Linear Models and Contrast Analysis were used to identify risk factors for infection. Results Overall seroprevalence was 34% in livestock and 41% in humans. Goats exhibited the highest prevalence (69.2%), while cattle had the lowest (22.6%). Mixed-species herds (Odds Ratio, OR = 2.96, CI [1.90–4.60]) and small ruminants-only herds (OR = 6.54, CI [3.65–11.72]) showed a significantly higher risk of seropositivity compared to cattle-only herds. Older cattle (OR = 5.23, CI [2.70–10.10]) and lactating females (OR = 2.87, CI [1.78–4.63]) represented significant risks for brucellosis in livestock. In humans, close contact with animals (OR = 7.20, CI [1.97–36.31]) and handling animals during parturition or aborted fetuses (OR = 2.37, CI [1.01–5.58]) were significant risk factors. Notably, no spatial association was found in seroprevalence between herds and nearby human communities. Conclusion The lack of spatial correlation between livestock and human seroprevalence suggests complex transmission dynamics, potentially involving endemic circulation in livestock and human infections from multiple sources of exposure to livestock. This study highlights the need for comprehensive zoonotic risk education and targeted intervention strategies. Further research is crucial to elucidate transmission pathways and improveBrucellainfection control. This includes developing robust methods for identifying infective species and implementing effective strategies to mitigateBrucellainfection in endemic regions.

Public, Environmental & Occupational Health↗

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↗

Atmospheric emission of nanoplastics from sewer pipe repairs

Nanoplastic particles are inadequately characterized environmental pollutants with significant adverse effects on aquatic and atmospheric systems, causing drastic impacts on human health through inhalation, ingestion, and skin penetration. At present, it is explicitly assumed that environmental nanoplastics (EnvNP) are weathering fragments of microplastic or larger plastic debris discharged into terrestrial and aquatic environments, while atmospheric occurrence of EnvNP is solely attributed to aerosolization by wind and other mechanical forces. However, sources and emissions of unintended EnvNP are poorly understood and are therefore largely unaccounted for in various risk assessments. In this work, we show that large quantities of EnvNP may be directly emitted into the atmosphere as steam laden waste components discharged from a commonly used technology to repair sewer pipes in urban areas. Comprehensive chemical analysis of the discharged waste condensate reveals abundant presence of insoluble colloids, which after drying form solid organic particles with composition and viscosity consistent with EnvNP. We suggest that airborne emissions of EnvNP from these globally used sewer repair practices may be prevalent in highly populated urban areas. Airborne emissions of these EnvNP particles may have important implications on air quality and toxicological levels in large urban areas that need to be mitigated.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

Updates to a Preliminary Probabilistic Performance Assessment Model for Radiological and Chemical Contamination at the West Valley Site, New York - 20420

The New York State Energy Research and Development Authority (NYSERDA) is the owner of the Western New York Nuclear Service Center (WNYNSC), a 1,351-ha site located approximately 48 km south of Buffalo, New York. In 1962, Nuclear Fuel Services, Inc. (NFS) entered into agreements with the Atomic Energy Commission and New York State to construct the first commercial reprocessing plant of nuclear fuel in the United States at the WNYNSC. NFS built and operated the spent fuel reprocessing plant and waste disposal facilities, processing 640 Mg (640 metric tons) of spent nuclear fuel from 1966 to 1972 under an Atomic Energy Commission license. Nuclear fuel reprocessing operations halted in 1972 and never restarted, leaving behind radioactive and chemical wastes. The U.S. Department of Energy (DOE) was required to complete certain waste management activities under the West Valley Demonstration Project (WVDP) Act of 1980 including decommissioning of WVDP facilities. As collaborating agencies, NYSERDA and the DOE are tasked with making decisions about decommissioning and risk reduction for the West Valley Site. Neptune and Company, Inc. (Neptune) was contracted to develop a probabilistic performance assessment (PPA) model to assist the agencies in their decision making process for decommissioning the WVDP and WNYNSC. One important tool that is needed in order to inform the decision-making process is a science-based model of the West Valley Site that evaluates potential future consequences for human health and the environment. This forms the core of the spatial domain of the West Valley PPA Model. The PPA Model, developed using the GoldSim system modeling software, is a tool intended to provide support for decision making that evaluates uncertainty, in a manner that is transparent, defensible, and robust. The PPA Model includes contaminant transport and health effects components, and is organized around geographically-grouped contaminated facilities. These include the waste disposal areas licensed by the U.S. Nuclear Regulatory Commission and the State of New York, a waste tank farm for storage of high level radioactive waste resulting from reprocessing operations, and several areas contaminated with radioactive and chemical constituents. The PPA Model evaluates contaminant transport from these sources to points of exposure across the site and into receiving surface waters and sediments. Hypothetical people and wildlife could be exposed to contamination at these locations, and the effects of these exposures are evaluated. Contaminant transport processes to be evaluated in the PPA Model include groundwater and surface water transport, contaminant translocation by plants and animals, diffusion, and erosion. The evaluation of exposures to people in this preliminary model is limited to a resident farmer scenario, and ecological assessment is performed at the level of a screening analysis. The results of these preliminary evaluations inform future model developments. PPA Model results are subjected to sensitivity analysis in order to determine those pathways and parameters that are most significant in influencing the results. This information allows analysts and decision makers to focus on those aspects of Site behavior and processes. With this information, the decision makers can drive informed, defensible decisions regarding decommissioning of the Site. This paper includes an update of the information presented at WM2019 [1]. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Astronauts Plasma-Derived Exosomes Induced Aberrant EZH2-Mediated H3K27me3 Epigenetic Regulation of the Vitamin D Receptor

There are unique stressors in the spaceflight environment. Exposure to such stressors may be associated with adverse effects on astronauts' health, including increased cancer and cardiovascular disease risks. Small extracellular vesicles (sEVs, i.e., exosomes) play a vital role in intercellular communication and regulate various biological processes contributing to their role in disease pathogenesis. To assess whether spaceflight alters sEVs transcriptome profile, sEVs were isolated from the blood plasma of 3 astronauts at two different time points: 10 days before launch (L-10) and 3 days after return (R+3) from the Shuttle mission. AC16 cells (human cardiomyocyte cell line) were treated with L-10 and R+3 astronauts-derived exosomes for 24 h. Total RNA was isolated and analyzed for gene expression profiling using Affymetrix microarrays. Enrichment analysis was performed using Enrichr. Furthermore, transcription factor (TF) enrichment analysis using the ENCODE/ChEA Consensus TF database identified gene sets related to the polycomb repressive complex 2 (PRC2) and Vitamin D receptor (VDR) in AC16 cells treated with R+3 compared to cells treated with L-10 astronauts-derived exosomes. Further analysis of the histone modifications using datasets from the Roadmap Epigenomics Project confirmed enrichment in gene sets related to the H3K27me3 repressive mark. Interestingly, analysis of previously published H3K27me3–chromatin immunoprecipitation sequencing (ChIP-Seq) ENCODE datasets showed enrichment of H3K27me3 in the VDR promoter. Collectively, our results suggest that astronaut-derived sEVs may epigenetically repress the expression of the VDR in human adult cardiomyocytes by promoting the activation of the PRC2 complex and H3K27me3 levels.

59 BASIC BIOLOGICAL SCIENCES↗