Reference Concentration Research Articles

Establishing indicators for assessing non-carcinogenic risks under chronic inhalation expo-sure to benzene and average annual mpc for benzene as per health risk criteria

Recently multiple new toxicological and epidemiologic data on negative effects produced by chemicals have become available; given that, it is necessary to improve quantitative criteria applied in health risk assessment. It is advisable to revise previously established reference concentrations and to make more precise lists of organs and systems affected by a chemical in concentrations which are either equal to reference one or exceed it. Our research aim was to establish a reference concentration for benzene and additional quantitative indicators of its effects (additional reference concentrations) on specific organs and systems under chronic inhalation exposure; another aim was to determine average annual MPC verified as per permissible lifetime carcinogenic risk using evolution models. The research allowed recommending 0.005 mg/m3 to be used as a reference concentration under chronic inhalation exposure to benzene; a decrease in quantity of B-lymphocytes was recommended as a critical effect since this decrease might produce negative effects on the blood and immune system. Additional reference concen-trations for benzene were fixed at 0.007 mg/m3 for the liver as a critical organ and 0.012 mg/mg3 for violated process of organism development as a critical effect. They can be used as additional indicators for assessing non-carcinogenic health risks under chronic inhalation exposure to benzene in its elevated concentrations. Our research results were used to substantiate average annual MPC for benzene in ambient air; its recommended value was 0.005 mg/m3 since it provided safety (absence of impermis-sible (unacceptable) lifetime health risk), probable carcinogenic effects taken into account.

Разработка параметров для оценки неканцерогенного риска при хроническом ингаляционном поступлении бензола и среднегодовой предельно допустимой концентрации бензола по критериям риска для здоровья населения

Recently multiple new toxicological and epidemiologic data on negative effects produced by chemicals have become available; given that, it is necessary to improve quantitative criteria applied in health risk assessment. It is advisable to revise previously established reference concentrations and to make more precise lists of organs and systems affected by a chemical in concentrations which are either equal to reference one or exceed it. Our research aim was to establish a reference concentration for benzene and additional quantitative indicators of its effects (additional reference concentrations) on specific organs and systems under chronic inhalation exposure; another aim was to determine average annual MPC verified as per permissible lifetime carcinogenic risk using evolution models. The research allowed recommending 0.005 mg/m3 to be used as a reference concentration under chronic inhalation exposure to benzene; a decrease in quantity of B-lymphocytes was recommended as a critical effect since this decrease might produce negative effects on the blood and immune system. Additional reference concen-trations for benzene were fixed at 0.007 mg/m3 for the liver as a critical organ and 0.012 mg/mg3 for violated process of organism development as a critical effect. They can be used as additional indicators for assessing non-carcinogenic health risks under chronic inhalation exposure to benzene in its elevated concentrations. Our research results were used to substantiate average annual MPC for benzene in ambient air; its recommended value was 0.005 mg/m3 since it provided safety (absence of impermis-sible (unacceptable) lifetime health risk), probable carcinogenic effects taken into account.

Study of the wave period effect on the time-averaged suspended sediment concentration distribution under the oscillatory sheet flow condition

ABSTRACT Existing sheet flow experimental data show the measured time-averaged suspended sediment concentration (TSSC) may increase, decrease, or even remain constant if the wave period decreases. With respect to the available sheet flow experimental data, it is confirmed that the TSSC of relatively fine sand undergoes three stages, i.e. first decreases, then increases, and finally decreases again in the case that the wave period decreases from 12 s to 2 s, whereas for the relatively coarse sand, its vertical profile remains almost unchanged. The criterion for identifying the relatively fine or coarse sand was proposed in terms of the nondimensional ratio between the settling velocity and the root-mean-square flow velocity. If this ratio is less than 0.04–0.043, it is deemed as relatively fine sand. Otherwise, it is classified as relatively coarse sand. Applying the classical gradient diffusion model, sediment diffusivity is confirmed to be insensitive to the wave period. Keeping other experimental conditions uniform, TSSCs with different wave periods are proportional to each other and only affected by the reference concentration. Subsequently, a simple quantitative expression considering the wave period effect on the TSSC under the oscillatory sheet flow regime was proposed and verified with the experimental data.

Concentration Bias in Reference Potentials and the pH-Effect on the Electrocatalysis of Hydrogen and Oxygen Evolution for Water Electrolysis

The electrolysis of water at low temperatures involves the transition from the liquid to the gas phase. The reactant, liquid water, has a concentration of around 55 mol/L, whereas gases such as hydrogen and oxygen with a nearly ideal behavior correspond to a concentration of only 0.04 mol/L at standard conditions (room temperature, pressure equal to 1 bar). Moreover, the oxygen and hydrogen molecules produced during electrolysis are first formed in a dissolved state in the electrolyte before escaping to the gas phase. The saturation concentrations of these gases in liquid water are around 0.001 mol/L at standard conditions, even lower than the concentrations in the gas phase. Accordingly the water electrolysis reaction involves a concentration change from approx. 55 mol/L for the reactant down to approx. 0.001 mol/L for the products. This dramatic concentration drop strongly contributes to the entropic part of the Gibbs free energy of the water splitting reaction, and it therefore implicitly biases the equilibrium voltage.We discuss why this concentration bias can be obstructive for a clear perspective on the reaction kinetics when using the equilibrium voltage, or potentials, as a reference [1]. To provide an unbiased reference voltage, we propose a definition of reference conditions with balanced concentrations on the reactant and product side. The theoretical equilibrium voltage corresponding to such balanced reactive conditions is an unbiased intrinsic reference for kinetic analysis, for which reason we denote it the kinetic reference voltage Ukin. For the electrochemical water splitting reaction, it has a value of Ukin = 1.441 V, which is in remarkable agreement with commonly observed onset voltages for macroscopic electrolysis rates.Applying the same concept of balanced reactive conditions to half-cell reactions, we define the kinetic reference potential Ekin. For a simple electrochemical redox couple Red ↔ Ox + e− with a 1:1 stoichiometry, the kinetic reference potential Ekin is simply equal to the standard equilibrium potential, because the standard reference concentrations are already balanced (1 mol/L for dissolved species). In contrast, for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), the standard reference concentrations are very different for reactants and products, and the corresponding standard equilibrium potentials suffer from concentration bias. Accordingly, the unbiased kinetic reference potentials of HER and OER are shifted with respect to the standard equilibrium potentials. These shifts are different in acidic and alkaline conditions and reveal an intriguing correlation with the experimentally observed effect of the pH value on the kinetics of HER and OER.The concept of balanced reactive reference conditions thus sheds a new light on the activation overvoltage in water electrolysis and the pH-effect in the electrocatalysis of HER and OER.[1] T. Binninger, A. Heinritz, R. Mohamed, Kinetic Reference Potential, pH-Effect, and Energy Recovery in Electrolysis of Water, ChemRxiv (2020), preprint, DOI: 10.26434/chemrxiv.12739091.v1

Risks to children from inhalation of aerosolized aqueous manganese emitted from ultrasonic humidifiers can be greater than for corresponding ingestion

The essential trace element manganese (Mn) can cause neurotoxicity with inhalation acknowledged as a more severe health and cognition threat than ingestion. Methods: Over a range of aqueous Mn concentrations present in tap water, this research characterizes exposures and risks for adults and 0.25, 1, 2.5, and 6 yr old children who ingest the water and inhale respirable particles produced by a room-sized ultrasonic humidifier filled with the same water. Aqueous Mn concentrations evaluated included 50 µg/L USEPA esthetic guideline, 80 µg/L WHO infant guideline, and 120 µg/L Canadian regulatory level. Airborne-particle-bound Mn concentrations were generated for water filling an ultrasonic humidifier under four realistic room conditions (33 m3 small or 72 m3 large) with varying ventilation rates from 0.2/h -1.5/h. Average daily doses (ADD) and reference intake doses were calculated for ingestion and 8-h inhalation of humidified air. Hazard quotients (HQ) compared the intake doses and reference doses. Multi-path particle dosimetry (MPPD) model quantified the particle deposition and deposited dose in children's and adults’ respiratory tracts. Results: At only 11 µg/L Mn, the resulting humidified air Mn exceeds USEPA's reference concentration of 0.05 µg/m3 Mn in small room with low, energy-efficient ventilation. Inhalation ADD are 2 magnitudes lower than ingestion ADD for identical water Mn concentrations and daily exposure frequency. Even so, ingestion HQs are approximately 0.2 but inhalation risk is significant (HQ>1) for children and adults when breathing Mn-humidified air under most small room conditions at 50, 80 or 120 µg/L Mn. MPPD model indicates inhaled Mn deposits in head and pulmonary regions, with greater Mn dose deposits in children than adults. Conclusion: Inhalation of Mn-particles produced from ultrasonic humidifiers can pose greater risks than ingestion at the same water concentration, especially for children. Aqueous Mn concentration and room size influence risks. Limiting manganese exposures and setting regulations requires consideration of both ingestion and inhalation of water.

Microdebrider is less aerosol-generating than CO2 laser and cold instruments in microlaryngoscopy

ObjectiveCOVID-19 spreads through aerosols produced in coughing, talking, exhalation, and also in some surgical procedures. Use of CO2 laser in laryngeal surgery has been observed to generate aerosols, however, other techniques, such cold dissection and microdebrider, have not been sufficiently investigated. We aimed to assess whether aerosol generation occurs during laryngeal operations and the effect of different instruments on aerosol production.MethodsWe measured particle concentration generated during surgeries with an Optical Particle Sizer. Cough data collected from volunteers and aerosol concentration of an empty operating room served as references. Aerosol concentrations when using different techniques and equipment were compared with references as well as with each other.ResultsThirteen laryngological surgeries were evaluated. The highest total aerosol concentrations were observed when using CO2 laser and these were significantly higher than the concentrations when using microdebrider or cold dissection (p < 0.0001, p < 0.0001) or in the background or during coughing (p < 0.0001, p < 0.0001). In contrast, neither microdebrider nor cold dissection produced significant concentrations of aerosol compared with coughing (p = 0.146, p = 0.753). In comparing all three techniques, microdebrider produced the least aerosol particles.ConclusionsMicrodebrider and cold dissection can be regarded as aerosol-generating relative to background reference concentrations, but they should not be considered as high-risk aerosol-generating procedures, as the concentrations are low and do not exceed those of coughing. A step-down algorithm from CO2 laser to cold instruments and microdebrider is recommended to lower the risk of airborne infections among medical staff.

The critical factors of landfill fire impact on air quality

Simulations show that landfill fires are a serious regional concern. This study presents a three-parameter method for assessing the impact of landfill fires on the atmosphere based on landfill fire data in Poland from 2018. HYSPLIT simulations were performed to assess the spatial impact of the particulate matter (PM) <10 μm (PM10) emitted during each fire in regions with elevated concentrations of PM10. Additionally, for each fire, the population exposed to an increased PM10 concentration due to the landfill fire was determined. Three parameters, namely the area and range of the PM concentrations and the population affected, were calculated for each additional concentration level and analyzed using geodetic information software. The analysis of these three parameters shows that despite being correlated for concentrations of 10 and 1 μg m−3, there are no equations that can eliminate any of the three parameters, and all of them are required for the proper assessment of landfill fire impacts on air quality. Choosing the arbitrary reference concentration levels in the assessment shows that our method is adaptable for any law, health regulation, or recommendation.

Connecting Claims and Outcomes: Applying Accessibility Criteria to Alternate Assessments

The study’s purpose was to evaluate how accessibility is forwarded through technical test specification and how specifications are influenced by policy guidance. Although universal design (UD) is frequently identified as a guiding principle in test development, Johnson, Trantham, and Usher-Tate (2019) found many assessment programs neither realize these promises, nor ensure the necessary steps for optimal accessibility. We reviewed assessment development approaches and features in light of UD principles by conducting a qualitative review of relationships between UD elements and Peer Review Critical Elements (2018), and the relationships between UD elements and “Criteria for Procuring Evaluating High-Quality Assessments (CCSSO, 2014) using expert judgment (Patton, 2002). Results illustrated where raters identified UD elements within policy guidance and showed a concentration of references to UD in test development processes, consistent with findings from previous studies (Davidson, 2019). Results suggest the limited definition of fairness and a view that accessibility is only a consideration at the item level may contribute to the lack of connection to these UD elements in Peer Review guidance.

Development of updated RfD and RfC values for medium carbon range aromatic and aliphatic total petroleum hydrocarbon fractions

ABSTRACT Using total petroleum hydrocarbon (TPH) measurements as a tool for assessing potential human health risks associated with exposures to petroleum products in the environment poses unique challenges, as TPH represents highly variable and complex mixtures containing hundreds of individual chemicals with wide-ranging chemical and physical properties. Current risk assessment practice generally involves analysis of environmental samples for various TPH fractions and summation of risk across those fractions. The United States Environmental Protection Agency (USEPA) derived provisional toxicity criteria for low, medium, and high carbon range aromatic and aliphatic hydrocarbon fractions over a decade ago. These criteria have been used, in whole or in part, to derive risk-based cleanup levels for TPH contamination in soil and groundwater. Herein, we evaluate and update oral and inhalation toxicity criteria for two of these fractions – medium carbon range aromatics and aliphatics – using, where applicable, newer data, updated modeling techniques, and new/alternative analyses of certain endpoints, human relevance, and uncertainty. The results of the analyses support an ~10-fold increase in the USEPA provisional reference concentration (p-RfC) values from 0.1 mg/m3 to 1 mg/m3 for both medium carbon range aromatics (different uncertainty factor) and aliphatics (new study and different judgment of toxicity data from existing study). Compared to the USEPA provisional oral reference dose (p-RfD) values for the medium carbon range aromatics and aliphatics of 0.03 mg/kg-day and 0.01 mg/kg-day, respectively, the present analyses suggest the RfD for medium carbon range aromatics could be increased >6.6-fold to 0.2 mg/kg-day (updated modeling and different uncertainty factors), and the RfD for medium carbon range aliphatics could be increased ~20-fold to 0.2 mg/kg-day (new study). These updated toxicity criteria could be used by regulatory agencies to reevaluate risk-based screening levels or by risk managers to support cleanup levels for medium carbon range aromatics and aliphatics, while still ensuring adequate health protection. Implications: Petroleum products represent complex mixtures of hydrocarbons broadly comprised of aliphatic compounds (straight-chain, branched-chain, and cyclic alkanes and alkenes) and aromatic compounds such as benzene, alkylbenzenes, and polycyclic aromatic hydrocarbons. The complex nature of petroleum products presents challenges for assessing potential health risks associated with exposure to petroleum hydrocarbon contamination in the environment. It has been over ten years since the U.S. Environmental Protection Agency derived provisional toxicity criteria for low, medium, and high carbon range aromatic and aliphatic hydrocarbon fractions. In that time, risk assessment guidance and tools have evolved, and new studies have been published. Our analyses indicate that current provisional toxicity criteria for medium carbon range aromatics and aliphatics fractions are overly conservative by approximately an order of magnitude.

Environmental Impact on Soil and Water Because of Mining Activities in the Eastern Part of Jiu Valley

Abstract Analysing environmental impacts of mining activities involves detailed studies of the interactions between technological activities/operations carried out in a mining operation and environmental components affected by them. In order to carry out a more complex environmental impact assessment caused by mining in the eastern part of Jiu Valley on soil and water 4 mining units have been considered in the study, these being mining unit Lonea, Petrila, and Livezeni with their belonging dumps. Main objective of this research is to analyse the impact caused by mining activities in Eastern part of Jiu Valley by the method of impact networks according to the model “causes - pressures, depreciation of the quality of environmental factors – affected parameters - impact”. Thus, impacts caused by the mining industry were identified based on the top-down typology, being shaped impact networks for underground coal exploitation and sterile material storage on the surface. The metal content of the dumps was also analysed in order to assess the degree of metals soil enrichment compared to the reference concentration of a blank sample. The analysis of the influence of the local rainfall regime aims to highlight the leaching potential of heavy metals in the body of the dump and the possibility of analysing the scenarios of extension of the pollution phenomenon to the saturated area. The study is addressed to researchers, environmental engineers, hydrogeologists and geologists who want to deepen the study of transfer mechanisms of contaminants from dumps to watercourses receiving areas and their dispersion in unsaturated and saturated areas.

Gaseous air pollutants and hospitalizations for mental disorders in 17 Chinese cities: Association, morbidity burden and economic costs

The short-term morbidity effects of gaseous air pollutants on mental disorders (MDs), and the corresponding morbidity and economic burdens have not been well studied. We aimed to explore the associations of ambient sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO) with MDs hospitalizations in 17 Chinese cities during 2015–2018, and estimate the attributable risk and economic costs of MDs hospitalizations associated with gaseous pollutants. City-specific relationships between gaseous pollutants and MDs hospitalizations were evaluated using over-dispersed generalized additive models, then combined to obtain the pooled effect. Concentration-response (C-R) curves of gaseous pollutants with MDs from each city were pooled to allow regional estimates to be derived. The morbidity and economic burdens of MDs hospitalizations attributable to gaseous pollutants were further assessed. A total of 171,939 MDs hospitalizations were included. We observed insignificant association of O3 with MDs. An interquartile range increase in SO2 at lag0 (9.1 μg/m³), NO2 at lag0 (16.7 μg/m³) and CO at lag2 (0.4 mg/m³) corresponded to a 3.02% (95%CI: 0.72%, 5.38%), 5.03% (95%CI: 1.84%, 8.32%) and 2.18% (95%CI: 0.40%, 4.00%) increase in daily MDs hospitalizations, respectively. These effects were modified by sex, season and cause-specific MDs. The C-R curves of SO2 and NO2 with MDs indicated nonlinearity and the slops were steeper at lower concentrations. Overall, using current standards as reference concentrations, 0.27% (95%CI: 0.07%, 0.48%) and 0.06% (95%CI: 0.02%, 0.10%) of MDs hospitalizations could be attributable to extra SO2 and NO2 exposures, and the corresponding economic costs accounted for 0.34% (95%CI: 0.08%, 0.60%) and 0.07% (95%CI: 0.03%, 0.11%) of hospitalization expenses, respectively. Moreover, using threshold values detected from C-R curves as reference concentrations, the above mentioned morbidity and economic burdens increased a lot. These findings suggest more strict emission control regulations are needed to protect mental health from gaseous pollutants.

Comparative sensitivity of children and adults to neurological effects of inhaled manganese

BACKGROUND AND AIM: Manganese (Mn) is an essential nutrient but a neurotoxicant at elevated concentrations. Inhalation exposure can bypass homeostatic regulations and enter the brain. The U.S. EPA’s 1993 inhalation reference concentration and ATSDR’s 2011 minimal risk level are based on neurological outcomes in adults. To understand whether more recent data could provide information on potential lifestage-based variations in susceptibility, we compared sensitivities to neurotoxicity in children and adults using Mn biomarker data. METHODS: We developed a literature search strategy and a Population, Exposures, Comparators, and Outcomes statement. The search covered 2011-2020, with supplemental backwards reference searching. Screening was performed using SWIFT and DistillerSR. Paired studies were identified based on concordant Mn source, biomarker, and outcome. Comparisons were made based on slope of the observed dose-response (children:adults). RESULTS:We identified five studies evaluating seven pairings of hair Mn and neurological outcomes in child and adult populations with environmental Mn inhalation exposure. Two Brazilian studies of children (ages 6-12) and one of adults reported effects on IQ; effects in both comparisons were stronger in children (203% and 121%). A paired study of children and adults in Ohio reported effects on five metrics of postural sway; children exhibited both stronger and weaker effects compared to adults (175% to 69%). CONCLUSIONS:Preliminary results from a small database of well-matched studies suggest that variability in neurological effects by lifestage is less than 10-fold. This conclusion should be interpreted with caution, given the limited available paired studies. Future work will consider the impact of study quality on these conclusions. Additional studies on Mn-exposed children with direct measurement of air concentrations would provide further understanding of the toxicity of inhaled Mn among susceptible lifestages. *The views expressed in this abstract are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency. KEYWORDS: Children's environmental health, Heavy metals, Risk assessment, Neurodevelopmental outcomes

Effects of Brownian motions and thermophoresis diffusions on the hematocrit and LDL concentration/diameter of pulsatile non-Newtonian blood in abdominal aortic aneurysm

LDL concentration is believed to be responsible for plaque formation that leads to atherosclerotic cardiovascular disease. We conducted this study to investigate the effects of hematocrits and LDL diameters on LDL concentration on the wall of an abdominal aortic aneurysm (AAA). The blood flow was considered to be a pulsatile and non-Newtonian flow whose viscosity was a function of hematocrits and strain rate. Lumen, Brownian, and thermophoresis diffusions were analyzed in LDL concentration. The results demonstrated that adding thermophoresis diffusion increases LDL concentration. Moreover, among three types of LDLs, including small LDLs, intermediate LDLs, and large LDLs, small LDLs were the ones with the highest concentration at the wall of the aneurysm. Furthermore, the effects of vorticity on diffusions were examined; it could be noted that the maximum Brownian diffusion appeared in vorticity places. Our results indicated that Brownian diffusion declines as hematocrit reaches 45% whereas thermophoresis diffusion increases. The current simulation investigated the effects of hematocrits, vorticity, Brownian, and thermophoresis diffusions on LDL concentration on the wall. Three types of LDL were taken into account for investigation of the effects of the diameter and reference concentration on LDL concentration. The outcomes of this study could be summarized as the following: the maximum amount of the wall shear stress appeared at 0.2T and at the upstream end of the AAA; moreover, thermophoresis diffusion increased small LDL concentration by 26% on the wall for hematocrit 45%.

Toxicological assessment method for evaluating the occupational risk of dynamic olfactometry assessors

The paper aims to propose a new method to evaluate the occupational exposure risk for examiners involved in dynamic olfactometry. Indeed, examiners are possibly exposed to hazardous pollutants potentially present in odorous samples. A standardized method to evaluate the examiners' occupational safety is not yet available and the existing models present some critical aspect if applied to real odorous samples (no uniform reference concentrations applied and presence of compounds for which no toxicity threshold is available). A deepening of assessment procedure to evaluate the occupation exposure risk for olfactometric assessors is necessary. This paper proposes a standardized approach for risk assessment in dynamic olfactometry. The proposed approach allows the quantification synthetic and conservative risk indices. In this model, the use of the hazard index for the odorous mixture was proposed to assess the non-carcinogenic risk; the calculation of the inhalation risk was applied to estimate the carcinogenic risk. Different databases can be used to retrieve proper occupational exposure limits, according to the proposed hierarchical basis. These implementations allow obtaining the complete characterization of real samples which can be used to calculate the minimum dilution factor for protecting the panellists’ health.

Co-exposure to manganese and lead and pediatric neurocognition in East Liverpool, Ohio

Exposure to metal mixtures may lead to health impacts greater than the effects associated with singular exposures. Two common childhood environmental exposures, manganese (Mn) and lead (Pb), are associated with similar adverse neurodevelopmental effects; however, the effects surrounding concurrent exposure to both metals remain unclear. We study the impact of joint exposure to Mn and Pb on cognitive performance in school-aged children participating in the Communities Actively Researching Exposure Study (CARES) based in East Liverpool, Ohio. Blood Pb levels were measured for each child (geometric mean (GM) = 1.13 μg/dL, range 0.30 μg/dL – 6.64 μg/dL). Mn was measured in participant blood, hair, and toenails with GMs of 10.1 μg/L, 360 ng/g, 0.974 μg/g, respectively. Trained team members administered the Wechsler Intelligence Scale for Children-IV (WISC-IV) to assess intelligence quotient (IQ). The WISC-IV provides scores for Full Scale IQ, Perceptual Reasoning, Processing Speed, Working Memory, and Verbal Comprehension. Interactions between blood Pb and all Mn biomarkers were tested in linear models adjusted for child sex, household income, and serum cotinine. Separate regression models were run for each of the Mn biomarkers. The cohort was comprised of 106 children with a mean age of 8.4 years. Interactions between blood Pb and hair Mn were significant (p < 0.05) for four out of the five IQ domains. The effect of blood Pb on IQ was more pronounced at higher levels of hair and toenail Mn. No significant associations were observed when characterizing the main effect of Mn using blood. Uncovering the health impacts associated with exposure mixtures is critical to understanding the impact of real-life conditions. Our findings suggest that joint exposure to Mn and Pb may produce heightened neurocognitive impacts even at blood Pb levels below the CDC reference concentration of 5 μg/dL.

Ideal versus Nonideal Transport of PFAS in Unsaturated Porous Media

Per- and poly-fluoroalkyl substances (PFAS) adsorb at air-water interfaces during transport in unsaturated porous media. This can cause surfactant-induced flow and enhanced retention that is a function of concentration, which complicates characterization and modeling of PFAS transport under unsaturated conditions. The influence of surfactant-induced flow and nonlinear air-water interfacial adsorption (AWIA) on PFAS transport was investigated with a series of miscible-displacement transport experiments conducted with a several-log range in input concentrations. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and ammonium perfluoro 2-methyl-3-oxahexanoate (GenX) were used as model PFAS. The results were interpreted in terms of critical reference concentrations associated with PFAS surface activities and their relationship to the relevancy of transport processes such as surfactant-induced flow and nonlinear AWIA for concentration ranges of interest. Analysis of the measured transport behavior of PFAS under unsaturated-flow conditions demonstrated that AWIA was linear when the input concentration was sufficiently below the critical reference concentration. This includes the absence of significant arrival-front self-sharpening and extended elution tailing of the breakthrough curves, as well as the similarity of retardation factors measured for a wide range of input concentrations. Independently-predicted simulations produced with a comprehensive flow and transport model that accounts for transient variably-saturated flow, surfactant-induced flow, nonlinear rate-limited solid-phase sorption, and nonlinear rate-limited AWIA provided excellent predictions of the measured transport. A series of simulations was conducted with the model to test the specific impact of various processes potentially influencing PFOS transport. The simulation results showed that surfactant-induced flow was negligible and that AWIA was effectively linear when the input concentration was sufficiently below the critical reference concentration. PFAS retention associated with AWIA can be considered to be ideal in such cases, thereby supporting the use of simplified mathematical models. Conversely, apparent nonideal transport behavior was observed for experiments conducted with input concentrations similar to or greater than the critical reference concentration.

Health Effects of Naphthalene Exposure: A Systematic Evidence Map and Analysis of Potential Considerations for Dose-Response Evaluation.

Background:Naphthalene is a polycyclic aromatic hydrocarbon that has been associated with health effects, including cancer. As the state of the science on naphthalene toxicity continues to evolve, updated toxicity reference value(s) may be required to support human health risk assessment.Objectives:We present a systematic evidence map of studies that could be used to derive toxicity reference value(s) for naphthalene.Methods:Human and animal health effect studies and physiologically based pharmacokinetic (PBPK) models were identified from a literature search based on populations, exposures, comparators, and outcomes (PECO) criteria. Human and animal studies meeting PECO criteria were refined to a smaller subset considered most informative for deriving chronic reference value(s), which are preferred for assessing risk to the general public. This subset was evaluated for risk of bias and sensitivity, and the suitability of each study for dose–response analysis was qualitatively assessed. Lowest observed adverse effect levels (LOAELs) were extracted and summarized. Other potentially relevant studies (e.g., mechanistic and toxicokinetic studies) were tracked as supplemental information but not evaluated further. Existing reference values for naphthalene are also summarized.Results:We identified 26 epidemiology studies and 16 animal studies that were considered most informative for further analysis. Eleven PBPK models were identified. The available epidemiology studies generally had significant risk of bias and/or sensitivity concerns and were mostly found to have low suitability for dose–response analysis due to the nature of the exposure measurements. The animal studies had fewer risk of bias and sensitivity concerns and were mostly found to be suitable for dose–response analysis.Conclusion:Although both epidemiological and animal studies of naphthalene provide weight of evidence for hazard identification, the available animal studies appear more suitable for reference value derivation. PBPK models and mechanistic and toxicokinetic data can be applied to extrapolate these animal data to humans, considering mode of action and interspecies metabolic differences. https://doi.org/10.1289/EHP7381

Risk assessment of excess mortality attribute to PM_(2.5) exposure in 5 cities in China in 2018

To assess the risk of excess mortality caused by exposure to PM_(2.5) in 5 cities in China. Surveillance data on daily concentration of PM_(2.5), meteorology and death-causes were collected from 2015 to 2018 in Harbin, Xi& apos; an, Nanjing, Chengdu and Guangzhou cities. Generalized additive model(GAM) was used to analyze acute exposure-response coefficients of PM_(2.5) exposure on the mortality. Using daily 24-hour average concentration of PM_(2.5) in 2018 to estimate the exposure levels of the population, with PM_(2.5) 24-hour average concentration limit of the ambient air quality standard(GB 3095-2012) for reference concentration(75 μg/m~3), and applicating the health risk assessment model, the excess deaths attribute to PM_(2.5) exposure in the 5 cities in 2018 was estimated. Attribute to PM_(2.5) exposure, the excess cases of death caused by circulatory system diseases in Harbin and Guangzhou were 35 and 92, the excess cases caused by respiratory diseases in Xi& apos; an was 70, the excess cases of caused by non-accident in Nanjing was 69, and the excess cases caused by non-accidental, respiratory and circulatory diseases in Chengdu were 588, 210 and 134 in 2018. PM_(2.5) exposure could increase the excess mortality risk, which varies among different cities.

Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO)

Threshold serum 25-hydroxyvitamin D [25(OH)D] concentrations for extraskeletal outcomes are uncertain and could differ from recommendations (20-30 ng/mL) for skeletal health. We aimed to identify and validate sex-specific threshold 25(OH)D concentrations for older adults' physical function. Using 5 large prospective, population-based studies-Age, Gene/Environment Susceptibility-Reykjavik (n=4858, Iceland); Health, Aging, and Body Composition (n=2494, United States); Invecchiare in Chianti (n=873, Italy); Osteoporotic Fractures in Men (n=2301, United States); and Study of Osteoporotic Fractures (n=5862, United States)-we assessed 16,388 community-dwelling adults (10,376 women, 6012 men) aged≥65 y. We analyzed 25(OH)D concentrations with the primary outcome (incident slow gait: women <0.8 m/s; men <0.825 m/s) and secondary outcomes (gait speed, incident self-reported mobility, and stair climb impairment) at median 3.0-y follow-up. We identified sex-specific 25(OH)D thresholds that best discriminated incident slow gait using machine learning in training data (2/3 cohort-stratified random sample) and validated using the remaining (validation) data and secondary outcomes. Mean age in the cohorts ranged from 74.4 to 76.5 y in women and from 73.3 to 76.6 y in men. Overall, 1112/6123 women (18.2%) and 494/3937 men (12.5%) experienced incident slow gait, 1098/7011 women (15.7%) and 474/3962 men (12.0%) experienced incident mobility impairment, and 1044/6941 women (15.0%) and 432/3993 men (10.8%) experienced incident stair climb impairment. Slow gait was best discriminated by 25(OH)D<24.0 ng/mL compared with 25(OH)D≥24.0 ng/mL in women (RR: 1.29; 95% CI: 1.10, 1.50) and 25(OH)D<21.0 ng/mL compared with 25(OH)D≥21.0 ng/mL in men (RR: 1.43; 95% CI: 1.01, 2.02). Most associations between 25(OH)D and secondary outcomes were modest; estimates were similar between validation and training datasets. Empirically identified and validated sex-specific threshold 25(OH)D concentrations for physical function for older adults, 24.0 ng/mL for women and 21.0 ng/mL for men, may inform candidate reference concentrations or the design of vitamin D intervention trials.

Physics‐Informed Neural Network Method for Forward and Backward Advection‐Dispersion Equations

AbstractWe propose a discretization‐free approach based on the physics‐informed neural network (PINN) method for solving the coupled advection‐dispersion equation (ADE) and Darcy flow equation with space‐dependent hydraulic conductivity . In this approach, , hydraulic head, and concentration fields are approximated with deep neural networks (DNNs). We assume that K(x) is given by its values on a grid, and we use these values to train the K DNN. The head and concentration DNNs are trained by minimizing the residuals of the flow equation and ADE and using the initial and boundary conditions as additional constraints. The PINN method is applied to one‐ and two‐dimensional forward ADEs, where its performance for various Péclet numbers (Pe) is compared with the analytical and numerical solutions. We find that the PINN method is accurate with errors of less than 1% and outperforms some conventional discretization‐based methods for large Pe. Next, we demonstrate that the PINN method remains accurate for the backward ADEs, with the relative errors in most cases staying under 5% compared to the reference concentration field. Finally, we show that when available, the concentration measurements can be easily incorporated in the PINN method and significantly improve (by more than 50% in the considered cases) the accuracy of the PINN solution of the backward ADE.