Environmental Health Risk Assessment Research Articles

Antagonistic effects of a COX1/2 inhibitor drug in human HepG2 cells exposed to an environmental carcinogen

Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when involving mutagens and carcinogens whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drugs and pollutant of emerging concern and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC50 and ⅕ IC50. While additive effects were found on levels of intracellular reactive oxygen species, antagonistic mixture effects were observed for genotoxicity. B[a]P induced DNA strand breaks, γH2AX activation, and micronuclei formation at ½ IC50 concentrations or lower while DFC only induced low levels of DNA strand breaks. Their mixture caused significantly lower levels of genotoxicity by all three endpoints compared to those expected based on concentration additivity. In addition, antagonistic mixture effects on CYP1 enzyme activity suggested that the observed reduced genotoxicity of B[a]P was due to its reduced metabolic activation as a result of enzymatic inhibition by DFC. Overall, the findings further support the increasing concern that co-exposure to environmental toxicants and their non-additive interactions can be a confounding factor that should not be neglected in environmental and human health risk assessment.

The impact of bioaerosol trajectories on microbial community assembly and physicochemical dynamics in the atmosphere

This study explored the assembly mechanisms and physicochemical dynamics of microbial communities within atmospheric bioaerosols, focusing on the influence of different aerial trajectories. Over two years, samples near Seoul were classified into ‘North’, ‘Southwest’, and ‘Others’ categories based on their aerial trajectories. Physicochemical analysis of the PM2.5 particles revealed distinct ion compositions for each cluster, reflecting diverse environmental influences. Microbial community analysis revealed that shared dominant bacterial phyla were present in all clusters. However, distinct taxonomic profiles and biomarkers were also evident, such as coastal bacteria in the ‘Southwest’ cluster correlating with wind speed, and arid soil-originated bacteria in the ‘North’ cluster correlating with cations. These findings demonstrate that biomarkers in each cluster are representative of the distinct environments associated with their aerial trajectories. Notably, cluster ‘Southwest’ the highest microbial diversity and a strong alignment with the neutral community model, suggesting a large influence of passive dispersal from marine environments. Contrarily, ‘North’ and ‘Others’ were more influenced by niche-dependent factors. This study highlights the complex interplay between environmental factors and microbial dynamics in bioaerosols and provides important insights for environmental monitoring and public health risk assessment.

Characteristic and mechanism of pollution by laser cleaning high-value vehicle parts with a complex structure in remanufacturing industry

Remanufacturing high-value vehicle parts is of substantial significance for the circular economy because it provides a second service life and reduces solid waste generation. Laser cleaning is a promising method in the remanufacturing industry owing to its high energy, precision, and efficiency. However, the pollution caused by laser cleaning remains unknown and has rarely been reported, limiting the application of this method. In this study, pollution removal and conversion using a high-energy laser were explored, and environmental life cycle and health risk assessments were conducted. The results showed that high-energy lasers might induce new organic pollutants, such as olefins, alkynes, and aldehydes. During laser cleaning, thermal elastic expansion and shock wave generation were the main mechanisms of rust removal, and evaporation and small-scope boiling were used for waste oil removal. The mean concentration of PM10 was above 7000 µg/m3 in laser rust removal, and the total concentration of volatile organic compounds (VOCs) was the highest in laser oil removal (∼ 2568 µg/m3). Particulate matter contained high amounts of Fe, Al, and Mn. An environmental life cycle assessment indicated that laser cleaning for stain removal significantly reduced the total environmental impact compared with that of traditional solvent-ultrasonic cleaning (∼ 40.0%) and sandblasting (∼ 83.3%). This study provides an environmental protection basis for increasing the use of laser cleaning in the remanufacturing industry.

Environmental Contamination and Health Risk Assessment of Heavy Metals in the Stream Sediments of Oued Kasseb (Northerwest of Tunisia) in the Vicinity of Abandoned Pb–Zn Mine

Environmental Contamination and Health Risk Assessment of Heavy Metals in the Stream Sediments of Oued Kasseb (Northerwest of Tunisia) in the Vicinity of Abandoned Pb–Zn Mine

High pesticide tolerance of S. mansoni: implications for the risk of schistosomiasis

BackgroundSchistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma. The pathogen is transmitted via freshwater snails. These snails are highly tolerant to agricultural pesticides and indirectly benefit from exposure due to adverse effects on their more sensitive enemy species. Pesticides in surface waters may thus increase the risk of schistosomiasis transmission unless they also affect the pathogen. We tested the tolerance of the free-swimming life stages (miracidia and cercariae) of Schistosoma mansoni to the insecticides diazinon and imidacloprid. We also investigated whether these pesticides decrease the ability of miracidia to infect and further develop as sporocysts within the host snail Biomphalaria pfeifferi.ResultsExposure to imidacloprid for 6 and 12 h immobilized 50% of miracidia at 150 and 16 µg/L, respectively (nominal EC50); 50% of cercariae were immobilized at 403 and 284 µg/L. Diazinon immobilized 50% of miracidia at 51 and 21 µg/L after 6 and 12 h; 50% of cercariae were immobilized at 25 and 13 µg/L. The observed insecticide tolerance is lower than those of the host snail B. pfeifferi and comparable to those of other commonly tested freshwater invertebrates. Exposure for up to 6 h decreased the infectivity of miracidia at high sublethal concentrations (48.8 µg imidacloprid/L and 10.5 µg diazinon/L, i.e. 20–33% of EC50), but not at lower concentrations commonly observed in the field (4.88 µg imidacloprid/L and 1.05 µg diazinon/L). The development of sporocysts within the snail host was not affected at any of these test concentrations.ConclusionsInsecticides did not affect the performance of S. mansoni at environmentally relevant concentrations. Particularly within its host snail the pathogen can escape exposure peaks that have been shown to affect other sensitive invertebrates and their biological control of host snails. Our findings suggest that freshwater pollution with agricultural pesticides increases the risk of schistosomiasis; they illustrate the need to integrate an environmental and public health risk assessment and management.

Source apportionment and risk assessment of soil heavy metals in the Huangshui River Basin using a hybrid model

Source apportionment and risk assessment of soil heavy metals (HMs) are essential for pollution control. However, inherent limitations in receptor models hinder accurate source apportionment, impacting outcomes of source-oriented risk assessment. A hybrid model was employed by combining two receptor models, absolute principal component score/multiple linear regression (APCS/MLR) and positive matrix factorization (PMF) models. Four primary pollution sources were identified, followed by an assessment of source-oriented environmental and human health risks in the Huangshui River Basin. Results revealed that Cr, Cd, and Ni average concentrations surpassed their background by 3.1, 2.1, and 1.9 times, respectively. Additionally, 54.29%, 13.34%, and 18.09% of Igeo values for Cr, Cd, and Ni were classified as “moderately contamination” or higher. Natural sources significantly influence Cu (90.2%) and As (71.4%). Cr (63.4%) and Ni (77.9%) mainly originated from agriculture and industry, respectively. Transportation sources emerged as the primary contributors to Pb (59.6%), Zn (48.6%), and Cd (47.2%). The environmental risk level in this study area remained acceptable. Ecological risk was mainly attributed to industrial activities (46.6%) and transportation (37.6%), with Cd being the predominant metal responsible for this risk. Although the noncarcinogenic risk was negligible for all populations, the carcinogenic risk demands attention, particularly concerning children. Industrial sources (67.0%) and Ni were identified as the main contributors to the carcinogenic risk. This study represents an attempt to develop a hybrid model, providing an effective approach to combine models for the accurate apportionment of pollution sources and the reduction of risks.

Spatiotemporal patterns of surface ozone exposure inequality in China.

Rising surface ozone (O3) levels in China are increasingly emphasizing the potential threats to public health, ecological balance, and economic sustainability. Using a 1km × 1km dataset of O3 concentrations, this research employs subpopulation demographic data combined with a population-weighted quality model. Its aim is to evaluate quantitatively the differences in O3 exposure among various subpopulations within China, both at a provincial and urban cluster level. Additionally, an exposure disparity indicator was devised to establish unambiguous exposure risks among significant urban agglomerations at varying O3 concentration levels. The findings reveal that as of 2018, the population-weighted average concentration of O3 for all subgroups has experienced a significant uptick, surpassing the average O3 concentration (118μg/m3). Notably, the middle-aged demographic exhibited the highest O3 exposure level at 135.7μg/m3, which is significantly elevated compared to other age brackets. Concurrently, there exists a prominent positive correlation between educational attainment and O3 exposure levels, with the medium-income bracket showing the greatest susceptibility to O3 exposure risks. From an industrial vantage point, the secondary sector demographic is the most adversely impacted by O3 exposure. In terms of urban-rural structure, urban groups in all regions had higher levels of exposure to O3 than rural areas, with North and East China having the most significant levels of exposure. These findings not only emphasize the intricate interplay between public health and environmental justice but further highlight the indispensability of segmented subgroup strategies in environmental health risk assessment. Moreover, this research furnishes invaluable scientific groundwork for crafting targeted public health interventions and sustainable air quality management policies.

Estimation of pan-European, daily total, fine-mode and coarse-mode Aerosol Optical Depth at 0.1° resolution to facilitate air quality assessments

Aerosol Optical Depth (AOD) data derived from satellites is crucial for estimating spatially-resolved PM concentrations, but existing AOD data over land remain affected by several limitations (e.g., data gaps, coarser resolution, higher uncertainty or lack of size fraction data), which weakens the AOD-PM relationship. We developed a 0.1° resolution daily AOD data set over Europe over the period 2003–2020, based on two-stage Quantile Machine Learning (QML) frameworks. Our approach first fills gaps in satellite AOD data and then constructs three components' models to obtain reliable full-coverage AOD along with Fine-mode AOD (fAOD) and Coarse-mode AOD (cAOD). These models are based on AERONET (AErosol RObotic NETwork) observations, Gap-filled satellite AOD, climate and atmospheric composition reanalyses. Our QML AOD products exhibit better quality with an out-of-sample R2 equal to 0.68 for AOD, 0.66 for fAOD and 0.65 for cAOD, which is 23–92 %, 11–13 % and 115–132 % higher than the corresponding satellite or reanalysis products, respectively. Over 91.6 %, 81.6 %, and 88.9 % of QML AOD, fAOD and cAOD predictions fall within ±20 % Expected Error (EE) envelopes, respectively. Previous studies reported that a weak satellite AOD-PM correlation across Europe (Pearson correlation coefficient (PCC) around 0.1). Our QML products exhibit higher correlations with ground-level PMs, particularly when broadly matched by size: AOD with PM10, fAOD with PM2.5, cAOD with PM coarse (R = 0.41, 0.45 and 0.26, respectively). Different AOD fractions more effectively distinct PM size fractions, than total AOD. Our QML aerosol dataset and models pioneer full-coverage, daily high-resolution monitoring of fine-mode and coarse-mode aerosols, effectively addressing existing AOD challenges for further PMs exposures' estimations. This dataset opens avenues for more in-depth exploration of the impacts of aerosols on human health, climate, visibility, and biogeochemical processes, offering valuable insights for air quality management and environmental health risk assessment.

Special Issue on “Heavy Metal Toxicity: Environmental and Human Health Risk Assessment”

Exposure to toxic metals is a well-known problem in industrialized countries [...]

Regulation of BTB (POZ) Structural Domain 6b by MicroRNA-222b in Zebrafish Embryos after Exposure to Di(2-ethylhexyl)phthalate at Low Concentrations.

Di-(2-ethylhexyl) phthalate (DEHP) is a sort of endocrine disruptor that induces abnormal physiological and biochemical activities such as epigenetic alterations, apoptosis, and oxidative stress. MicroRNAs (miRNAs) are a class of short noncoding RNAs that may regulate the expression of many protein-coding genes when organisms are exposed to environmental chemicals. miR-222b is a differentially expressed miRNA after DEHP exposure. miRNA-mRNA prediction suggested that BTB (POZ) structural domain 6b (BTBD6B) might be a target mRNA of miR-222b, and DEHP exposure altered its expression. However, the correlation between miR-222b and BTBD6B has not been experimentally confirmed. The aim of this study was to investigate the regulation of BTBD6B by miR-222b in zebrafish embryos under the effect of low concentration of DEHP. Dual fluorescent protein assays and dual luciferase reporter gene assays confirmed the interaction between miR-222b and the 3'-untranslated region (3'-UTR) of BTBD6B. Ectopic expression assays showed that miR-222b could negatively regulate BTBD6B in ZF4 cells. However, the relative expression of miR-222b and BTBD6B was significantly higher at both transcriptional and post-transcriptional levels in zebrafish embryos exposed to low concentrations of DEHP. The results of this study improved our understanding of the molecular mechanism of DEHP exposure toxicity. It identified that the aberrant expression of miR-222b/BTBD6B may be one of the mechanisms of DEHP toxicity, which can provide a theoretical reference and scientific basis for environmental management and biological health risk assessment.

Spatial distribution, related environmental factors and health risk assessment of microcystins in Lake Qilu, a eutrophic plateau lake

Spatial distribution, related environmental factors and health risk assessment of microcystins in Lake Qilu, a eutrophic plateau lake

Environmental Health Risk Analysis of Mercury (Hg) Heavy Metal Exposure (Study on People Consuming Milkfish Around Konawe Industrial Area)

Background: Industrial activities of mining material processing have the potential to cause water pollution. Activities in the Konawe Industrial Estate also require a Steam Power Plant, which has the potential to produce mercury metal (Hg) sourced from coal as raw material. This study aims to analyse the environmental health risks of Hg heavy metal exposure in people who consume milkfish from the Konawe Regency industrial area.
 Methods: This type of research is quantitative research with Field Research and Laboratory Research methods. The population in this study consisted of 2 subjects, namely people living in the Konawe Industrial Estate area and milkfish specimens. Community samples totaled 97 people and specimen samples were taken at 4 pond locations. Data analysis using Environmental Health Risk Assessment (ERA).
 Results: The results of the study obtained the average concentration of mercury heavy metal (Hg) in milkfish was 0.003 mg / kg, the large intake of respondents in consuming milkfish for mercury heavy metal (Hg) was 0.00891 mg / kg / day, and the level of risk of respondents and pollution based on the RQ calculation value was still < 1 .
 Conclusion: People who consume milkfish from the Konawe Industrial Estate do not have a risk of health problems for now and in the next 30 years. Risk management to prevent the emergence of risks is to maintain the rate of intake and frequency of exposure.

Environmental health risk assessment of urban water sources based on fuzzy set theory

Abstract Water pollution and protection of water resources have become an urgent task for humanity today and are also important components of environmental risk assessment. In response to the problems of high risk level and low risk credibility in the current environmental health risk assessment of urban water sources, this article aims to use fuzzy set theory to comprehensively evaluate the environmental quality and quickly monitor the safety of urban water sources. Therefore, this article analyzed the health factors of the urban water source environment and then studied the content and uncertainty analysis of health risk assessment. Finally, it constructed a health risk assessment system and proposed corresponding water environment protection strategies. In the experimental section, the risk level and risk credibility of the water environment were analyzed. Through comparison, it was found that the risk level in the new water environment health risk assessment was 0.16 lower than that in the traditional water environment health risk assessment, and the risk credibility was 0.11 higher than that in the traditional water environment health risk assessment. The water quality monitoring effect in the new water environment health risk assessment was 7.3% higher than that in the traditional water environment health risk assessment, The health hazard effect is 8.2% lower than traditional water environment health risk assessment. In summary, water environment health risk assessment plays an important role in protecting the water source environment. Health risk assessment of the water environment helps to reduce water pollution, improve water quality, and ultimately improve human health. Moreover, using fuzzy set theory makes it easier to comprehensively and efficiently evaluate the water environment. The innovation of this article lies in paying attention to the importance of fuzzy set theory in water pollution risk assessment and applying fuzzy technology to water pollution control strategies, to better improve water quality and optimize water source environmental health risk assessment methods.

Evaluation Of Drainage Canal Mitigation In Banjarmasin City Post Hydrometeorological Disaster

Data from the Environmental Health Risk Assessment (EHRA) study in 2012 stated that 52% of inundation in Banjarmasin City was caused by a problematic drainage system, the causes of which included siltation of the canals and the large number of weeds growing around the drainage canals, which would interfere with the function of the drainage canals. The data used are road canal cross-sectional dimensions, topographical data, canal alignment data, and land use data in North Banjarmasin Sub District. The calculation analysis method uses the Mononobe method. The results of these calculations will later be used for modeling which are indicated to exceed the water capacity, of course also by adding topographical parameters, land use, and canal alignment. Meanwhile, the planned discharge data from the results of the calculated rainfall and the measuring data of the channel cross-sectional dimensions are used for detailed modeling of the channel cross-section using HecRas. The condition of drainage channels is over-capacity, influenced by the presence of several channels covered with bushes and concrete, the amount of sediment that has not been dredged, the absence of an adequate catchment area system due to the characteristics of the soil in the form of peat soil.

Environmental cadmium pollution and health risk assessment in rice-wheat rotation area around a smelter.

Cadmium (Cd) pollution induced by smelting process is of great concern worldwide. However, the comprehensive risk assessment of Cd exposures in smelting areas with farming coexist is lacking. In this study, atmospheric deposition, soil, surface and drinking water, rice, wheat, vegetable, fish, pork, and human hair samples were collected in rice-wheat rotation area near nonferrous smelter to investigate smelting effect on environmental Cd pollution and human health. Results showed high Cd deposition (0.88-2.61mgm-2year-1) combined with high bioavailability (37-42% totality) in study area. Moreover, 90%, 83%, 57%, and 3% of sampled soil, wheat, rice, and vegetable of Cd were higher than national allowable limits of China, respectively, indicating smelting induced serious environmental Cd pollution. Especially, higher Cd accumulation occurred in wheat compared to rice by factors of 1.5-2.0. However, as for Cd exposure to local residents, due to rice as staple food, rice intake ranked as main route and accounted for 49-53% of total intake, followed by wheat and vegetable. Cd exposure showed high potential noncarcinogenic risks with hazard quotient (HQ) of 0.63-4.99 using Monte Carlo probabilistic simulation, mainly from crop food consumption (mean 94% totality). Further, residents' hair Cd was significant correlated with HQ of wheat and rice ingestion, highlighting negative impact of cereal pollution to resident health. Therefore, smelting process should not coexist with cereal cultivating.

Metabolic network and proteomic expression perturbed by cyclosporine A to model microbe Escherichia coli

Cyclosporine A (CsA) is a model drug that has caused great concern due to its widespread use and abuse in the environment. However, the potential harm of CsA to organisms also remains largely unknown, and this issue is exceptionally important for the health risk assessment of antibiotics. To address this concern, the crosstalk between CsA stress and cellular metabolism at the proteomic level in Escherichia coli was investigated and dissected in this study. The results showed that CsA inhibited E. coli growth in a time-dependent manner. CsA induced reactive oxygen species (ROS) overproduction in a dose- and time-dependent manner, leading to membrane depolarization followed by cell apoptosis. In addition, translation, the citric acid cycle, amino acid biosynthesis, glycolysis and responses to oxidative stress and heat were the central metabolic pathways induced by CsA stress. The upregulated proteins, including PotD, PotF and PotG, controlled cell growth. The downregulated proteins, including SspA, SspB, CstA and DpS, were regulators of self-feedback during the starvation process. And the up- and downregulated proteins, including AtpD, Adk, GroS, GroL and DnaK, controlled energy production. These results provide an important reference for the environmental health risk assessment of CsA.

Environmental pollution status and health risk assessment of selective heavy metal(oid)s in Iran's agricultural soils: A review

The assessment of heavy metal(oid) concentrations in agricultural soil holds significant importance due to its impact on crop safety and quality, as well as the potential risks it poses to human health. This review utilized secondary online published data to evaluate the contamination levels of seven HMs (As, Cd, Cu, Cr, Ni, Pb, and Zn) in Iranian farmland soils. As a result, 31 research papers were collected to compile a dataset offering a comprehensive analysis of HM concentrations, distribution, sources, ecological risks, and potential health risks. The findings indicated that mean concentrations of Ni and Cd exceeded their corresponding permissible levels in farmland soils, while other HMs remained below this threshold. The mean Igeo (geoaccumulation index) values followed the sequence Ni > As > Cu > Cr > Zn > Pb > Cd, with Igeo values suggesting low to slight enrichment for the studied HMs. Pollution index (PI) results revealed notable contamination of As in various provinces, including Kurdistan, Hamedan, Tehran, Mazandaran, West Azerbaijan, Kermanshah, Hormozgan, Golestan, and the Kamfiruz region of Fars. Elevated contamination of Pb and Cd was observed in Fars (Shiraz region), and Cr and Ni in the Sabzevar area farmland soils. As, Cd, and Cu exhibited higher ecological risks (EI) compared to Zn, Cr, Ni, and Pb. The potential ecological risks (PER) ranged from 9.9 to 244.6, indicating low to moderate risk levels. Non-carcinogenic assessments indicated that ingestion was the primary exposure pathway to HMs in Iranian farmland soils, followed by inhalation and dermal contact. Total hazard index (HI) values for studied HMs did not exceed 1, indicating no significant non-carcinogenic risk for both population age groups. This study highlights the current lack of well-documented scientific reports on the status of HMs in agricultural farmland soils across 12 other provinces in Iran, emphasizing the need for further investigation. Moreover, the bioavailability of HMs in agricultural soils significantly influences HM content in crops, underscoring the need for future research to ascertain HM concentrations in different soil fractions.

Environmental health risk assessment and source apportion of heavy metals using chemometrics and pollution indices in the upper Yamuna river basin, India

River Yamuna is the largest tributary of the Ganges with great economic importance, and provides water for about 57 million people and accounts for more than 70% of Delhi's water supply. Various pollution indices and chemometric methods were used to investigate heavy metal pollution, associated risks, and probable sources in the upper Yamuna river water. A total of 56 river water samples, 28 each in pre and post-monsoon season were collected and analysed for 15 heavy metals. The findings reveal that Al (38.66 ± 21.14 μg/L), As (16.52 ± 15.81 μg/L), and Mn (41.06 ± 89.25 μg/L) in pre-monsoon and Al (45.77 ± 29.46 μg/L), As (10.30 ± 12.15 μg/L), Fe (48.03 ± 81.11 μg/L), and Mn (31.02 ± 70.13 μg/L) in post-monsoon exceeded the Bureau of Indian Standards (BIS) acceptable limits. The pollution indices (HPI, NPI, HEI, and Cd) indicate that most locations are low to moderately polluted, except for the lower catchment. Health indices, i.e., hazard Index (HI) and incremental lifetime cancer risk (ILCR), suggest that the prolonged consumption of river water may cause potential human health hazards. In contrast, the water is suitable for domestic and other uses as the dermal risk is less prominent. The ecological risk index (ERI) of pre (0.22–58.75) and post-monsoon (0.12–44.21) were in the low-risk category (<110), indicating no ecological risk associated with heavy metals. In pre and post-monsoon, four principal components (PCs) described 73.97% and 76.18% of the total variance respectively, suggesting the mixed impact of numerous geogenic and anthropogenic sources in the region's water chemistry. Cluster analysis demonstrates that the lower catchment samples (National Capital Region, Delhi) significantly vary from each other due to wastewater discharge, industrialisation, and rapid urbanization, while the upper and mid-catchment samples are less distinct. Hence, more than 90% of the Yamuna water is extracted from the upper region; present findings may aid in developing an effective catchment scale management strategy.

Per- and polyfluoroalkyl substances and cardiometabolic diseases: A review.

Per- and polyfluoroalkyl substances (PFAS) are a group of persistent and widespread environmental pollutants that represent a high concern for human health. They have been shown to be associated with several important physiological processes such as lipid metabolism and the immune system. Consequently, PFAS are suspected to play a role in cardiometabolic disease development. However, the evidence regarding associations between PFAS and overt cardiovascular disease and type 2 diabetes remains limited and inconsistent. To address this, we conducted a review of the epidemiological evidence. A deeper understanding of potential underlying molecular mechanisms may help to explain inconsistencies in epidemiological findings. Thus, to gain more mechanistic insight, we also summarized evidence from omics and laboratory studies into an adverse outcome pathway framework. Our observations indicate the potential for associations of PFAS with multiple molecular pathways that could have opposite associations with disease risk, which could be further modified by mixture composition, lifestyle factors or genetic polymorphisms. This identifies the need for exposome studies considering mixture effects, the use of multi-omics data to gain insight in relevant pathways and the integration of epidemiological and laboratory studies to enhance mechanistic understanding and causal inference. Improved comprehension is essential for environmental health risk assessments.

Quantitative relationships of FAM50B and PTCHD3 methylation with reduced intelligence quotients in school aged children exposed to lead: Evidence from epidemiological and in vitro studies

At present, the application of DNA methylation (DNAm) biomarkers in environmental health risk assessment (EHRA) is more challenging due to the unclearly quantitative relationship between them. We aimed to explore the role of FAM50B and PTCHD3 at the level of signaling pathways, and establish the quantitative relationship between them and children's intelligence quotients (IQs). DNAm of target regions was measured in multiple cell models and was compared with the human population data. Then the dose-response relationships of lead exposure with neurotoxicity and DNAm were established by benchmark dose (BMD) model, followed by potential signaling pathway screening. Results showed that there was a quantitative linear relationship between children's IQs and FAM50B/PTCHD3 DNAm (DNAm between 51.40 % - 78.78 % and 31.41 % - 74.19 % for FAM50B and PTCHD3, respectively), and this relationship was more significant when children's IQs > 90. The receiver operating characteristic (ROC) and calibration curves showed that FAM50B/PTCHD3 DNAm had a satisfying accuracy and consistency in predicting children's IQs, which was confirmed by sensitivity analysis of gender and CpG site grouping data. In cell experiments, there was also a quantitative linear relationship between FAM50B DNAm and reactive oxygen species (ROS) production, which was mediated by PI3K-AKT signaling pathway. In addition, the lead BMD of ROS was close to that of FAM50B DNAm, suggesting that FAM50B DNAm was a suitable biomarker for the risk assessments of adverse outcomes induced by lead. Taken collectively, these results suggest that FAM50B/PTCHD3 can be applied to EHRA and the prevention/intervention of adverse effects of lead on children's IQs.