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In the present study, we isolated linalool, geraniol, carvacrol, thymol, menthol and eugenol; synthesised their phenoxyacetic acid derivatives; and assessed their phytotoxic and genotoxic potentials against weeds and agricultural crops. Moreover, the fungicidal activity of both categories of compounds against 12 fungi was examined. Finally, using probabilistic assessment based on Risk Quotient (RQ) by the Monte Carlo simulation (MCS) method, we examined human health risks via oral exposure to these compounds. Toxic potencies to plants demonstrated that all parameters and related indices including germination percentage, mean germination time, germination rate, root length, shoot length, seedling length and vigour index dose-dependently decreased in both weeds and agricultural crops. Based on the comet assay, DNA damage was observed in the root meristems of the plants. Consequently, a significant decrease was observed in head DNA, whereas a significant increase in tail DNA was observed in response to treatments. Besides, the natural components and semisynthetic molecules showed a broad spectrum of fungicidal traits. However, eugenol and eugenoxyacetic acid inhibitory effects on the growth of the tested fungi were similar to that of benomyl. Our probabilistic health risk assessment indicated di minimis risk for natural components and their phenoxyacetic acid derivatives. Sensitivity analysis showed that concentrations of residues of the compounds had the most significant effect on risk. Current findings could offer a platform for developing sustainable approaches to reduce chemical residues and their consequent risks to the environment and human health. [ABSTRACT FROM AUTHOR]

Background: Per- and polyfluoroalkyl substances (PFAS) are commonly utilized in consumer products. While earlier studies have suggested potential impacts of certain PFAS on serum concentrations of vitamin D, these investigations were constrained to a limited set of conventional PFAS. Moreover, they did not specifically focus on populations with longer duration of PFAS exposure and potentially higher blood PFAS levels, such as older adults, and lacked adequate evidence to examine sex-related disparities. Methods: This observational investigation utilized cross-sectional data obtained from the U.S. NHANES spanning the years 2003 to 2018. Survey-weighted multiple regression models were employed to evaluate the relationship between PFAS exposure and vitamin D concentrations. Multi-pollutant models were employed to evaluate the association between PFAS mixtures and vitamin D concentrations. Subsequently, environmental risk scores (ERS) were constructed to gauge associations with vitamin D concentrations. ERS was computed through a weighted linear combination of PFAS, utilizing calculations from ridge regression and adaptive elasticity network (adENET) methodologies. All analyses were stratified by sex. Results: The study encompassed 3,853 older adults. Our analysis revealed a negative association between PFOA, PFOS, PFNA, and MeFOSAA and serum vitamin D concentrations. In analyses examining mixed exposures, various models consistently indicated an inverse association between PFAS mixed exposure and vitamin D concentrations. Moreover, an increase in ERS of PFAS across the interquartile range was associated with a decrease in vitamin D concentrations (Q4 vs. Q1, adENET: β: -0.083, 95% CI: -0.117, -0.048; ridge regression: β: -0.077, 95% CI: -0.111, -0.042). Notably, these associations were exclusively observed within the female population. Conclusions: Our study indicates that heightened exposure to PFAS correlates with diminished serum vitamin D concentrations in females aged 60 years and older, evident in both single and mixed exposures. These findings find support in in vitro mechanistic studies, suggesting that PFAS may impact the metabolism of 25(OH)D, consequently affecting vitamin D concentrations. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl and polyfluoroalkyl(PFAS) substances are the most common environmental pollutants, which has an inconsistent association with hyperuricemia across different populations. This study explored the relationship between hyperuricemia and different gender PFAS and PFAS mixtures, using data from two cycles of the NHANES from 2015-2018. Weighted logistic regression results showed that the correlation between individual PFAS and hyperuricemia was significant only in men. Compared to the reference quartile, the fourth quartile of n-PFOA increased the risk of hyperuricemia in men (OR: 2.79, 95% CI: 1.50, 5.18). The Qgcomp model results showed that each quartile increase in the serum concentration of PFAS mixtures was associated with an increased likelihood of hyperuricemia in the total population, with odds ratios (OR) for men and women being 1.74 (95% CI: 1.26, 2.40), and 2.04 (95% CI: 1.35, 3.16), respectively. we concluded that PFAS might increase the risk of hyperuricemia in adults. [ABSTRACT FROM AUTHOR]

Background: Co-exposure to multiple volatile organic compounds (VOCs) is common in daily life. However, few studies have evaluated the associations between the patterns of simultaneous exposure to multiple VOCs and the risk of hyperuricemia. Methods: This study included 7490 adults from the National Health and Nutrition Examination Survey conducted between 2003 and 2012. The K-means clustering method was applied to cluster eight kinds of VOCs in the blood into various co-exposure patterns, including benzene, bromodichloromethane, chloroform, dibromochloromethane, 1,4-dichlorobenzene, ethylbenzene, methyl tertiary-butyl ether (MTBE), and o-xylene. Binary logistic regression analysis was utilized to assess the association between single VOCs, the co-exposure patterns of multiple VOCs, and the hyperuricemia risk. Restricted cubic spline functions were utilized to investigate the non-linear relationships. Results: Based on eight VOCs, four characteristic co-exposure patterns were generated. Compared with the low-level exposure group, the levels of volatile organic compound (VOC) co-exposure in cluster 2, characterized by relatively high levels of MTBE and moderate levels of bromodichloromethane, chloroform, and dibromochloromethane, were associated with increased hyperuricemia risk, with an odds ratio of 1.32 (1.02, 1.71). Increasing levels of bromodichloromethane and chloroform were significantly associated with an increased risk of hyperuricemia. A strong J-shaped relationship was found between MTBE and hyperuricemia. Conclusions: This study indicated that blood bromodichloromethane and chloroform were positively associated with hyperuricemia risk. Blood MTBE had a J-shaped association with hyperuricemia. In addition, the significant association of the co-exposure patterns of multiple VOCs in the blood with hyperuricemia risk was observed. Changing VOC co-exposure patterns may play a crucial role in the occurrence of hyperuricemia. [ABSTRACT FROM AUTHOR]

ZnO nanoparticles (ZnONPs) and carbon nanotubes (CNTs) are frequently used nanoparticles with unique features. Aquatic organisms are exposed to a combination of contaminants in natural water systems, so the combination effect of two or more nanomaterials has caused much concern. In this study, the toxicity to the liver of common carp was explored under four weeks of exposure to single ZnONPs or in combination with multi-walled CNTs (MWCNTs). The results demonstrated that ZnONPs induced pathological changes and apoptosis in the liver. In combination, decreased pathological changes were observed in the LSC-ZnONPs group (50 mg L-1 ZnONPs and 0.25 mg L-1 MWCNTs) at the microscopic level and ultrastructural level, and increased pathological changes in the HSC-ZnONPs group (50 mg L-1 ZnONPs and 2.5 mg L-1 MWCNTs). A 52% reduction in the percentage of TUNEL-positive nuclei in the LSC-ZnONPs group and a 33% increase in the HSC-ZnONPs group were observed compared to the ZnONPs group. The mRNA expression of apoptosis-related genes, including caspase3, BAX, and XBP1, were significantly up-regulated in the exposure groups, confirming the occurrence of apoptosis. Significantly decreased caspase 3 and BAX mRNA levels in the co-exposure groups were detected compared to the ZnONPs group. Nevertheless, the XBP1 mRNA level was significantly upregulated in the LSC-ZnONPs group, but downregulated in the HSC-ZnONPs group, indicating multiple signal pathways involved in the apoptosis. In conclusion, a low concentration of MWCNTs (0.25 mg L-1) decreased the toxic effect of ZnONPs on common carp, but a high concentration of MWCNTs (2.5 mg L-1) enhanced it. This study will contribute to developing future risk assessment and management strategies for nanomaterials. [ABSTRACT FROM AUTHOR]

Knowledge regarding the combined toxicity mechanism of bisphenol compounds and microplastics (MPs) on organisms remains limited. In this study, we first developed an accurate and sensitive method to simultaneously quantify two bisphenol compounds and evaluate their accumulation and tissue distribution after co-exposure with MPs in zebrafish. Then, we determined the bioaccumulation potential of bisphenol A (BPA) and bisphenol S (BPS) in adult zebrafish in the absence and presence of MPs. Bisphenol compounds were found to accumulate in different tissues of zebrafish, with BPS showing lower accumulation levels compared to BPA. Importantly, we discovered that the presence of MPs could exacerbate the accumulation of bisphenol compounds in biological tissues. These findings highlight the enhanced bioavailability and risk posed by the co-exposure of bisphenol compounds and MPs, underscoring the need for further investigation into their combined environmental and biological health impacts. [ABSTRACT FROM AUTHOR]

Abstract Background Per- and polyfluoroalkyl substances (PFAS) are commonly utilized in consumer products. While earlier studies have suggested potential impacts of certain PFAS on serum concentrations of vitamin D, these investigations were constrained to a limited set of conventional PFAS. Moreover, they did not specifically focus on populations with longer duration of PFAS exposure and potentially higher blood PFAS levels, such as older adults, and lacked adequate evidence to examine sex-related disparities. Methods This observational investigation utilized cross-sectional data obtained from the U.S. NHANES spanning the years 2003 to 2018. Survey-weighted multiple regression models were employed to evaluate the relationship between PFAS exposure and vitamin D concentrations. Multi-pollutant models were employed to evaluate the association between PFAS mixtures and vitamin D concentrations. Subsequently, environmental risk scores (ERS) were constructed to gauge associations with vitamin D concentrations. ERS was computed through a weighted linear combination of PFAS, utilizing calculations from ridge regression and adaptive elasticity network (adENET) methodologies. All analyses were stratified by sex. Results The study encompassed 3,853 older adults. Our analysis revealed a negative association between PFOA, PFOS, PFNA, and MeFOSAA and serum vitamin D concentrations. In analyses examining mixed exposures, various models consistently indicated an inverse association between PFAS mixed exposure and vitamin D concentrations. Moreover, an increase in ERS of PFAS across the interquartile range was associated with a decrease in vitamin D concentrations (Q4 vs. Q1, adENET: β: -0.083, 95% CI: -0.117, -0.048; ridge regression: β: -0.077, 95% CI: -0.111, -0.042). Notably, these associations were exclusively observed within the female population. Conclusions Our study indicates that heightened exposure to PFAS correlates with diminished serum vitamin D concentrations in females aged 60 years and older, evident in both single and mixed exposures. These findings find support in in vitro mechanistic studies, suggesting that PFAS may impact the metabolism of 25(OH)D, consequently affecting vitamin D concentrations.

Abstract Background Previous studies have shown significant associations between individual fat-soluble vitamins (FSVs) and metabolic syndromes (MetS). However, evidence on the multiple FSVs co-exposure and MetS odds is limited. Given that individuals are typically exposed to different levels of FSVs simultaneously, and FSVs can interact with each other. It’s necessary to explore the association between multiple FSVs co-exposure and MetS odds. This study aims to address this gap in general U.S. adults aged ≥ 20 years. Methods We conducted a cross-sectional study utilizing data from the National Health and Nutrition Examination Surveys (NHANESs) 2003–2006 and 2017–2018. Three FSV, including vitamin A (VA), vitamin E (VE), and vitamin D (VD), and MetS diagnosed according to the ATP III guidelines were selected as exposure and outcome, respectively. Multivariable-adjusted logistic model was used to explore the associations of individual FSV exposure with MetS odds and MetS components. Restricted cubic splines were performed to explore the dose–response relationships among them. The quantile g-computation method was adopted to explore the associations of multiple FSVs co-exposure with MetS odds and MetS components. Results The presented study included a total of 13,975 individuals, with 2400 (17.17%) were diagnosed with MetS. After adjusting for various confounders, a positive linear pattern was observed for serum VA and VE and MetS associations. Serum VD was found to be negatively associated with MetS in a linear dose–response way. For each component of MetS, higher serum VA and VE were associated with higher triglyceride and high-density lipoprotein; higher serum VD was negatively associated with triglyceride, blood pressure, and fasting plasma glucose. MetS odds increased by 15% and 13%, respectively, in response to one quartile increase in FSVs co-exposure index (qgcomp) in the conditional model (OR = 1.15, 95%CI: 1.06, 1.24) and the marginal structural model (OR = 1.13, 95%CI: 1.06, 1.20). Besides, co-exposure to VA, VE, and VD was positively associated with triglyceride, high-density lipoprotein, and blood pressure levels. Conclusion Findings in the present study revealed that high serum VA and VE levels were associated with elevated MetS odds, while serum VD was inversely associated with MetS odds. FSVs co-exposure was positively associated with MetS odds.

Background: Previous studies have shown significant associations between individual fat-soluble vitamins (FSVs) and metabolic syndromes (MetS). However, evidence on the multiple FSVs co-exposure and MetS odds is limited. Given that individuals are typically exposed to different levels of FSVs simultaneously, and FSVs can interact with each other. It's necessary to explore the association between multiple FSVs co-exposure and MetS odds. This study aims to address this gap in general U.S. adults aged ≥ 20 years. Methods: We conducted a cross-sectional study utilizing data from the National Health and Nutrition Examination Surveys (NHANESs) 2003–2006 and 2017–2018. Three FSV, including vitamin A (VA), vitamin E (VE), and vitamin D (VD), and MetS diagnosed according to the ATP III guidelines were selected as exposure and outcome, respectively. Multivariable-adjusted logistic model was used to explore the associations of individual FSV exposure with MetS odds and MetS components. Restricted cubic splines were performed to explore the dose–response relationships among them. The quantile g-computation method was adopted to explore the associations of multiple FSVs co-exposure with MetS odds and MetS components. Results: The presented study included a total of 13,975 individuals, with 2400 (17.17%) were diagnosed with MetS. After adjusting for various confounders, a positive linear pattern was observed for serum VA and VE and MetS associations. Serum VD was found to be negatively associated with MetS in a linear dose–response way. For each component of MetS, higher serum VA and VE were associated with higher triglyceride and high-density lipoprotein; higher serum VD was negatively associated with triglyceride, blood pressure, and fasting plasma glucose. MetS odds increased by 15% and 13%, respectively, in response to one quartile increase in FSVs co-exposure index (qgcomp) in the conditional model (OR = 1.15, 95%CI: 1.06, 1.24) and the marginal structural model (OR = 1.13, 95%CI: 1.06, 1.20). Besides, co-exposure to VA, VE, and VD was positively associated with triglyceride, high-density lipoprotein, and blood pressure levels. Conclusion: Findings in the present study revealed that high serum VA and VE levels were associated with elevated MetS odds, while serum VD was inversely associated with MetS odds. FSVs co-exposure was positively associated with MetS odds. [ABSTRACT FROM AUTHOR]

Purpose: The radiation protection community has been particularly attentive to the risks of delayed effects on offspring from low dose or low dose-rate exposures to ionizing radiation. Despite this, the current epidemiologic studies and scientific data are still insufficient to provide the necessary evidence for improving risk assessment guidelines. This literature review aims to inform future studies on multigenerational and transgenerational effects. It primarily focuses on animal studies involving in utero exposure and discusses crucial elements for interpreting the results. These elements include in utero exposure scenarios relative to the developmental stages of the embryo/fetus, and the primary biological mechanisms responsible for transmitting heritable or hereditary effects to future generations. The review addresses several issues within the contexts of both multigenerational and transgenerational effects, with a focus on hereditary perspectives. Conclusions: Knowledge consolidation in the field of Developmental Origins of Health and Disease (DOHaD) has led us to propose a new study strategy. This strategy aims to address the transgenerational effects of in utero exposure to low dose and low dose-rate radiation. Within this concept, there is a possibility that disruption of epigenetic programming in embryonic and fetal cells may occur. This disruption could lead to metabolic dysfunction, which in turn may cause abnormal responses to future environmental challenges, consequently increasing disease risk. Lastly, we discuss methodological limitations in our studies. These limitations are related to cohort size, follow-up time, model radiosensitivity, and analytical techniques. We propose scientific and analytical strategies for future research in this field. [ABSTRACT FROM AUTHOR]

Introduction: Understanding multi-pathogen infections/exposures in livestock is critical to inform prevention and control measures against infectious diseases. We investigated the co-exposure of foot-and-mouth disease virus (FMDV), Brucella spp., Leptospira spp., and Coxiella burnetii in cattle in three zones stratified by land use change and with different wildlife-livestock interactions in Narok county, Kenya. We also assessed potential risk factors associated with the transmission of these pathogens in cattle. Methods: We identified five villages purposively, two each for areas with intensive (zone 1) and moderate wildlife-livestock interactions (zone 2) and one for locations with low wildlife-livestock interactions (zone 3). We sampled 1,170 cattle from 390 herds through a cross-sectional study and tested the serum samples for antibodies against the focal pathogens using enzymelinked immunosorbent assay (ELISA) kits. A questionnaire was administered to gather epidemiological data on the putative risk factors associated with cattle's exposure to the investigated pathogens. Data were analyzed using the Bayesian hierarchical models with herd number as a random effect to adjust for the within-herd clustering of the various co-exposures among cattle. Results: Overall, 88.0% (95% CI: 85.0-90.5) of the cattle tested positive for at least one of the targeted pathogens, while 41.7% (95% CI: 37.7-45.8) were seropositive to at least two pathogens. FMDV and Brucella spp. had the highest co-exposure at 33.7% (95% CI: 30.9-36.5), followed by FMDV and Leptospira spp. (21.8%, 95% CI: 19.5-24.4), Leptospira spp. and Brucella spp. (8.8%, 95% CI: 7.2-10.6), FMDV and C. burnetii (1.5%, 95% CI: 0.7-2.8), Brucella spp. and C. burnetii (1.0%, 95% CI: 0.3-2.2), and lowest for Leptospira spp. and C. burnetii (0.3%, 95% CI: 0.0-1.2). Cattle with FMDV and Brucella spp., and Brucella spp. and Leptospira spp. co-exposures and those simultaneously exposed to FMDV, Brucella spp. and Leptospira spp. were significantly higher in zone 1 than in zones 2 and 3. However, FMDV and Leptospira spp. co-exposure was higher in zones 1 and 2 than zone 3. Discussion/conclusion: We recommend the establishment of a One Health surveillance system in the study area to reduce the morbidity of the targeted zoonotic pathogens in cattle and the risks of transmission to humans. [ABSTRACT FROM AUTHOR]

Respiratory co-exposure to ambient PM2.5 and electronic cigarettes (e-cigarettes) frequently occurs in public. However, the combined effects on human respiratory health have not been well documented. To discuss potential co-effects and possible biological mechanisms, A549/THP-1 co-cultures and BEAS-2B cells were exposed to unvapedtobacco or mint-flavored e-liquids (0–7.2% v/v), e-cigarette aerosol extract (ECE, 0–50% v/v), PM2.5 (60 μg/mL), or PM2.5 + ECE for 24 h. Cell viability assessments on e-liquids, ECE, PM2.5 + ECE showed that the mint flavor exhibited higher cytotoxicity compared to the tobacco flavor in both A549/THP-1 and BEAS-2B. However, the influence of flavors on ROS levels and mRNA expression of inflammatory markers (IL-6, TNF-α, IL-8, IL-1β) after ECE exposure demonstrated inconsistency in the two cell models. PM2.5 + ECE treatment notably elevated ROS production and inflammation responses compared to ECE alone exposure. Only co-exposure induced a significant increase in nuclear transcription factor-κB p65 (NF-κB p65) and NOD-like receptor 3 (NLRP3) protein expression regardless of flavors. Our results indicate that PM2.5-treated cells exacerbate the adverse effects induced by ECE in both A549/THP-1 and BEAS-2B cells. Flavors in unvaped e-liquids affect cytotoxicity, oxidative stress and inflammation response, but these effects vary depending on the vaping process and the specific cell line. [ABSTRACT FROM AUTHOR]

Humans and animals encounter a summation of exposures during their lifetime (the exposome). In recent years, the scope of the exposome has begun to include microplastics. Microplastics (MPs) have increasingly been found in locations, including in animal gastrointestinal tracts, where there could be an interaction with Salmonella enterica serovar Typhimurium, one of the commonly isolated serovars from processed chicken. However, there is limited knowledge on how gut microbiomes are affected by microplastics and if an effect would be exacerbated by the presence of a pathogen. In this study, we aimed to determine if acute exposure to microplastics in vitro altered the gut microbiome membership and activity. The microbiota response to a 24 h co-exposure to Salmonella enterica serovar Typhimurium and/or low-density polyethylene (PE) microplastics in an in vitro broiler cecal model was determined using 16S rRNA amplicon sequencing (Illumina) and untargeted metabolomics. Community sequencing results indicated that PE fiber with and without S. Typhimurium yielded a lower Firmicutes/Bacteroides ratio compared with other treatment groups, which is associated with poor gut health, and overall had greater changes to the cecal microbial community composition. However, changes in the total metabolome were primarily driven by the presence of S. Typhimurium. Additionally, the co-exposure to PE fiber and S. Typhimurium caused greater cecal microbial community and metabolome changes than either exposure alone. Our results indicate that polymer shape is an important factor in effects resulting from exposure. It also demonstrates that microplastic-pathogen interactions cause metabolic alterations to the chicken cecal microbiome in an in vitro chicken cecal mesocosm. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess if pre-exposure to water copper and/or polyvinyl chloride microparticles affects the transcriptional responses of common carp, Cyprinus carpio, to saltwater exposure. Fish were exposed to 0.25 mg/L copper alone (Cu) or in the presence of 0.5 mg/L polyvinyl chloride microparticles (Cu-MPVC) for 14 days, followed by 72 hours of salt water exposure (0 to 13 ppt NaCl). The copper content in the gills and the expression of heat shock protein (hsp70) and cytochrome P450 family 1 (cyp1a) transcripts were examined. The results showed that gill copper levels increased significantly (P = 0.008) in the Cu and Cu-MPVC treatments after 14 days of exposure, compared to the control fish; the Cu and Cu-MPVC treatments had similar gill copper levels. After 14 days of exposure, branchial expression of the hsp70 and cyp1a genes was significantly up-regulated in the Cu and Cu-MPVC treatments. Exposure to salt water led to a significant down-regulation of the gene transcripts in all treatments after 24 h of exposure. At this point, the Cu and Cu-MPVC treatments showed transcripts similar to those of the control fish prior to saltwater exposure. The fish treated with Cu-MPVC showed significantly higher hsp70 expression 72 h after saltwater exposure than the other treatments. At this time point, the control and Cu fish had significantly lower cyp1a expression than before saltwater exposure. In conclusion, the present data suggest that copper exposure induces stress in the fish gills, and the presence of MPCV in the water hampers normal transcriptomic responses of the fish gills to saltwater exposure. [ABSTRACT FROM AUTHOR]

There is limited evidence about the gender- and obesity-specific effects of personal care product and plasticizing chemicals (PCPPCs) on short sleep duration in adults. We evaluated the gender- and obesity-specific association of co-exposure to PCPPCs and short sleep duration among adults aged 20–60 years using the National Health and Nutrition Examination Survey (NHANES) 2011–2016, a secondary data source from the United States. Seventeen PCPPCs, including five phenols, two parabens, and ten phthalates, were detected, and sleep duration was assessed among 3012 adults. Logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were employed. We found that bisphenol A (BPA), mono (caboxy-isooctyl) phthalate (MCOP), and mono (3-carboxypropyl) phthalate (MCPP) were consistently positively associated with short sleep duration in both females and males regardless of obesity status, except for BPA with general obesity. In particular, mono benzyl phthalate (MBzP) revealed a positive association in females, mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) revealed a positive association in males, and MiBP revealed a positive association in abdominal obesity. Similar associations were observed in the mixture. Our study highlights that PCPPCs are independently associated with an increasing risk of short sleep duration in adults both individually and as a mixture; however, gender- and obesity-specific differences may have little effect on certain individual PCPPCs on short sleep duration. [ABSTRACT FROM AUTHOR]

Occupational exposures are generally complex, workers are exposed with more than one hazardous agent in work environment. Combined exposure to noise and benzene is common in occupational environments. Sub-acute exposure to benzene vapors can induce oxidative stress in serum. Additionally, noise exposure leads to non-auditory effects, such as oxidative stress. However, In the authors' research scope, a study aimed at investigating the effect of co-exposure to noise and benzene on the oxidative stress of rat serum has not been found. The purpose of this study is to investigate the effect of co-exposure to noise and benzene on oxidative stress. In this study, 24 Wistar albino male rats were divided into four groups: the control group (1), the group exposed to white noise with an intensity of 100 dB and a frequency of 250–8KHz (2), the group exposed to benzene vapors with a concentration of 300 PPM (3), and the group co-exposed to white noise with an intensity of 100 dB and benzene vapors with a concentration of 300 PPM. Oxidative stress induced was investigated by serum oxidative stress indices, including lipid peroxidation (MDA), total oxidative capacity (TOS), and antioxidant activity indices (SOD) and (GSH), as well as total antioxidant capacity (TAC).The results showed that exposure to noise and benzene, both separately and combined, can lead to oxidative stress in rat serum, increasing serum oxidant indices MDA and TOS while decreasing serum antioxidant indices TAC, SOD, and GSH was detected in groups exposed to noise and benzene. The findings indicate that the serum oxidative stress caused by the co- exposure to noise and benzene is significantly higher than separate exposure to noise or benzene, also Co-exposure to noise and benzene can have an almost additive effect on increasing serum oxidative stress in rats. This study highlights the importance of studying co-exposure to physical and chemical hazardous agents in the work environment.

Microplastics and antibiotics are emerging contaminants in agricultural soil that can have negative effects on crops. However, limited research has been conducted on the effects of the polypropylene (PP) microplastic and sulfamethoxazole (SMX) co-exposure on crops, specifically regarding the impact of PP microplastics on SMX uptake and transport in crops. In this study, hydroponic experiments were carried out using lettuce (Lactuca sativa L.), PP microplastics (1.0 g L−1), and SMX (0.5 mg L−1 or 2.5 mg L−1) to investigate the individual and co-exposure effects of PP microplastics and SMX on Lettuce growth, explore the uptake and translocation of SMX in lettuce and elucidate the underlying mechanism of PP microplastic impact on SMX uptake. Results demonstrated that co-exposure to 1.0 g L−1 of PP microplastics and 0.5 mg L−1 of SMX resulted in an enhanced toxic effect. However, no intensified toxic effect on the lettuce was observed when 1.0 g L−1 PP microplastics were added in the presence of 2.5 mg L−1 SMX, indicating that the SMX dominated the toxic effect on lettuce at high concentrations. Additionally, the study found that the water absorption process controlled by the aquaporin and transpiration contributed to the uptake and translocation of SMX in lettuce. When exposed to PP microplastics, no impact was observed on the aquaporin contents of the lettuce while the transpiration rate was significantly decreased by 31.6 % - 44.2 % resulting from microplastics adhered to the root surface. Therefore, in the presence of 2.5 mg L−1 SMX, the SMX uptake in the lettuce root was inhibited by 35.9 % (P < 0.05) when exposed to 1.0 g L−1 PP microplastic. This work deepens our understanding of the behaviour of microplastics and antibiotics in the terrestrial environment.

Abstract There is indisputable evidence that the environment, humans and wildlife are continuously exposed not to single but to multiple chemicals from different sources. Exposure to these mixtures can lead to combined risks not yet sufficiently addressed in any of the European chemical legislations. Under the REACH regulation for industrial chemicals, specific environmental mixture assessments are challenged by a lack of data on toxicity, use and exposures and the communication of data along the supply chain. Within the Chemicals Strategy for Sustainability the European Commission proposed to introduce (a) mixture allocation factor(s) (MAF) as regulatory management tool to reduce exposures, effects and potential risks of unintentional mixtures. The MAF is proposed to be applied as default value within the chemical safety assessments undertaken by companies under REACH. Here, we critically review the relevant literature discussing the conceptual background of the MAF and approaches to derive its magnitude. The analysis focuses on the environment and key issues for an implementation in regulatory practise together with remaining uncertainties and needs for possible ways forward. At this stage introducing a MAF in REACH Annex I appears the most pragmatic and immediately implementable measure to address risks from unintentional mixtures in the environment. A so-called MAFceiling appears as the preferred option of policy makers, since it would only affect relevant substances close to their respective risk threshold. While the magnitude of a MAF will be decided politically, the choice of methods and assumptions to derive its size should be clear and transparent, build on the available scientific evidence and take account for uncertainties. A MAF will be most effective reducing environmental releases and exposure levels if risk mitigation measures are implemented in practise. Its socioeconomic impacts and costs need to be assessed in a balanced way together with the benefits for the environment, society, and for companies—also in comparison to the efforts needed for specific mixture risk assessments. In the future and with the experiences gathered in practise, a discussion is needed on how to assess and regulate unintentional mixtures across different pieces of chemicals legislation to consider the true exposure situation and ensure harmonisation.

Objectives Little is known about occupational co-exposure. The objective was to assess the prevalence of exposure and co-exposure to biomechanical factors and neurotoxic chemicals in French workers in 2017. Methods Data from the French representative survey SUMER 2017 (SUrveillance Médicale des Expositions aux Risques professionnels) were analyzed. A total of 25 118 workers were included. Exposure to 4 biomechanical factors (manual handling of loads, forceful joint exertion, repetitive movements, and hand-arm transmitted vibrations) and 18 neurotoxic chemicals (n-hexane, perchloroethylene, trichloroethylene, etc.) were assessed using a questionnaire during face-to-face interviews with occupational physicians. Results Among men, 22.9% were exposed to at least one biomechanical factor and 10.2% were exposed to at least one neurotoxic chemical, mainly single exposures. Among women, 10.8% were exposed to at least one biomechanical factor and 3.1% were exposed to at least one neurotoxic chemical, also mainly single exposures. Occupational co-exposure to biomechanical factors and neurotoxic chemicals was observed among 4.8% of men and 0.7% of women. Workers under 30 yr old, blue-collar workers and those working in small companies were more co-exposed than other workers. In men, the prevalence of co-exposure was higher in the construction sector compared to other economic activities. Discussion This study stresses the importance of considering multiple occupational exposures while the current prevention measures are designed to focus on preventing occupational factors individually. [ABSTRACT FROM AUTHOR]

There is indisputable evidence that the environment, humans and wildlife are continuously exposed not to single but to multiple chemicals from different sources. Exposure to these mixtures can lead to combined risks not yet sufficiently addressed in any of the European chemical legislations. Under the REACH regulation for industrial chemicals, specific environmental mixture assessments are challenged by a lack of data on toxicity, use and exposures and the communication of data along the supply chain. Within the Chemicals Strategy for Sustainability the European Commission proposed to introduce (a) mixture allocation factor(s) (MAF) as regulatory management tool to reduce exposures, effects and potential risks of unintentional mixtures. The MAF is proposed to be applied as default value within the chemical safety assessments undertaken by companies under REACH. Here, we critically review the relevant literature discussing the conceptual background of the MAF and approaches to derive its magnitude. The analysis focuses on the environment and key issues for an implementation in regulatory practise together with remaining uncertainties and needs for possible ways forward. At this stage introducing a MAF in REACH Annex I appears the most pragmatic and immediately implementable measure to address risks from unintentional mixtures in the environment. A so-called MAFceiling appears as the preferred option of policy makers, since it would only affect relevant substances close to their respective risk threshold. While the magnitude of a MAF will be decided politically, the choice of methods and assumptions to derive its size should be clear and transparent, build on the available scientific evidence and take account for uncertainties. A MAF will be most effective reducing environmental releases and exposure levels if risk mitigation measures are implemented in practise. Its socioeconomic impacts and costs need to be assessed in a balanced way together with the benefits for the environment, society, and for companies—also in comparison to the efforts needed for specific mixture risk assessments. In the future and with the experiences gathered in practise, a discussion is needed on how to assess and regulate unintentional mixtures across different pieces of chemicals legislation to consider the true exposure situation and ensure harmonisation. [ABSTRACT FROM AUTHOR]

Co-exposure soil studies of pollutants are necessary for an appropriate ecological risk assessment. Here, we examined the effects of two-component mixtures of metal oxide nanoparticles (ZnO NPs or goethite NPs) with the insecticide chlorpyrifos (CPF) under laboratory conditions in short-term artificial soil assays using Eisenia andrei earthworms. We characterized NPs and their mixtures by scanning electron microscopy, atomic force microscopy, dynamic light scattering and zeta potential, and evaluated effects on metal accumulation, oxidative stress enzymes, and neurotoxicity related biomarkers in single and combined toxicity assays. Exposure to ZnO NPs increased Zn levels compared to control in single and combined exposure (ZnO NPs + CPF) at 72 h and 7 days, respectively. In contrast, there was no indication of Fe increase in organisms exposed to goethite NPs. One of the most notable effects on oxidative stress biomarkers was produced by single exposure to goethite NPs, showing that the worms were more sensitive to goethite NPs than to ZnO NPs. Acetylcholinesterase and carboxylesterase activities indicated that ZnO NPs alone were not neurotoxic to earthworms, but similar degrees of inhibition were observed after single CPF and ZnO NPs + CPF exposure. Differences between single and combined exposure were found for catalase and superoxide dismutase (goethite NPs) and for glutathione S-transferase (ZnO NPs) activities, mostly at 72 h. These findings suggest a necessity to evaluate mixtures of NPs with co-existing contaminants in soil, and that the nature of metal oxide NPs and exposure time are relevant factors to be considered when assessing combined toxicity, as it may have an impact on ecotoxicological risk assessment. [ABSTRACT FROM AUTHOR]

The co-occurrence of heavy metals and microplastics (MPs) is an emerging issue that has attracted considerable attention. However, the interaction of nickel oxide nanoparticle (nano-NiO) combined with MPs in soil was poorly researched. Here, experiments were conducted to study the influence of nano-NiO (200 mg/kg) and polyethylene (PE) MPs with different concentrations (0.1, 1, and 10%) and sizes (13, 50, and 500 µm) on earthworms for 28 days. Compared to control, the damage was induced by PE and nano-NiO, which was evaluated by biomarker Integrated Biomarker Response index: version 2 (IBRv2) based on six biomarkers including SOD, POD, CAT, MDA, AChE, Na+/K+-ATPase and cellulase. The majority of the chosen biomarkers showed significant but complicated responses with increasing contaminant concentrations after 28 days of exposure. Moreover, the joint effect was assessed as antagonism by the effect addition index (EAI). Overall, this work expands our understanding of the combined toxicity of PE and nano-NiO in soil ecosystems. [ABSTRACT FROM AUTHOR]

Individual typical endocrine-disrupting chemicals (EDCs), including organophosphate triesters (OPEs), parabens, triclosan (TCS), bisphenols, benzophenones (BPs), phthalates (PAEs), and synthetic phenolic antioxidants (SPAs), are associated with renal dysfunction. However, the combined effects and underlying mechanisms of mixed EDC exposure on renal function remain unclear. Two hundred ninety-nine adult participants were enrolled in the cross-sectional survey conducted in Guangzhou, China. Urinary levels of 7 OPEs, 6 parabens, TCS, 14 bisphenols, 8 BPs, 15 PAEs, 4 SPAs, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were determined, and estimated glomerular filtration rate (eGFR) was served as the outcome index. We found elevated levels of diphenyl phosphate (DPP), bisphenol A (BPA), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-butyl phthalate (MBP) showed dose-responsive associations with eGFR decline, However, nonlinear associations were observed for bis(2-butoxyethyl) hydrogen phosphate (BBOEP), TCS, 4-hydroxybenzophenone (HBP), mono-n-pentyl phthalate (MnPP), and mono-benzyl phthalate (MBzP). The quantile-based g-computation model demonstrated that a quartile increase in the EDC mixture corresponded to a 0.383-SD decrease (95% CI − 0.658 ~ − 0.108, P = 0.007) in eGFR. Notably, BPA was identified as the primary contributor to this effect. Moreover, 8-OHdG mediated the eGFR decline associated with EDC mixtures with a mediation proportion of 25.49%. A sex-modified effect was also observed (P = 0.004), indicating that exposure to the mixture of EDC was linked to more pronounced renal dysfunction in females. Our novel findings suggest that exposure to a typical mixture of EDCs is associated with renal dysfunction in the general adult population of Southern China. Furthermore, 8-OHdG may play a role in the pathogenesis of EDC mixture-related renal dysfunction. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are prevalent organic pollutants in the environment; however, limited research has been conducted to explore their potential effects on sleep disorders. This study aims to investigate the relationship between single and mixed PAHs exposures and sleep disorders. This study analyzed National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2016, involving 7730 adult participants. To examine the relationship between PAHs exposure and sleep disorders, we employed survey-weighted multivariate logistic regression models and restricted cubic spline (RCS) models to evaluate single PAHs exposure. Additionally, we employed three mixed-exposure models to examine the relationship between combined PAHs exposure and sleep disorders. After adjusting for covariates, our analyses revealed positive associations between several urinary PAHs metabolites (1-hydroxynaphthalene (1-NAP), 2-NAP, 3-hydroxyfluorene (3-FLU), 2-FLU, and 1-hydroxypyrene (1-PYR)) and sleep disturbance. Consistency across various analytical methods underscores a discernible positive correlation between simultaneous exposure to PAHs and sleep disorders. This association is predominantly influenced by the presence of NAP and FLU. Remarkably, a positive relationship between combined PAHs exposure and sleep disorders emerged within the younger and middle-aged demographic but did not manifest within the elderly population. In conclusion, our study provides new epidemiological evidence suggesting that both single and mixed PAHs exposures may increase the risk of sleep disorders. Further prospective investigations are necessary to validate these findings. • PAHs exposure was positively associated with sleep disorders risk. • NAP and FLU of PAHs are the main risk factors for sleep disorders. • Elevated PAHs exposure among individuals aged 20–59 is linked to an increased risk of sleep disorders. [ABSTRACT FROM AUTHOR]

Co-exposure to multiple parasites can alter parasite success and host life history when compared to single infections. These infection outcomes can be affected by the order of parasite arrival, the host immune response, and the interspecific interactions among co-infecting parasites. In this study, we examined how the arrival order of two trematode parasites, Schistosoma mansoni and Echinostoma caproni, influenced parasite ecology and the life history of their snail host, Biomphalaria glabrata. Snail hosts were exposed to E. caproni cercariae before, with, and after their exposure to S. mansoni miracidia. We then measured the effects of this timing on infection prevalence, infection intensity of E. caproni metacercariae, and cercarial output of S. mansoni, as well as on snail reproduction and survival. Snails infected only with S. mansoni and snails exposed to E. caproni after S. mansoni both shed more cercariae than simultaneously exposed snails. Additionally, S. mansoni prevalence was lower in snails that were first exposed to E. caproni compared to snails that were exposed to E. caproni after S. mansoni. Moreover, snails exposed to E. caproni before S. mansoni did not differ in their survival compared to control snails, whereas simultaneously exposed snails and snails exposed to E. caproni after S. mansoni had lower survival than control snails. Combined, this prevalence and survival data suggest a potential protective role of early E. caproni exposure. The timing of E. caproni exposure impacts S. mansoni establishment and reproduction, but host survival patterns are likely driven by S. mansoni prevalence alone. [ABSTRACT FROM AUTHOR]

Lead (Pb) and arsenic (As) are commonly occurring heavy metals in the environment and produce detrimental impacts on the central nervous system. Although they have both been indicated to exhibit neurotoxic properties, it is not known if they have joint effects, and their mechanisms of action are likewise unknown. In this study, zebrafish were exposed to different concentrations of Pb (40 μg/L, 4 mg/L), As (32 μg/L, 3.2 mg/L) and their combinations (40 μg/L + 32 μg/L, 4 mg/L + 3.2 mg/L) for 30 days. The histopathological analyses showed significant brain damage characterized by glial scar formation and ventricular enlargement in all exposed groups. In addition, either Pb or As staining inhibited the swimming speed of zebrafish, which was enhanced by their high concentrations in a mixture. To elucidate the underlying mechanisms, we examined changes in acetylcholinesterase (AChE) activity, neurotransmitter (dopamine, 5-hydroxytryptamine) levels, HPI axis-related hormone (cortisol and epinephrine) contents and neurodevelopment-related gene expression in zebrafish brain. The observations suggest that combined exposure to Pb and As can cause abnormalities in swimming behavior and ultimately exacerbate neurotoxicity in zebrafish by interfering with the cholinergic system, dopamine and 5-hydroxytryptamine signaling, HPI axis function as well as neuronal development. This study provides an important theoretical basis for the mixed exposure of heavy metals and their toxicity to aquatic organisms. [ABSTRACT FROM AUTHOR]

Organophosphate flame retardants 2-ethylhexyldiphenyl phosphate (EHDPP) and cadmium (Cd) are ubiquitous in environmental matrices, and dermal absorption is a major human exposure pathway. However, their detrimental effects on the human epidermis remain largely unknown. In this study, human keratinocytes (HaCaT cells) were employed to examine the toxicity and underlying mechanisms of co-exposure to EHDPP and Cd. Their influence on cell morphology and viability, oxidative damage, apoptosis, and tight junction were determined. The results showed that co-exposure decreased cell viability by >40 %, induced a higher level of oxidative damage by increasing the generation of reactive oxygen species (1.3 folds) and inhibited CAT (79 %) and GPX (90 %) activities. Moreover, Cd exacerbated EHDPP-induced mitochondrial disorder and cellular apoptosis, which was evidenced by a reduction in mitochondrial membrane potential and an elevation of cyt-c and Caspase-3 mRNA expression. In addition, greater loss of ZO-1 immunoreactivity at cellular boundaries was observed after co-exposure, indicating skin epithelial barrier function disruption, which may increase the human bioavailability of contaminants via the dermal absorption pathway. Taken together, oxidative damage, cell apoptosis, and tight junction disruption played a crucial role in EHDPP + Cd triggered cytotoxicity in HaCaT cells. The detrimental effects of EHDPP + Cd co-exposure were greater than individual exposure, suggesting the current health risk assessment or adverse effects evaluation of individual exposure may underestimate their perniciousness. Our data imply the importance of considering the combined exposure to accurately assess their health implication.

Excessive urbanization leads to considerable nature deficiency and abundant artificial infrastructure in urban areas, which triggered intensive discussions on people's exposure to green space and outdoor artificial light at night (ALAN). Recent academic progress highlights that people's exposure to green space and outdoor ALAN may be confounders of each other but lacks systematic investigations. This study investigates the associations between people's exposure to green space and outdoor ALAN by adopting the three most used research paradigms: population-level residence-based, individual-level residence-based, and individual-level mobility-oriented paradigms. We employed the green space and outdoor ALAN data of 291 Tertiary Planning Units in Hong Kong for population-level analysis. We also used data from 940 participants in six representative communities for individual-level analyses. Hong Kong green space and outdoor ALAN were derived from high-resolution remote sensing data. The total exposures were derived using the spatiotemporally weighted approaches. Our results confirm that the negative associations between people's exposure to green space and outdoor ALAN are universal across different research paradigms, spatially non-stationary, and consistent among different socio-demographic groups. We also observed that mobility-oriented measures may lead to stronger negative associations than residence-based measures by mitigating the contextual errors of residence-based measures. Our results highlight the potential confounding associations between people's exposure to green space and outdoor ALAN, and we strongly recommend relevant studies to consider both of them in modeling people's health outcomes, especially for those health outcomes impacted by the co-exposure to them.

The aim of the present study was to assess if pre-exposure to water copper and/or polyvinyl chloride microparticles affects the transcriptional responses of common carp, Cyprinus carpio, to saltwater exposure. Fish were exposed to 0.25 mg/L copper alone (Cu) or in the presence of 0.5 mg/L polyvinyl chloride microparticles (Cu-MPVC) for 14 days, followed by 72 hours of salt water exposure (0 to 13 ppt NaCl). The copper content in the gills and the expression of heat shock protein (hsp70) and cytochrome P450 family 1 (cyp1a) transcripts were examined. The results showed that gill copper levels increased significantly (P = 0.008) in the Cu and Cu-MPVC treatments after 14 days of exposure, compared to the control fish; the Cu and Cu-MPVC treatments had similar gill copper levels. After 14 days of exposure, branchial expression of the hsp70 and cyp1a genes was significantly up-regulated in the Cu and Cu-MPVC treatments. Exposure to salt water led to a significant down-regulation of the gene transcripts in all treatments after 24 h of exposure. At this point, the Cu and Cu-MPVC treatments showed transcripts similar to those of the control fish prior to saltwater exposure. The fish treated with Cu-MPVC showed significantly higher hsp70 expression 72 h after saltwater exposure than the other treatments. At this time point, the control and Cu fish had significantly lower cyp1a expression than before saltwater exposure. In conclusion, the present data suggest that copper exposure induces stress in the fish gills, and the presence of MPCV in the water hampers normal transcriptomic responses of the fish gills to saltwater exposure.

BackgroundEpidemiological evidence regarding circulating carotenoids and mortality risk remains conflicting, and most studies focus on the impact of individual carotenoids. This study aimed to elucidate the effects of co-exposure to multiple serum carotenoids on mortality risk.MethodsWe enrolled 22,472 participants aged ≥20 from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and NHANES 2003–2006. Baseline serum levels of five major carotenoids (α-carotene, β-carotene, lycopene, β-cryptoxanthin, and lutein/zeaxanthin) were measured, and individuals were followed up until December 31, 2019. Carotenoid co-exposure patterns were identified using the K-means method. Cox proportional hazard models were used to investigate the associations between carotenoid exposure and mortality risk.ResultsDuring a median follow-up of 16.7 years, 7,901 deaths occurred. K-means clustered participants into low-level, low-lycopene, high-lycopene, and high-level exposure groups. In the fully adjusted model, low-lycopene, high-lycopene, and high-level exposure groups had significantly lower all-cause mortality risks compared to the low-level exposure group, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.79 (0.72, 0.87), 0.75 (0.67, 0.84), and 0.67 (0.61, 0.74), respectively. For cardiovascular disease mortality, the high-lycopene exposure group had a 27% reduced risk (HR: 0.73, 95% CI: 0.61–0.86), and the high-level exposure group had a 21% reduced risk (HR: 0.79, 95% CI: 0.67–0.93). For cancer mortality, the high-lycopene and high-level exposure groups had 30% and 35% lower risks, with HRs (95% CIs) of 0.70 (0.57, 0.86) and 0.65 (0.54, 0.79), respectively.ConclusionThis study revealed that co-exposure to multiple serum carotenoids was associated with reduced mortality risk, highlighting the potential health benefits of increased carotenoid intake. Further investigation is warranted to elucidate the underlying mechanisms of interactions among different carotenoids.

Background: Childhood exposure to polycyclic aromatic hydrocarbons (PAHs) or lead (Pb) is associated with epigenetic modifications. However, the effects of their co-exposures on IGF1 (Insulin-like growth factor 1) methylation and the potential role in child physical growth are unclear. Methods: From our previous children study (N = 238, ages of 3–6), 75 children with higher total concentrations of urinary ten hydroxyl PAH metabolites (∑10OH-PAHs) from an e-waste recycling area, Guiyu, and 75 with lower ∑10OH-PAHs from Haojiang (reference area) were included. Pb and IGF1 P2 promoter methylation in peripheral blood were also measured. Multivariable linear regression analyses were performed to estimate individual associations, overall effects and interactions of co-exposure to OH-PAHs and Pb on IGF1 methylation were further explored using Bayesian kernel machine regression. Results: Methylation of IGF1 (CG-232) was lower (38.00 vs. 39.74 %, P

IntroductionUnderstanding multi-pathogen infections/exposures in livestock is critical to inform prevention and control measures against infectious diseases. We investigated the co-exposure of foot-and-mouth disease virus (FMDV), Brucella spp., Leptospira spp., and Coxiella burnetii in cattle in three zones stratified by land use change and with different wildlife-livestock interactions in Narok county, Kenya. We also assessed potential risk factors associated with the transmission of these pathogens in cattle.MethodsWe identified five villages purposively, two each for areas with intensive (zone 1) and moderate wildlife-livestock interactions (zone 2) and one for locations with low wildlife-livestock interactions (zone 3). We sampled 1,170 cattle from 390 herds through a cross-sectional study and tested the serum samples for antibodies against the focal pathogens using enzyme-linked immunosorbent assay (ELISA) kits. A questionnaire was administered to gather epidemiological data on the putative risk factors associated with cattle’s exposure to the investigated pathogens. Data were analyzed using the Bayesian hierarchical models with herd number as a random effect to adjust for the within-herd clustering of the various co-exposures among cattle.ResultsOverall, 88.0% (95% CI: 85.0–90.5) of the cattle tested positive for at least one of the targeted pathogens, while 41.7% (95% CI: 37.7–45.8) were seropositive to at least two pathogens. FMDV and Brucella spp. had the highest co-exposure at 33.7% (95% CI: 30.9–36.5), followed by FMDV and Leptospira spp. (21.8%, 95% CI: 19.5–24.4), Leptospira spp. and Brucella spp. (8.8%, 95% CI: 7.2–10.6), FMDV and C. burnetii (1.5%, 95% CI: 0.7–2.8), Brucella spp. and C. burnetii (1.0%, 95% CI: 0.3–2.2), and lowest for Leptospira spp. and C. burnetii (0.3%, 95% CI: 0.0–1.2). Cattle with FMDV and Brucella spp., and Brucella spp. and Leptospira spp. co-exposures and those simultaneously exposed to FMDV, Brucella spp. and Leptospira spp. were significantly higher in zone 1 than in zones 2 and 3. However, FMDV and Leptospira spp. co-exposure was higher in zones 1 and 2 than zone 3.Discussion/conclusionWe recommend the establishment of a One Health surveillance system in the study area to reduce the morbidity of the targeted zoonotic pathogens in cattle and the risks of transmission to humans.

Background: Co-exposure to multiple volatile organic compounds (VOCs) is common in daily life. However, few studies have evaluated the associations between the patterns of simultaneous exposure to multiple VOCs and the risk of hyperuricemia. Methods: This study included 7490 adults from the National Health and Nutrition Examination Survey conducted between 2003 and 2012. The K-means clustering method was applied to cluster eight kinds of VOCs in the blood into various co-exposure patterns, including benzene, bromodichloromethane, chloroform, dibromochloromethane, 1,4-dichlorobenzene, ethylbenzene, methyl tertiary-butyl ether (MTBE), and o-xylene. Binary logistic regression analysis was utilized to assess the association between single VOCs, the co-exposure patterns of multiple VOCs, and the hyperuricemia risk. Restricted cubic spline functions were utilized to investigate the non-linear relationships. Results: Based on eight VOCs, four characteristic co-exposure patterns were generated. Compared with the low-level exposure group, the levels of volatile organic compound (VOC) co-exposure in cluster 2, characterized by relatively high levels of MTBE and moderate levels of bromodichloromethane, chloroform, and dibromochloromethane, were associated with increased hyperuricemia risk, with an odds ratio of 1.32 (1.02, 1.71). Increasing levels of bromodichloromethane and chloroform were significantly associated with an increased risk of hyperuricemia. A strong J-shaped relationship was found between MTBE and hyperuricemia. Conclusions: This study indicated that blood bromodichloromethane and chloroform were positively associated with hyperuricemia risk. Blood MTBE had a J-shaped association with hyperuricemia. In addition, the significant association of the co-exposure patterns of multiple VOCs in the blood with hyperuricemia risk was observed. Changing VOC co-exposure patterns may play a crucial role in the occurrence of hyperuricemia.

Bluetongue is an arthropod-borne viral infection that is notifiable in several countries and causes significant economic losses and major concerns for ruminant trade. In this study, we investigated bluetongue 1seroprevalence in the Campania region, southern Italy, in cattle and buffalo populations, and assessed which factors were correlated with a high risk of exposure. The infection was widespread, as evidenced by the high individual (43.6%) and herd prevalence (85.4%). The highest prevalence was found in adult animals. Among the climatic factors analyzed, average temperature played a prominent role, being capable of affecting the probability of being positive for this infection. Surprisingly, exposure to Schmallenberg virus did not predispose animals to be positive for bluetongue virus, even though these infections share the same vector (Culicoides). Our data, consistent with those in the literature, suggest the transversal spread of bluetongue virus in the Mediterranean area, and indicate a limited co-exposure rate between Bluetongue and Schmallenberg viruses. [ABSTRACT FROM AUTHOR]

3,3′,4,4′,5-Pentachlorobiphenyl (PCB126) is the most toxic congener of dioxin-like polychlorinated biphenyls (DL PCBs), while nanoplastics (NPs) have recently emerged as significant marine pollutants, both posing threats to aquatic organisms and human health. They coexist in the environment, but their comprehensive toxicological effects remain unclear. In this study, zebrafish embryos were simultaneously exposed to PCB126 and 80-nanometer nanoplastyrene (NPS). Researchers utilized fluorescence microscopy, qPCR, histopathological examination, and transcriptomic sequencing to investigate the developmental toxicity of different concentrations of PCB126 and NPS individually or in combination on zebrafish embryos and larvae. Results indicate that the chorion significantly impedes the accumulation of NPS (p < 0.05). It is noteworthy that this barrier effect diminishes upon simultaneous exposure to PCB126. In this experiment, the semi-lethal concentration of PCB126 for larvae was determined to be 6.33 μg/L. Exposure to PCB126 induces various deformities, primarily mediated through the aryl hydrocarbon receptor (AHR). Similarly, exposure to NPS also activates AHR, leading to developmental impairments. Furthermore, transcriptomic sequencing revealed similar effects of PCB126 and NPS on the gene expression trends in zebrafish larvae, but combined exposure to both exacerbates the risk of cancer and induces more severe cardiac toxicity. At this level, co-exposure to PCB126 and NPS adversely affects the development of zebrafish larvae. This study contributes to a deeper understanding of the in vivo accumulation of DL polychlorinated biphenyls and microplastics in actual aquatic environments and their impact on fish development.

Aflatoxin B1 (AFB1), a common mycotoxin, can occur in agricultural products. As a metabolite of AFB1, aflatoxin M1 (AFM1) mainly exist in dairy products. These two mycotoxins threaten human health, although it is unclear how they affect the function of the intestinal barrier. In this study, mice were exposed to AFB1 (0.3 mg/kg body b.w.) and AFM1(3.0 mg/kg b.w.) either individually or in combination for 28 days to explore the main differentially expressed proteins (DEPs) and the associated enriched pathways. These findings were preliminarily verified by the transcriptomic and proteomic analyses in differentiated Caco-2 cells. The results revealed that AFB1 and AFM1 exposure in mice disrupted the function of the intestinal barrier, and the combined toxicity was greater than that of each toxin alone. Further proteomic analysis in mice demonstrated that the mechanisms underlying these differences could be explained as follows: (i) lipid metabolism was enriched by AFB1-induced DEPs. (ii) protein export pathway was stimulated by AFM1-induced DEPs. (iii) cell metabolic ability was inhibited (as evidenced by changes in UDP-GT1, UDP-GT2, and Gatm6), apoptosis was induced (MAP4K3), and epithelial cell integrity was disrupted (Claudin7 and IQGAP2), resulting in more extensive intestinal damage after combined treatment. In conclusion, the hazardous impact of co-exposure to AFB1 and AFM1 from proteomic perspectives was demonstrated in the present study.

Various phthalic acid esters (PAEs) such as dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) co-exist with nanopollutants in aquatic environment. In this study, Daphnia magna was exposed to nano-CuO and DBP or BBP at environmental relevant concentrations for 21-days to investigate these combined toxic effects. Acute EC50 values (48 h) of nano-CuO, DBP, and BBP were 12.572 mg/L, 8.978 mg/L, and 4.785 mg/L, respectively. Results showed that co-exposure with nano-CuO (500 μg/L) for 21 days significantly enhanced the toxicity of DBP (100 μg/L) and BBP (100 μg/L) to Daphnia magna by 18.37% and 18.11%, respectively. The activities of superoxide dismutase, catalase, and glutathione S-transferase were enhanced by 10.95% and 14.07%, 25.63% and 25.91%, and 39.93% and 35.01% in nano-CuO+DBP and nano-CuO+BBP treatments as compared to the individual exposure groups, verifying that antioxidative defense responses were activated. Furthermore, the co-exposure of nano-CuO and PAEs decreased the population richness and diversity microbiota, and changed the microbial community composition in Daphnia magna. Metabolomic analysis elucidated that nano-CuO + PAEs exposure induced stronger disturbance on metabolic network and molecular function, including amino acid, nucleotides, and lipid metabolism-related metabolic pathways, as comparison to PAEs single exposure treatments. In summary, the integration of physiological, microflora, and untargeted metabolomics analysis offers a fresh perspective into the potential ecological risk associated with nanopollutants and phthalate pollution in aquatic ecosystems.

AimThe association between vitamins and eczema has garnered attention, yet few studies have evaluated the effects of co-exposure to multiple vitamins on this condition. This study aims to assess the association of vitamin mixtures with eczema in children.MethodsThis cross-sectional study analyzed data from 2,244 children aged 6–17 years from the National Health and Nutrition Examination Surveys. Eczema served as the primary outcome. Six serum vitamins, namely, vitamins A, B6, B12, C, D, and E, were the main variables. Weighted multivariate logistic regression was adopted to analyze the association between each serum vitamin and eczema. Odds ratios (OR) with a 95% confidence interval (CI) were calculated. Bayesian kernel machine regression (BKMR) analysis and the quantile g-computation (qgcomp) model were used to evaluate the association of co-exposure to multiple vitamins with eczema.ResultsIn total, 10.83% of children (n = 243) developed eczema. After adjusting for confounding factors, we observed that compared with the reference group (vitamin B12 with second quartile), the OR for eczema was 0.604 (95% CI: 0.373–0.978, P = 0.041) for the first quartile of vitamin B12. Both BKMR analysis and the qgcomp model consistently showed that co-exposure to the six vitamins was positively correlated with the risk of eczema, with vitamin B6 contributing most to the overall effect. In BKMR analyses, we observed an interaction between vitamins B6 and B12 concerning eczema risk.ConclusionCo-exposure to vitamins A, C, B6, B12, D, and E was found to be associated with an increased risk of eczema in children, with vitamin B6 as the greatest positive contributor driving the overall effect.

In the severe pollution area of nanoplastics (NPs) and cadmium ions (Cd2+), the joint effects of their high environmental concentrations on primary producers may differ from those of low environmental doses. Thus, we investigated the physiological changes, cell morphology, molecular dynamic simulation, phenotypic interactions, and metabolomics responses of C. pyrenoidosa to high environmental concentrations of NPs and Cd2+ after 12-d acclimation. After 12-d cultivation, mono-NPs and mono-Cd2+ reduced cell density and triggered antioxidant enzymes, extracellular polymeric substances (EPS) production, and cell aggregation to defend their unfavorable effects. Based on the molecular dynamic simulation, the chlorine atoms of the NPs and Cd2+ had charge attraction with the nitrogen and phosphorus atoms in the choline and phosphate groups in the cell membrane, thereby NPs and Cd2+ could adsorb on the cells to destroy them. In the joint exposure, NPs dominated the variations of ultrastructure and metabolomics and alleviated the toxicity of NPs and Cd2+. Due to its high environmental concentration, more NPs could compete with the microalgae for Cd2+ and thicken cell walls, diminishing the Cd2+ content and antioxidant enzymes of microalgae. NPs addition also decreased the EPS content, while the bound EPS with –CN bond was kept to detoxicate Cd2+. Metabolomics results showed that the NPs downregulated nucleotide, arachidonic acid, and tryptophan metabolisms, while the Cd2+ showed an opposite trend. Compared with their respective exposures, metabolomics results found the changes in metabolic molecules, suggesting the NPs_Cd2+ toxicity was mitigated by balancing nucleotide, arachidonic acid, tryptophan, and arginine and proline metabolisms. Consequently, this study provided new insights that simultaneous exposure to high environmental concentrations of NPs and Cd2+ mitigated microalgae cellular toxicity, which may change their fates and biogeochemical cycles in aquatic systems.

Phthalic acid esters (PAEs) are widely used as plasticizers and have been suggested to engender adverse effects on glucose metabolism. However, epidemiological data regarding the PAE mixture on type 2 diabetes (T2DM), as well as the mediating role of oxidative stress are scarce. This case-control study enrolled 206 T2DM cases and 206 matched controls in Guangdong Province, southern China. The concentrations of eleven phthalate metabolites (mPAEs) and the oxidative stress biomarker 8-hydroxy-2′-deoxyguanosine (8-OHdG) in urine were determined. Additionally, biomarkers of T2DM in paired serum were measured to assess glycemic status and levels of insulin resistance. Significantly positive associations were observed for mono-(2-ethylhexyl) phthalate (MEHP) and Mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with T2DM (P < 0.001). Restricted cubic spline modeling revealed a non-linear dose-response relationship between MEHHP and T2DM (Pnon-linear = 0.001). The Bayesian kernel machine regression and quantile g-computation analyses demonstrated a significant positive joint effect of PAE exposure on T2DM risk, with MEHHP being the most significant contributor. The mediation analysis revealed marginal evidence that oxidative stress mediated the association between the mPAEs mixture and T2DM, while 8-OHdG respectively mediated 26.88 % and 12.24 % of MEHP and MEHHP on T2DM risk individually (Pmediation < 0.05). Di(2-ethylhexyl) phthalate (DEHP, the parent compound for MEHP and MEHHP) was used to further examine the potential molecular mechanisms by in silico analysis. Oxidative stress may be crucial in the link between DEHP and T2DM, particularly in the reactive oxygen species metabolic process and glucose import/metabolism. Molecular simulation docking experiments further demonstrated the core role of Peroxisome Proliferator Activated Receptor alpha (PPARα) among the DEHP-induced T2DM. These findings suggest that PAE exposure can alter oxidative stress via PPARα, thereby increasing T2DM risk.

Knowledge regarding the combined toxicity mechanism of bisphenol compounds and microplastics (MPs) on organisms remains limited. In this study, we first developed an accurate and sensitive method to simultaneously quantify two bisphenol compounds and evaluate their accumulation and tissue distribution after co-exposure with MPs in zebrafish. Then, we determined the bioaccumulation potential of bisphenol A (BPA) and bisphenol S (BPS) in adult zebrafish in the absence and presence of MPs. Bisphenol compounds were found to accumulate in different tissues of zebrafish, with BPS showing lower accumulation levels compared to BPA. Importantly, we discovered that the presence of MPs could exacerbate the accumulation of bisphenol compounds in biological tissues. These findings highlight the enhanced bioavailability and risk posed by the co-exposure of bisphenol compounds and MPs, underscoring the need for further investigation into their combined environmental and biological health impacts.

There is limited evidence about the gender- and obesity-specific effects of personal care product and plasticizing chemicals (PCPPCs) on short sleep duration in adults. We evaluated the gender- and obesity-specific association of co-exposure to PCPPCs and short sleep duration among adults aged 20–60 years using the National Health and Nutrition Examination Survey (NHANES) 2011–2016, a secondary data source from the United States. Seventeen PCPPCs, including five phenols, two parabens, and ten phthalates, were detected, and sleep duration was assessed among 3012 adults. Logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were employed. We found that bisphenol A (BPA), mono (caboxy-isooctyl) phthalate (MCOP), and mono (3-carboxypropyl) phthalate (MCPP) were consistently positively associated with short sleep duration in both females and males regardless of obesity status, except for BPA with general obesity. In particular, mono benzyl phthalate (MBzP) revealed a positive association in females, mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) revealed a positive association in males, and MiBP revealed a positive association in abdominal obesity. Similar associations were observed in the mixture. Our study highlights that PCPPCs are independently associated with an increasing risk of short sleep duration in adults both individually and as a mixture; however, gender- and obesity-specific differences may have little effect on certain individual PCPPCs on short sleep duration.

This study has suggested an occupational exposure limit (OEL) based on the co-exposure approach in an iron-foundry industry. Respirable dust was collected in an iron casting industry using the NIOSH 0600 method. The DNA damage was obtained by comet assay. The lower confidence interval of the benchmark dose (BMDL) was employed for exposure limit evaluation. The estimated BMDL of the cell line was extrapolated to human subjects. Based on the Hill model, a BMDL 1.65 µg for chemical mixture has been estimated for the A549 cell line. According to uncertainty factors, permitted daily exposure (PDE) was predicted in humans. However, PDE of 3.9 μg/m3 was specified as the time-weighted average limit for toxic respirable dust in the casting industry. In this study, OEL for active respirable dust in the casting industry has been proposed. The industry-based standard for active respirable dust has been proposed for better management of co-exposure. [ABSTRACT FROM AUTHOR]

The potential impact of the combination of a high‐fat diet (HFD) and polystyrene nanoplastics (PS‐NPs) on fertility cannot be ignored, especially when the fertility rate is declining. However, it has not attracted considerable attention. In this study, an obese mouse model was established using an HFD, and the reproductive function of male mice was evaluated after intragastric administration of 100 μL of a 10 mg/mL PS‐NP suspension for 4 weeks. By determining the morphology and vitality of sperm and related indicators of testosterone production, it was found that PS‐NPs aggravated the destruction of sperm mitochondrial structure, decrease sperm activity, and testosterone production in HFD‐fed mice. To comprehensively analyze the injury mechanism, the integrity of the blood testicular barrier (BTB) and the function of Leydig and Sertoli cells were further analyzed. It was found that PS‐NPs could destroy BTB, promote the degeneration of Leydig cells, reduce the number of Sertoli cells, and decrease lactate secretion in HFD‐fed mice. PS‐NPs further interfered with redox homeostasis in the testicular tissues of HFD‐fed mice. This study found that PS‐NPs could aggravate the damage to the reproductive system of obese male mice by further perturbing its redox homeostasis and revealed the potential health risk of PS‐NPs exposure under an HFD. [ABSTRACT FROM AUTHOR]

The phenomenon of population aging has brought forth the challenge of frailty. Nevertheless, the contribution of environmental exposure to frailty remains ambiguous. Our objective was to investigate the association between phenols, phthalates (PAEs), and polycyclic aromatic hydrocarbons (PAHs) with frailty. We constructed a 48-item frailty index using data from the National Health and Nutrition Examination Survey (NHANES). The exposure levels of 20 organic contaminants were obtained from the survey circle between 2005 and 2016. The association between individual organic contaminants and the frailty index was assessed using negative binomial regression models. The combined effect of organic contaminants was examined using weighted quantile sum (WQS) regression. Dose–response patterns were modeled using generalized additive models (GAMs). Additionally, an interpretable machine learning approach was employed to develop a predictive model for the frailty index. A total of 1566 participants were included in the analysis. Positive associations were observed between exposure to MIB, P02, ECP, MBP, MHH, MOH, MZP, MC1, and P01 with the frailty index. WQS regression analysis revealed a significant increase in the frailty index with higher levels of the mixture of organic contaminants (aOR, 1.12; 95% CI, 1.05–1.20; p < 0.001), with MIB, ECP, COP, MBP, P02, and P01 identified as the major contributors. Dose–response relationships were observed between MIB, ECP, MBP, P02, and P01 exposure with an increased risk of frailty (both with p < 0.05). The developed predictive model based on organic contaminants exposure demonstrated high performance, with an R2 of 0.9634 and 0.9611 in the training and testing sets, respectively. Furthermore, the predictive model suggested potential synergistic effects in the MIB-MBP and P01-P02 pairs. Taken together, these findings suggest a significant association between exposure to phthalates and PAHs with an increased susceptibility to frailty. [ABSTRACT FROM AUTHOR]

Objective: Although the effect of vitamins on the risk of mortality in diabetic patients has been reported, most studies focus on individual vitamins. However, humans are often exposed to multiple vitamins simultaneously in daily life. Therefore, it is worth exploring the effects of co-exposure to multiple vitamins on the risk of mortality in diabetic patients. Methods: This study included diabetic patients aged ≥20WD years who participated in NHANES from 2003 to 2006. An unsupervised K-means clustering method was used to cluster eight vitamins in serum into several patterns of co-exposure to multiple vitamins, and the Cox proportional hazards model was used to evaluate the impact of different patterns of coexposure to multiple vitamins on the risk of all-cause mortality in diabetic patients. Results: Three patterns of co-exposure to multiple vitamins were generated based on K-means clustering, namely, low-level, moderate-level, and high-level. Among the 484 diabetic patients, with a median follow-up of 13.7 years, a total of 211 deaths occurred. After adjusting for covariates, the individual vitamins had varying effects on the risk of all-cause mortality in diabetic patients. Compared to the low-level group of co-exposure to multiple vitamins, the high-level group significantly reduced the risk of all-cause mortality in diabetic patients, with a HR of 0.42 (95% CI: 0.20, 0.87). Subgroup analysis demonstrated that high levels of co-exposure to multiple vitamins significantly reduced the risk of all-cause mortality in males, individuals aged ≥ 60 years, and non-Hispanic White people with diabetes compared to the low-level group, with HR of 0.42 (95% CI: 0.18, 0.98), 0.53 (95% CI: 0.26, 0.98), and 0.26 (95% CI: 0.12, 0.58) respectively. Conclusion: While individual vitamins had different effects on the risk of all-cause mortality in patients with diabetes, high-level co-exposure to multiple vitamins significantly reduced the risk of all-cause mortality in patients with diabetes, with differences observed among genders, ages, and race. This suggests that when developing vitamin intervention strategies for patients with diabetes, consideration should be given not only to the dosage of individual vitamins but also to the variations between different population groups. [ABSTRACT FROM AUTHOR]

Tobacco misuse as a comorbidity of schizophrenia is frequently established during adolescence. However, comorbidity markers are still missing. Here, the method of label-free proteomics was used to identify deregulated proteins in the medial prefrontal cortex (prelimbic and infralimbic) of male and female mice modelled to schizophrenia with a history of nicotine exposure during adolescence. Phencyclidine (PCP), used to model schizophrenia (SCHZ), was combined with an established model of nicotine minipump infusions (NIC). The combined insults led to worse outcomes than each insult separately when considering the absolute number of deregulated proteins and that of exclusively deregulated ones. Partially shared Reactome pathways between sexes and between PCP, NIC and PCPNIC groups indicate functional overlaps. Distinctively, proteins differentially expressed exclusively in PCPNIC mice reveal unique effects associated with the comorbidity model. Interactome maps of these proteins identified sex-selective subnetworks, within which some proteins stood out: for females, peptidyl-prolyl cis-trans isomerase (Fkbp1a) and heat shock 70 kDa protein 1B (Hspa1b), both components of the oxidative stress subnetwork, and gamma-enolase (Eno2), a component of the energy metabolism subnetwork; and for males, amphiphysin (Amph), a component of the synaptic transmission subnetwork. These are proposed to be further investigated and validated as markers of the combined insult during adolescence. [ABSTRACT FROM AUTHOR]