Search

Uric acid (UA) and C-reactive protein (CRP) may interact synergistically to accelerate the initiation and progression of cardiovascular disease (CVD). This study investigated the effects of a combination of high UA and high CRP on the risks of CVD. A total of 90,270 participants recruited from the Kailuan study were included, who were divided into four groups according to the presence/absence of hyperuricemia and inflammation. Cox regression was applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CVD. C-statistics, net classification index (NRI), and integrated discrimination improvement (IDI) were used to compare the incremental predictive of UA, CRP, and their combined effects on CVD. Mediation analysis was to explore the impact of CRP on the association between UA and CVD. Over a median follow-up of 14.95 years, we identified 11398 incident CVD cases. Compared to the low UA/low CRP group, the high UA/low CRP, low UA/high CRP and high UA/high CRP groups showed progressively higher risks of CVD, HR (95% CI): 1.18(1.10–1.27), 1.27(1.21–1.33) and 1.50 (1.33–1.69), respectively. The incorporation of UA and CRP into the traditional China-PAR model led to improvement in the C-statistic, NRI, and IDI, and was better than incorporation of either UA or CRP alone. Mediation analysis showed that CRP mediated the association between UA and CVD, accounting for 11.57% of the total effects. High UA/high CRP is associated with increased risks of CVD. Incorporation of both UA and CRP provided additional value for risk stratification. • The primary finding of this study was that the combination of high UA and high CRP was associated with increased risks of CVD, which was age-dependent. • The association between UA and CVD was mediated by CRP, suggesting proper control of CRP can be effective to reduce the effects of UA on CVD. • Compared to incorporating either UA or CRP alone, incorporating both UA and CRP into the traditional China-PAR model showed the best incremental value. • The effects of combined exposure to high UA and high CRP on different outcome events had site differences, with a higher risk of CHD and HF than stroke. [ABSTRACT FROM AUTHOR]

• A time-course progression was noted in PFBS innate toxicity. • Hypoxia was more potent than PFBS to disrupt sex endocrine system. • Hypoxia was the major driver of estrogenic activity in coexposure group. • Hypoxia suspended the egg spawn of marine medaka. • PFBS and hypoxia combination skewed the balance of thyroid hormones. Perfluorobutanesulfonate (PFBS) is an emerging pollutant capable of potently disrupting the sex and thyroid endocrine systems of teleosts. However, the hypoxic and temporal variation in PFBS endocrine disrupting toxicity remain largely unknown. In the present study, adult marine medaka were exposed to environmentally realistic concentrations of PFBS (0 and 10 µg/L) under normoxia or hypoxia conditions for 7 days, aiming to explore the interactive behavior between PFBS and hypoxia. In addition, PFBS singular exposure was extended till 21 days under normoxia to elucidate the time-course progression in PFBS toxicity. The results showed that hypoxia inhibited the growth and caused the suspension of egg spawn regardless of PFBS exposure. With regard to the sex endocrine system, 7-day PFBS exposure led to an acute stimulation of transcriptional profiles in females, which, subsequently, recovered after the 21-day exposure. The potency of hypoxia to disturb the sex hormones was much stronger than PFBS. A remarkable increase in estradiol concentration was noted in medaka blood after hypoxia exposure. Changes in sex endocrinology of coexposed fish were largely determined by hypoxia, which drove the formation of an estrogenic environment. PFBS further enhanced the endocrine disrupting effects of hypoxia. However, the hepatic synthesis of vitellogenin and choriogenin, two commonly used sensitive biomarkers of estrogenic activity, failed to initiate in response to the estrogen stimulus. Compared to sex endocrine system, disturbances in thyroidal axis by PFBS or hypoxia were relatively mild. Overall, the present findings will advance our toxicological understanding about PFBS pollutant under the interference of hypoxia. [Display omitted] [ABSTRACT FROM AUTHOR]

Elucidating the combined exposure of agrochemicals is essential for safeguarding human health and agroecosystem safety. A rapid and high-sensitivity UHPLC-MS/MS method was developed for simultaneous quantification of nine compounds in sorghum by an assembly-line optimization process with a limit of quantitation of 0.001 mg/kg. The concentration variation of atrazine, quinclorac, fluroxypyr-meptyl and metabolites was reflected by terminal magnitudes of ≤0.0665 mg/kg. Additionally, atrazine was dealkylated to deethyl atrazine and desethyl desisopropyl atrazine at concentrations of 0.0014–0.0058 mg/kg during the sorghum harvest. Acceptable health hazardous of atrazine and quinclorac for all life cycle populations were comparatively assessed via deterministic and probabilistic models, in which atrazine gained an 83.55 % share of cumulative dietary risks. Rural residents had significantly higher risks than urban residents, and children were the most sensitive group. Despite the low health risks, combined exposure to herbicides and their metabolites should be continuously stressed, given their cumulative amplification effects. [Display omitted] • A ≤ 4.3 min tracing methodology was developed for nine compounds in sorghum. • Fates of mixed herbicides were revealed at a terminal magnitude of ≤ 0.0665 mg/kg. • Atrazine was dealkylated to DEA and DACT at concentrations of 0.0014–0.0058 mg/kg. • Atrazine had an 83.55 % share of cumulative dietary risks. • Health hazards of herbicides differed significantly among regions and ages. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are emerging pollutants with a broad distribution in marine environments. They can interact with other pollutants and be bioaccumulated by marine bivalves, which can be consumed by humans. This is the first review that focuses on the presence and effects of PAHs, single or combined with other pollutants, in commercial marine bivalves. Around the world, researchers have detected several PAHs in valuable marine bivalves and reported immunological, genotoxic, neurotoxic, physiological, reproductive, and biochemical effects in these species caused by exposure to PAHs, alone or combined with other pollutants, using efficient and accurate methods. Commercial marine bivalves contaminated with PAHs may pose a risk to marine food chains and environments and to human health. We recommend further research on the abundance and neurotoxic, physiological, reproductive and biochemical effects of PAHs, alone and with other pollutants, in commercial marine bivalves and more human health risk assessments. • Polycyclic aromatic hydrocarbons (PAHs) are emerging pollutants. • PAHs have a ubiquitous distribution in marine ecosystems. • PAHs are bioaccumulated by valuable marine bivalve species. • PAHs, alone or with other pollutants, cause numerous impacts on marine bivalves. • Consumption of PAH-contaminated marine bivalves can compromise human health. [ABSTRACT FROM AUTHOR]

The escalating presence of microplastics and heavy metals in marine environments significantly jeopardizes ecological stability and human health. Despite this, research on the combined effects of microplastics/nanoplastics (MPs/NPs) and heavy metals on marine organisms remains limited. This study evaluated the impact of two sizes of polystyrene beads (approximately 2 μm and 200 nm) combined with cadmium (Cd) on the ciliate species Euplotes vannus. Results demonstrated that co-exposure of MPs/NPs and Cd markedly elevated reactive oxygen species (ROS) levels in ciliates while impairing antioxidant enzyme activities, thus enhancing oxidative damage and significantly reducing carbon biomass in ciliates. Transcriptomic profiling indicated that co-exposure of MPs/NPs and Cd potentially caused severe DNA damage and protein oxidation, as evidenced by numerous differentially expressed genes (DEGs) associated with mismatch repair, DNA replication, and proteasome function. Integrated transcriptomic and metabolomic analysis revealed that DEGs and differentially accumulated metabolites (DAMs) were significantly enriched in the TCA cycle, glycolysis, tryptophan metabolism, and glutathione metabolism. This suggests that co-exposure of MPs/NPs and Cd may reduce ciliate abundance and carbon biomass by inhibiting energy metabolism and antioxidant pathways. Additionally, compared to MPs, the co-exposure of NPs and Cd exhibited more severe negative effects due to the larger specific surface area of NPs, which can carry more Cd. These findings provide novel insights into the toxic effects of MPs/NPs and heavy metals on protozoan ciliates, offering foundational data for assessing the ecological risks of heavy metals exacerbated by MPs/NPs. [Display omitted] • MPs/NPs can serve as carriers for transporting Cd and increasing its toxicity. • Co-exposure to MPs/NPs and Cd led to a notable decline in ciliate carbon biomass. • Ciliates treated with MPs/NPs and Cd developed severe oxidative stress response. • Co-exposure to MPs/NPs and Cd caused transcriptomic and metabolomic disorders. • Co-exposure to NPs and Cd had more severe adverse effects than MPs with Cd. [ABSTRACT FROM AUTHOR]

There is growing interest in interactions of microplastics (MPs) with other pollutants. However, there is limited understanding of the combined effects of MPs and silver nanoparticles (AgNPs) on nontarget soil organisms. This work aimed to examine the effects of exposure to various AgNPs' concentrations alone (0, 0.1, 1, 10, 100, 1000 mg kg−1, 50 nm) and in combination with polyvinyl chloride microplastics (PVC MPs, 80−250 μm) at 0.1% concentration for 28 days on reproduction, Ag accumulation, C/N ratio, and isotopic fractionation of the standard soil fauna collembolan Folsomia candida. Results showed that compared to the AgNPs exposure alone, the presence of MPs significantly reduced reproduction by 51.4% and markedly increased Ag content in collembolans by 87.7% at 1000 mg kg−1 AgNPs, which evidenced a synergistic effect. Co-exposure to MPs and AgNPs resulted in a noticeable reduction in the C/N ratio in F. candida body tissues by 9.90% and 5.27% at 1 and 10 mg kg−1 AgNPs, respectively, showing additive and synergistic effects. Additionally, this co-exposure altered stable isotope fractionation, with the highest increments of δ15N by 32.3% and inhibition of δ13C by 2.62%, demonstrating the turnover of nutrients shift in the collembolan tissues. Collectively, this study demonstrates that con-current exposure to environmentally relevant concentration of MPs and relatively high doses of AgNPs synergistically induces toxic effects on F. candida , leading to Ag accumulation and reproduction decline. These findings imply that MPs could alter collembolans' responses to AgNPs exposure, potentially enhancing the metal ions' bioavailability in soil environments and posing ecotoxicological threats to soil-dwelling organisms. [Display omitted] • Co-exposure to MPs and AgNPs reduces the reproduction of collembolan. • The presence of MPs enhances the accumulation of Ag in collembolan. • Co-existence of MPs and AgNPs introduces reduction in collembolan' C/N ratio. • Co-occurrence of MPs and AgNPs tends to increase δ15N and decrease δ13C. [ABSTRACT FROM AUTHOR]

By growing the electrical power networks and electronic devices, electromagnetic fields (EMF) have become an inseparable part of the modern world. Considering the inevitable exposure to a various range of EMFs, especially at extremely low frequencies (ELF-EMF), investigating the biological effects of ELF-EMFs on biological systems became a global issue. The possible adverse consequences of these exposures were studied, along with their potential therapeutic capabilities. Also, their biological impacts in combination with other chemical and physical agents, specifically ionizing radiation (IR), as a co-carcinogen or as adjuvant therapy in combination with radiotherapy were explored. Here, we review the results of several in-vitro and in-vivo studies and discuss some proposed possible mechanisms of ELF-EMFs' actions in combination with IR. The results of these experiments could be fruitful to develop more precise safety standards for environmental ELF-EMFs exposures. Furthermore, it could evaluate the therapeutic capacities of ELF-EMFs alone or as an improver of radiotherapy. [ABSTRACT FROM AUTHOR]

In recent years, the concentrations of cadmium (Cd) and diclofenac (DCF) in water have frequently exceeded the standard; however, the toxic effects of these two pollutants on grass carp under single and combined exposure are unknown. In this study, the concentrations of pollutants in different tissues were detected, and the toxicities of the two pollutants to grass carp under different exposure conditions were compared based on growth traits, biochemical responses, gut microbiome, and transcriptomes. Based on these findings, the brain showed the lowest levels of Cd and DCF accumulation. Oxidative stress and pathological damage were observed in the brain and intestines. Changes in the structure and abundance of the gut microflora affect the synthesis of neurotransmitters, such as GABA and steroids. Differentially expressed genes in the brain were enriched in circadian rhythm functions. The expression of PER , CLOCK , 1L-1β , 1L-17 , and other genes are related to the abundance of Akkermansia , which indicates that the disorder of gut microflora will affect the normal circadian rhythm of the brain. All indices in the recovery group showed an increasing trend. Overall, the toxicity of Cd and DCF showed antagonism, and a single exposure had a stronger effect on gut microorganisms and circadian rhythm, which provided a scientific basis for exploring the comprehensive effects of different pollutants. [Display omitted] • Cd and DCF can accumulate in different tissues and inhibit the growth of grass carp. • Oxidative stress and pathological damage occurred in the brain and intestine. • Exposure to Cd and DCF disrupts the homeostasis and function of gut microflora. • Cd and DCF exposure can affect the normal circadian rhythm of the brain. • After seven days of recovery, the damage of grass carp gradually recovered. [ABSTRACT FROM AUTHOR]

Marine organisms commonly encounter co-stress resulting from the coexistence of microplastics (MPs) and heavy metals pollution in marine environments. Nevertheless, the combined effects and toxicity mechanisms of MPs and heavy metals on marine organisms remain unclear. This study integrated growth, physiological, morphological, and biochemical markers to assess the individual and combined toxicity of polyvinyl chloride MPs (PVC MPs, 1 × 104 particles/L) and copper (Cu, 200 μg/L) on marine jacopever (Sebastes schlegelii). The results revealed that co-exposure to MPs and Cu had a more detrimental impact on jacopever compared to the single-exposure groups, as evidenced by the enhanced growth inhibition, respiratory stress, and hepatotoxicity. This phenomenon may be attributed to PVC MPs accelerating the accumulation of Cu in jacopever liver. Therefore, peroxidation damage occurred in the co-exposed liver and may result in liver dysfunction. These findings contribute valuable insights into the risks associated with the coexistence of MPs and heavy metal pollution in marine ecosystems. [Display omitted] • The combined toxicity of PVC MPs and Cu to marine jacopever were investigated. • Co-exposure to PVC MPs and Cu caused more severe toxicity than single exposures. • PVC MPs played a role in accelerating the accumulation of Cu in jacopever liver. • PVC MP had a notable impact on hepatic lipid metabolism. • Co-exposure to PVC MPs and Cu resulted in oxidative damage and dysfunction in liver. [ABSTRACT FROM AUTHOR]

Chemical exposure can indirectly affect leaf microbiota communities, but the mechanism driving this phenomenon remains largely unknown. Results revealed that the co-exposure of glyphosate and multi-carbon nanotubes (CNTs) caused a synergistic inhibitory effect on the growth and metabolism of Arabidopsis thaliana shoots. However, only a slight inhibitory effect was induced by nanotubes or glyphosate alone at the tested concentrations. Several intermediate metabolites of nitrogen metabolism and fatty acid synthesis pathways were upregulated under the combined treatment, which increased the amount of energy required to alleviate the disruption caused by the combined treatment. Additionally, compared with the two individual treatments, the glyphosate/nanotube combination treatment induced greater fluctuations in the phyllosphere bacterial community members with low abundance (relative abundance (RA) <1%) at both the family and genus levels, and among these bacteria some plant growth promotion and nutrient supplement related bacteria were markable increased. Strikingly, strong correlations between phyllosphere bacterial diversity and metabolites suggested a potential role of leaf metabolism, particularly nitrogen and carbohydrate metabolism, in restricting the range of leaf microbial taxa. These correlations between phyllosphere bacterial diversity and leaf metabolism will improve our understanding of plant-microbe interactions and the extent of their drivers of variation and the underlying causes of variability in bacterial community composition. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • The responses of bulk and rhizosphere microorganisms to pesticides were different. • Rhizospheres were more sensitive to azoxystrobin and oxytetracycline. • The rhizosphere resists stress by enhancing network stability and complexity. • Co-exposure to azoxystrobin and oxytetracycline caused antagonistic effects. • Antagonism affects organic-degrading bacteria and ABC transporters. The rhizosphere is one of the key determinants of plant health and productivity. Mixtures of pesticides are commonly used in intensified agriculture. However, the combined mechanisms underlying their impacts on soil microbiota remain unknown. The present study revealed that the rhizosphere microbiota was more sensitive to azoxystrobin and oxytetracycline, two commonly used pesticides, than was the microbiota present in bulk soil. Moreover, the rhizosphere microbiota enhanced network complexity and stability and increased carbohydrate metabolism and xenobiotic biodegradation as well as the expression of metabolic genes involved in defence against pesticide stress. Co-exposure to azoxystrobin and oxytetracycline had antagonistic effects on Arabidopsis thaliana growth and soil microbial variation by recruiting organic-degrading bacteria and regulating ABC transporters to reduce pesticide uptake. Our study explored the composition and function of soil microorganisms through amplicon sequencing and metagenomic approaches, providing comprehensive insights into the synergistic effect of plants and rhizosphere microbiota on pesticides and contributing to our understanding of the ecological risks associated with pesticide use. [ABSTRACT FROM AUTHOR]

Pentachlorophenol (PCP) - cadmium (Cd) complex pollution has been identified as a form of persistent soil pollution in south China, exerting detrimental impacts on the indigenous soil bacterial communities. Hence, it is worthwhile to investigate whether and how bacterial populations alter in response to these pollutants. In this study, Escherichia coli was used as a model bacterium. Results showed that PCP exposure caused bacterial cell membrane permeability changes, intracellular ROS elevation, and DNA fragmentation, and triggered apoptosis-like cell death at low exposure concentration and necrosis at high exposure concentration. Cd exposure caused severe oxidative damage and cell necrosis in the tested bacterial strain. The co-exposure to PCP and Cd elevated the ROS level, stimulated the bacterial caspase activity, and induced DNA fragmentation, thereby leading to an apoptosis-like cell death. In conclusion, PCP-Cd complex pollution can cause bacterial population to decrease through apoptosis-like cell death pathway. However, it is worth noting that the subpopulation survives under the complex pollution stress. [Display omitted] • PCP exposure triggered bacterial apoptosis-like cell death and necrosis. • Cd exposure caused severe bacterial oxidative damage and cell necrosis. • The co-exposure caused bacterial oxidative stress and apoptosis-like cell death. • Bacterial cell membrane depolarization can be a potential ultrasensitive indicator. [ABSTRACT FROM AUTHOR]

Microplastic pollution is widespread in the natural environment, and its enrichment, inherent adsorbability, and toxicity are key concerns in society. However, few studies of the effects of microplastic toxicity on the reproduction of fish have been reported. In this study, we investigated the effects of exposure to environmentally relevant concentrations of polystyrene microplastics (PS) and cadmium (Cd) alone and in combination for 28 days on the gonad development and reproduction of rare minnow (Gobiocypris rarus). Decreased condition factor, number of spawning events, number of eggs per spawning, and average hatching rate were detected in fish in the treatment groups. These changes were likely due to long-term oxidative stress and inflammation, which inhibited the development of gonads and further affected the reproduction function of rare minnow. The effects of treatment on oxidative stress, inflammation, and expression of genes related to gonad development differed between female and male fish in the treatment groups. PS alone exposure resulted in a significant reduction in the number of eggs per spawning and average hatching rate, but these effects were not observed in the Cd and PS + Cd groups. These results provide new insights into the ecotoxicological effects of microplastics in the natural environment. [Display omitted] • PS and Cd affected the condition factor and gonad development. • PS and Cd induced inflammation and oxidative stress. • Environmentally relevant concentration PS affected reproduction of rare minnow. • The effects difference between the females and males. [ABSTRACT FROM AUTHOR]

and nano-pollutants are receiving increased research attention. However, the effects of the interactions and co-exposure to these pollutants in soil are yet to be fully elucidated. This work aimed to investigate the effects of co-exposure to polyethylene microplastics (PEMPs) and nano-ZnO (nZnO) in soil on the growth, nutrient uptake, and distribution of the peanut (Arachis hypogaea L.) and soil microbial community. Results revealed that 500 mg kg−1 nZnO significantly decreased the dry weight of peanut root, stem, leaf, and fruit by 84.4%, 79.1%, 87.3%, and 95.8%, respectively, compared with the control. Co-exposure treatments significantly alleviated this trend. Co-exposure treatments further decreased Zn concentration in peanuts by 30.3%–58.9% compared with nZnO single exposure. The distribution of Zn in peanut stems also maintained a consistent trend with the concentration and primarily occurred in the vascular bundles near the epidermis. Co-exposure and PE treatments increased the abundance of soil bacteria primarily because many PE particles entered the soil to build more living space for bacteria. These findings showed that composite pollution had a robust disturbing effect on the soil–peanut system, and the two pollutants were primarily physically adsorbed. PE particles can adsorb nZnO and then become the carrier of nanoparticles. [Display omitted] [ABSTRACT FROM AUTHOR]

The use of bisphenol A (BPA) in manufacturing of plastics is being gradually replaced by presumably safer analogues such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF). Despite their widespread occurrence in the environment, there is a knowledge gap in their toxicological profiles. We investigated cytotoxic/genotoxic effects as well as changes in the expression of selected genes involved in the xenobiotic metabolism, response to oxidative stress and DNA damage upon exposure to BPs and their mixtures in human hepatocellular carcinoma HepG2 cells. BPS and BPF slightly decreased the viability of HepG2 cells, while BPAF was the most cytotoxic compound tested. BPA, BPF and BPAF induced the formation of DNA double strand breaks determined with γH2AX assay, while BPS was inactive (5–20 μg/mL). All four BPs up-regulated the expression of CYP1A1 and UGT1A1 , while BPS up-regulated and BPAF down-regulated also the expression of GST1A. Only BPA up-regulated oxidative stress responsive gene GCLC , while BPAF up-regulated the expression of CDKN1A and GADD45a. At concentrations relevant for human exposure (ng/mL range) BPA and its analogues as individual compounds and in mixtures did not exert genotoxic activity, whereas BPA and BPAF as well as the mixtures up-regulated the expressions of CYP1A1 and UGT1A1. Unlabelled Image • BPF and BPAF showed higher cytotoxic/genotoxic potential than BPA in HepG2 cells. • BPS showed the lowest cytotoxic/genotoxic potential compared to BPA. • At low environmentally relevant concentrations, BPs did not induce DNA damage. • At combined exposure, BPs induced additive effects in the expression of specific genes. • Not all BPA analogues present safer replacement for BPA. [ABSTRACT FROM AUTHOR]

Abstract Exposure to particulate matter (PM), such as mineral particles and biological particles/components may be linked to aggravation of respiratory diseases, including asthma. Here we report that exposure to Aspergillus fumigatus hyphae fragments (AFH) and lipopolysaccharide (LPS) induced both mRNA synthesis and release of pro-inflammatory interleukin-1 beta (IL-1β) in both human THP-1 monocytes (THP-1 Mo) and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 monocytes (THP-1 macrophages; THP-1 Ma); while Min-U-Sil alone enhanced the release of IL-1β only in THP-1 Ma. Co-exposure to LPS or AFH with Min-U-Sil caused a synergistic release of IL-1β when compared to single exposures. In contrast, Min-U-Sil did not markedly change LPS- and AFH-induced release of tumor necrosis factor alpha (TNF-α). The combined exposures did not increase the LPS- and AFH-induced expression of IL-1β mRNA. Notably, the AFH- and LPS-induced IL-1β responses with and without co-exposure to Min-U-Sil in THP-1 Mo were found to be caspase-dependent as shown by inhibition with zYVAD-fmk. Furthermore, co-exposure with AFH and Min-U-Sil resulted in similar synergistic releases of IL-1β in primary human airway macrophages (AM; sputum), peripheral blood monocyte-derived macrophages (MDM) and in the human bronchial epithelial cell line (BEAS-2B). In conclusion, AFH induce both the synthesis and release of IL-1β. However, Min-U-Sil further enhanced the cleavage of the induced pro-IL-1β. Highlights • A. fumigatus hyphae induced release of IL-1β in THP-1 monocytes and macrophages • Hyphae and silica synergistically enhanced IL-1β-release in THP-1 cells • Synergistic effect was caspase-dependent • Synergistic effects were also seen in primary human macrophages/lung epithelial cells • Primed cells may represent a relevant model to study particle pollution [ABSTRACT FROM AUTHOR]

The ecological risk posed by MCs-producing M. aeruginosa and elevated ammonia to fish in actual aquatic environments remains uncertain. To address this knowledge gap, we conducted simulations to investigate the endocrine-reproductive toxicity of prolonged exposure (45 d) to Microcystis aeruginosa (2 × 10^6 cells/mL) and 30 mg/L total ammonia nitrogen (TAN) in zebrafish under environmentally relevant conditions. Our results showed that exposure to M. aeruginosa significantly inhibited the body weight, increased gonadosomatic index (GSI), delayed oocyte development, and disrupted endocrine hormonal balance (reduced gonadotropin-releasing hormone (GnRH), and increased estradiol (E2) and testosterone (T)). Mechanistically, it should be attributed to the over-expression of hypothalamic-pituitary-gonadal-liver (HPGL) axis-related genes (cyp11a and cyp17) induced by M. aeruginosa. On the other hand, TAN exposure caused mild damage to zebrafish ovarian tissue and promoted an increase of T levels by inducing the upregulation of steroid hormone synthesis gene (3βhsd) expression in the ovary. It is worth noting that the dysregulation of E2/T ratio in zebrafish ovaries may be attributed to the inhibition of cyp19a1a by both M. aeruginosa and TAN. These results were further confirmed by changes in steroidogenic enzymes activities in the M. aeruginosa or TAN treated groups. Our findings indicated that exposure to M. aeruginosa and TAN had adverse impacts on the reproductive system of zebrafish. And the combined exposure of M. aeruginosa and TAN had more severe effects on the body weight, GSI, pathological changes, hormone levels and HPGL-axis related gene expression in female zebrafish. These results provide compelling evidence regarding the potential risks for reproductive health associated with M. aeruginosa and TAN in eutrophic water bodies experiencing M. aeruginosa blooms, and contribute to the development of effective strategies for monitoring and managing these toxins in aquatic ecosystems. [Display omitted] • M. aeruginosa and ammonia induced ovarian tissue damage in zebrafish. • M. aeruginosa and ammonia increased the levels of sex hormones in the ovary. • M. aeruginosa and ammonia altered the expression of HPGL axis-related genes. • Ammonia enhanced the destruction of zebrafish reproductive system by M. aeruginosa. [ABSTRACT FROM AUTHOR]

Association between organochlorine pesticides (OCPs) exposure and type 2 diabetes mellitus (T2DM) remains contradictory, and the evidence is mostly focused on a single exposure. Here, we assessed the associations between individual and combined OCPs exposure and T2DM, and explored the underlying mechanism of sex hormones and the methylation levels of sex hormone receptors in above associations. A case-control study with 1812 participants was performed. Gas chromatography mass spectrometry, liquid chromatography-tandem mass spectrometry, and pyrosequencing were used to measure plasma OCPs, serum sex hormones, and whole blood methylation levels of sex hormone receptors, respectively. Generalized linear models were used to analyze the relationships between OCPs, sex hormones, the methylation levels of sex hormone receptors, and T2DM. Quantile based g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) were employed to assess the combined OCPs exposure. The roles of sex hormones and the methylation levels of their receptors were evaluated by moderating mediation models. After adjusting for covariates, each unit (2.718 ng/ml) increase in p,p'-DDE was associated with a higher risk of T2DM in males (odds ratio (OR) and 95% confidence interval (CI): 1.066 (1.023, 1.112)). QGC and BKMR showed a positive combined effect in the associations of OCPs mixtures on T2DM among premenopausal females, and positive effects but not statistically significant among males and postmenopausal females. p,p'-DDE was the largest contributor for the positive associations. Furthermore, testosterone mediated 21.149% of the associations of p,p'-DDE with T2DM moderated by the androgen receptor methylation (ARm) located in CpG island 1. Individual and mixtures of OCPs exposure were positively linked to elevated risk of T2DM. Testosterone and ARm may participate in the related processes of OCPs with T2DM, providing new insights into the adverse endocrine effects caused by OCPs and specific pathways for the etiology and control of diabetes. [Display omitted] • Individual and mixtures of OCPs exposure were positively related to T2DM risk. • Higher OCPs levels were observed to be related to lower serum testosterone levels. • A negative correlation between OCPs and androgen receptor methylation (ARm). • Testosterone and ARm plays a mediator and moderator between OCPs and T2DM. • This provides new insights into the pathways for the etiology and control of T2DM. [ABSTRACT FROM AUTHOR]

Nanoplastics and heavy metals are common pollutants in coastal environments with high concerns, but their joint ecological risk to marine primary productivity remains unclear. In this study, the effects of 7, 70, 700 μg/L lead (Pb) single exposure and in combination with 200 μg/L polystyrene nanoplastics (NPs, 70 nm) on marine microalga Platymonas helgolandica were investigated. Pb single exposure induced a dose-dependent inhibition on the growth of P. helgolandica , which was associated with the reduced photosynthetic efficiency and nutrient accumulation. Compared to Pb single exposure, the addition of NPs significantly reduced the photosynthetic efficiency and aggravated the damage to cell structure. Reduced esterase activity and increased membrane permeability also indicated that NPs exacerbated the adverse effects of Pb on P. helgolandica. Thus, co-exposure to NPs and Pb induced more severe impacts on marine microalgae, suggesting that the joint ecological risk of NPs and heavy metals to marine primary productivity merits more attention. [Display omitted] • Pb exposure showed a dose-dependent inhibition on the growth of P. helgolandica. • NPs and Pb combined exposure induced higher mortality and membrane permeability. • NPs and Pb combined exposure reduced esterase activities and pigment content. • Inhibition of photosynthesis in Pb-exposed P. helgolandica was enhanced by NPs. • NPs induced greater cell structure damage in P. helgolandica compared Pb exposure. [ABSTRACT FROM AUTHOR]

Carbazole (CZ) and eight polyhalogenated carbazoles (PHCZs) were quantified by GC–MS in sediments of 12 estuaries, the interface linking large industrial and living areas to the Bohai Sea, China. These pollutants, heavy metals, and environmental factors caused integrated exposure to sediment bacteria. Four PHCZ congeners were detectable, with ΣPHCZs ranging from 0.56 to 15.94 ng/g dw. The dominant congeners were 3,6-dichlorocarbazole (36-CCZ) and 3-chlorocarbazole (3-CCZ), with a mean contribution of 72.6 % and 20.2 %. Significant positive correlations were found between 36-CCZ and both total organic carbon and heavy metals. Redundancy analysis of microbial variation implicated no impacts from PHCZs. Correlation analysis demonstrated an increase in abundance of Rhodocyclaceae but a decrease in Bacteroides-acidifaciens-JCM- 10556 with presence of PHCZs, suggesting that these bacteria can be used as potential contamination indicators. The combined exposure of heavy metals, nutrients, and PHCZs may also increase toxicity and biological availability, adversely affecting the ecosystem and human health. • First detection of PHCZs in sediments of 12 rivers around the Bohai Sea. • The most abundant congener of PHCZs was 36-CCZ, followed by 3-CCZ. • 36-CCZ and 3-CCZ may come from the same source or from mutual transformation. • Elevated TOC can promote microbial growth and contaminant adsorption. • PHCZs, heavy metals, physicochemical factors, and bacteria promoted each other. [ABSTRACT FROM AUTHOR]

Previous work has shown that mice exposed to dibutyl phthalate (DBP) adsorbed onto multi-walled carbon nanotubes (MWCNTs), via tail vein injection, displayed black lesions in their lungs. To investigate the mechanism causing this toxicity in the lung tissue, we performed an experiment with rats, exposing them to DBP adsorbed onto MWCNTs via a tail vein injection for 14 days. The results revealed pulmonary edema and greyish-black lung tissue in the MWCNTs and the MWCNTs + DBP combined exposure groups. In the combined exposure group there was evident alveolar fragmentation and adhesion, and lung tissue sections showed significant levels of black particles. Sections of the non-cartilaginous region of the trachea had significant folding of the pseudostratified ciliated columnar epithelium and marked thickening of the submucosa. In broncho alveolar lavage fluid, the number of leukocytes (WBC), lymphocytes (Lym), neutrophils (Neu), and eosinophils (Eos), as well as levels of immunoglobulin E (IgE), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 1β (IL-1β) were all significantly higher. TNF-α, IL-6, signal transducer and activator of transcription 3 (STAT3), and α-smooth muscle actin (α-SMA) mRNA expression were all elevated in the lung tissue. The combined exposure group, which had considerable airway remodeling, had a greater degree of tracheal constriction and luminal narrowing, according to the results of the α-SMA immunofluorescence assay. According to these experimental findings, the exposure to both MWCNTs and DBP seemed to have a synergistic effect and exacerbated rats' impaired respiratory function that resulted from exposure to MWCNTs alone. • Combined exposure to MWCNTs and DBP synergistically exacerbates airway inflammation. • The MWCNTs adsorbed to the DBP can attach to the lung quickly, causing severe pathological damage. • Overexpression of α-SMA is cause of tracheal constriction and lumen narrowing. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is a trichothecene toxin that mainly produced by strains of Fusarium spp. DON contamination is widely distributed and is a global food safety threat. Existing studies have expounded its harmful effects on growth inhibition, endocrine disruption, immune function impairment, and reproductive toxicity. In energy metabolism, DON suppresses appetite, reduces body weight, triggers lipid oxidation, and negatively affects cholesterol and fatty acid homeostasis. In this study, high-fat diet (HFD) induced obese C57BL/6J mice were orally treated with 0.1 mg/kg bw/d and 1.0 mg/kg bw/d DON for 4 weeks. The lipid metabolism of mice and the molecular mechanisms were explored. The data showed that although DON reduced body weight and fat mass in HFD mice, it significantly increased their serum triglyceride concentrations, disturbance of serum lipid metabolites, impaired glucose, and resulted in insulin intolerance in mice. In addition, the transcriptional and expression changes of lipid metabolism genes in the liver and epididymis (EP) adipose indicate that the DON-mediated increase in serum triglycerides is caused by lipoprotein lipase (LPL) inhibition in EP adipose. Furthermore, DON down-regulates the expression of LPL through the PPARγ signaling pathway in EP adipose. These results are further confirmed by the serum lipidomics analysis. In conclusion, DON acts on the PPARγ pathway of white adipose to inhibit the expression of LPL, mediate the increase of serum triglyceride in obese mice, disturb the homeostasis of lipid metabolism, and increase the risk of cardiovascular disease. This study reveals the interference mechanism of DON on lipid metabolism in obese mice and provides a theoretical basis for its toxic effect in obese individuals. [ABSTRACT FROM AUTHOR]

Abstract As human co-exposure to natural toxins through food and water is inevitable, risk assessments to safeguard health are necessary. Aflatoxin B 1 and fumonisin B 1 , frequent co-contaminants of maize and microcystin-LR, produced in freshwater by cyanobacteria are all naturally occurring potent toxins that threaten human health. Populations in the poorest regions of the world may suffer repeated simultaneous exposure to these contaminants. Using High Content Analysis, multiple cytotoxicity endpoints were measured for the individual toxins and mixtures in various cell lines. Results highlighted that significant cytotoxic effects were observed for aflatoxin B 1 in all cell lines while no cytotoxic effects were observed for fumonisin B1 or microcystin-LR. Aflatoxin B 1 /microcystin-LR was cytotoxic in the order HepG2 > Caco-2 > MDBK. Fumonisin B 1 /microcystin-LR affected MDBK cells. The ternary mixture was cytotoxic to all cell lines. Most combinations were additive, however antagonism was observed for binary and ternary mixtures in HepG2 and MDBK cell lines at low and high concentrations. Synergy was observed in all cell lines, including at low concentrations. The combination of these natural toxins may pose a significant risk to populations in less developed countries. Furthermore, the study highlights the complexity around trying to regulate for human exposure to multiple contaminants. Graphical abstract Image 1 Highlights • Significant cytotoxic effects were observed for Aflatoxin B 1 at 1.6 μM in all cell lines. • No cytotoxic effects were observed for fumonisin B 1 or microcystin-LR in any cell lines. • Binary and ternary mixtures induced cytotoxicity in various endpoints in all cell lines tested. • Most of the combinatory effects observed in all three cell lines were additive. • Antagonism and synergy were for binary and ternary mixtures, HepG2 cells were most affected. [ABSTRACT FROM AUTHOR]

Road traffic induces air and noise pollution in urban environments having negative impacts on human health. Thus, estimating exposure to road traffic air and noise pollution (hereafter, air and noise pollution) is important in order to improve the understanding of human health outcomes in epidemiological studies. The aims of this review are (i) to summarize current practices of modelling and exposure assessment techniques for road traffic air and noise pollution (ii) to highlight the potential of existing tools and techniques for their combined exposure assessment for air and noise together with associated challenges, research gaps and priorities. The study reviews literature about air and noise pollution from urban road traffic, including other relevant characteristics such as the employed dispersion models, Geographic Information System (GIS)-based tool, spatial scale of exposure assessment, study location, sample size, type of traffic data and building geometry information. Deterministic modelling is the most frequently used assessment technique for both air and noise pollution of short-term and long-term exposure. We observed a larger variety among air pollution models as compared to the applied noise models. Correlations between air and noise pollution vary significantly (0.05–0.74) and are affected by several parameters such as traffic attributes, building attributes and meteorology etc. Buildings act as screens for the dispersion of pollution, but the reduction effect is much larger for noise than for air pollution. While, meteorology has a greater influence on air pollution levels as compared to noise, although also important for noise pollution. There is a significant potential for developing a standard tool to assess combined exposure of traffic related air and noise pollution to facilitate health related studies. GIS, due to its geographic nature, is well established and has a significant capability to simultaneously address both exposures. [ABSTRACT FROM AUTHOR]

As the accumulation of microplastics (MPs) in the environment continues to rise, more concerns focus on the health risk of combined exposure to MPs and other contaminants. The aim of this study is to investigate the influences of MPs on the tissue-accumulation of cadmium (Cd) in zebrafish and explore the related chronic toxic effects induced by combined exposure of Cd and MPs. After co-exposure to MPs and Cd for 3 weeks, 20 and 200 μg/L MPs increased the accumulation of Cd in zebrafish livers (46% and 184%), guts (10% and 25%) and gills (9% and 46%). The Cd accumulation was gill > gut > liver. Comprehensive analyzes of biochemical biomarkers, histopathological observation and functional gene expression firstly demonstrated that the presence of MPs enhanced the toxicity of Cd on zebrafish and the combined exposure caused oxidative damage and inflammation in zebrafish tissues. Collectively, our results highlight the chronic effects of combined exposure to MPs and heavy metals. [ABSTRACT FROM AUTHOR]

Many studies have demonstrated that microplastics (MPs) can combine with various coexisting chemical pollutants, increasing their bioavailability and changing the combined toxicity to organisms. However, information on the combined effects of MPs and amitriptyline (AMI, a widely used tricyclic antidepressant) on aquatic species is still limited. In this study, we exposed zebrafish to MPs (2-μm polystyrene beads, 0.44 mg/L), AMI (2.5 μg/L), and their mixture for 7 days and investigated the alternation in their behaviors and ocular oxidative stress. As a result, combined exposure to MPs and AMI could significantly elevate locomotor activity, increase the frequency and duration of shoaling behavior in zebrafish, and alter their post-stimulation behaviors. Although combined exposure to MPs and AMI exhibited stronger behavioral toxicity than individual exposure, no significant interactive effects on the behavioral traits were detected, suggesting that the combined behavioral toxicity appeared to be an additive effect. However, their combined exposure to MPs or AMI significantly decreased the ocular levels of SOD, CAT, and GSH in zebrafish, with significant interaction effects on the CAT activity and GSH content. Significant correlations between some post-stimulation behavioral traits and ocular levels of SOD, CAT, and GSH in zebrafish were detected, suggesting that ocular oxidative stress induced by combined exposure to MPs and AMI may play an important role in their behavioral toxicity. [Display omitted] • Signal exposure to MPs or AMI elevated social interaction in zebrafish. • Their co-exposure altered activity, social interaction and responses to stimulation. • MPs and AMI exhibited additive effects on the behavioral traits of zebrafish. • Ocular oxidative stress was induced by co-exposure but not by signal exposures. • Ocular oxidative stress exhibited significant correlations with behavioral traits. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) and tetracycline are both emerging environmental pollutants that threaten human health. The toxic impacts of their single and coexposure on the intestine and gut microbiota have not been well studied in mammals. Given the spatial functional characteristics of the intestine, it is important to know whether the toxicities of MPs and tetracycline in different intestinal segments are distinct. This study investigated the pathological and functional injuries of different intestinal segments and the microbial disorder upon exposure to polystyrene microplastics (PS-MPs) and/or tetracycline hydrochloride (TCH). Both PS-MPs and TCH altered the intestinal morphology and induced functional impairment. However, the PS-MPs primarily damaged the colon, while TCH mainly damaged the small intestine, especially the jejunum. Combined treatment evoked ameliorative adverse effects on the intestinal segments except for the ileum. Gut microbiota analysis revealed that PS-MPs and/or TCH decreased gut microbiota diversity, especially PS-MPs. In addition, PS-MPs and TCH affected the microflora metabolic processes, especially protein absorption and digestion. Gut microbiota dysbiosis could partly lead to the physical and functional damage induced by PS-MPs and TCH. These findings enhance our knowledge regarding the hazards of coexisting microplastics and antibiotics for mammalian intestinal health. [Display omitted] • PS-MPs and TCH exposure injured the intestinal tract of mice and impacts varied spatially. • Combined exposure had a negative effect on gut segments except for the ileum. • PS-MPs and/or TCH decreased gut microbiota diversity. • Results support further evaluation of impacts of microplastics and antibiotics on mammalian intestinal health. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) are a newly emerging type of pollutants. To date, MPs have been found in the atmosphere, soil, water, and even in human samples, posing a non-negligible threat to humans. Furthermore, multiple heavy metals have been found to co-exist with MPs or be absorbed by MPs. This leads to a widespread concern about their combined toxicity, which is currently elusive. Herein, we investigated the single or combined toxic effects of polystyrene MPs (PS-MPs) and cadmium chloride (CdCl 2) on the liver and hepatocytes. After co-incubation, cadmium (Cd) can be absorbed by PS-MPs, resulting in physiochemical alterations of PS-MPs. In vivo and in vitro experiments revealed that PS-MPs solely or together with CdCl 2 induced ferroptosis in hepatocytes, a newly defined programmed cell death characterized by lipid oxidation and iron accumulation. PS-MPs exerted more ferroptotic effect on hepatocytes than CdCl 2 , and combined exposure to PS-MPs and CdCl 2 enhanced their ferroptotic effect, mainly by stimulating reactive oxygen species (ROS) production and inhibiting antioxidant activity. Upon single or combined exposure to PS-MPs and CdCl 2 , the induction of ferroptosis in hepatocytes can be inhibited by N-acetyl-cysteine (NAC, an ROS scavenger), deferoxamine (DFO, an iron chelator), and particularly ferrostatin-1 (Fer-1, a specific ferroptosis inhibitor). Fer-1 efficiently rescued the cell viability of hepatocytes upon exposure to PS-MPs and CdCl 2 through enhancing the antioxidant system via upregulating GPX4 and SLC7A11. These findings would contribute to an in-depth understanding of the single and combined toxicity of microplastics and cadmium. [Display omitted] • Ferroptosis co-occurs with hepatic injury caused by cadmium. • Microplastics induce more ferroptotic effect on hepatocytes than cadmium. • Inhibiting ferroptosis rescues cells upon exposure to microplastics and cadmium. [ABSTRACT FROM AUTHOR]

Chronic kidney disease with uncertain etiology (CKDu) in Sri Lanka has attracted much attention as a global health issue. However, how environmental factors in local drinking water induce kidney damage in organisms is still elusive. We investigated multiple environmental factors including water hardness and fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM) to elucidate their toxic effects on CKDu risk in zebrafish. Acute exposure affected renal development and inhibited the fluorescence of Na, K-ATPase alpha1A4:GFP zebrafish kidney. Chronic exposure influenced the body weight of both genders of adult fish and induced kidney damage by histopathological analyses. Furthermore, the exposure significantly disturbed differential expression genes (DEGs), diversity and richness of gut microbiota, and critical metabolites related to renal functions. The transcriptomic analysis revealed that kidney-related DEGs were linked with renal cell carcinoma, proximal tubule bicarbonate reclamation, calcium signaling pathway, and HIF-1 signaling pathway. The significantly disrupted intestinal microbiota was closely related to the environmental factors and H&E score, which demonstrated the mechanisms of kidney risks. Notably, the Spearman correlation analysis indicated that the changed bacteria such as Pseudomonas , Paracoccus , and ZOR0006 , etc were significantly connected to the DEGs and metabolites. Therefore, the assessment of multiple environmental factors provided new insights on "bio-markers" as potential therapies of the target signaling pathways, metabolites, and gut bacteria to monitor or protect residents from CKDu. [Display omitted] • Acute exposure to environmental factors affected zebrafish kidney development. • Chronic exposure to adult zebrafish induced kidney damages by H&E and TEM analysis. • Transcriptomic profile provided the renal function-related DEGs and signaling pathways. • The dominant gut microbiota was disrupted and closely linked to chronic exposure. • Correlation analyses of "bio-markers" (DEGs, bacteria, metabolites) were performed for CKDu risks. [ABSTRACT FROM AUTHOR]

Joint toxicity is an important issue during the risk assessment of environmental pollutants. Contamination of heavy metals and persistent organic pollutants (POPs) under the environmental and biological settings poses substantial health risk to humans. Although previous studies demonstrated the co-occurrence of cadmium and decabrominated diphenyl ether (BDE-209) in environmental mediums, food chains and even human body, their potentially joint toxicities remain elusive thus far. Our investigation here with respect to the hepatotoxicity in vitro clearly demonstrated that combined exposure of cadmium and BDE-209 aggravated the injuries in hepatocytes, which was evidenced by the additive effects on the induction of remarkable morphological alternations, LDH release, cell apoptosis and necrosis, impairment of mitochondrial activity and transmembrane potential. Enhanced ROS production was one of the mechanisms for cell apoptosis and death upon joint treatment. Additionally, more cadmium-treated cells underwent apoptosis than BDE-209-treated cells while more ROS was generated with BDE-209 treatment, indicating that other mechanisms might be involved in cadmium-induced apoptosis. Our results would be helpful for evaluating the joint-hepatotoxicity upon combined exposure of cadmium and BDE-209 as well as investigating the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Diclofop-methyl (DM), a common post-emergence herbicide, is frequently used in agricultural production. Silver nanoparticles (AgNPs) are one of the most widely used nanoparticles, and as such, have been detected and monitored in several environmental systems. Here we investigated the interactive effects of DM and AgNPs on the physiological morphology, photosynthesis and antioxidant system of Arabidopsis thaliana . Our results demonstrated that a 1.0 mg/L DM treatment had no significant effect on the fresh weight of plant shoots and the content of total chlorophyll and anthocyanin. However, a 0.5 mg/L AgNPs treatment was found to significantly inhibit plant growth and chlorophyll synthesis, and was found to cause more severe oxidative damage in plants compared to the effects observed in a hydroponic suspension in which DM and AgNPs were jointly present. Meanwhile, the relative transcript levels of photosynthesis related genes ( psb A, rbc L, pgrl1 A and pgrl1 B) in the combined group were found to be slightly increased compared to transcript levels in the AgNPs group, in order to maintain ATP generation at relatively normal levels in order to repair light damage. One explanation for these observed antagonistic effects was that the existence of DM affects the stability of AgNPs and reduced Ag + release from AgNPs in the mixed solution. Thereupon, the Ag + -content was found to decrease in shoots and roots in the combined group by 15.2% and 9.4% respectively, compared to the AgNPs group. The coexistence of herbicides and nanomaterials in aquatic environments or soil systems will continue to exist due to their wide usages. Our current study highlights that the antagonistic effects between DM and AgNPs exerted a positive impact on A. thaliana growth. [ABSTRACT FROM AUTHOR]

Carbon disulfide (CS 2 ) is used in industry; it has been shown to have neurotoxic effects, causing central and distal axonopathies.However, it is not considered cochleotoxic as it does not affect hair cells in the organ of Corti, and the only auditory effects reported in the literature were confined to the low-frequency region. No reports on the effects of combined exposure to low-frequency noise and CS 2 have been published to date. This article focuses on the effects on rat hearing of combined exposure to noise with increasing concentrations of CS 2 (0, 63,250, and 500 ppm, 6 h per day, 5 days per week, for 4 weeks). The noise used was a low-frequency noise ranging from 0.5 to 2 kHz at an intensity of 106 dB SPL. Auditory function was tested using distortion product oto-acoustic emissions, which mainly reflects the cochlear performances. Exposure to noise alone caused an auditory deficit in a frequency area ranging from 3.6 to 6 kHz. The damaged area was approximately one octave (6 kHz) above the highest frequency of the exposure noise (2.8 kHz); it was a little wider than expected based on the noise spectrum.Consequently, since maximum hearing sensitivity is located around 8 kHz in rats, low-frequency noise exposure can affect the cochlear regions detecting mid-range frequencies. Co-exposure to CS 2 (250-ppm and over) and noise increased the extent of the damaged frequency window since a significant auditory deficit was measured at 9.6 kHz in these conditions.Moreover, the significance at 9.6 kHz increased with the solvent concentrations. Histological data showed that neither hair cells nor ganglion cells were damaged by CS 2 . This discrepancy between functional and histological data is discussed. Like most aromatic solvents, carbon disulfide should be considered as a key parameter in hearing conservation régulations. [ABSTRACT FROM AUTHOR]

Occupational noise can damage workers' hearing, and the phenomenon is even more dangerous when noise is associated with an ototoxic solvent. Aromatic solvents are known to provoke chemical-induced hearing loss, but little is known about the effects on hearing of carbon disulfide (CS2) when combined with noise. Co-exposure to CS2 and noise may have a harmful effect on hearing, but the mechanisms involved are not well understood. For instance, CS2 is not thought to have a cochleotoxic effect, but rather it is thought to cause retrocochlear hearing impairment. In other words, CS2 could have a distal neuropathic effect on the auditory pathway. However, a possible pharmacological effect of CS2 on the central nervous system (CNS) has never been mentioned in the literature. The aim of this study was to assess, in rats, the effects of a noise (continuous vs. impulse), associated with a low concentration of CS2 [(short-term threshold limit value) x 10 as a safety factor] on the peripheral auditory receptor. The noise, whatever its nature, was an octave band noise centered at 8 kHz, and the 250-ppm CS2 exposure lasted 15 min per hour, 6 h per day, for 5 consecutive days. The impact of the different experimental conditions on hearing loss was assessed using distortion product oto-acoustic emissions and histological analyses. Although the LEX,8 h (8-h time-weighted average exposure) for the impulse noise was lower (84 dB SPL) than that for the continuous noise (89 dB SPL), it appeared more damaging to the organ of Corti, in particular to the outer hair cells. CS2 exposure alone did not have any effect on the organ of Corti, but co-exposure to continuous noise with CS2 was less damaging than exposure to continuous noise alone. In contrast, the cochleo-traumatic effects of impulse noise were significantly enhanced by co-exposure to CS2. Therefore, CS2 can clearly modulate the middle-ear reflex function. In fact, CS2 may have two distinct effects: firstly, it has a pharmacological effect on the CNS, modifying the trigger of the acoustic reflex; and secondly, it can make the organ of Corti more susceptible to impulse noise. The pharmacological effects on the CNS and the effects of CS2 on the organ of Corti are discussed to try to explain the overall effect of the solvent on hearing. Once again, the results reported in this article show that the temporal structure (continuous vs. impulse) of noise should be taken into consideration as a key parameter when establishing hearing conservation regulations. [ABSTRACT FROM AUTHOR]

• Exposure to PS+AMI significantly increased the SOD and CAT activities. • More severe gut damage was observed in the PS+AMI group. • Exposure to PS+AMI altered the gut bacterial communities of zebrafish. • Exposure to PS+AMI disordered the predicted metabolic functions of gut microbiota. The potential toxicity of microplastics (MPs) and hydrophilic pharmaceuticals to aquatic organisms has recently raised great public concern, yet their combined effects on aquatic organisms remain largely unknown. Herein, the combined effects of MPs and the commonly prescribed amitriptyline hydrochloride (AMI) on the intestinal tissue and gut microbiota of zebrafish (Danio rerio) were investigated. Adult zebrafish were exposed to microplastics (polystyrene, PS, 440 µg/L), AMI (2.5 µg/L), PS+AMI (440 µg/L PS + 2.5 µg/L AMI), and dechlorinated tap water (control) for 21 days, respectively. Our results showed that zebrafish rapidly ingested PS beads and accumulated them in the gut. Exposure to PS+AMI significantly enhanced the SOD and CAT activities compared to the control group, suggesting that combined exposure might increase ROS production in the zebrafish gut. Exposure to PS+AMI led to severe gut injuries, including cilia defects, partial absence and cracking of intestinal villi. Exposure to PS+AMI caused shifts in the gut bacterial communities, increasing the abundance of Proteobacteria and Actinobacteriota , and decreasing the abundance of Firmicutes, Bacteroidota and beneficial bacteria Cetobacterium , which caused dysbiosis in the gut microbiota, and subsequently may induce intestinal inflammation. Furthermore, exposure to PS+AMI disordered the predicted metabolic functions of gut microbiota, but functional changes in the PS+AMI group at KEGG level 1 and level 2 were not significantly different from those in the PS group. The results of this study extend our knowledge of the combined effects of MPs and AMI on the health of aquatic organisms, and will be helpful in assessing the combined effects of MPs and tricyclic antidepressants on aquatic organisms. [ABSTRACT FROM AUTHOR]

An increasing number of microplastics have been detected in aquatic environments, causing various damage to organisms. The size of microplastics affects the toxicity once they enter the organisms. Meanwhile, there is an increasing variety of Endocrine-disrupting chemicals (EDCs) present in aquatic environments. Androstenedione (AED) is a typical EDC. In this study, we used polystyrene microspheres of 80 nm (NPs) and 8 μm (MPs) as materials to simulate environmental contaminants in the aquatic environment with AED. We used female mosquitofish (Gambusia affinis) as the research object to investigate the effects of microplastics on fish in waters containing AED. We compared different sizes of particles accumulation in some tissues of fish and variation of enzyme activities (SOD, LDH, CAT), and the content of MDA in the gut. MPs, NPs, and AED combined exposure test investigated mRNA profiles of immune-related genes (IL-1β , IL-6 , IL-8 , IL-10) and hormone receptor genes (ARα , ARβ , ERα , ERβ) in the liver of fish. Our results indicated that MPs emerged in various tissues (gill, gut, and liver) of mosquitofish. Besides, NPs and MPs caused enteric abnormal enzyme activity after 48 h of exposure, which was particularly pronounced in the MPs-AED group. MPs induced significant upregulation of inflammatory factors and gonadal factor genes after 96 h of exposure, which was more pronounced when co-exposed with AED. In conclusion, NPs and MPs caused mechanisms of immune damage and inflammatory response. MPs were found to be more likely to cause adverse reactions than NPs, and these responses were enhanced by the combined effects of AED. This study demonstrated that AED can exacerbate the negative effects of MPs and NPs on mosquitofish. It provided an important basis for the effective assessment of MPs and NPs on bioaccumulation and biochemical status of mosquitofish. Additionally, it serves as a foundation to investigate the interactive effects of microplastics and EDCs in living organisms. [Display omitted] • MPs can accumulate tissue-specific in various tissues (gill, gut and liver) of mosquitofish. • MPs caused more severe oxidative damage than NPs, and the co-exposure of AED with MPs may have exacerbated the damage. • MPs induced significant upregulation of inflammatory and gonadal gene expression. • Co-exposure of AED with MPs more significantly induced target genes expression. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) are able to interact with diverse contaminants in sediments. However, the impacts of MPs on sediment properties and bacterial community structure in heavy metal-contaminated sediments remain unclear. In this study, we investigated the adsorption of Pb(II) by sediment-MPs mixtures and the effects of different concentration MPs on sediment enzyme activities, DOM fractions, and Pb bioavailability in riverine sediments, and further explored the response of sediment microbial community to Pb in the presence of MPs. The results indicated that the addition of MPs significantly decreased the adsorption amount of Pb(II) by sediments, especially decreased by 12.6% at 10% MPs treatment. Besides, the changes in enzyme activities, DOM fractions exhibited dose-dependent effects of MPs. The higher level of MPs (5% and 10%) tends to transform Pb into more bioavailable fractions in sediments. Also, MPs amendment was observed to alter sediment bacterial community structures, and community differences were evident in the uncontaminated and lead-contaminated sediments. Therein, significant increase of Bacteroidota , Proteobacteria and decrease of Firmicutes abundance in Pb-contaminated sediment at the phylum level were observed. These findings are expected to provide comprehensive information for assessing the combined ecological risks of heavy metals and MPs in riverine sediments. [Display omitted] • The adsorption capacity of sediment for Pb(II) decreased with the content of MPs. • The changes in sediment enzyme activities and DOC structures varied with MPs concentration. • High doses of MPs increased the bioavailability of Pb in sediments. • MPs had a greater impact on bacterial community in Pb-contaminated sediments. [ABSTRACT FROM AUTHOR]

Unintentional chemical mixtures that are present in the environment are of societal concern as the (environmental) chemicals contained therein, either singly or in combination, may possess properties that are hazardous (toxic) for human health. The current regulatory practice, however, is still largely based on evaluating single chemical substances one-by-one. Over the years various research efforts have delivered tools and approaches for risk assessment of chemical mixtures, but many of these were not considered sufficiently mature for regulatory implementation. This is (partly) due to mixture risk assessment (MRA) being very complex because of the large number of chemicals present in the environment. A key element in risk assessment is information on actual exposures in the population of interest. To date, information on actual personal (internal) mixture exposures is largely absent, severely limiting MRA. The use of human biomonitoring data may improve this situation. Therefore, we investigated within the European Human Biomonitoring Initiative (HBM4EU) various approaches to assess combined exposures and MRA. Based on the insights and lessons learnt in the context of the HBM4EU project, conclusions as well as recommendations for policy development regarding chemical mixtures and for further research were drafted. These conclusions and recommendations relate to both exposure and adverse health effects in humans. The recommendations were discussed with stakeholders in a workshop held in October 2021. There was considerable support and agreement with the spirit, scope and intention of the draft recommendations. Here we describe the lessons learnt on mixture risk assessment through the HBM4EU project and present the final recommendations. Overall, HBM4EU results demonstrated the potential of human biomonitoring as an instrument to obtain insight into the real-life mixtures the human population is exposed to. Also, HBM4EU results demonstrated that chemical mixtures are of public health concern. In the majority of the cases, it was possible to identify risk drivers, i.e. chemicals that contribute more strongly than others to the health risk. The novel approaches to identify co-occurrence patterns demonstrated clusters of co-occurring chemicals; chemicals in these mixture clusters are regulated independently under different legislative frameworks. Moreover, HBM4EU data and expertise can support a science-based derivation of a Mixture Assessment Factor and gauge potential impacts on the population's exposure to chemicals. While further expansion is needed on various aspects of the mixture activities carried out in the context of HBM4EU, application of available methodologies for mixture risk assessment should already be implemented to the degree possible. [Display omitted] • Human biomonitoring (HBM) gives valuable insights in exposures to chemical mixtures. • Network & statistical analyses show clusters in co-occurring chemicals in humans. • Chemicals in clusters are regulated independently in different regulatory silos. • Case studies clearly show that chemical mixtures are of public health concern. • HBM data and expertise can support a science-based Mixture Assessment Factor. [ABSTRACT FROM AUTHOR]

The potential interactions between the diverse pollutants that can be released into the environment and the resulting outcomes are a challenging issue that needs to be further examined. This in vitro study was aimed to assess potential toxic effects caused by combined exposure to tetrabromobisphenol A, a flame retardant widely used and frequently detected in aquatic matrices, and commercially available polystyrene nanoparticles as reference material to evaluate nanoplastics risks. Our results, using freshwater fish cell lines and a set of relevant cytotoxicity endpoints including cell viability, oxidative stress, and DNA damage, provide additional mechanistic insights that could help to fully characterize the toxicity profiles of tetrabromobisphenol A and polystyrene nanoparticles. Furthermore, we describe subtle changes in cell viability as well as the generation of oxidative DNA damage after coexposure to subcytotoxic concentrations of the tested pollutants. [Display omitted] • Tetrabromobisphenol A (TBBPA) and polystyrene nanoplastics (PSNPs) joint toxicity was studied. • RTgill-W1 was the most sensitive among the three fish cell line assayed. • Subtle effects of PSNPs upon TBBPA toxicity were detected. • Oxidative DNA damage was observed only after combined exposure to TBBPA and PSNPs. [ABSTRACT FROM AUTHOR]

Organisms are frequently exposed to mixtures of chemical contaminants in the environment, causing a potential “cocktail effect”, or combined effect. The joint action of different molecules with similar or different modes of action could result in a potentially unlimited number of additives, synergistic or antagonistic combinations. Since the large number of contaminants makes it impossible to perform ecotoxicity tests for each potential mixture, a robust approach for prospective environmental risk assessment of chemical mixtures is needed. A number of recent publications by the European Commission and the authorities in charge prove the increasing interest that is spreading in the European community towards the topic of the assessment of chemical mixtures. The current EU regulation for Plant Protection Products authorization (Reg. 1107/2009 EC) explicitly requires the evaluation of the potential combined effects of active substances. We reviewed current methods and limitations of mixture assessment of pesticides (7 fungicides and 4 herbicides) through the analysis of the approaches adopted to investigate possible risks for different non-target organisms. The Concentration Addition (CA) approach was the most used approach to predict multiple toxicity to non-target organisms. The guidance for birds and mammals first introduced standard procedures to assess the multiple toxicity based on on CA concept. The recent aquatic EFSA guidance introduced some requirements to evaluate potential mixture toxicity, while the current guidance requirements for terrestrial organisms still lack clear indications on how to conduct the assessment. Moreover, new indications come from the draft guidance for the assessment of terrestrial plants and in-soil organisms. However, the approval and implementation of these new guidelines are still at a developmental stage. Some final considerations are drawn on the future possibilities to improve risk assessment procedures so as to identify harmful effects of pesticides mixtures on non-target organisms. [ABSTRACT FROM AUTHOR]

The two most widely used brominated flame retardants (BFRs), decabromodiphenyl ether (BDE209) and tetrabromobisphenol A (TBBPA), co-exist prevalently with heavy metals (HM), at e-waste recycling sites (EWRSs). The laboratory incubation we conducted, which 50 g of dried soil spiked with Pb, Cd, BDE209 and TBBPA, were incubated 180 d in the dark at 25 °C, and kept the soil moisture at 60%. The results demonstrated that the inhibition ratio of 4 kinds of the enzyme (catalase, dehydrogenase, polyphenol oxidase and urease) in the combined of BFRs and HMs treatments were −127%–66%, -72%–49%, -52%–76% and 54%–107% respectively, and in TBBPA or BDE209 contaminant treatments were −135%–18%, -16%–31%, -18%–15% and −17%–83% respectively. Urease was more sensitive to the combined contamination than catalase, dehydrogenase and Polyphenol oxidase. BDE209 exhibited a higher eco-toxicological potential to soil enzymatic activity than TBBPA. The co-existence of HM induces a stronger response of enzymatic activity to the artificial contamination. The availability of the residual fraction in the later stage of incubation, along with the results of principal component analysis demonstrated that there may be different mechanisms responsible for the generation of residual and extractable fractions of HM. [ABSTRACT FROM AUTHOR]

Formaldehyde and benzene are the two major indoor air pollutants due to their prevalence and toxicity. This study aimed to explore the toxic effect on the spleen and relevant immune responses of Balb/c mice caused by exposure to a combination of formaldehyde and benzene. Balb/c mice were divided randomly into five groups (n = 9/group): blank control group (Ctrl); solvent ([corn] Oil) control; formaldehyde only (FA, 3 mg/m 3 ); benzene only (BZ, 150 mg/kg BW); and, formaldehyde + benzene group (FA + BZ). Exposures were performed for 8 h/day, 5 day/week, for 2 weeks. Tail blood was collected after the final exposure; 24-h later, the mice were euthanized to permit assessment of a variety of immune endpoints. The endpoints’ three areas were: (1) in living mice, body weight and delayed-type hypersensitivity (DTH) responses; (2) in blood, immune cell counts and serum antibody levels (serum hemagglutination); and, (3) in spleen samples, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), caspase-3 (cell apoptosis) levels and lymphocyte proliferation. In this study we fund (1) BZ and FA + BZ exposure can lead to the reduction in the number of some immune cells in peripheral blood; (2) Formaldehyde has certain synergistic effects on benzene-induced cytotoxicity in peripheral blood, (3) FA, BZ and FA + BZ exposure can lead to ROS and GSH depletion in spleen cells, and spleen cell apoptosis (caspase-3 increased) may be one of the downstream events, decreased splenic lymphocyte proliferation; and (4) the FA + BZ combined exposure can lead to the decreased body weight, serum antibody level (by serum hemagglutination assay). [ABSTRACT FROM AUTHOR]