Enhanced Toxicity of Bisphenols Together with UV Filters in Water: Identification of Synergy and Antagonism in Three-Component Mixtures.

Contaminants of emerging concern (CEC) localize in the biome in variable combinations of complex mixtures that are often environmentally persistent, bioaccumulate and biomagnify, prompting a need for extensive monitoring. Many cosmetics include UV filters that are listed as CECs, such as benzophenone derivatives (oxybenzone, OXYB), cinnamates (2-ethylhexyl 4-methoxycinnamate, EMC) and camphor derivatives (4-methylbenzylidene-camphor, 4MBC). Furthermore, in numerous water sources, these UV filters have been detected together with Bisphenols (BPs), which are commonly used in plastics and can be physiologically detrimental. We utilized bioluminescent bacteria (Microtox assay) to monitor these CEC mixtures at environmentally relevant doses, and performed the first systematic study involving three sunscreen components (OXYB, 4MBC and EMC) and three BPs (BPA, BPS or BPF). Moreover, a breast cell line and cell viability assay were employed to determine the possible effect of these mixtures on human cells. Toxicity modeling, with concentration addition (CA) and independent action (IA) approaches, was performed, followed by data interpretation using Model Deviation Ratio (MDR) evaluation. The results show that UV filter sunscreen constituents and BPs interact at environmentally relevant concentrations. Of notable interest, mixtures containing any pair of three BPs (e.g., BPA + BPS, BPA + BPF and BPS + BPF), together with one sunscreen component (OXYB, 4MBC or EMC), showed strong synergy or overadditive effects. On the other hand, mixtures containing two UV filters (any pair of OXYB, 4MBC and EMC) and one BP (BPA, BPS or BPF) had a strong propensity towards concentration dependent underestimation. The three-component mixtures of UV filters (4MBC, EMC and OXYB) acted in an antagonistic manner toward each other, which was confirmed using a human cell line model. This study is one of the most comprehensive involving sunscreen constituents and BPs in complex mixtures, and provides new insights into potentially important interactions between these compounds.

Genotoxicity of selected pharmaceuticals, their binary mixtures, and varying environmental conditions - study with human adenocarcinoma cancer HT29 cell line.

Pharmaceutical residues are present in the environment in mixtures and their adverse effects may also result from interactions that occur between compounds. Studies presented in this work focus on genotoxicity of pharmaceuticals from different therapeutic groups in mixtures and in individual solutions impacted with different environmental conditions assessed using comet assay (alkaline approach). Binary mixtures of pharmaceuticals (in different concentration ratios) and in individual solutions impacted with pH change (range from 5.5 to 8.5) or addition of inorganic ions, were incubated with HT29 cells and after 24 h time period cells were tested for the presence of DNA damage. To estimate whether mixtures act more (synergistic) or less (antagonistic) efficiently Concentrations Addition (CA) and Independent Action (IA) approaches were applied followed by a calculation of the Model Deviation Ratio (MDR) to determine deviation from the predicted values. Addition of inorganic ions mainly reduced their genotoxicity. Diclofenac s. was the most susceptible to potassium, fluoride, and bromide ions. Change of the pH of pharmaceutical solutions had significant impact on genotoxicity of diclofenac s. and fluoxetine h. Among mixtures, more commonly observed interactions were synergistic ones, exactly twenty-five cases (ten pairs containing chloramphenicol or oxytetracycline h.) and ten cases of antagonism (four for pairs containing chloramphenicol or fluoxetine h.). The results obtained indicate that interactions between tested compounds occur frequently and can lead to DNA damage. This topic especially concerning in vitro tests using cells is still rare, however, it should not be neglected.

Integrating Statistical and Machine-Learning Approach for Meta-Analysis of Bisphenol A-Exposure Datasets Reveals Effects on Mouse Gene Expression within Pathways of Apoptosis and Cell Survival.

Bisphenols are important environmental pollutants that are extensively studied due to different detrimental effects, while the molecular mechanisms behind these effects are less well understood. Like other environmental pollutants, bisphenols are being tested in various experimental models, creating large expression datasets found in open access storage. The meta-analysis of such datasets is, however, very complicated for various reasons. Here, we developed an integrating statistical and machine-learning model approach for the meta-analysis of bisphenol A (BPA) exposure datasets from different mouse tissues. We constructed three joint datasets following three different strategies for dataset integration: in particular, using all common genes from the datasets, uncorrelated, and not co-expressed genes, respectively. By applying machine learning methods to these datasets, we identified genes whose expression was significantly affected in all of the BPA microanalysis data tested; those involved in the regulation of cell survival include: Tnfr2, Hgf-Met, Agtr1a, Bdkrb2; signaling through Mapk8 (Jnk1)); DNA repair (Hgf-Met, Mgmt); apoptosis (Tmbim6, Bcl2, Apaf1); and cellular junctions (F11r, Cldnd1, Ctnd1 and Yes1). Our results highlight the benefit of combining existing datasets for the integrated analysis of a specific topic when individual datasets are limited in size.

Multivariate Statistical Approach for Nephrines in Women with Obesity.

Catecholamines are physiological regulators of carbohydrate and lipid metabolism during stress, but their chronic influence on metabolic changes in obese patients is still not clarified. The present study aimed to establish the associations between the catecholamine metabolites and metabolic syndrome (MS) components in obese women as well as to reveal the possible hidden subgroups of patients through hierarchical cluster analysis and principal component analysis. The 24-h urine excretion of metanephrine and normetanephrine was investigated in 150 obese women (54 non diabetic without MS, 70 non-diabetic with MS and 26 with type 2 diabetes). The interrelations between carbohydrate disturbances, metabolic syndrome components and stress response hormones were studied. Exploratory data analysis was used to determine different patterns of similarities among the patients. Normetanephrine concentrations were significantly increased in postmenopausal patients and in women with morbid obesity, type 2 diabetes, and hypertension but not with prediabetes. Both metanephrine and normetanephrine levels were positively associated with glucose concentrations one hour after glucose load irrespectively of the insulin levels. The exploratory data analysis showed different risk subgroups among the investigated obese women. The development of predictive tools that include not only traditional metabolic risk factors, but also markers of stress response systems might help for specific risk estimation in obesity patients.

Stabilities of bisphenol A diglycidyl ether, bisphenol F diglycidyl ether, and their derivatives under controlled conditions analyzed using liquid chromatography coupled with tandem mass spectrometry.

Bisphenol A diglycidyl ether (BADGE), bisphenol F diglycydyl ether (BFDGE), and their related compounds are widely used as precursors in production of epoxy resins. The high reactivity of these compounds makes the development of analytical methodologies that ensure appropriate metrological accuracy crucial. Consequently, we aimed to determine whether and to what extent the composition of the solution and storage conditions affect the stability of selected BADGE and BFDGE derivatives. The stabilities of these compounds were studied using liquid chromatography-tandem mass spectrometry with electrospray ionization (HPLC-ESI-MS/MS). The chromatographic method elaborated here has allowed for separation of the analytes in time shorter than 6 min, for both methanol and acetonitrile-based mobile phases. The obtained calibration curves for all analytes were linear in the range tested. The values of limit of detection (LODs) were in the range of 0.91-2.7 ng/mL, while values of limit of quantitation (LOQs) were in the range of 2.7-5.7 ng/mL. The chosen experimental conditions were compared in terms of the content of organic solvent in solution, storage temperature, and time. Our results show that the content of BADGE, BADGE·HCl, BFDGE, three-ring NOGE decreased with increasing water content (> 40% v/v). For BADGE and three-ring NOGE, significant changes in concentration were noted as early as 24 h after the test solutions had been prepared. In addition, a reduction in the storage temperature (4 to - 20 °C) reduced the rate of transformation of the monitored analytes. Our study will increase quality control in future research and may increase the reliability of the obtained results. Graphical abstract.

Influence of Storage Time and Temperature on the Toxicity, Endocrine Potential, and Migration of Epoxy Resin Precursors in Extracts of Food Packaging Materials.

The aim of the present study was to establish a standard methodology for the extraction of epoxy resin precursors from several types of food packages (cans, multi-layered composite material, and cups) with selected simulation media (distilled water, 5% ethanol, 3% dimethyl sulfoxide, 5% acetic acid, artificial saliva) at different extraction times and temperatures (factors). Biological analyses were conducted to determine the acute toxicity levels of the extracts (with Vibrio fischeri bacteria) and their endocrine potential (with Saccharomyces cerevisiae yeasts). In parallel, liquid chromatography-tandem mass spectrometry was performed to determine levels of bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (mixture of isomers, BFDGE), ring novolac glycidyl ether (3-ring NOGE), and their derivatives. The variation induced by the different experimental factors was statistically evaluated with analysis of variance simultaneous component analysis (ASCA). Our findings demonstrate the value of using a holistic approach to best partition the effects contributing to the end points of these assessments, and offer further guidance for adopting such a methodology, thus being a broadly useful reference for understanding the phenomena related to the impacts of food packaging materials on quality for long- and short-term storage, while offering a general method for analysis.

Assessment of the Bulgarian Wastewater Treatment Plants' Impact on the Receiving Water Bodies.

Deterioration of water quality is a major problem world widely according to many international non-governmental organizations (NGO). As one of the European Union (EU) countries, Bulgaria is also obliged by EU legislation to maintain best practices in assessing surface water quality and the efficiency of wastewater treatment processes. For these reasons studies were undertaken to utilize ecotoxicological (Microtox®, Phytotoxkit FTM, Daphtoxkit FTM), instrumental (to determine pH, electrical conductivity (EC), chemical oxygen demand, total suspended solids (TSS), total nitrogen (N) and phosphorus (P), chlorides, sulphates, Cr, Co, Cu, Cd, Ba, V, Mn, Fe, Ni, Zn, Se, Pb), as well as advanced chemometric methods (partial least squares-discriminant analysis (PLS-DA)) in data evaluation to comprehensively assess wastewater treatment plants' (WWTPs) effluents and surface waters quality around 21 major Bulgarian cities. The PLS-DA classification model for the physicochemical parameters gave excellent discrimination between WWTP effluents and surface waters with 93.65% correct predictions (with significant contribution of EC, TSS, P, N, Cl, Fe, Zn, and Se). The classification model based on ecotoxicological data identifies the plant test endpoints as having a greater impact on the classification model efficiency than bacterial, or crustaceans' endpoints studied.

Modeling and MANOVA studies on toxicity and endocrine potential of packaging materials exposed to different extraction schemes.

The stability of the linings of packaging that is in contact with the goods stored has been of major concern during decades of the development of packaging materials. In this work, an attempt was undertaken to assess the applicability of using two bioassays (Microtox® and XenoScreen YES/YAS) in estimating the stability of packaging (cans, caps, multilayer material) and the impact of their degradation on the toxicity of some simulated media. The assessment of the impact of packaging storage conditions (temperature, disinfection, preservation, extracting and washing solvents) was planned and performed with i) regression modeling of the experimental effects on the ecotoxicity readings, ii) ANOVA and MANOVA estimation of the experimental conditions as significant factors affecting the toxicity results and iii) FTIR analysis of the packages. It is shown that the effects of temperature and extraction solvents could be quantitatively assessed by the agreement between all methods applied. It can be stated that temperature and acidity as well as the alcohol content in the sensitive media have the greatest impact on the toxicity of the extract and thus on the stability of the internal lining and the extractability of xenobiotics.

Phytoavailability of potentially toxic elements from industrially contaminated soils to wild grass.

Topsoil and grass samples from 14 sites located in different distances from three copper mining factories and a copper smelter were collected in Srednogorie, Bulgaria. The paper discusses results of studies on the mobility of potentially toxic elements (As, Cd, Cr, Cu, Mn, Ni, Pb, Zn) from contaminated soils to wild grass Cynodon dactylon in terms of transfer (TF: soil to plant) and phytoavailability (PF: EDTA (ethylenediaminetetraacetic acid)-soluble to plant) factors. Soils located close to mine and smelter factories were heavily contaminated by As and Cu reaching levels up to 500 mg/kg and 2400 mg/kg, respectively for As and Cu. At seven sites arsenic and copper in grass were over the normal levels (1 mg/kg As; 20 mg/kg Cu). The content of Cu in grass averaged 63 mg/kg exceeding the maximum allowable for sheep. Relationship between PF and TF values was found for As, Cd, Cu, Ni, Pb, Zn but not for Mn and Cr. To some extent the soil pH, TOM (total organic matter) and CaCO3 content are related to the phytoavailability of As, Cd and Cu since for Zn and Pb this relation is attributed to Al- and Fe-content of soil. Statistically significant correlation coefficients were determined between the EDTA-soluble fraction of soil and content in grass in the case of As, Cd, Cr, Cu, Mn and Pb indicating the suitability of the short procedure for phytoavailability studies of those elements. The application of hierarchical cluster analysis and self-organizing maps of Kohonen made it possible to reveal specific hidden relationships between the soil variables and transfer factors as well as between the sampling locations. This additional information helps in more detailed interpretation of phytoavailability and transfer processes in the region of interest. The novelty in this study is achieved by careful consideration of the possibility of using EDTA extracts of the toxic metals in investigating of the phytoavailability and transfer processes soil/plant. Additionally, chemometric expertise used makes it possible to differentiate the behavior of each toxic metal in the processes studied. The combination of easy option for rapid extraction and intelligent data analysis gives a new perspective for contributions in explanation of the complex interactions between soils and plants when assessing pollution events in a certain environment.

Assessment of ecotoxicity and total volatile organic compound (TVOC) emissions from food and children's toy products.

The development of new methods for identifying a broad spectrum of analytes, as well as highly selective tools to provide the most accurate information regarding the processes and relationships in the world, has been an area of interest for researchers for many years. The information obtained with these tools provides valuable data to complement existing knowledge but, above all, to identify and determine previously unknown hazards. Recently, attention has been paid to the migration of xenobiotics from the surfaces of various everyday objects and the resulting impacts on human health. Since children are among those most vulnerable to health consequences, one of the main subjects of interest is the migration of low-molecular-weight compounds from toys and products intended for children. This migration has become a stimulus for research aimed at determining the degree of release of compounds from popular commercially available chocolate/toy sets. One of main objectives of this research was to determine the impact of time on the ecotoxicity (with Vibrio fischeri bioluminescent bacteria) of extracts of products intended for children and to assess the correlation with total volatile organic compound emissions using basic chemometric methods. The studies on endocrine potential (with XenoScreen YES/YAS) of the extracts and showed that compounds released from the studied objects (including packaging foils, plastic capsules storing toys, most of toys studied and all chocolate samples) exhibit mostly androgenic antagonistic behavior while using artificial saliva as extraction medium increased the impact observed. The impact of time in most cases was positive one and increased with prolonging extraction time. The small-scale stationary environmental test chambers - µ-CTE™ 250 system was employed to perform the studies aimed at determining the profile of total volatile organic compounds (TVOCs) emissions. Due to this it was possible to state that objects from which the greatest amounts of contaminants are released are plastic containers (with emission rate falling down from 3273 to 2280 ng/g of material at 6 h of conditioning in elevated temperature).

Chemometric Assessment and Best-Fit Function Modelling of the Toxic Potential of Selected Food Packaging Extracts.

Food packaging materials constitute an ever more threatening environmental pollutant. This study examined options to specifically assess the ecotoxicity of packaged wastes, such as cans, subjected to various experimental treatments (in terms of extraction media, time of exposure, and temperature) that imitate several basic conditions of the process of food production. The extracts were studied for their ecotoxicity with bioluminescent Vibrio fischeri bacteria. The first objective of this study was to find patterns of similarity between different experimental conditions; we used multivariate statistical methods, such as hierarchical cluster analysis, to interpret the impact of experimental conditions on the ecotoxicity signals of the package extracts. Our second objective was to apply best-fit function modelling for additional data interpretation, taking into account, that ecotoxicity for various temperature conditions is time- and temperature dependent. We mathematically confirmed that chemometric data treatment allows for better understanding how different experimental conditions imitating the real use of food packaging. We also demonstrate that the level of ecotoxicity depends on different extraction media, time of exposure, and temperature regime.

Binary Mixtures of Selected Bisphenols in the Environment: Their Toxicity in Relationship to Individual Constituents.

Bisphenol A (BPA) is one of the most popular and commonly used plasticizer in the industry. Over the past decade, new chemicals that belong to the bisphenol group have increasingly been used in industrial applications as alternatives to BPA. Nevertheless, information on the combined effects of bisphenol (BP) analogues is insufficient. Therefore, our current study aimed to find the biological response modulations induced by the binary mixtures of BP compounds. We determined the toxicity levels in Microtox and XenoScreen YES/YAS assays for several BP analogs alone, and for their binary mixtures. The results obtained constituted the database for chemometric intelligent data analysis to evaluate the possible interactions occurring in the mixtures. Several chemometric/biophysical models have been used (concentration addition-CA, independent action-IA and polynomial regression calculations) to realize this aim. The best fitting was found for the IA model and even in this description strong evidence for synergistic behaviors (modes of action) of some bisphenol analogue mixtures was demonstrated. Bisphenols A, S, F and FL were proven to be of significant endocrine threat (with respect to XenoScreen YES/YAS assay); thus, their presence in mixtures (including presence in tissues of living organisms) should be most strictly monitored and reported.

Application of chemometric techniques in studies of toxicity of selected commercially available products for infants and children.

The goal of the present study is to assess the impact of the experimental conditions for extraction procedures (time of extraction, thermal treatment and type of extraction media) as applied to several baby and infant products checked for their possible ecotoxicological response when tested by various ecotoxicity tests (Microtox®, Ostracodtoxkit F™ and Xenoscreen YES/YAS™). The systems under consideration are multidimensional by nature and, therefore, the appropriate assessment approach was intelligent data analysis (chemometrics). Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were selected as reliable data mining methods for the interpretation of the ecotoxicity data. We show that the different experimental conditions have a significant impact on the ecotoxicity levels observed, especially those measured by Microtox® and Ostracodtoxkit F™ tests. The time of contact proves to be a very significant factor for all extraction media and ecotoxicity test procedures. The present study is a pioneering effort to offer a specific expert approach for analysing links between the type of test measurement methodology and imposed experimental conditions to mimic real-life circumstances in the use of baby and infant products.

Novel approach to ecotoxicological risk assessment of sediments cores around the shipwreck by the use of self-organizing maps.

Marine and coastal pollution plays an increasingly important role due to recent severe accidents which drew attention to the consequences of oil spills causing widespread devastation of marine ecosystems. All these problems cannot be solved without conducting environmental studies in the area of possible oil spill and performing chemometric evaluation of the data obtained looking for similar patterns among pollutants and optimize environmental monitoring during eventual spills and possible remediation actions - what is the aim of the work presented. Following the chemical and ecotoxicological studies self-organising maps technique has been applied as a competitive learning algorithm based on unsupervised learning process. Summarizing it can be stated that biotests enable assessing the impact of complex chemical mixtures on the organisms inhabiting particular ecosystems. Short and simple application of biotests cannot easily explain the observable toxicity without more complex chemometric evaluation of datasets obtained describing dependence between xenobiotics and toxicological results.

The exposure to UV filters: Prevalence, effects, possible molecular mechanisms of action and interactions within mixtures.

Substances that can absorb sunlight and harmful UV radiation such as organic UV filters are widely used in cosmetics and other personal care products. Since humans use a wide variety of chemicals for multiple purposes it is common for UV filters to co-occur with other substances either in human originating specimens or in the environment. There is increasing interest in understanding such co-occurrence in form of potential synergy, antagonist, or additive effects of biological systems. This review focuses on the collection of data about the simultaneous occurrence of UV filters oxybenzone (OXYB), ethylexyl-methoxycinnamate (EMC) and 4-methylbenzylidene camphor (4-MBC) as well as other classes of chemicals (such as pesticides, bisphenols, and parabens) to understand better any such interactions considering synergy, additive effect and antagonism. Our analysis identified >20 different confirmed synergies in 11 papers involving 16 compounds. We also highlight pathways (such as transcriptional activation of estrogen receptor, promotion of estradiol synthesis, hypothalamic-pituitary-gonadal (HPG) axis, and upregulation of thyroid-hormone synthesis) and proteins (such as Membrane Associated Progesterone Receptor (MAPR), cytochrome P450, and heat shock protein 70 (Hsp70)) that can act as important key nodes for such potential interactions. This article aims to provide insight into the molecular mechanisms on how commonly used UV filters act and may interact with other chemicals.

The effects of the IM1-12Br ionic liquid and the oxytetracycline mixture on selected marine and brackish microorganisms.

The number of applications and commercialized processes utilizing ionic liquids has been increasing, and it is anticipated that this trend will persist and even intensify in the future. Ionic liquids possess desirable characteristics, such as low vapor pressure, good water solubility, amphiphilicity, and stability. Nevertheless, these properties can influence their environmental behavior, resulting in resistance to biotic and abiotic degradation and subsequent water contamination with more harmful derivatives. However, there is a notable scarcity of data regarding the impact of mixtures comprising ionic liquids and other micropollutants. Identifying potential potentiation of ionic liquids (Ils) toxicity in the presence of other xenobiotics is a proactive risk assessment measure. Therefore, the study aims to fill an important knowledge gap and identify possible interactions between imidazolium-based ionic liquid (IM1-12Br) and the common antibiotic oxytetracycline (OXTC). During 11-day experiments, selected marine, brackish and freshwater microorganisms (diatom Phaeodactylum tricornutum, cyanobacterium Microcystis aeruginosa and green algae Chlorella vulgaris) were exposed to binary mixtures of target substances. The assessed responses encompassed chlorophyll a kinetic parameters related to photosynthesis efficiency, as well as pigment concentrations, specifically phycobilin content. Additionally, the impact on the luminescent marine bacterium Aliivibrio fischeri has been evaluated. Significant effects on the growth, photosynthetic processes, and pigment content were observed in all the targeted microorganisms. The concentration addition (CA) and independent action (IA) mathematical models followed by the Model Deviation Ratio (MDR) evaluation enabled the identification of mainly synergistic interactions in the studied mixtures. The findings of present study offer valuable insights into the impacts of ionic liquids and other organic micropollutants.

The effect of sunscreen 4-methylbenzylidene camphor in different and reproductive models, its bioaccumulation and molecular effects on ligand-receptor interaction, and protein expression.

4-Methylbenzylidene camphor (4-MBC) is a photo-absorbing UV filter prevalently used in cosmetics, which can be absorbed into circulation and cause systemic effects. 4-MBC is continued to be released in the environment despite the growing knowledge about its bioaccumulation and endocrine disrupting effects. Previous reviews have mentioned UV-filter together but this review considers 4-MBC alone, due to its prevalence and concerning health effects. This review considers 4-MBC's potential effects on human health regarding systemic and molecular effects, with the main focus on reproduction. Also, the potential bioaccumulation and interactions with receptor systems such as the oestrogen receptors ß and α, and progesterone receptor are covered. Additionally, previous studies about 4-MBC's effects on mRNA and protein expression, especially in the prostate and the brain are analysed. Furthermore, 4-MBC is reported to act with inflammatory pathways by activating p38 MAPK and NF-κB, leading to the production of inflammatory TNF-α and IL-6. 4-MBC was also found to induce apoptosis and inhibit cell proliferation and DNA repair. In conclusion, 4-MBC has wide-ranging effects in many different models interacting with multiple pathways causing long-term effects even at low doses and this knowledge can guide governmental risk assessment, regulation divisions and chemical industries.

Toxicity assessment of sediments associated with the wreck of s/s Stuttgart in the Gulf of Gdansk (Poland).

The paper presents the results of toxicity determinations carried out on sediment samples collected in the vicinity of the wreck of the German s/s Stuttgart (the southern part of the Gulf of Gdansk, off the Polish coast) in relation to the determination of polycyclic aromatic hydrocarbons (PAHs). The toxicity of surface and core sediment samples was assessed using two biotest organisms-the bioluminescent bacteria Vibrio fischeri and the ostracod Heterocypris incongruens. PAH levels in these samples were determined by GC-MS. The surface sediments collected at W2 (ca. 34 m north of the shipwreck) and W4 (ca. 415 m north-east of the wreck) as well as the core sediments collected at WR3 (ca. 400 m north-east of the wreck) were the most heavily polluted with substances toxic to the biotest organisms. The chronic and acute toxicities in the case of most of the surface sediment samples studied are correlated. This may suggest that not only hydrophobic chemicals (like PAHs from fuel residues) but also more polar chemicals (resulting from the conversion of aromatic hydrocarbons) are responsible for the toxicity levels found. There is a clear dependence between the levels of chronic toxicity and PAH concentrations in the core sediment samples. In addition, a simultaneous decrease in the PAH content and chronic toxicity was noted in all the core sediment samples at depths below 80 cm.

Role of the Synergistic Interactions of Environmental Pollutants in the Development of Cancer.

There is a growing awareness that the large number of environmental pollutants we are exposed to on a daily basis are causing major health problems. Compared to traditional studies that focus on individual pollutants, there are relatively few studies on how pollutants mixtures interact. Several studies have reported a relationship between environmental pollutants and the development of cancer, even when pollutant levels are below toxicity reference values. The possibility of synergistic interactions between different pollutants could explain how even low concentrations can cause major health problems. These intricate that molecular interactions can occur through a wide variety of mechanisms, and our understanding of the physiological effects of mixtures is still limited. The purpose of this paper is to discuss recent reports that address possible synergistic interactions between different types of environmental pollutants that could promote cancer development. Our literature studies suggest that key biological pathways are frequently implicated in such processes. These include increased production of reactive oxygen species, activation by cytochrome P450, and aryl hydrocarbon receptor signaling, among others. We discuss the need to understand individual pathological vulnerability not only in relation to basic genetics and gene expression, but also in terms of measurable exposure to contaminants. We also mention the need for significant improvements in future studies using a multitude of disciplines, such as the development of high-throughput study models, better tools for quantifying pollutants in cancer patients, innovative pharmacological and toxicological studies, and high-efficiency computer analysis, which allow us to analyze the molecular mechanisms of mixtures.

Determination of EC50 toxicity data of selected heavy metals toward Heterocypris incongruens and their comparison to "direct-contact" and microbiotests.

The sensitivity of Heterocypris incongruens to selected heavy metal ions is discussed. Although the Ostracodtoxkit ® has been present on the market for a few years, data on its selectivity and sensitivity to toxicants is scarce; such data is indispensable when interpreting the results of sediment toxicity. The LC(50) and EC(50) results with the Ostracodtoxkit ® are compared with those obtained with other commercially available "direct-contact" tests (utilizing Hyalella azteca and Chironomus riparius) and microbiotests for assessing the toxicity of aqueous samples (Vibrio fischeri, Daphnia magna, and Selenastrum capricornatum). The sensitivity of H. incongruens to metal ions (Cd(2+)> >Hg(2+)> Cu(2+)>Cr(6+ )>Ni(2+) ≈ Mn(7+)>Zn(2+)>Pb(2+)>Li(1+ )> Fe(3+)) was found to be similar to that of H. azteca and of C. riparius. The Ostracodtoxkit ® has shown itself to be an efficient and reliable element of test batteries for toxicity determination.