Toxics, Volume 9, Issue 11 (November 2021) – 47 articles

The toxicity of cigarette smoke (CS) is largely attributed to its ability to generate reactive oxygen species (ROS). Reportedly, CS generates superoxide in cell culture systems by stimulating the cells to produce superoxide and through direct chemical reactions with components of the culture media. In this study, we investigated CS-induced superoxide formation in biocompatible aqueous media and its characteristics. Cigarette smoke extract (CSE) and total particulate matter (TPM) were prepared from the mainstream smoke of 3R4F reference cigarettes. CSE and TPM generated superoxide in Hank’s balanced salt solution (HBSS), Dulbecco’s modified Eagle media (DMEM), and blood plasma, but not in distilled water and phosphate-buffered saline. Each constituent of HBSS in solution was tested, and bicarbonate was found to be responsible for the superoxide generation. More than half of the superoxide formation was abolished by pretreating CSE or TPM with peroxidase, indicating that the substrates of peroxidase, presumably peroxides and peroxy acids, mainly contributed to the superoxide production. In conclusion, the presence of bicarbonate in experimental conditions should be considered carefully in studies of the biological activity of CS. Furthermore, the local amount of bicarbonate in exposed tissues may be a determinant of tissue sensitivity to oxidative damage by CS. Full article

This study demonstrates the utility of an updated mass balance model for predicting the distribution of organic chemicals in in vitro test systems (IV-MBM EQP v2.0) and evaluates its performance with empirical data. The IV-MBM EQP v2.0 tool was parameterized and applied to four independent data sets with measured ratios of bulk medium or freely-dissolved to initial nominal concentrations (e.g., C24/C0 where C24 is the measured concentration after 24 h of exposure and C0 is the initial nominal concentration). Model performance varied depending on the data set, chemical properties (e.g., “volatiles” vs. “non-volatiles”, neutral vs. ionizable organics), and model assumptions but overall is deemed acceptable. For example, the r² was greater than 0.8 and the mean absolute error (MAE) in the predictions was less than a factor of two for most neutral organics included. Model performance was not as good for the ionizable organic chemicals included but the r² was still greater than 0.7 and the MAE less than a factor of three. The IV-MBM EQP v2.0 model was subsequently applied to several hundred chemicals on Canada’s Domestic Substances List (DSL) with nominal effects data (AC50s) reported for two in vitro assays. We report the frequency of chemicals with AC50s corresponding to predicted cell membrane concentrations in the baseline toxicity range (i.e., >20–60 mM) and tabulate the number of chemicals with “volatility issues” (majority of chemical in headspace) and “solubility issues” (freely-dissolved concentration greater than water solubility after distribution). In addition, the predicted “equivalent EQP blood concentrations” (i.e., blood concentration at equilibrium with predicted cellular concentration) were compared to the AC50s as a function of hydrophobicity (log octanol-water partition or distribution ratio). The predicted equivalent EQP blood concentrations exceed the AC50 by up to a factor of 100 depending on hydrophobicity and assay conditions. The implications of using AC50s as direct surrogates for human blood concentrations when estimating the oral equivalent doses using a toxicokinetic model (i.e., reverse dosimetry) are then briefly discussed. Full article

Since the animal test ban on cosmetics in the EU in 2013, alternative in vitro safety tests have been actively researched to replace in vivo animal tests. For the development and evaluation of a new test method, reference chemicals with quality in vivo data are essential to assess the predictive capacity and applicability domain. Here, we compiled a reference chemical database (ChemSkin DB) for the development and evaluation of new in vitro skin irritation tests. The first candidates were selected from 317 chemicals (source data n = 1567) searched from the literature from the last 20 years, including previous validation study reports, ECETOC, and published papers. Chemicals showing inconsistent classification or those that were commercially unavailable, difficult or dangerous to handle, prohibitively expensive, or without quality in vivo or in vitro data were removed, leaving a total of 100 chemicals. Supporting references, in vivo Draize scores, UN GHS/EU CLP classifications and commercial sources were compiled. Test results produced by the approved methods of OECD Test No. 439 were included and compared using the classification table, scatter plot, and Pearson correlation analysis to identify the false predictions and differences between in vitro skin irritation tests. These results may provide an insight into the future development of new in vitro skin irritation tests. Full article

Sulfamethoxazole (SMX) is a frequently used antibiotic for the treatment of urinary tract, respiratory, and intestinal infections and as a supplement in livestock or fishery farming to boost production. The release of SMX into the environment can lead to the development of antibiotic resistance among the microbial community, which can lead to frequent clinical infections. SMX removal from water is usually done through advanced treatment processes, such as adsorption, photocatalytic oxidation, and biodegradation. Among them, the advanced oxidation process using TiO₂ and its composites is being widely used. TiO₂ is a widely used photocatalyst; however, it has certain limitations, such as low visible light response and quick recombination of e⁻/h⁺ pairs. Integrating the biochar with TiO₂ nanoparticles can overcome such limitations. The biochar-supported TiO₂ composites showed a significant increase in the photocatalytic activities in the UV-visible range, which resulted in a substantial increase in the degradation of SMX in water. The present review has critically reviewed the methods of biochar TiO₂ composite synthesis, the effect of biochar integration with the TiO₂ on its physicochemical properties, and the chemical pathways through which the biochar/TiO₂ composite degrades the SMX in water or aqueous solution. The degradation of SMX using photocatalysis can be considered a useful model, and the research studies presented in this review will allow extending this area of research on other types of similar pharmaceuticals or pollutants in general in the future. Full article

This work presents the results of experimental tests to evaluate the effects of prolonged contamination by Cr on Moso Bamboo (MB) (Phyllostachys pubescens) and the adaptability of the MB to the Mediterranean climate. A preliminary test on the MB was developed in the laboratory, simulating irrigation under Mediterranean conditions (600 mm per year) and tropical conditions (1800 mm per year), to evaluate the rate of growth and the MB’s capability for Cr phytoextraction from contaminated soil. The tolerance of MB to Cr was also performed showing a good response of the plant to 100 mg Cr/L solution, utilized for irrigation of the pots. The results show that the rate of MB’s removal of Cr from soil ranged from 49.2% to 61.7% as a function of the soil degree of contamination, which varied from approx. 100 mg/kg to 300 mg/kg. The distribution of Cr in the various sections of the bamboo revealed that the greater percentage was present in rhizomes: 42%, equal to 114 mg Cr for 600 mm per year, and 50%, equal to 412 mg Cr for 1800 mm per year. A noteworthy diffusion of the metal towards the outermost parts of the plant was shown. The values of Cr retained in the stems and leaves of MB tissues were quite high and varied from 1100 mg/kg to 1700 mg/kg dry weight. Full article

Inhibition, one of the building blocks of executive function, is the ability to focus one’s attention despite interference from external stimuli. It undergoes substantial development during adolescence and may be susceptible to adverse impacts of prenatal exposure to chemical mixtures, yet few studies have explored this association. The New Bedford Cohort (NBC) is a birth cohort of residents living near the New Bedford Harbor Superfund site in Massachusetts. Among adolescents from the NBC, we investigated the association of biomarkers of prenatal exposure to organochlorines (DDE, HCB, PCBs) and metals (Pb, Mn) with inhibition, assessed with the Delis–Kaplan Executive Function System Design Fluency (non-verbal task) and Color–Word Interference (verbal task) subtests. An exploratory mixtures analysis using Bayesian kernel machine regression (BKMR) informed a traditional multivariable regression approach. NBC adolescents are diverse with 29% non-white and 31% in a low-income household at birth. Cord serum organochlorine concentrations and cord blood metals concentrations were generally similar to other birth cohorts. In BKMR models, we observed a suggestive adverse association of the chemical mixture with Color–Word Interference but not Design Fluency. In covariate-adjusted linear regression models including all five chemical exposure measures, a doubling of cord blood Mn was associated with poorer Color–Word Interference completion time scaled scores (difference = −0.74; 95% CI: −1.34, −0.14). This study provided evidence of an adverse joint association between prenatal exposure to a five-chemical mixture and verbal inhibition in adolescence with exposure to Mn potentially driving this overall association. Full article

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers. OPEs have been released into various environments (e.g., water, sediments, dust and air, and soil). To investigate the occurrence and distribution of OPEs in various environments in China, this review collects and discusses the published scientific studies in this field. Chlorinated OPEs, as flame retardants, are the predominant OPEs found in the environment. The analysis of data revealed large concentration variations among microenvironments, including inflowing river water (range: 0.69–10.62 µgL⁻¹), sediments (range: 0.0197–0.234 µg/g), dust (range: 8.706–34.872 µg/g), and open recycling sites’ soil (range: 0.122–2.1 µg/g). Moreover, OPEs can be detected in the air and biota. We highlight the overall view regarding environmental levels of OPEs in different matrices as a starting point to monitor trends for China. The levels of OPEs in the water, sediment, dust, and air of China are still low. However, dust samples from electronic waste workshop sites were more contaminated. Human activities, pesticides, electronics, furniture, paint, plastics and textiles, and wastewater plants are the dominant sources of OPEs. Human exposure routes to OPEs mainly include dermal contact, dust ingestion, inhalation, and dietary intake. The low level of ecological risk and risk to human health indicated a limited threat from OPEs. Furthermore, current challenges and perspectives for future studies are prospected. A criteria inventory of OPEs reflecting the levels of OPEs contamination association among different microenvironments, emerging OPEs, and potential impact of OPEs on human health, particularly for children are needed in China for better investigation. Full article

The mercury that is released from the centralized treatment of municipal solid waste is an important source of atmospheric mercury. We chose the main urban area of Changchun as a representative area. Environmental factors such as total mercury content, temperature, wind speed, and other factors were measured in samples from the trash cans of two types of collection points (trash cans and garbage stations), the topsoil under the selected trash cans, and the ambient air above the selected trash cans. The potential ecological risks of mercury pollution were evaluated. The results showed that the mercury content levels of all sample types in the refuse transfer station were higher than the garbage cans and there were no significant differences observed between soil surface mercury and garbage cans. The mercury content levels in the atmosphere and the surface soil at the garbage collection points were found to increase along the cascade relationship of the garbage collection. However, there were no correlations observed between the atmospheric mercury content levels and the surface soil mercury content levels with the attachments and the sum of the former two. There were no correlations observed between surface soil and the attachments, or among the attachments, surface soil, and the atmospheric mercury content levels. The mercury content levels in the attachments, surface soil, and atmosphere of the garbage collection points in the study area were negatively correlated with the loop lines. Meanwhile, the potential ecological risk indexes of the garbage cans and garbage stations were found to be high. The chronic non-carcinogenic risks of mercury to children and adults were determined to be very low. The risks of mercury to children were higher when compared with adults. The highest non-carcinogenic risks of mercury pollution were determined to be within the central area of Changchun. Full article

The linear dose–response relationship has long been assumed in assessments of health risk from an incremental chemical emission relative to background emissions. In this study, we systematically examine the relevancy of such an assumption with real-world data. We used the reported emission data, as background emissions, from the 2017 U.S. National Emission Inventory for 95 organic chemicals to estimate the central tendencies of exposures of the general U.S. population. Previously published nonlinear dose–response relationships for chemicals were used to estimate health risk from exposure. We also explored and identified four intervals of exposure in which the nonlinear dose–response relationship may be linearly approximated with fixed slopes. Predicted rates of exposure to these 95 chemicals are all within the lowest of the four intervals and associated with low health risk. The health risk may be overestimated if a slope on the dose–response relationship extrapolated from toxicological assays based on high response rates is used for a marginal increase in emission not substantially higher than background emissions. To improve the confidence of human health risk estimates for chemicals, future efforts should focus on deriving a more accurate dose–response relationship at lower response rates and interface it with exposure assessments. Full article

Mine wastes from the La Aurora mine in the state of Guanajuato were generated by the flotation process and placed in four tailing dumps on the local stream while the plant operated. Given that these wastes contain toxic elements, it is important to establish their impact on the quality of several surrounding natural sources of water that are considered potential drinking water supplies. This study identified four water source types, in which the contents of arsenic (As), mercury (Hg), and thallium (Tl) were exceeded, according to international guideline values for drinking water quality. The first type of aqueous sample corresponded to leachates produced by rainwater infiltration in tailings and water–mineral waste interactions. The second type corresponded to surface water along the Xichú and La Laja Streams, and the third and fourth types involved two groundwater well samples and spring samples, respectively. The Chiquito Stream was used as a reference area that had not been impacted by the mine wastes. The isotopic signatures associated with δ³⁴S_sulfate and δ¹⁸O_sulfate compositions from the El Ojo de Agua spring are similar to those of the Santa María River and are different from those of the mine waste leachates. This study shows evidence of the presence of As in the El Ojo de Agua spring, which results from dissolution of secondary mineral phases that were produced by alteration of the mine wastes, which then migrated along the Xichú Stream system until reaching the spring. These As-bearing fine particles are prone to dissolution when in contact with this water source. Principal component analysis revealed that the observed As, Tl, and Hg can be attributed to weathering of the mine wastes. However, the results suggest that a natural contribution of these elements could be associated with rainwater–igneous rock interactions. Full article

An extensive literature exists regarding the cellular, physiological, and genetic effects of cadmium (Cd)—A highly toxic, but commonly used trace metal in modern industry. However, limited data are available on its epigenetic effects, especially for terrestrial sentinel invertebrates. We determined Cd retention, total DNA methylation, and the methylation status of 5′ end of the Cd-MT gene in the hepatopancreas of the brown garden snail, Cornu aspersum, fed Cd sulfate for four weeks. Bodyweight changes and survival were also measured. Hepatopancreas cadmium increased in a dose-dependent manner from the third-lowest dose onward, with very large amounts being found for the highest treatment group. However, no mortalities occurred, irrespective of dietary Cd dose. We identified significant genome-wide hypermethylation in specimens given the highest dose, which overlapped with a significant bodyweight decrease. The Cd-MT gene showed an unmethylated 5′ end of the Cd-MT gene and this status was not affected by cadmium exposure. Hepatopancreas DNA methylation is as sensitive as bodyweight to non-lethal concentrations of dietary Cd given as cadmium sulfate but less responsive than tissue accumulation. Such an exposure event, by contrast, does not affect the methylation status of the Cd-MT gene 5′ end. Full article

Plastic pollution is an increasing environmental problem, but a comprehensive understanding of its effect in the environment is still missing. The wide variety of size, shape, and polymer composition of plastics impedes an adequate risk assessment. We investigated the effect of differently sized polystyrene beads (1-, 3-, 6-µm; PS) and polyamide fragments (5–25 µm, PA) and non-plastics items such as silica beads (3-µm, SiO₂) on the population growth, reproduction (egg ratio), and survival of two common aquatic micro invertebrates: the rotifer species Brachionus calyciflorus and Brachionus fernandoi. The MPs were combined with food quantity, limiting and saturating food concentration, and with food of different quality. We found variable fitness responses with a significant effect of 3-µm PS on the population growth rate in both rotifer species with respect to food quantity. An interaction between the food quality and the MPs treatments was found in the reproduction of B. calyciflorus. PA and SiO₂ beads had no effect on fitness response. This study provides further evidence of the indirect effect of MPs in planktonic rotifers and the importance of testing different environmental conditions that could influence the effect of MPs. Full article

The Hg accumulation in different commercial varieties of Oryzasativa L. was evaluated in the region of La Mojana, Colombia, where rice cultivation has become the staple food of the population living in this area. The varieties studied were Fedearroz-473 (FA473), Fedearroz-2000 (FA2000), and Fedearroz-Mocari (FAM). Soil spiked at different Hg levels was evaluated, (130, 800, and 1500 µg kg⁻¹) using a 3² factorial design that consisted of 3 (rice varieties) × 3 (Hg contents). The biomass, 1000-grain weight, and the accumulation of Hg in the roots, grains, and husks were determined. The highest biomass was found in the FA473 (308.76 ± 108.26 g), and the lowest was found in FAM (144.04 ± 26.45 g) in the 1500 µg kg⁻¹ Hg soil in both cases. The weight per 1000-grains decreased significantly in the soil containing 800 µg of Hg kg⁻¹. Hg accumulation in the organs of the evaluated varieties was higher in the roots, followed by in the husks and grains. The Hg in the rice grains of the evaluated varieties presented levels close to the permissible limit of the Chinese standard (20 μg Hg kg⁻¹) in the evaluated soils and were only exceeded by FA473. Although in natural soil concentrations, the non-cancer health risk (HQ) from rice consumption was lower for FA473 and FAM; Hg enrichment in the soil of La Mojana region may endanger the health of future populations due to their high consumption of rice. Full article

Exposure to chemicals is influenced by associations between the individual’s location and activities as well as demographic and physiological characteristics. Currently, many exposure models simulate individuals by drawing distributions from population-level data or use exposure factors for single individuals. The Residential Population Generator (RPGen) binds US surveys of individuals and households and combines the population with physiological characteristics to create a synthetic population. In general, the model must be supported by internal consistency; i.e., values that could have come from a single individual. In addition, intraindividual variation must be representative of the variation present in the modeled population. This is performed by linking individuals and similar households across income, location, family type, and house type. Physiological data are generated by linking census data to National Health and Nutrition Examination Survey data with a model of interindividual variation of parameters used in toxicokinetic modeling. The final modeled population data parameters include characteristics of the individual’s community (region, state, urban or rural), residence (size of property, size of home, number of rooms), demographics (age, ethnicity, income, gender), and physiology (body weight, skin surface area, breathing rate, cardiac output, blood volume, and volumes for body compartments and organs). RPGen output is used to support user-developed chemical exposure models that estimate intraindividual exposure in a desired population. By creating profiles and characteristics that determine exposure, synthetic populations produced by RPGen increases the ability of modelers to identify subgroups potentially vulnerable to chemical exposures. To demonstrate application, RPGen is used to estimate exposure to Toluene in an exposure modeling case example. Full article

Spilled mineral oils in the marine environment pose a number of challenges to sampling and analysis. Mineral oils are complex assemblages of hydrocarbons and additives, the composition of which can vary considerably depending on the source oil and product specifications. Further, the marine microbial and chemical environment can be harsh and variable over short times and distances, producing a rigorous source of hydrocarbon degradation of a mineral oil assemblage. Researchers must ensure that any measurements used to determine the nature and extent of the oil release, the fate and transport of the mineral oil constituents, and any resultant toxicological effects are derived using representative data that adhere to the study’s data quality objectives (DQOs). The purpose of this paper is to provide guidance for crafting obtainable DQOs and provide insights into producing reliable results that properly underpin researchers’ findings when scrutinized by others. Full article

The use of non-forced multi-compartmented exposure systems has gained importance in the assessment of the contamination-driven spatial avoidance response. This new paradigm of exposure makes it possible to assess how contaminants fragment habitats, interfering in the spatial distribution and species’ habitat selection processes. In this approach, organisms are exposed to a chemically heterogeneous scenario (a gradient or patches of contamination) and the response is focused on identifying the contamination levels considered aversive for organisms. Despite the interesting results that have been recently published, the use of this approach in ecotoxicological risk studies is still incipient. The current review aims to show the sensitivity of spatial avoidance in non-forced exposure systems in comparison with the traditional endpoints used in ecotoxicology under forced exposure. To do this, we have used the sensitivity profile by biological groups (SPBG) to offer an overview of the highly sensitive biological groups and the species sensitive distribution (SSD) to estimate the hazard concentration for 5% of the species (HC₅). Three chemically different compounds were selected for this review: copper, glyphosate, and Ag-NPs. The results show that contamination-driven spatial avoidance is a very sensitive endpoint that could be integrated as a complementary tool to ecotoxicological studies in order to provide an overview of the level of repellence of contaminants. This repellence is a clear example of how contamination might fragment ecosystems, prevent connectivity among populations and condition the distribution of biodiversity. Full article

Chemotherapy-induced peripheral neuropathy (CIPN) is widely recognized as a potentially severe toxicity that often leads to dose reduction or discontinuation of cancer treatment. Symptoms may persist despite discontinuation of chemotherapy and quality of life can be severely compromised. The clinical symptoms of CIPN, and the cellular and molecular targets involved in CIPN, are just as diverse as the wide variety of anticancer agents that cause peripheral neurotoxicity. There is an urgent need for extensive molecular and functional investigations aimed at understanding the mechanisms of CIPN. Furthermore, a reliable human cell culture system that recapitulates the diversity of neuronal modalities found in vivo and the pathophysiological changes that underlie CIPN would serve to advance the understanding of the pathogenesis of CIPN. The demonstration of experimental reproducibility in a human peripheral neuronal cell system will increase confidence that such an in vitro model is clinically useful, ultimately resulting in deeper exploration for the prevention and treatment of CIPN. Herein, we review current in vitro models with a focus on key characteristics and attributes desirable for an ideal human cell culture model relevant for CIPN investigations. Full article

The xenoestrogenicity of some plasticisers (phthalates and bisphenol A) is documented in the literature and may pose a risk to female reproductive health. The aim of this study was to assess exposure to six phthalates. This was achieved by measuring their respective metabolites (mono-ethylphthalate (MEP); mono-n-butylphthalate (MnBP); mono-n-ottylphthalate (MnOP); and monobenzylphthalate (MBzP)), as well as the sum of two of the diethyl-hexyl phthalate metabolites-(∑DEHP) and bisphenol A (BPA) in a female population with infertility problems, and by conducting a correlation analysis between infertility factors, work activities, and lifestyle habits, in order to formulate a causal hypothesis. A cross-sectional epidemiological study was carried out and women under 43 years of age were recruited from an assisted reproduction technology (ART) center; the sample of 186 women was given a specific questionnaire and a spot urine sample was collected. Phthalate metabolites and urinary BPA were analyzed by HPLC/MS/MS. The results showed significantly higher mean values for MEP in women with recurrent pregnancy loss (RPL) (820.5 ± 1929.5 µg/g of creatinine) and idiopathic infertility (230.0 ± 794.2 µg/g of creatinine) than in women with other infertility factors (76.9 ± 171.8 µg/g of creatinine). Similarly, for MnOP levels, women with idiopathic infertility (2.95 ± 3.44 µg/g of creatinine) showed significantly higher values than women with the other infertility factors taken together (1.35 ± 2.05 µg/g of creatinine). Women with tubal factors of infertility, RPL, and endocrine dysfunctions show higher values of DEHP (p = 0.032). Considering occupations, women working in commerce showed more than twice as much urinary BPA levels (1.10 ± 0.48 µg/g of creatinine) compared to women working in other industries (0.45 ± 0.35 µg/g of creatinine). The presence of significantly higher values of certain phthalates, DEHP in particular, especially in women with RPL and idiopathic infertility, suggests a possible involvement of these compounds as competing factors in reproductive issues. The study of sources of exposure suggested that the working activity in trade, as a casher in particular, represents a major one for BPA (p = 0.015). Full article

Acrylamide in food is formed by the Maillard reaction. Numerous studies have shown that acrylamide is a neurotoxic and carcinogenic compound. The aim of this study was to determine the level of acrylamide in breast milk at different lactation stages and to evaluate the impact of breastfeeding women’s diet on the content of this compound in breast milk. The acrylamide level in breast milk samples was determined by LC–MS/MS. Breastfeeding women’s diet was evaluated based on the 24 h dietary recall. The median acrylamide level in colostrum (n = 47) was significantly (p < 0.0005) lower than in the mature milk (n = 26)—0.05 µg/L and 0.14 µg/L, respectively. The estimated breastfeeding women’s acrylamide intake from the hospital diet was significantly (p < 0.0001) lower than that from the home diet. We found positive—although modest and borderline significant—correlation between acrylamide intake by breastfeeding women from the hospital diet µg/day) and acrylamide level in the colostrum (µg/L). Acrylamide has been detected in human milk samples, and a positive correlation between dietary acrylamide intake by breastfeeding women and its content in breast milk was observed, which suggests that the concentration can be reduced. Breastfeeding women should avoid foods that may be a source of acrylamide in their diet. Full article

Water quality is continuously affected by anthropogenic and environmental conditions. A significant issue of the Indian rivers is the massive water pollution, leading to the spreading of different diseases due to its daily use. Therefore, this study investigates three aspects. The first one is testing the hypothesis of the existence of a monotonic trend of the series of eight water parameters of the Brahmaputra River recorded for 17 years at ten hydrological stations. When this hypothesis was rejected, a loess trend was fitted. The second aspect is to assess the water quality using three indicators (WQI)–CCME WQI, British Colombia, and a weighted index. The third aspect is to group the years and the stations in clusters used to determine the regional (spatial) and temporal trend of the WQI series, utilizing a new algorithm. A statistical analysis does not reject the hypothesis of a monotonic trend presence for the spatially distributed data but not for the temporal ones. Hierarchical clustering based on the computed WQIs detected two clusters for the spatially distributed data and two for the temporal-distributed data. The procedure proposed for determining the WQI temporal and regional evolution provided good results in terms of mean absolute error, root mean squared error (RMSE), and mean absolute percentage error (MAPE). Full article

Contamination of the soil and water environment with harmful substances can be associated with many activities carried out on the railway. The problem is particularly relevant to liquid fuel loading and refueling facilities as well as to increased traffic at railway junctions. Studies were conducted in the area of railway junction Zduńska Wola Karsznice in central Poland (Łódź Voivodeship). Soil samples were collected from specific research points: from the inter-railway (A), 5 m from the main track (B), from the embankment—10 m from the main track (C), and from the side track (D), at the depth of 0–5 cm (1) and 20 cm (2). The following analyses were made: granulometric composition, pH in H₂O, and percent content of carbonates (CaCO₃). PHEs were determined in the fractions: 0.25 ≤ 0.5 mm, 0.1 ≤ 0.25 mm, and 0.05 ≤ 0.1 mm: Pb, Cd, Cr, Co, Cu, Ni, Zn, Sr by inductively coupled plasma mass spectrometry technique (ICP-MS/TOF OPTIMass 9500). The objectives of the study were (1) to assess PHEs (potentially harmful elements) contamination of the topsoil level of railway area, (2) to determine the correlation between the concentration of PHEs and the size of the fraction, and (3) to identify the areas (places) where the highest concentrations of PHEs were recorded. Based on the studied parameters, significant differentiation in soil properties of the areas in Zduńska Wola Karsznice was found. The analyses carried out showed that the accumulation of potentially harmful elements was as follows: Cu > Zn > Sr > Pb > Ni > Cr > Co > Cd. The average concentrations of Cu, Zn, Sr, Pb, Ni, Cr, Co and Cd were 216.0; 152.1; 97.8; 64.6; 15.2; 14.4; 3.1 and 0.2 mg·kg⁻¹ d.w., respectively. These contaminations occur in the topsoil layer of the railway embankment, which suggests a railway transport origin. The highest concentrations of PHEs were recorded in samples collected from close to the rails (inter-railway, side track), and in the embankment (10 m from the track) in the very fine sand fraction (0.05 ≤ 0.1 mm). The high accumulation index of copper, cadmium and lead in the surface layer of soil indicate their anthropogenic origin. The results presented in the paper can be used in local planning and spatial development of this area, taking into account all future decisions about ensuring environmental protection, including groundwater and soils. Full article

Acrylamide (AA) present in food is considered a harmful compound for humans, but it exerts an impact on microorganisms too. The aim of this study was to evaluate the impact of acrylamide (at conc. 0–10 µg/mL) on the growth of bacteria (Leuconostoc mesenteroides, Lactobacillus acidophilus LA-5) and yeasts (Saccharomyces cerevisiae, Kluyveromyces lactis var. lactis), which are used for food fermentation. Moreover, we decided to verify whether these microorganisms could utilise acrylamide as a nutritional compound. Our results proved that acrylamide can stimulate the growth of L. acidophilus and K. lactis. We have, to the best of our knowledge, reported for the first time that the probiotic strain of bacteria L. acidophilus LA-5 is able to utilise acrylamide as a source of carbon and nitrogen if they lack them in the environment. This is probably due to acrylamide degradation by amidases. The conducted response surface methodology indicated that pH as well as incubation time and temperature significantly influenced the amount of ammonia released from acrylamide by the bacteria. In conclusion, our studies suggest that some strains of bacteria present in milk fermented products can exert additional beneficial impact by diminishing the acrylamide concentration and hence helping to prevent against its harmful impact on the human body and other members of intestinal microbiota. Full article

Mifepristone (RU-486), a synthetic steroid with potent antiprogestogen and anti-glucocorticoid properties, has been widely used in clinical practice. Its effect on the endometrium, ovary, and fallopian tube has been well reported in many human and animal studies. However, its direct impact on post-implantation embryos remains underexplored. Additionally, some women choose to keep their pregnancy after mifepristone treatment fails. Thus, the potential risk remains controversial. Hence, this study investigated the direct effects of mifepristone on the development of mice blastocysts in vitro in terms of implantation and post-implantation. We detected the level of progesterone (P4) associated with ovulation in vivo. The presence of progesterone receptors (PRs) in blastocysts and post-implantation embryos was also evaluated. Cultured embryos were treated directly with mifepristone. We further examined embryonic implantation and post-implantation of blastocysts in vitro to evaluate the direct effects of mifepristone on embryos by the assessment of embryonic outgrowth and differential cell staining. In the oviduct lumen, the P4 level dramatically increased at 48 h and slightly decreased at 72 and 96 h following ovulation. PR was expressed in blastocysts not only in the preimplantation stage but also in the early post-implantation period. In the evaluation of developmental stages, mifepristone significantly reduced the successful ratio of developing into the late egg cylinder and the early somite stage. In addition, it further decreased the cell number of the embryos’ inner cell mass and trophectoderm. We herein provide evidence that mifepristone affects blastocyst viability directly and inhibits post-implantation embryo development in vitro. Furthermore, our data reveal a potential risk of fetus fatality and developmental problems when pregnancies are continued after mifepristone treatment fails. Full article

Agricultural lands, especially those where wheat is cultivated, in the vicinity of intense anthropogenic activities may be laden with potentially toxic elements (PTEs), resulting in increased risk for human health. In this study we monitored three regions located in central Greece, currently cultivated with wheat: Domokos and Eretria, two areas with abandoned chromium mines, but never studied before, and the industrial area of Volos, near a major steel factory. All soils were alkaline with medium CaCO₃ content. As expected, Cr was extremely high in the first two areas (705.2 in Eretria and 777.5 mg kg⁻¹ in Domokos); Ni was also found elevated (1227 in Eretria, 1315 in Domokos and 257.6 mg kg⁻¹ in the steel factory), while other harmful metals (Cd, Cu, Pb and Zn) were rather low. As a result, pollution load index, a cumulative index showing the contamination level of an area, was higher than 1.0 in all three areas (Eretria = 2.20, Domokos = 2.28, and steel factory = 1.61), indicating high contamination and anthropogenic inputs. As for the wheat parts (shoots and grains), they were found to have no elevated concentrations of any of the measured metals in all three study areas, probably due to the alkaline soil pH that decelerates metal mobility. This was also confirmed by the very low soil-to-plant transfer coefficient values for all metals. In assessing the possible risk concerning human health, we found that the soil-to-human pathway would induce no significant risk (exhibited by hazard index of less than 1.0), while the risk from grain-to-human resulted in considerable risk for human health in the steel factory of Volos (where HI > 1.0). Our findings suggest that rural areas never studied before with a history in some offensive anthropogenic activity can prove to be a contamination hotspot; we regard this study as a pivotal for similarly never-visited-before areas casually cultivated with wheat (or other important crops for human nutrition). We further recognize the need for a more in-depth study that would acknowledge the geochemical speciation of the studied metals and also monitor other important crops and their possible uptake of PTEs. Full article

Pharmacogenetics analyzes the individual behavior of DNA genes after the administration of a drug. Pharmacogenetic research has been implemented in recent years thanks to the improvement in genome sequencing techniques and molecular genetics. In addition to medical purposes, pharmacogenetics can constitute an important tool for clarifying the interpretation of toxicological data in post-mortem examinations, sometimes crucial for determining the cause and modality of death. The purpose of this systematic literature review is not only to raise awareness among the forensic community concerning pharmacogenetics, but also to provide a workflow for forensic toxicologists to follow in cases of unknown causes of death related to drug use/abuse. The scientific community is called on to work hard in order to supply evidence in forensic practice, demonstrating that this investigation could become an essential tool both in civil and forensic contexts. The following keywords were used for the search engine: (pharmacogenetics) AND (forensic toxicology); (pharmacogenetics) AND (post-mortem); (pharmacogenetics) AND (forensic science); and (pharmacogenetics) AND (autopsy). A total of 125 articles were collected. Of these, 29 articles were included in this systematic review. A total of 75% of the included studies were original articles (n = 21) and 25% were case reports (n = 7). A total of 78% (n = 22) of the studies involved deceased people for whom a complete autopsy was performed, while 22% (n = 6) involved people in good health who were given a drug with a subsequent pharmacogenetic study. The most studied drugs were opioids (codeine, morphine, and methadone), followed by antidepressants (tricyclic antidepressants and venlafaxine). Furthermore, all studies highlighted the importance of a pharmacogenetics study in drug-related deaths, especially in cases of non-overdose of drugs of abuse. This study highlights the importance of forensic pharmacogenetics, a field of toxicology still not fully understood, which is of great help in cases of sudden death, deaths from overdose, deaths after the administration of a drug, and also in cases of complaint of medical malpractice. Full article

The effects of bisphenol A (BPA) on asthma have been reported in various in vitro, animal, and human epidemiologic studies. However, epidemiological studies on the effects of bisphenol S (BPS) and bisphenol F (BPF), which are substitutes of BPA, on asthma are lacking. The purpose of this study was to identify the association between BPA, BPS, and BPF and asthma. An asthma-related questionnaire; urinary BPA, BPS, BPF; and the possible confounders were analyzed among 922 adolescents aged 12–17 years who participated in the Korean National Environmental Health Survey 2016. In males, urinary BPA, BPS, and BPF did not show a significant relationship with the lifetime prevalence of asthma. In females, urinary BPS was higher in the asthma group (p < 0.01). High urinary BPS showed a significant relationship with a high odds ratio (OR) of lifetime asthma prevalence in the model adjusted for possible confounders (p < 0.05). High urinary BPS was particularly associated with an increase in the OR of asthma diagnosed after the age of 60 months (p < 0.01). Urinary BPS was significantly associated with asthma diagnosis, especially after the age of 60 months, among Korean adolescent females. Full article

Exposure to air pollutants increases levels of circulating glucocorticoid stress hormones that exert profound effects relevant to health and disease. However, the nature and magnitude of tissue-level effects are modulated by factors that regulate local glucocorticoid activity; accordingly, inter-individual differences could contribute to susceptibility. In the present study, we characterized effects of ozone (O₃) inhalation on glucocorticoid-regulating factors in the lungs of rat strains with contrasting hypothalamic–pituitary–adrenal stress axis responses. Hyper-responsive Fischer (F344) and less responsive Lewis (LEW) rats were exposed to air or 0.8 ppm O₃ for 4 h by nose-only inhalation. Levels of the high-specificity and -affinity corticosteroid-binding globulin protein increased in the lungs of both strains proportional to the rise in corticosterone levels following O₃ exposure. Ozone reduced the ratio of 11β-hydroxysteroid dehydrogenase type 1 (HSDB1)/HSDB2 mRNA in the lungs of F344 but not LEW, indicating strain-specific transcriptional regulation of the major glucocorticoid metabolism factors that control tissue-level action. Intercellular adhesion molecule (ICAM)-1 and total elastase activity were increased by O₃ in both strains, consistent with extravasation and tissue remodeling processes following injury. However, mRNA levels of inflammatory markers were significantly higher in the lungs of O₃-exposed LEW compared to F344. The data show that strain differences in the glucocorticoid response to O₃ are accompanied by corresponding changes in regulatory factors, and that these effects are collectively associated with a differential inflammatory response to O₃. Innate differences in glucocorticoid regulatory factors may modulate the pulmonary effects of inhaled pollutants, thereby contributing to differential susceptibility. Full article

Microplastics (MPs)’ ingestion has been demonstrated in several aquatic organisms. This process may facilitate the hydrophobic waterborne pollutants or chemical additives transfer to biota. In the present study the suitability of a battery of biomarkers on oxidative stress, physiology, tissue function and metabolic profile was investigated for the early detection of adverse effects of 21-day exposure to polystyrene microplastics (PS-MPs, sized 5–12 μm) in the liver and gills of zebrafish Danio rerio and perch, Perca fluviatilis, both of which are freshwater fish species. An optical volume map representation of the zebrafish gill by Raman spectroscopy depicted 5 μm diameter PS-MP dispersed in the gill tissue. Concentrations of PS-MPs close to the EC₅₀ of each fish affected fish physiology in all tissues studied. Increased levels of biomarkers of oxidative damage in exposed fish in relation to controls were observed, as well as activation of apoptosis and autophagy processes. Malondialdehyde (MDA), protein carbonyls and DNA damage responses differed with regard to the sensitivity of each tissue of each fish. In the toxicity cascade gills seemed to be more liable to respond to PS-MPs than liver for the majority of the parameters measured. DNA damage was the most susceptible biomarker exhibiting greater response in the liver of both species. The interaction between MPs and cellular components provoked metabolic alterations in the tissues studied, affecting mainly amino acids, nitrogen and energy metabolism. Toxicity was species and tissue specific, with specific biomarkers responding differently in gills and in liver. The fish species that seemed to be more susceptible to MPs at the conditions studied, was P. fluviatilis compared to D. rerio. The current findings add to a holistic approach for the identification of small sized PS-MPs’ biological effects in fish, thus aiming to provide evidence regarding PS-MPs’ environmental impact on wild fish populations and food safety and adequacy. Full article

Biomarkers in exposure assessment are defined as the quantifiable targets that indicate the exposure to hazardous chemicals and their resulting health effect. In this study, we aimed to identify, validate, and characterize the mRNA biomarker that can detect the exposure of sodium cyanide. To identify reliable biomarkers for sodium cyanide exposure, critical criteria were defined for candidate selection: (1) the expression level of mRNA significantly changes in response to sodium thiocyanate treatment in transcriptomics results (fold change > 2.0 or <0.50, adjusted p-value < 0.05); and (2) the mRNA level is significantly modulated by sodium cyanide exposure in both normal human lung cells and rat lung tissue. We identified the following mRNA biomarker candidates: ADCY5, ANGPTL4, CCNG2, CD9, COL1A2, DACT3, GGCX, GRB14, H1F0, HSPA1A, MAF, MAT2A, PPP1R10, and PPP4C. The expression levels of these candidates were commonly downregulated by sodium cyanide exposure both in vitro and in vivo. We functionally characterized the biomarkers and established the impact of sodium cyanide on transcriptomic profiles using in silico approaches. Our results suggest that the biomarkers may contribute to the regulation and degradation of the extracellular matrix, leading to a negative effect on surrounding lung cells. Full article

Methylmercury (MeHg) is a well-known neurotoxicant; however, its role in metabolic diseases has been gaining wider attention. Chronic exposure to MeHg in human populations shows an association with diabetes mellitus and metabolic syndrome (MS). As the incidences of both obesity and MS are on the rise globally, it is important to understand the potential role of MeHg in the development of the disease. There is a dearth of information on dietary interactions between MeHg and lipids, which play an important role in developing MS. We have previously shown that MeHg increases food seeking behaviors, lipid levels, fat storage, and pro-adipogenic gene expression in C. elegans fed the standard OP50 Escherichia coli diet. However, we hypothesized that these metabolic changes could be prevented if the worms were fed a bacterial diet lower in lipid content. We tested whether C. elegans developed metabolic alterations in response to MeHg if they were fed two alternative E. coli strains (HT115 and HB101) that are known absorb significantly less lipids from their media. Additionally, to explore the effect of a high-lipid and high-cholesterol diet on MeHg-induced metabolic dysfunction, we supplemented the OP50 strain with twice the standard concentration of cholesterol in the nematode growth media. Wild-type worms fed either the HB101 or HT115 diet were more resistant to MeHg than the worms fed the OP50 diet, showing a significant right-hand shift in the dose–response survival curve. Worms fed the OP50 diet supplemented with cholesterol were more sensitive to MeHg, showing a significant left-hand shift in the dose–response survival curve. Changes in sensitivity to MeHg by differential diet were not due to altered MeHg intake in the worms as measured by inductively coupled mass spectrometry. Worms fed the low-fat diets showed protection from MeHg-induced metabolic changes, including decreased food consumption, lower triglyceride content, and lower fat storage than the worms fed either of the higher-fat diets. Oxidative stress is a common characteristic of both MeHg exposure and high-fat diets. Worms fed either OP50 or OP50 supplemented with cholesterol and treated with MeHg had significantly higher levels of reactive oxygen species, carbonylated proteins, and loss of glutathione than the worms fed the HT115 or HB101 low-lipid diets. Taken together, our data suggest a synergistic effect of MeHg and dietary lipid levels on MeHg toxicity and fat metabolism in C. elegans, which may affect the ability of MeHg to cause metabolic dysfunction. Full article