Toxics

The Electrophilic Allergen Screening Assay (EASA) has emerged as a promising in chemico method to detect the first key event in the adverse outcome pathway (AOP) for skin sensitization. This assay functions by assessing the depletion of one of two probe molecules (4-nitrobenzenethiol (NBT) and pyridoxylamine (PDA)) in the presence of a test compound (TC). The initial development of EASA utilized a cuvette format resulting in multiple measurement challenges such as low throughput and the inability to include adequate control measurements. In this study, we describe the redesign of EASA into a 96-well plate format that incorporates in-process control measurements to quantify key sources of variability each time the assay is run. The data from the analysis of 67 TCs using the 96-well format had 77% concordance with animal data from the local lymph node assay (LLNA), a result consistent with that for the direct peptide reactivity assay (DPRA), an OECD test guideline (442C) protein binding assay. Overall, the measurement science approach described here provides steps during assay development that can be taken to increase confidence of in chemico assays by attempting to fully characterize the sources of variability and potential biases and incorporate in-process control measurements into the assay. Full article

With the abundance of chemicals in the environment that could potentially cause neurodevelopmental deficits, there is a need for rapid testing and chemical screening assays. This study evaluated the developmental toxicity and behavioral effects of 61 chemicals in zebrafish (Danio rerio) larvae using a behavioral Light/Dark assay. Larvae (n = 16–24 per concentration) were exposed to each chemical (0.0001–120 μM) during development and locomotor activity was assessed. Approximately half of the chemicals (n = 30) did not show any gross developmental toxicity (i.e., mortality, dysmorphology or non-hatching) at the highest concentration tested. Twelve of the 31 chemicals that did elicit developmental toxicity were toxic at the highest concentration only, and thirteen chemicals were developmentally toxic at concentrations of 10 µM or lower. Eleven chemicals caused behavioral effects; four chemicals (6-aminonicotinamide, cyclophosphamide, paraquat, phenobarbital) altered behavior in the absence of developmental toxicity. In addition to screening a library of chemicals for developmental neurotoxicity, we also compared our findings with previously published results for those chemicals. Our comparison revealed a general lack of standardized reporting of experimental details, and it also helped identify some chemicals that appear to be consistent positives and negatives across multiple laboratories. Full article

Bisphenol A (BPA) and heavy metals are widespread contaminants in the environment. However, the combined toxicities of these contaminants are still unknown. In this study, the bioluminescent bacteria Vibrio qinghaiensis Q67 was used to detect the single and combined toxicities of BPA and heavy metals, then the joint effects of these contaminants were evaluated. The results show that chronic toxicities of chromium (Cr), cadmium (Cd), lead (Pb), arsenic (As), mercury (Hg), nickel (Ni), and BPA were time–dependent; in fact, the acute toxicities of these contaminants were stronger than the chronic toxicities. Furthermore, the combined toxicities of BPA and heavy metals displayed BPA + Hg > BPA + Cr > BPA + As > BPA + Ni > BPA + Pb > BPA + Cd in the acute test and BPA + Hg > BPA + Cd > BPA + As > BPA + Cd in the chronic test, which suggested that the combined toxicity of BPA and Hg was stronger than that of other mixtures in acute as well as chronic tests. Additionally, both CA and IA models underestimated the toxicities of mixtures at low concentrations but overestimated them at high concentrations, which indicates that CA and IA models were not suitable to predict the toxicities of mixtures of BPA and heavy metals. Moreover, the joint effects of BPA and heavy metals mainly showed antagonism and additive in the context of acute exposure but synergism and additive in the context of chronic exposure. Indeed, the difference in the joint effects on acute and chronic exposure can be explained by the possibility that mixtures inhibited cell growth and luminescence in chronic cultivation. The chronic toxicity of the mixture should be considered if the mixture results in the inhibition of the growth of cells. Full article

The use of lanthanides is increasing in our society, whether in communication technologies, transportation, electronics or medical imaging. Some lanthanides enter urban wastewater and flow through municipal wastewater treatment plants (WWTPs). However, little is known about the effectiveness of treatment processes to remove these elements and the concentrations released in effluents to receiving waters. The main objective of this study was to investigate the fate of lanthanides in various wastewater treatment processes. A secondary objective was to better understand the fate of medical gadolinium (Gd) complexes; anthropogenic inputs were differentiated from geological sources using an approach based on concentration normalization with respect to chondrite Post-Archean Australian Shale (PAAS). The hypothesis was that most lanthanides, especially of geological origin, are associated with the particulate phase and could be efficiently removed by WWTPs. To monitor these elements in different WWTPs, various urban influents and effluents from simple aerated lagoons to advanced treatments were sampled in Canada. The results showed that the rates of lanthanide removal by treatment processes decrease with their atomic number; from 95% for cerium (Ce) to 70% for lutetium (Lu), except for Gd, which was minimally removed. The normalization approach permitted the determination of the origin of Gd in these wastewaters, i.e., medical application versus the geological background. By distinguishing the geogenic Gd fraction from the anthropogenic one, the removal efficiency was evaluated according to the origin of the Gd; nearly 90% for geogenic Gd and a rate varying from 15% to 50% in the case of anthropogenic Gd. The processes using alum as the flocculating agent had the highest removal efficiency from wastewater. Full article

The study was aimed at assessing the influence of urban informal settlement on trace element accumulation in road dust from the Ekurhuleni Metropolitan Municipality, South Africa, and their possible health implications. The concentration of major and trace elements was determined using the wavelength dispersive XRF method. The major elements in descending order were SiO₂ (72.76%), Al₂O₃ (6.90%), Fe₂O₃ (3.88%), CaO (2.71%), K₂O (1.56%), Na₂O (0.99%), MgO (0.94%), MnO (0.57%), TiO₂ (0.40%), and P₂O₅ (0.16%), with SiO₂ and P₂O₅ at above-average shale values. The average mean concentrations of 17 trace elements in decreasing order were Cr (637.4), Ba (625.6), Zn (231.8), Zr (190.2), Sr (120.2), V (69), Rb (66), Cu (61), Ni (49), Pb (30.8), Co (17.4), Y (14.4), Nb (8.6), As (7.2), Sc (5.8), Th (4.58), and U (2.9) mg/kg. Trace elements such as Cr, Cu, Zn, Zr, Ba, and Pb surpassed their average shale values, and only Cr surpassed the South African soil screening values. The assessment of pollution through the geo-accumulation index (Igeo) revealed that road dust was moderately to heavily contaminated by Cr, whereas all other trace elements were categorized as being uncontaminated to moderately contaminated. The contamination factor (CF) exhibited road dust to be very highly contaminated by Cr, moderately contaminated by Zn, Pb, Cu, Zr, and Ba, and lowly contaminated by Co, U, Nb, Ni, As, Y, V, Rb, Sc, Sr, and Th. The pollution load index (PLI) also affirmed that the road dust in this study was very highly polluted by trace elements. Moreover, the results of the enrichment factor (EF) categorized Cr as having a significant degree of enrichment. Zn was elucidated as being minimally enriched, whereas all other trace elements were of natural origin. The results of the non-carcinogenic risk assessment revealed a possibility of non-carcinogenic risks to both children and adults. For the carcinogenic risk, the total CR values in children and adults were above the acceptable limit, signifying a likelihood of carcinogenic risk to the local inhabitants. From the findings of this study, it can be concluded that the levels of trace elements in the road dust of this informal settlement had the possibility to contribute to both non-carcinogenic and carcinogenic risks, and that children were at a higher risk than the adult population. Full article

Epidemiologic studies have suggested an association between agrochemical exposure and risk of renal injury. Farmers face great risks to developing adverse effects. The most appropriate biomarker related to renal injury needs to be developed to encounter earlier detection. We aim to study the association between early renal biomarker and occupational herbicide exposure in maize farmers, Thailand. Sixty-four farmers were recruited and interviewed concerning demographic data, herbicide usage, and protective behavior. Two spot urines before (pre-work task) and after (post-work task) herbicide spraying were collected. To estimate the intensity of exposure, the cumulative herbicide exposure intensity index (cumulative EII) was also calculated from activities on the farm, type of personal protective equipment (PPE) use, as well as duration and frequency of exposure. Four candidate renal biomarkers including π-GST, sirtuin-1, mitochondrial DNA (mtDNA) were measured. Most subjects were male and mostly sprayed three herbicides including glyphosate-based herbicides (GBH), paraquat, and 2,4-dichlorophenoxyacetic acid (2,4-D). A type of activity in farm was mixing and spraying herbicide. Our finding demonstrated no statistical significance of all biomarker levels between pre- and post-work task urine. To compare between single and cocktail use of herbicide, there was no statistical difference in all biomarker levels between pre- and post-work task urine. However, the urinary mtDNA seems to be increased in post-work task urine. Moreover, the cumulative EII was strongly associated with change in mtDNA content in both ND-1 and COX-3 gene. The possibility of urinary mtDNA as a valuable biomarker was promising as a noninvasive benchmark for early detection of the risk of developing renal injury from herbicide exposure. Full article

The female reproductive system is dependent upon the health of the ovaries. The ovaries are responsible for regulating reproduction and endocrine function. Throughout a female’s reproductive lifespan, the ovaries undergo continual structural changes that are crucial for the maturation of ovarian follicles and the production of sex steroid hormones. Phthalates are known to target the ovaries at critical time points and to disrupt normal reproductive function. The US population is constantly exposed to measurable levels of phthalates. Phthalates can also pass placental barriers and affect the developing offspring. Phthalates are frequently prevalent as mixtures; however, most previous studies have focused on the effects of single phthalates on the ovary and female reproduction. Thus, the effects of exposure to phthalate mixtures on ovarian function and the female reproductive system remain unclear. Following a brief introduction to the ovary and its major roles, this review covers what is currently known about the effects of phthalate mixtures on the ovary, focusing primarily on their effects on folliculogenesis and steroidogenesis. Furthermore, this review focuses on the effects of phthalate mixtures on female reproductive outcomes. Finally, this review emphasizes the need for future research on the effects of environmentally relevant phthalate mixtures on the ovary and female reproduction. Full article

In this study, a nanocomposite of cerium oxide-zinc (CeO₂-Zn; 26 ± 11 nm) based on the antioxidant rare-earth cerium oxide (CeO₂) nanoparticles (NPs) with the modifier zinc (Zn) was synthesized by sintering method and characterized. Its bio-response was examined in human umbilical-vein-derived endothelial (HUVE) cells to get insight into the components of vascular system. While NPs of CeO₂ did not significantly alter cell viability up to a concentration of 200 µg/mL for a 24 h exposure, 154 ± 6 µg/mL of nanocomposite CeO₂-Zn induced 50% cytotoxicity. Mechanism of cytotoxicity occurring due to nanocomposite by its Zn content was compared by choosing NPs of ZnO, possibly the closest nanoparticulate form of Zn. ZnO NPs lead to the induction of higher reactive oxygen species (ROS) (DCF-fluorescence), steeper depletion in antioxidant glutathione (GSH) and a greater loss of mitochondrial membrane potential (MMP) as compared to that induced by CeO₂-Zn nanocomposite. Nanocomposite of CeO₂-Zn, on the other hand, lead to significant higher induction of superoxide radical (O₂^•−, DHE fluorescence), nitric oxide (NO, determined by DAR-2 imaging and Griess reagent) and autophagic vesicles (determined by Lysotracker and monodansylcadeverine probes) as compared to that caused by ZnO NP treatment. Moreover, analysis after triple staining (by annexin V-FITC, PI, and Hoechst) conducted at their respective IC50s revealed an apoptosis mode of cell death due to ZnO NPs, whereas CeO₂-Zn nanocomposite induced a mechanism of cell death that was significantly different from apoptosis. Our findings on advanced biomarkers such as autophagy and mode of cell death suggested the CeO₂-Zn nanocomposite might behave as independent nanostructure from its constituent ones. Since nanocomposites can behave independently of their constituent NPs/elements, by creating nanocomposites, NP versatility can be increased manifold by just manipulating existing NPs. Moreover, data in this study can furnish early mechanistic insight about the potential damage that could occur in the integrity of vascular systems. Full article

The threat of toxic metals to food security and human health has become a high-priority issue in recent decades. As the world’s main food crop source, the safe cultivation of rice has been the focus of much research, particularly the restoration of toxic metals in paddy fields. Therefore, in this paper, we focus on the effects of toxic metals on rice, as well as the removal or repair methods of toxic metals in paddy fields. We also provide a detailed discussion of the sources and monitoring methods of toxic metals pollution, the current toxic metal removal, and remediation methods in paddy fields. Finally, several important research issues related to toxic metals in paddy field systems are proposed for future work. The review has an important guiding role for the future of heavy metal remediation in paddy fields, safe production of rice, green ecological fish culture, and human food security and health. Full article

The concentration of pesticide residues in agricultural products at harvest can change during subsequent processing steps. This change, commonly expressed as Processing Factor (PF), is influenced by the raw agricultural commodity, and the processing conditions, as well as the properties of the substances. As it is not possible to conduct processing studies for all possible combinations of pesticide × process × product, new approaches for determining processing factors are needed. Wine was chosen as the object of the present study because it is a widely consumed product. Furthermore, it is already known that the concentration of pesticide residues can change considerably during the processing of grapes into wine, substantiating the need for PFs for a large number of pesticides. The aim of the present study was to investigate the correlation between selected physicochemical properties and PFs. In addition, the influence of different winemaking processes was explored. For this purpose, 70 processing studies conducted by pesticide manufacturers in the framework of regulatory procedures were evaluated in detail and PFs were derived for 20 pesticides. For wine, a good correlation between the PF and the octanol-water partition coefficient of the substances was found, depending on the specific production methods used. Exemplarily, the coefficient of determination for white wine was 0.85, and 0.81 for red wine, when thermovinification was applied. These results can serve as the basis for a predictive model to be validated further with future winemaking studies for pesticides. Full article

The level and composition of air pollution have changed during the coronavirus disease 2019 (COVID-19) pandemic. However, the association between air pollution and pediatric respiratory disease emergency department (ED) visits during the COVID-19 pandemic remains unclear. The study was retrospectively conducted between 2017 and 2020 in Kaohsiung, Taiwan, from 1 January 2020 to 1 May 2020, defined as the period of the COVID-19 pandemic, and 1 January 2017 to 31 May 2019, defined as the pre-COVID-19 pandemic period. We enrolled patients under 17 years old who visited the ED in a medical center and were diagnosed with respiratory diseases such as pneumonia, asthma, bronchitis, and acute pharyngitis. Measurements of particulate matter (PM) with aerodynamic diameters of <10 μm (PM₁₀) and < 2.5 μm (PM_2.5), nitrogen dioxide (NO₂), and Ozone (O₃) were collected. During the COVID-19 pandemic, an increase in the interquartile range of PM_2.5, PM₁₀, and NO₂ levels was associated with increases of 72.5% (95% confidence interval [CI], 50.5–97.7%), 98.0% (95% CI, 70.7–129.6%), and 54.7% (95% CI, 38.7–72.6%), respectively, in the risk of pediatric respiratory disease ED visits on lag 1, which were greater than those in the pre-COVID-19 pandemic period. After adjusting for temperature and humidity, the risk of pediatric respiratory diseases after exposure to PM_2.5 (inter p = 0.001) and PM₁₀ (inter p < 0.001) was higher during the COVID-19 pandemic. PM_2.5, PM₁₀, and NO₂ may play important roles in pediatric respiratory events in Kaohsiung, Taiwan. Compared with the pre-COVID-19 pandemic period, the levels of PM_2.5 and PM₁₀ were lower; however, the levels were related to a greater increase in ED during the COVID-19 pandemic. Full article

Recently, an increasing number of chemical compounds are being characterized as endocrine disruptors since they have been proven to interact with the endocrine system, which plays a crucial role in the maintenance of homeostasis. Glyphosate is the active substance of the herbicide Roundup^®, bisphenol A (BPA) and di (2-ethylhexyl) phthalate (DEHP) are used as plasticizers, while triclosan (TCS), methyl (MePB), propyl (PrPB), and butyl (BuPB) parabens are used as antimicrobial agents and preservatives mainly in personal care products. Studies indicate that exposure to these substances can affect humans causing developmental problems and problems in the endocrine, reproductive, nervous, immune, and respiratory systems. Although there are copious studies related to these substances, there are few in vivo studies related to combined exposure to these endocrine disruptors. The aim of the present pilot study is the investigation and assessment of the above substances’ toxicity in rabbits after twelve months of exposure to glyphosate (both pure and commercial form) and to a mixture of all the above substances at subtoxic levels. The lack of data from the literature concerning rabbits’ exposure to these substances and the restrictions of the 3Rs Principle will result in a limited number of animals available for use (four animals per group, twenty animals in total). Full article

Oil-contaminated soil is a major societal problem for humans and the environment. In this study, the pyrolysis method was applied to oil-contaminated soil used as a landfill and gas station site in Korea. The removal efficiency of the main components of oil-contaminated soils, such as total petroleum hydrocarbons (TPH), polyaromatic hydrocarbons (PAHs), unresolved complex mixture (UCM), and alkylated PAHs (Alk-PAHs) were measured, and the effect of temperature, treatment time, and moisture content on pyrolysis efficiency was studied. In order to evaluate the risk of soil from which pollutants were removed through pyrolysis, integrated ecotoxicity was evaluated using Daphnia magna and Allivibrio fischeri. The chemical and biological measurements in this study include contaminants of emerging concerns (CECs). Results showed that the pyrolysis was more efficient with higher treatment temperatures, moisture content, and treatment times. In addition, toxicity was reduced by 99% after pyrolysis, and the degree of toxicity was evaluated more sensitively in Allivibrio fischeri than in Daphnia magna. This study shows that weathered oil-contaminated soil can be effectively treated in a relatively short time through pyrolysis, as well as provides information on efficient conditions and the assessment of ecotoxicity. Full article

Coral reefs have been declining globally at a historically unprecedented rate. Ultraviolet (UV) filters used in sunscreens may contribute to this decline at local scales, which has already led to bans on various organic UV filters in some regions. However, the underlying studies for these bans demonstrated significant flaws in the experimental design due to a lack of validated and standardized testing methods for corals. This study aimed to investigate options for the development of a standard acute toxicity test for the larval stage of scleractinian corals. Planula larvae of two brooding (Leptastrea purpurea and Tubastraea faulkneri) and two spawning (Acropora digitifera and A. millepora) species were exposed to the organic UV filter benzophenone-3 (BP3) for 48 h under static conditions. We observed interspecific variations in toxicity, with A. digitifera being the most sensitive (LC₅₀ = 0.75 µg L⁻¹) and T. faulkneri the least sensitive (LC₅₀ = 2951.24 µg L⁻¹) species. Inhibition of settlement was found to be a useful endpoint leading to an EC₅₀ of 1.84 µg L⁻¹ in L. purpurea larvae. Although the analytical challenges of measuring lipophilic substances in small volume test setups remain, the here applied test design and selected endpoints are suitable for further validation and subsequent standardization. Full article

Chemical analysis was performed on sediment samples collected in two sampling sessions (July and October) from Podu Iloaiei Dam Lake, one of the most important water resources used for aquaculture in north-eastern Romania. The concentration of 15 trace elements (TEs), 8 refractory elements (REs), and 15 rare earth elements (REEs)—determined using inductively coupled plasma mass spectrometry—showed variability largely dependent of the sampling points and collection time. Manganese was the most abundant TE, V and Cr were the most abundant REs, while Ce was one of the most abundant REEs. The cerium negative anomaly and Gd positive anomaly were observed in the Chondrite-normalized distributions. In October, the Ce anomaly showed significant negative correlation with Mn, emphasizing the water body oxidation potential. The identified positive Gd anomaly was most likely associated with the use of Gd-chelating agents in magnetic resonance imaging in Iasi, the largest medical hub in north-eastern Romania. Principal component analysis extracted three factors explaining 96.0% of the observed variance, i.e., rock weathering, leaching from soil surface, contributions from urban stormwater and atmospheric deposition (50.9%), pedological contributions (23.7%), and mixed anthropogenic sources (e.g., traffic, waste discharge, agricultural activities; 21.4%). The evaluation of pollution indices highlighted low and moderate degrees of contamination for most of the elements and a considerable degree of contamination for Cd. Assigned Cd sources included fertilizers and pesticides used in the near agricultural areas or the high traffic road located near the lake. Since contamination of aquatic ecosystems with harmful elements is a human health concern, further monitoring of specific vectors in the food chain of the investigated dam lake will be of the utmost importance. Full article

In order to prevent the spread of COVID-19, contingency measures in the form of lockdowns were implemented all over the world, including in Croatia. The aim of this study was to detect if those severe, imposed restrictions of social interactions reflected on the water quality of rivers receiving wastewaters from urban areas. A total of 18 different pharmaceuticals (PhACs) and illicit drugs (IDrgs), as well as their metabolites, were measured for 16 months (January 2020–April 2021) in 12 different locations at in the Sava and Drava Rivers, Croatia, using UHPLC coupled to LCMS. This period encompassed two major Covid lockdowns (March–May 2020 and October 2020–March 2021). Several PhACs more than halved in river water mass flow during the lockdowns. The results of this study confirm that Covid lockdowns caused lower cumulative concentrations and mass flow of measured PhACs/IDrgs in the Sava and Drava Rivers. This was not influenced by the increased use of drugs for the treatment of the COVID-19, like antibiotics and steroidal anti-inflammatory drugs. The decreases in measured PhACs/IDrgs concentrations and mass flows were more pronounced during the first lockdown, which was stricter than the second. Full article

The Beijing–Tianjin–Hebei (BTH) region in China is a rapid development area with a dense population and high-pollution, high-energy-consumption industries. Despite the general idea that the coking industry contributes greatly to the total emission of potentially harmful elements (PHEs) in BTH, quantitative analysis on the PHE pollution caused by coking is rare. This study collected the pollutant discharge data of coking enterprises and assessed the risks of coking plants in BTH using the soil accumulation model and ecological risk index. The average contribution rate of coking emissions to the total emissions of PHEs in BTH was ~7.73%. Cross table analysis indicated that there was a close relationship between PHEs discharged by coking plants and PHEs in soil. The accumulation of PHEs in soil and their associated risks were calculated, indicating that nearly 70% of the coking plants posed a significant ecological risk. Mercury, arsenic, and cadmium were the main PHEs leading to ecological risks. Scenario analysis indicated that the percentage of coking plants with high ecological risk might rise from 8.50% to 20.00% as time progresses. Therefore, the control of PHEs discharged from coking plants in BTH should be strengthened. Furthermore, regionalized strategies should be applied to different areas due to the spatial heterogeneity of risk levels. Full article

This study aims at providing bee products and derivatives of medicinal plant consumers with a multifaceted perspective on mineral elements occurring in the soils of two forest zones in the vicinity of North Dobrogea (Romania) by (1) analyzing the pollution levels of the soils at three sites (denoted by DS, PH, and ST) in the study region, using different indicators; (2) providing the results of the transfer of metals from the soil to Sambucus nigra L. (SnL), Hypericum perforatum (Hp), and Tilia tomentosa (Tt). The statistical analysis of the series collected at these locations shows no difference between the elements’ concentrations (as a whole). Still, the values of the geo-accumulation index (I_geo) classify the soils as being soils that are moderately to highly contaminated with Cd (and not contaminated with Cu, Mn, or Zn) with respect to the European background values. The cumulative indices—the degree of contamination (DC), the pollution load index (PLI), the Nemerow integrated pollution index (NIPI), and the potential ecological risk index (PERI) indicated the highest contamination in DS (which is a tourist area). To assess the accumulation of different metals in plants, the enrichment factors (EF) were computed. In over 75% of cases, EF was above 1, indicating a high degree of enrichment with different metals. The highest values were those for Cu (41.10 in DS for SnL), and Cd (12.85 in DS for Tt). The results showed that there were different degrees of accumulation between microelements and trace elements in the plants. Tt acted as a bioaccumulator for almost all of the studied elements (K, Mg, Na, Fe, Mn, Cu, Zn, and Cd). Full article