Toxics, Volume 10, Issue 5 (May 2022) – 76 articles

Recent studies indicated renal toxicity and interstitial nephritis in patients receiving leflunomide (LEFN), but the exact mechanism is still unknown. The transforming growth factor β (TGFβ)/p53/Smad2/3 pathway crucially mediates renal fibrosis. We aimed to assess the nephrotoxic effect of LEFN in mice and the possible role of TGFβ-stimulated p53/SMAD2/3 signaling. The study design involved distributing sixty male albino mice into four groups: (i) vehicle-treated mice, (ii) LEFN (2.5 mg/kg), (iii) LEFN (5 mg/kg), and (iv) LEFN (10 mg/kg). The drug was given orally every 48 h and continued for 8 weeks. Blood samples were then taken from mice for the determination of kidney function parameters. Right kidneys were used for histopathologic staining and immunohistochemistry, whereas left kidneys were frozen and used for Western blot analysis of the target proteins, p-p53 and Smad2/3. Results indicated that chronic administration of LEFN in mice resulted in a four- and nine-fold increase in serum urea and creatinine levels, respectively. Kidney specimens stained with hematoxylin and eosin or periodic acid–Schiff showed significant histopathological manifestations, such as cellular irregularity, interstitial congestion, and moderate lymphocytic inflammatory infiltrate in mice treated with LEFN. Western blotting indicated upregulation of the p-p53/Smad2/3 proteins. LEFN, especially in the highest dose (10 mg/kg), produced prominent nephrotoxicity in mice. This toxicity is mediated through stimulating fibrotic changes through TGFβ-stimulated p53/Smad2/3 signaling and induction of glomerular and tubular apoptosis. An improved understanding of LEFN-induced nephrotoxicity would have great implications in the prediction, prevention, and management of leflunomide-treated rheumatic patients, and may warrant further clinical studies for following up these toxidromes. Full article

Appropriate human health risk assessment (HHRA) is desire in modern regulatory toxicology, especially for elemental impurity studies. The aim of this article is the comprehensive HHRA of two heavy metals impurities—Cd and Pb in herbal medicinal products (HMP) as Menthae piperitae tinctura (Mentha × piperita L., folium) available in Polish pharmacies. These phytopharmaceuticals registered in EU are very common and usually applied OTC products by adults and also children/adolescents. For this purpose, we applied double regulatory approach, including: (1) requirements of ICH Q3D R1 guideline about elemental impurities and (2) additionally margin of exposure (MoE)-based concept to cover also specific population groups. Raw results shows that Cd and Pb were present in all analyzed HMP with Mentha × piperita L., folium (PTM1–PTM10) available in Polish pharmacies. In all samples, Cd impurities (in the range: 0.305–0.506 µg/L) were greatly lower than Pb impurities (in the range: 1.122–4.4921 µg/L). The HHRA of Cd and Pb impurities considering ICH Q3D R1 guideline-based approach made it possible to conclude that all results were below the permissible limit set by FAO/WHO for medicinal herbs and plants in different countries (300 µg/kg for Cd and 10,000 µg/kg for Pb). Additionally, the estimated daily intake of investigated elemental impurities compared to the PDE value confirm all samples safety. The second approach, an MoE-based strategy, indicated that the obtained values of MoE for Cd and Pb in daily dose for each samples were above 10,000; hence, exposure to these elemental impurities would not cause a health risk for all investigated population groups (children, adolescents, and adults). To the best our knowledge, this article is the first study about heavy metals impurities level in final HMPs as Menthae piperitae tinctura (Mentha × piperita L., folium) available in Polish pharmacies. Full article

Pharmaceuticals are widely acknowledged to be a threat to aquatic life. Over the last two decades, the steady use of biologically active chemicals for human health has been mirrored by a rise in the leaking of these chemicals into natural environments. The aim of this work was to detect the toxicity of sodium fluoride (NaF) exposure and platinum-derived drugs in an ecological setting on aquatic organism development. From 24 to 96 h post-fertilization, zebrafish embryos were treated to dosages of NaF 10 mg/L⁻¹ + cisplatin (CDDP) 100 μM, one with NaF 10 mg/L⁻¹ + carboplatin (CARP) 25 μM, one with NaF 10 mg/L⁻¹ + CDDP 100 μM + CARP 25 μM. Fluoride exposure in combination with Cisplatin and Carboplatin (non-toxic concentration) had an effect on survival and hatching rate according to this study. Additionally, it significantly disturbed the antioxidant defense system and increased ROS in zebrafish larvae. NaF 10 mg/L⁻¹ associated with CDDP 100 μM and CARP 25 μM, increased the production of apoptosis-related proteins (caspase 3, bax, and bcl-2) and the downregulation of acetylcholinesterase (AChE) activity, while no effect was seen for the single exposure. Full article

Lead (Pb) is a widespread and nondegradable environmental pollutant and affects several organs through oxidative mechanisms. This study was conducted to investigate the antioxidant protective effect of glycine betaine (GB) against Pb-induced renal and hepatic injury. Male albino rats (n = 45) were divided into three groups: G1 untreated control, G2 Pb-acetate (50 mg/kg/day), and G3 Pb-acetate (50 mg/kg/day) plus GB (250 mg/kg/day) administered for 6 weeks. For G3, Pb-acetate was administered first and followed by GB at least 4 h after. Pb-acetate treatment (G2) resulted in a significant decrease in renal function, including elevated creatinine and urea levels by 17.4% and 23.7%, respectively, and nonsignificant changes in serum uric acid levels. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphates (ALP) activities were significantly increased with Pb treatment by 37.6%, 59.3%, and 55.1%, respectively. Lipid peroxidation level was significantly increased by 7.8 times after 6 weeks of Pb-acetate treatment. The level of reduced glutathione (GSH-R) significantly declined after Pb-acetate treatment. Pb-acetate treatment also reduced the activities of superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutathione peroxidase (GSH-PX) by 74.1%, 85.0%, and 40.8%, respectively. Treatment of Pb-intoxicated rats with GB resulted in a significant reduction in creatinine, urea, ALT, AST, and lipid peroxidation, as well as a significant increase in the level of GSH-R and in the activities of ALP, SOD, GST, and GSH-PX. The molecular interaction between GB and GSH-PX indicated that the activation of GSH-PX in Pb-intoxicated rats was not the result of GB binding to the catalytic site of GSH-PX. The affinity of GB to bind to the catalytic site of GSH-PX is lower than that of H₂O₂. Thus, GB significantly mitigates Pb-induced renal and liver injury through the activation of antioxidant enzymes and the prevention of Pb-induced oxidative damage in the kidney and liver. Full article

Nanoplastics (NPs) are particles ranging in size between 1 and 1000 nm, and they are a form of environmental contaminant of great ecotoxicological concern. Although NPs are widespread across ecosystems, they have only recently garnered growing attention from both the scientific community and regulatory bodies. The present study reviews scientific literature related to the exposure and effects of NPs and identifies research gaps that impede the finalization of related environmental risk assessments (ERAs). Approximately 80 articles published between 2012 and 2021 were considered. Very few studies (eight articles) focused on the presence of NPs in biotic matrices, whereas the majority of the studies (62 articles) assessed the lethal and sublethal effects of NPs on aquatic and terrestrial organisms. Whilst many studies focused on nude NPs, only a few considered their association with different aggregates. Amongst NPs, the effects of polystyrene are the most extensively reported to date. Moreover, the effects of NPs on aquatic organisms are better characterized than those on terrestrial organisms. NP concentrations detected in water were close to or even higher than the sublethal levels for organisms. An ERA framework specifically tailored to NPs is proposed. Full article

Anticholinesterase pesticides are a main cause of the intentional or accidental poisoning of animals. Anticholinesterases include several substances that cause the overstimulation of both central and peripheral acetylcholine-dependent neurotransmission. Forensic analyses of poisoning cases require high levels of expertise, are costly, and often do not provide reliable quantitative information for unambiguous conclusions. The purpose of the present study was to develop and validate a method of high-performance liquid chromatography with diode array detector (HPLC–DAD) for the identification and quantitation of n-methyl carbamates, organophosphates and respective metabolites from biological samples of animals that were suspected of poisoning. HPLC–DAD is reliable, fast, simplistic and cost-effective. The method was validated for biological samples obtained from stomach contents, liver, vitreous humor and blood from four different animal species. The validation of the method was achieved using the following analytical parameters: linearity, precision, accuracy, selectivity, recovery, and matrix effect. The method showed linearity at the range of 25–500 μg/mL, and the correlation coefficient (r2) values were >0.99 for all matrices. Precision and accuracy were determined by the (a) coefficient of variation (CV), (b) relative standard deviation low-quality control (LQC), (c) medium-quality control (QCM), and (d) high-quality control (QCA). The indicated parameters were all less than 15%. The recovery of analytes ranged from 31 to 71%. The analysis of results showed no significant interfering peaks due to common xenobiotics or matrix effects. The abovementioned method was used to positively identify pesticide analytes in 44 of the 51 animal samples that were suspected of poisoning, demonstrating its usefulness as a forensic tool. Full article

The prevalence of neurodevelopmental disorders (NDDs) is rapidly rising, suggesting a confluence of environmental factors that are likely contributing, including developmental exposure to environmental contaminants. Unfortunately, chemical exposures and social stressors frequently occur simultaneously in many communities, yet very few studies have sought to establish the combined effects on neurodevelopment or behavior. Social deficits are common to many NDDs, and we and others have shown that exposure to the chemical flame retardant mixture, Firemaster 550 (FM 550), or paternal deprivation impairs social behavior and neural function. Here, we used a spontaneously prosocial animal model, the prairie vole (Microtus ochrogaster), to explore the effects of perinatal chemical (FM 550) exposure alone or in combination with an early life stressor (paternal absence) on prosocial behavior. Dams were exposed to vehicle (sesame oil) or 1000 µg FM 550 orally via food treats from conception through weaning and the paternal absence groups were generated by removing the sires the day after birth. Adult offspring of both sexes were then subjected to open-field, sociability, and a partner preference test. Paternal deprivation (PD)-related effects included increased anxiety, decreased sociability, and impaired pair-bonding in both sexes. FM 550 effects include heightened anxiety and partner preference in females but reduced partner preference in males. The combination of FM 550 exposure and PD did not exacerbate any behaviors in either sex except for distance traveled by females in the partner preference test and, to a lesser extent, time spent with, and the number of visits to the non-social stimulus by males in the sociability test. FM 550 ameliorated the impacts of parental deprivation on partner preference behaviors in both sexes. This study is significant because it provides evidence that chemical and social stressors can have unique behavioral effects that differ by sex but may not produce worse outcomes in combination. Full article

Background: The objective of this study is to evaluate the effects of traffic on human health comparing biomonitoring data measured during the COVID-19 lockdown, when restrictions led to a 40% reduction in airborne benzene in Rome and a 36% reduction in road traffic, to the same parameters measured in 2021. Methods: Biomonitoring was performed on 49 volunteers, determining the urinary metabolites of the most abundant traffic pollutants, such as benzene and PAHs, and oxidative stress biomarkers by HPLC/MS-MS, 28 elements by ICP/MS and metabolic phenotypes by NMR. Results: Means of s-phenylmercaputric acid (SPMA), metabolites of naphthalene and nitropyrene in 2020 are 20% lower than in 2021, while 1-OH-pyrene was 30% lower. A reduction of 40% for 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodGuo) and 60% for 8-oxo-7,8-dihydroguanine (8-oxoGua) were found in 2020 compared to 2021. The concentrations of B, Co, Cu and Sb in 2021 are significantly higher than in the 2020. NMR untargeted metabolomic analysis identified 35 urinary metabolites. Results show in 2021 a decrease in succinic acid, a product of the Krebs cycle promoting inflammation. Conclusions: Urban pollution due to traffic is partly responsible for oxidative stress of nucleic acids, but other factors also have a role, enhancing the importance of communication about a healthy lifestyle in the prevention of cancer diseases. Full article

It is very important to increase phytoremediation efficiency in practice in suitable climatic conditions for plant growth through multiple harvests. Solanum nigrum L. is a Cd hyperaccumulator. In the present experiment, after applying different types of N fertilizers (NH₄HCO₃, NH₄Cl, (NH₄)₂SO₄, CH₄N₂O), root and shoot biomasses and Cd phytoextraction efficiency of S. nigrum effectively improved (p < 0.05). Shoot biomasses of S. nigrum harvested at the first florescence stage plus the amounts at the second florescence stage were higher than those harvested at the maturation stage, which indicates that S. nigrum Cd phytoaccumulation efficiency was higher in the former compared to the latter as there was no clear change in Cd concentration (p < 0.05). The pH value and extractable Cd contents showed no changes, regardless of whether N fertilizer was added or not at different growth stages. In addition, after N fertilizer was applied, H₂O₂ and malondialdehyde (MDA) contents in S. nigrum in vivo were lower compared to those that had not received N addition (CK); similarly, the concentration of proline was decreased as well (p < 0.05). The activity of the antioxidant enzyme catalase (CAT), harvested at different growth periods after four types of N fertilizer applications, obviously decreased in S. nigrum shoots, while peroxidase (POD) and superoxide dismutase) (SOD) activities increased (p < 0.05). Our study demonstrated that (NH₄)₂SO₄ treatment exerted the most positive effect and CH₄N₂O the second most positive effect on S. nigrum Cd phytoremediation efficiency in double harvests at florescence stages, and the growth conditions were better than others. Full article

Perfluorooctane sulfonate (PFOS) is a persistent, widely present organic pollutant. PFOS can enter the human body through drinking water, ingestion of food, contact with utensils containing PFOS, and occupational exposure to PFOS, and can have adverse effects on human health. Increasing research shows that the liver is the major target of PFOS, and that PFOS can damage liver tissue and disrupt its function; however, the exact mechanisms remain unclear. In this study, we reviewed the adverse effects of PFOS on liver tissue and cells, as well as on liver function, to provide a reference for subsequent studies related to the toxicity of PFOS and liver injury caused by PFOS. Full article

Fine particulate matter (PM_2.5) is dangerous to human health. At midnight on 31 December, in Ecuadorian cities, people burn puppets and fireworks, emitting high amounts of PM_2.5. On 1 January 2022, concentrations between 27.3 and 40.6 µg m⁻³ (maximum mean over 24 h) were measured in Cuenca, an Andean city located in southern Ecuador; these are higher than 15 µg m⁻³, the current World Health Organization guideline. We estimated the corresponding PM_2.5 emissions and used them as an input to the Weather Research and Forecasting with Chemistry (WRF-Chem 3.2) model to simulate the change in PM_2.5 concentrations, assuming these emissions started at 18:00 LT or 21:00 LT on 31 December 2021. On average, PM_2.5 concentrations decreased by 51.4% and 33.2%. Similar modeling exercises were completed for 2016 to 2021, providing mean decreases between 21.4% and 61.0% if emissions started at 18:00 LT. Lower mean reductions, between 2.3% and 40.7%, or even local increases, were computed for emissions beginning at 21:00 LT. Reductions occurred through better atmospheric conditions to disperse PM_2.5 compared to midnight. Advancing the burning time can help reduce the health effects of PM_2.5 emissions on 31 December. Full article

Many endocrine-disrupting chemicals (EDCs) have a ubiquitous presence in our environment due to anthropogenic activity. These EDCs can disrupt hormone signaling in the human and animal body systems including the very important hypothalamic-pituitary-thyroid (HPT) axis causing adverse health effects. Thyroxine (T4) and triiodothyronine (T3) are hormones of the HPT axis which are essential for regulation of metabolism, heart rate, body temperature, growth, development, etc. In this study, potential endocrine-disrupting activity of the most common phthalate plasticizer, DEHP, and emerging non-phthalate alternate plasticizers, DINCH, ATBC, and DEHA against thyroid hormone receptor (TRα) were characterized. The structural binding characterization of indicated ligands was performed against the TRα ligand binding site employing Schrodinger’s induced fit docking (IFD) approach. The molecular simulations of interactions of the ligands against the residues lining a TRα binding pocket, including bonding interactions, binding energy, docking score, and IFD score were analyzed. In addition, the structural binding characterization of TRα native ligand, T3, was also done for comparative analysis. The results revealed that all ligands were placed stably in the TRα ligand-binding pocket. The binding energy values were highest for DINCH, followed by ATBC, and were higher than the values estimated for TRα native ligand, T3, whereas the values for DEHA and DEHP were similar and comparable to that of T3. This study suggested that all the indicated plasticizers have the potential for thyroid hormone disruption with two alternate plasticizers, DINCH and ATBC, exhibiting higher potential for thyroid dysfunction compared to DEHA and DEHP. Full article

Cigarette smoke (CS) is the major risk factor for chronic obstructive pulmonary disease (COPD) and can induce systemic manifestations, such as skeletal muscle derangement. However, inconsistent findings of muscle derangement were reported in previous studies. The aim of the present study was to consolidate the available evidence and assess the impact of CS on muscle derangement in rodents. A comprehensive literature search of five electronic databases identified ten articles for final analysis. Results showed that the diaphragm, rectus femoris, soleus, and gastrocnemius exhibited significant oxidative to glycolytic fiber conversions upon CS exposure. In contrast, the extensor digitorum longus (EDL), plantaris, and tibialis did not exhibit a similar fiber-type conversion after CS exposure. Hindlimb muscles, including the quadriceps, soleus, gastrocnemius, and EDL, showed significant reductions in the CSA of the muscle fibers in the CS group when compared to the control group. Changes in inflammatory cytokines, exercise capacity, and functional outcomes induced by CS have also been evaluated. CS could induce a shift from oxidative fibers to glycolytic fibers in high-oxidative muscles such as the diaphragm, rectus femoris, and soleus, and cause muscle atrophy, as reflected by a reduction in the CSA of hindlimb muscles such as the quadriceps, soleus, gastrocnemius, and EDL. Full article

The unique physicochemical properties of silver nanoparticles (AgNPs) make them useful in a wide range of sectors, increasing their propensity for human exposure, as well as the need for thorough toxicological assessment. The biodistribution of silver, hematological parameters and GSH/GSSG levels in the lung and liver were studied in mice that were intratracheally instilled with AgNP (5 and 50 nm) and AgNO₃ once a week for 5 weeks, followed by a recovery period of up to 28 days (dpi). Data was gathered to build a PBPK model after the entry of AgNPs into the lungs. AgNPs could be absorbed into the blood and might cross the physiological barriers and be distributed extensively in mice. Similar to AgNO₃, AgNP5 induced longer-lasting toxicity toward blood cells and increased GSH levels in the lung. The exposure to AgNP50 increased the GSH from 1 dpi onward in the liver and silver was distributed to the organs after exposure, but its concentration decreased over time. In AgNP5 treated mice, silver levels were highest in the spleen, kidney, liver and blood, persisting for at least 28 days, suggesting accumulation. The major route for excretion seemed to be through the urine, despite a high concentration of AgNP5 also being found in feces. The modeled silver concentration was in line with the in vivo data for the heart and liver. Full article

To fulfill sustainability principles, a three-site field experiment was conducted to screen suitably mixed passivators from lime + biochar (L + C, 9000 kgha⁻¹ with a rate of 1:1) and lime + biochar + sepiolite (L + C + S, 9000 kg ha⁻¹ with a rate of 1:1:1), in Yuecheng (YC), Zhuji (ZJ), and Fuyang (FY), where there are typical contaminated soils, in South China. Treated with passivators in soil, DTPA-extractable Cd, Crand Pb in soil were decreased by 9.87–26.3%, 37.2–67.5%, and 19.0–54.2%, respectively; Cd, Cr, and Pb in rice were decreased by 85.9–91.5%, 40.0–76.5%, and 16.4–45.4%, respectively; and these were followed by slightly higher efficacy of L + C + S than L + C. The differences between L + C and L + C + S mainly lie in soil microbial communities, enzymes, and fertility. In YC, treatment with L + C + S increased microbial carbon and activities of urease (EC3.5.1.5) and phosphatase (EC3.1.3.1) by 21.0%, 85.5%, and 22.3%; while treatment with L + C decreased microbial carbon and activities of phosphatase and sucrose (EC3.2.1.26) by 1.31%, 34.9%, and 43.4%, respectively. Moreover, the treatment of FY soils with L + C + S increased microbial carbon and activities of urease, phosphatase, and sucrase by 35.4%, 41.6%, 27.9%, and 7.37%; and L + C treatment only increased the microbial carbon and the activity of phosphatase by 3.14% and 30.3%, respectively. Furthermore, the organic matter and available nitrogen were also increased by 8.8–19.0% and 7.4–14.6% with L + C + S treatments, respectively. These suggested that the combination of L + C + S stimulated the growth of soil microbial communities and increased the activity of soil enzymes. Therefore, the L + C + S strategy can be a practical and effective measure for safe rice production as it was more suitable for the remediation of heavy metals in our experimental sites. Full article

Many pathological conditions and certain airway exposures are associated with oxidative stress (OS). Malondialdehyde (MDA) is an end-product of the oxidation of lipids in our cells and is present in all biological matrices including exhaled breath condensate (EBC). To use MDA as a biomarker of OS in EBC, a reference interval should be defined. Thus, we sought to summarize reference values reported in healthy adult populations by performing a systematic review and meta-analysis using a standardized protocol registered in PROSPERO (CRD42020146623). Articles were retrieved from four major databases and 25 studies with 28 subgroups were included. Defining the distribution of MDA measured in reference populations with a detection combined with a separation technique still represents a challenge due to the low number of studies available, different analytical methods used, and questionable methodological qualities of many studies. The most salient methodological drawbacks have been in data collection and reporting of methods and study results by the researchers. The lack of compliance with the recommendations of the European Respiratory Society and American Thoracic Society was the major limitation in the current research involving EBC. Consequently, we were unable to establish a reference interval for MDA in EBC. Full article

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