Toxics

Risk assessment of chemicals is usually conducted for individual chemicals whereas mixtures of chemicals occur in the environment. Considering that neuroactive chemicals are a group of contaminants that dominate the environment, it is then imperative to understand the combined effects of mixtures. The commonly used models to predict mixture effects, namely concentration addition (CA) and independent action (IA), are thought to be suitable for mixtures of similarly or dissimilarly acting components, respectively. For mixture toxicity prediction, one important challenge is to clarify whether to group neuroactive substances based on similar mechanisms of action, e.g., same molecular target or rather similar toxicological response, e.g., hyper- or hypoactivity (effect direction). We addressed this by using the spontaneous tail coiling (STC) of zebrafish embryos, which represents the earliest observable motor activity in the developing neural network, as a model to elucidate the link between the mechanism of action and toxicological response. Our objective was to answer the following two questions: (1) Can the mixture models CA or IA be used to predict combined effects for neuroactive chemical mixtures when the components share a similar mode of action (i.e., hyper- or hypoactivity) but show different mechanism of action? (2) Will a mixture of chemicals where the components show opposing effect directions result in an antagonistic combined effect? Results indicate that mixture toxicity of chemicals such as propafenone and abamectin as well as chlorpyrifos and hexaconazole that are known to show different mechanisms of action but similar effect directions were predictable using CA and IA models. This could be interpreted with the convergence of effects on the neural level leading to either a collective activation or inhibition of synapses. We also found antagonistic effects for mixtures containing substances with opposing effect direction. Finally, we discuss how the STC may be used to amend risk assessment. Full article

The green chemistry method is the preferred approach for synthesizing metal and metal oxide nanoparticles because of its low toxicity, environmental friendliness, feasibility, and safety to human health compared with other chemical or physical methods. The present work reports the phytogenic synthesis of palladium nanoparticles (PdNPs) using an aqueous extract of Matricaria recutita (Chamomile). The phytochemical-mediated synthesis of PdNPs is an economical and eco-friendly approach without using toxic elements as reducing and capping or stabilizing agents. The UV-visible spectroscopic characterization was initially used to confirm the preparation of PdNPs using an aqueous extract of M. recutita flowers as a bioreductant for the reduction of Pd²⁺ to Pd⁰ without using any extra capping and reducing agents. The appearance of surface plasmon resonance (SPR) peak at 286 nm confirmed the formation of M. recutita extract-based PdNPs. Furthermore, the PdNPs were characterized by TEM, SEM, EDX, XRD, XPS, and FTIR to confirm their proper synthesis. The thermogravimetric analysis (TGA) was implemented to interpret the decomposition pattern and thermal stability of as-synthesized PdNPs. The biosynthesized PdNPs were further applied as a nanocatalyst in degradation of an azo dye Congo red (CR) in the presence of NaBH₄. The catalytic reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) was also investigated in the presence of NaBH₄. All the catalytic reactions were performed in water, and no significant loss in catalytic activity was observed after recovery and reusability of the biosynthesized PdNPs. Full article

Zingiber ottensii Valeton (ZO) exhibits pharmacological activity and has long been used in traditional medicine. However, reports about its safety profiles are limited. The present study aimed to evaluate the phytochemical profile and the toxic effects of ZO essential oil on the development of zebrafish and acute oral toxicity in rats. The essential oil was isolated from ZO rhizomes, and phytochemicals were analyzed using a gas chromatography–mass spectrometer (GC–MS). The embryotoxic and teratogenic effects of ZO essential oil were evaluated in zebrafish embryos and larvae and the acute oral toxicity was determined in rats. GC–MS results showed the essential oil contained zerumbone as a major phytoconstituent (24.73%). The zebrafish embryotoxicity of ZO essential oil appeared to be concentration- and time-dependent manner, with a moderate LC₅₀ (1.003 µg/mL). Teratogenicity in zebrafish embryos also included morphological defects, decreased hatchability, and reduced heart rate. In rats, ZO essential oil (2000 mg/kg, p.o.) resulted in no mortality or significant toxicities. These findings suggest that ZO has embryotoxic and teratogenic effects in zebrafish embryos but does not result in death or acute oral toxicity in rats. Further long-term toxicity studies are needed to confirm the safety of products developed from ZO essential oil. Full article

Persistent organic pollutants (POPs) are among the most relevant and dangerous contaminants in soil, from where they can be transferred to crops. Additionally, livestock animals may inadvertently consume relatively high amounts of soil attached to the roots of the vegetables while grazing, leading to indirect exposure to humans. Therefore, periodic monitoring of soils is crucial; thus, simple, robust, and powerful methods are needed. In this study, we have tested and validated an easy QuEChERS-based method for the extraction of 49 POPs (8 PBDEs, 12 OCPs, 11 PAHs, and 18 PCBs) in soils and their analysis by GC-MS/MS. The method was validated in terms of linearity, precision, and accuracy, and a matrix effect study was performed. The limits of detection (LOD) were established between 0.048 and 3.125 ng g⁻¹ and the limits of quantification (LOQ) were between 0.5 and 20 ng g⁻¹, except for naphthalene (50 ng g⁻¹). Then, to verify the applicability of the validated method, we applied it to a series of 81 soil samples from farms dedicated to mixed vegetable cultivation and vineyards in the Canary Islands, both from two modes of production (organic vs. conventional) where residues of OCPs, PCBs, and PAHs were found. Full article

Novel per- and polyfluoroalkyl substances (PFAS) were recently identified in drinking water sources throughout North Carolina. These include the perfluoroether acids (PFEAs) perfluoro-2-methoxyacetic acid (PFMOAA), perfluoro-2-methoxypropanoic acid (PFMOPrA), and perfluoro-4-methoxybutanioc acid (PFMOBA). Little toxicological data exist for these PFEAs. Therefore, the present study described signs of toxicity and immunotoxicity following oral exposure. Adult male and female C57BL/6 mice were exposed once/day for 30 days to PFMOAA (0, 0.00025, 0.025, or 2.5 mg/kg), PFMOPrA, or PFMOBA (0, 0.5, 5, or 50 mg/kg). A dose of 7.5 mg/kg of perfluorooctanoic acid (PFOA) was used as a positive control. Terminal body weights, and absolute liver, spleen, or thymus weights did not differ by dose for any compound; exposure to 50 mg/kg of PFMOBA increased relative liver weights in males. Changes in splenic cellularity were observed in males exposed to PFMOPrA and decreased numbers of B and natural killer (NK) cells were observed in males and females exposed to PFMOBA. Exposure did not alter NK cell cytotoxicity or T cell-dependent antibody responses at doses administered. Our results indicate that these “understudied” PFAS have toxicological potential but require additional investigation across endpoints and species, including humans, to understand health effects via drinking water exposure. Full article

Organophosphate (OP) pesticides can transfer from mother to fetus via the placenta and amniotic fluid and may affect the development of infants. This study aims to evaluate the associations between maternal OP concentrations collected in the 1st–2nd trimester and the 3rd trimester of pregnancy and the infant developmental performance. The Screening Test of the Bayley Scales of Infants and Toddler Development, Third Edition (BSID–III screening test) was used to assess development performance at 2 and 6 months of age. Multiple regression analysis showed a negative correlation between cognitive performance at 2 months and maternal diethylthiophosphate (DETP) levels in the 1st–2nd trimester (β ± SE = −0.012 ± 0.004, p < 0.05). We also found that expressive communication and fine motor performance at 6 months were negatively associated with maternal diethyldithiophosphate (DEDTP) levels in the 3rd trimester (β ± SE = −0.047 ± 0.016, p < 0.05, and β ± SE = −0.044 ± 0.017, p < 0.05, respectively). These results suggest that maternal ethylated OP concentrations at different timing of exposure during pregnancy may influence different aspects of infant developmental performance. Full article

The peripheral (axonal) neuropathy associated with repeated exposure to aliphatic and aromatic solvents that form protein-reactive γ-diketones shares some clinical and neuropathological features with certain metabolic neuropathies, including type-II diabetic neuropathy and uremic neuropathy, and with the largely sub-clinical nerve damage associated with old age. These conditions may be linked by metabolites that adduct and cross-link neuroproteins required for the maintenance of axonal transport and nerve fiber integrity in the peripheral and central nervous system. Full article

Recent epidemiological studies suggest that prenatal exposure to acetaminophen (APAP) is associated with increased risk of Autism Spectrum Disorder (ASD), a neurodevelopmental disorder affecting 1 in 59 children in the US. Maternal and prenatal exposure to pesticides from food and environmental sources have also been implicated to affect fetal neurodevelopment. However, the underlying mechanisms for ASD are so far unknown, likely with complex and multifactorial etiology. The aim of this study was to explore the potential effects of APAP and pesticide exposure on development with regards to the etiology of ASD by highlighting common genes and biological pathways. Genes associated with APAP, pesticides, and ASD through human research were retrieved from molecular and biomedical literature databases. The interaction network of overlapping genetic associations was subjected to network topology analysis and functional annotation of the resulting clusters. These genes were over-represented in pathways and biological processes (FDR p < 0.05) related to apoptosis, metabolism of reactive oxygen species (ROS), and carbohydrate metabolism. Since these three biological processes are frequently implicated in ASD, our findings support the hypothesis that cell death processes and specific metabolic pathways, both of which appear to be targeted by APAP and pesticide exposure, may be involved in the etiology of ASD. This novel exposures-gene-disease database mining might inspire future work on understanding the biological underpinnings of various ASD risk factors. Full article

Due to their beneficial properties, the use of zinc oxide nanoparticles (ZnO NP) is constantly increasing, especially in consumer-related areas, such as food packaging and food additives, which is leading to an increased oral uptake of ZnO NP. Consequently, the aim of our study was to investigate the cellular uptake of two differently sized ZnO NP (<50 nm and <100 nm; 12–1229 µmol/L) using two human intestinal cell lines (Caco-2 and LT97) and to examine the possible resulting toxic effects. ZnO NP (<50 nm and <100 nm) were internalized by both cell lines and led to intracellular changes. Both ZnO NP caused time- and dose-dependent cytotoxic effects, especially at concentrations of 614 µmol/L and 1229 µmol/L, which was associated with an increased rate of apoptotic and dead cells. ZnO NP < 100 nm altered the cell cycle of LT97 cells but not that of Caco-2 cells. ZnO NP < 50 nm led to the formation of micronuclei in LT97 cells. The Ames test revealed no mutagenicity for both ZnO NP. Our results indicate the potential toxicity of ZnO NP after oral exposure, which should be considered before application. Full article

The aim of this study was twofold. Firstly, we performed a land capability class determination of the agricultural soils from the Abu Dhabi Emirate, the United Arab Emirates, based on the concentrations of 17 chemical elements determined in the soil samples collected from 84 locations. Secondly, we assess the soil pollution with different metals, using several pollution indices. The results of Principal Component Analysis (PCA) shows that four principal components (PCs) are responsible for describing the total metals concentrations’ variance, the highest contribution on PC1 being that of Mn, and Cr, on PC2 that of Fe, on PC3 that of Cu, and on PC4 that of Al. After determining the optimal number of clusters, we classified the sites into three clusters, while the studied metals were grouped function on their concentrations. Then, we used five indices to assess the pollution level of the soil at the study sites and in the clusters. The geo—accumulation index (I_geo) indicates uncontamination/moderately contamination with Cu in cluster 1, uncontaminated/moderately contaminate soils with Cd, Cu, and Ni in cluster 2, and uncontaminated/moderately contaminated soil with Cu and moderately contaminated with Pb, Zn, and Ni in cluster 3. By comparison, the enrichment factors overestimate the pollution of the studied sites. The pollution load index (PLI) indicates a baseline level of pollution at 14 sites and the deterioration of the soil quality at four sites. The Nemerow pollution index provides similar results as PLI. Full article

We explored the potential role of zinc (Zn) and zinc transporters in protection against cytotoxicity of cadmium (Cd) in a cell culture model of human urothelium, named UROtsa. We used real-time qRT-PCR to quantify transcript levels of 19 Zn transporters of the Zrt-/Irt-like protein (ZIP) and ZnT gene families that were expressed in UROtsa cells and were altered by Cd exposure. Cd as low as 0.1 µM induced expression of ZnT1, known to mediate efflux of Zn and Cd. Loss of cell viability by 57% was seen 24 h after exposure to 2.5 µM Cd. Exposure to 2.5 µM Cd together with 10–50 µM Zn prevented loss of cell viability by 66%. Pretreatment of the UROtsa cells with an inhibitor of glutathione biosynthesis (buthionine sulfoximine) diminished ZnT1 induction by Cd with a resultant increase in sensitivity to Cd cytotoxicity. Conversely, pretreatment of UROtsa cells with an inhibitor of DNA methylation, 5-aza-2’-deoxycytidine (aza-dC) did not change the extent of ZnT1 induction by Cd. The induced expression of ZnT1 that remained impervious in cells treated with aza-dC coincided with resistance to Cd cytotoxicity. Therefore, expression of ZnT1 efflux transporter and Cd toxicity in UROtsa cells could be modulated, in part, by DNA methylation and glutathione biosynthesis. Induced expression of ZnT1 may be a viable mechanistic approach to mitigating cytotoxicity of Cd. Full article

Two aerobic granular sludge (AGS) sequential batch reactors were operated at a mild (15 °C) temperature for 180 days. One of those bioreactors was exposed to a mixture of diclofenac, naproxen, trimethoprim, and carbamazepine. The AGS system, operating under pressure from emerging contaminants, showed a decrease in COD, BOD₅, and TN removal capacity, mainly observed during the first 100 days, in comparison with the removal ratios detected in the control bioreactor. After an acclimatisation period, the removal reached high-quality effluent for COD and TN, close to 95% and 90%, respectively. In the steady-state period, trimethoprim and diclofenac were successfully removed with values around 50%, while carbamazepine and naproxen were more recalcitrant. The dominant bacterial OTUs were affected by the presence of a mixture of pharmaceutical compounds, under which the dominant phylotypes changed to OTUs classified among the Pseudomonas, Gemmobacter, and Comamonadaceae. The RT-qPCR and qPCR results showed the deep effects of pharmaceutical compounds on the number of copies of target genes. Statistical analyses allowed for linking the total and active microbial communities with the physico-chemical performance, describing the effects of pharmaceutical compounds in pollution degradation, as well as the successful adaptation of the system to treat wastewater in the presence of toxic compounds. Full article

The cytotoxicity and microbicidal capacity of seven organic solvents commonly applied for studying plant extracts and bioactive compounds were systematically investigated based on international standards. Four cell lines of normal (CCL-1, HaCaT) or tumor (A-375, A-431) tissue origin, seven bacterial and one fungal strain were used. The impact of the least toxic solvents in the determination of in vitro cytotoxicity was evaluated using a standardized extract from Vaccinium macrocarpon containing 54.2% v/v proanthocyanidins (CystiCran^®). The solvents ethanol, methoxyethanol and polyethylene glycol were the least cytotoxic to all cell lines, with a maximum tolerated concentration (MTC) between 1 and 2% v/v. Ethanol, methanol and polyethylene glycol were mostly suitable for antimicrobial susceptibility testing, with minimum inhibitory concentrations (MICs) ≥ 25% v/v. The MTC values of the solvents dimethyl sulfoxide, dimethoxyethane and dimethylformamide varied from 0.03% to 1.09% v/v. The MICs of dimethyl sulfoxide, methoxyethanol and dimethoxyethane were in the range of 3.125–25% v/v. The cytotoxic effects of CystiCran^® on eukaryotic cell lines were directly proportional to the superimposed effect of the solvents used. The results of this study can be useful for selecting the appropriate solvents for in vitro estimation of the cytotoxic and growth inhibitory effects of bioactive molecules in eukaryotic and prokaryotic cells. Full article

Co-cropping is an eco-friendly strategy to improve the phytoremediation capacity of plants growing in soils contaminated with heavy metals such as cadmium (Cd). This study was conducted to investigate the effects of co-cropping Indian mustard (Brassicajuncea) and silage maize (Zeamays) and applying peat on the phytoremediation of a Cd-contaminated acid paddy soil via characterizing plant growth and Cd uptake in pot experiments. There were six planting patterns (Control: no plants; MI-2 and MI-4: mono-cropping of Indian mustard at low and high densities, respectively; MS: mono-cropping of silage maize; CIS-2 and CIS-4: co-cropping of Indian mustard at low and high densities with silage maize, respectively) and two application rates of peat (NP: 0; WP: 30 g kg⁻¹). When Indian mustard and silage maize were co-cropped, the shoot biomass of Indian mustard plants per pot was significantly (p < 0.05) lower than that obtained in the mono-cropping systems, with a substantial reduction (55–72%) in the same plant density group. The shoot biomass of silage maize plants in the mono-cropping systems did not differ significantly from that in the co-cropping systems regardless of the density of Indian mustard. The growth-promoting effect of the peat application was more pronounced in Indian mustard than silage maize. Under the low density of Indian mustard, the co-cropping systems significantly (p < 0.05) decreased Cd uptake by silage maize. Additionally, soil amendment with peat significantly (p < 0.05) increased shoot Cd removal rate and Cd translocation factor value in the co-cropping systems. Taken together, the results demonstrated that silage maize should be co-cropped with Indian mustard at an appropriate density in Cd-polluted soils to achieve simultaneous remediation of Cd-contaminated soils (via Indian mustard) and production of crops (here, silage maize). Peat application was shown to promote the removal of Cd from soil and translocation of Cd into shoots and could contribute to enhanced phytoremediation of Cd-contaminated acid paddy soil. Full article

Background: Di-2-ethylhexyl phthalate (DEHP), a phthalate compound found in medical devices, may cause toxic effects in premature infants. In this study, the objective is to quantify DEHP exposures from various intravenous and respiratory therapy devices, and to use these values to predict typical exposure for an infant in a neonatal unit. Methods: Common IV products used on infants are directed through various types of IV tubing (IVT) and analyzed for DEHP content. DEHP exposure for infants receiving respiratory therapy was determined indirectly through analysis of urine DEHP metabolites. By deriving these values for DEHP we calculated the daily exposure to DEHP from common IV fluids (IVF) and respiratory devices during hospitalization in a neonatal unit. Results: IVF labeled DEHP-positive showed very high concentrations of DEHP, but when passed through IVT, substantial amounts were adsorbed. DEHP was undetectable with all DEHP-negative IVF tests, except when passed through DEHP-positive IVT. The DEHP leached from most respiratory devices was relatively modest, except that detected from bubble CPAP. In 14 very low birthweight infants, the mean DEHP exposure was 182,369 mcg/kg over 81.2 days of the initial hospitalization. Ninety-eight percent of the exposure was from respiratory devices, with bubble CPAP accounting for 95% of the total DEHP exposure in these infants. Conclusions: The DEHP exposure in our neonatal unit can be reduced markedly by avoiding or modifying bubble CPAP equipment and avoiding IV tubing containing DEHP. Full article

Iodine deficiency is the main environmental factor leading to thyroid cancer. At the same time iodine excess may also contribute to thyroid cancer. Potassium iodate (KIO₃), which is broadly used in salt iodization program, may increase oxidative damage to membrane lipids (lipid peroxidation, LPO) under experimental conditions, with the strongest damaging effect at KIO₃ concentration of ~10 mM (corresponding to physiological iodine concentration in the thyroid). Melatonin and indole-3-propionic acid (IPA) are effective antioxidative indoles, each of which protects against KIO₃-induced LPO in the thyroid. The study aims to check if melatonin used together with IPA (in their highest achievable in vitro concentrations) reveals stronger protective effects against KIO₃-induced LPO in porcine thyroid homogenates than each of these antioxidants used separately. Homogenates were incubated in the presence of KIO₃ (200; 100; 50; 25; 20; 15; 10; 7.5; 5.0; 2.5; 1.25; 0.0 mM) without/with melatonin (5 mM) or without/with IPA (10 mM) or without/with melatonin + IPA, and then, to further clarify the narrow range of KIO₃ concentrations, against which melatonin + IPA reveal cumulative protective effects, the following KIO₃ concentrations were used: 20; 18.75; 17.5; 16.25; 15; 13.75; 12.5; 11.25; 10; 8.75; 7.5; 0.0 mM. Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. Protective effects of melatonin + IPA were stronger than those revealed by each antioxidant used separately, but only when LPO was induced by KIO₃ in concentrations from 18.75 mM to 8.75 mM, corresponding to physiological iodine concentration in the thyroid. In conclusion, melatonin and indole-3-propionic acid exert cumulative protective effects against oxidative damage caused by KIO₃, when this prooxidant is used in concentrations close to physiological iodine concentrations in the thyroid. Therefore, the simultaneous administration of these two indoles should be considered to prevent more effectively oxidative damage (and thereby thyroid cancer formation) caused by iodine compounds applied in iodine prophylaxis. Full article

Pharmaceuticals and hormones (PhACs) enter the aquatic environment in multiple ways, posing potential adverse effects on non-target organisms. They have been widely detected in drinking water sources, challenging water companies to reassure good quality drinking water. The aim of this study was to evaluate the concentration of sixteen PhACs in both raw and treated drinking water sources in the Metropolitan Area of Turin—where Società Metropolitana Acque Torino (SMAT) is the company in charge of the water cycle management—and evaluate the potential human health risks associated to these compounds. Multivariate spatial statistical analysis techniques were used in order to characterize the areas at higher risk of pollution, taking into account the already existing SMAT sampling points’ network. Health risks were assessed considering average detected concentrations and provisional guideline values for individual compounds as well as their combined mixture. As reported in the just-issued Drinking Water Directive 2020/2184/UE, in order to establish priority substances, a risk assessment of contaminants present in raw drinking water sources is required for monitoring, identifying potential health risks and, if necessary, managing their removal. The results showed negligibly low human health risks in both raw water sources and treated water. Full article

Flavoring agents are added to cigarettes to improve taste. There are mostly permitted food additives, but some of them are restricted for use in food, cosmetics, and toys, since they can cause allergic reactions. Previous studies have investigated the levels of flavoring agents in tobacco but none has focused on their content in filter tips and capsules. Moreover, no studies have assessed the risk of adding allergenic flavoring agents in cigarettes. Here, we developed and validated a simultaneous analysis method for 25 allergenic flavoring agents and menthol with gas chromatography–tandem mass spectrometry to determine levels of flavoring agents in the tobacco, filter tips, and capsules of 54 commercial cigarettes in Korea. All cigarettes contained at least one allergenic flavoring agent regardless of the inclusion of flavoring capsules. Importantly, the filter tips and the capsules contained higher levels of flavoring agents than tobacco, highlighting the importance of the quantification of flavoring agents in these parts of cigarettes. Nevertheless, the risk assessment based on their levels in cigarettes suggested that their exposure was maintained at a safe level. However, the risk assessed from maximum menthol, linalool, and cinnamaldehyde exceeded one-tenth of derived no-effect levels, suggesting the need for further studies on their risk to human health. Full article

The quantification and identification of saccharides in pristine marine aerosols can provide useful information for determining the contributions of anthropogenic and natural sources of the aerosol. However, individual saccharide compounds in pristine marine aerosols that exist in trace amounts are difficult to analyze due to their low concentrations. Thus, in this study, we applied gas chromatography–tandem mass spectrometry (GC-MS/MS) in multiple reaction monitoring (MRM) mode to analyze the particulate matter with an aerodynamic diameter equal or less than 2.5 μm (PM_2.5) samples, and the results were compared with those of conventional GC-MS. To investigate the chemical properties of pristine marine aerosols, 12 PM_2.5 samples were collected while aboard Araon, an ice-breaking research vessel (IBRV), as it sailed from Incheon, South Korea to Antarctica. The method detection limits of GC-MS/MS for 10 saccharides were 2–22-fold lower than those of GC-MS. Consequently, the advantages of GC-MS/MS include (1) more distinct peak separations, enabling the accurate identification of the target saccharides and (2) the quantification of all individual saccharide compounds with concentrations outside the quantifiable range of GC-MS. Accordingly, the time resolution for sampling saccharides in pristine marine aerosols can be improved with GC-MS/MS. Full article