Editor's Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

Order results
Result details
Results per page
Select all
Export citation of selected articles as:

Article

Article
Predicting the Bioconcentration Factor in Fish from Molecular Structures
Toxics 2022, 10(10), 581; https://doi.org/10.3390/toxics10100581 - 30 Sep 2022
Viewed by 716
Abstract
The bioconcentration factor (BCF) is one of the metrics used to evaluate the potential of a substance to bioaccumulate into aquatic organisms. In this work, linear and non-linear regression QSARs were developed for the prediction of log BCF using different computational approaches, and [...] Read more.
The bioconcentration factor (BCF) is one of the metrics used to evaluate the potential of a substance to bioaccumulate into aquatic organisms. In this work, linear and non-linear regression QSARs were developed for the prediction of log BCF using different computational approaches, and starting from a large and structurally heterogeneous dataset. The new MLR-OLS and ANN regression models have good fitting with R2 values of 0.62 and 0.70, respectively, and comparable external predictivity with R2ext 0.64 and 0.65 (RMSEext of 0.78 and 0.76), respectively. Furthermore, linear and non-linear classification models were developed using the regulatory threshold BCF >2000. A class balanced subset was used to develop classification models which were applied to chemicals not used to create the QSARs. These classification models are characterized by external and internal accuracy up to 84% and 90%, respectively, and sensitivity and specificity up to 90% and 80%, respectively. QSARs presented in this work are validated according to regulatory requirements and their quality is in line with other tools available for the same endpoint and dataset, with the advantage of low complexity and easy application through the software QSAR-ME Profiler. These QSARs can be used as alternatives for, or in combination with, existing models to support bioaccumulation assessment procedures. Full article
Show Figures

Figure 1

Article
Arbuscular Mycorrhizal Fungal Inoculation Increases Organic Selenium Accumulation in Soybean (Glycine max (Linn.) Merr.) Growing in Selenite-Spiked Soils
Toxics 2022, 10(10), 565; https://doi.org/10.3390/toxics10100565 - 26 Sep 2022
Viewed by 654
Abstract
Selenium (Se) is an essential trace element for humans. Arbuscular mycorrhizal fungi (AMF) play a crucial role in increasing plant micronutrient acquisition. Soybean (Glycine max (Linn.) Merr.) is a staple food for most people around the world and a source of Se. [...] Read more.
Selenium (Se) is an essential trace element for humans. Arbuscular mycorrhizal fungi (AMF) play a crucial role in increasing plant micronutrient acquisition. Soybean (Glycine max (Linn.) Merr.) is a staple food for most people around the world and a source of Se. Therefore, it is necessary to study the mechanism of Se intake in soybean under the influence of AMF. In this study, the effects of fertilization with selenite and inoculation with different AMF strains (Claroideoglomus etunicatum (Ce), Funneliformis mosseae (Fm)) on the accumulation and speciation of Se in common soybean plants were discussed. We carried out a pot experiment at the soil for 90 days to investigate the impact of fertilization with selenite and inoculation with Ce and Fm on the Se fractions in soil, soybean biomass, accumulation and speciation of Se in common soybean plants. The daily dietary intake of the Se (DDI) formula was used to estimate the risk threshold of human intake of Se from soybean seeds. The results showed that combined use of both AMF and Se fertilizer could boost total Se and organic Se amounts in soyabean seeds than that of single Se application and that it could increase the proportion of available Se in soil. Soybean inoculated with Fm and grown in soil fertilized with selenite had the highest organic Se. The results suggest that AMF inoculation could promote root growth, more soil water-soluble Se and higher Se uptake. The maximum Se intake of soybean for adults was 93.15 μg/d when treated with Se fertilizer and Fm, which satisfies the needs of Se intake recommended by the WHO. Combined use of AMF inoculation and Se fertilizer increases the bioavailable Se in soil and promotes the total Se concentration and organic Se accumulation in soybean. In conclusion, AMF inoculation combined with Se fertilization can be a promising strategy for Se biofortification in soybean. Full article
(This article belongs to the Special Issue Safety Utilization and Remediation of Heavy Metal Polluted Farmland)
Show Figures

Graphical abstract

Communication
Evaluation of Skin Irritation of Acids Commonly Used in Cleaners in 3D-Reconstructed Human Epidermis Model, KeraSkinTM
Toxics 2022, 10(10), 558; https://doi.org/10.3390/toxics10100558 - 24 Sep 2022
Viewed by 2055
Abstract
Cleaners such as dishwashing liquids contain various chemicals that cause skin damage. Alkaline agents used in cleaners alter the lipid composition of the skin and damage the skin barrier. However, little is known about the effects of acids used in cleaners on the [...] Read more.
Cleaners such as dishwashing liquids contain various chemicals that cause skin damage. Alkaline agents used in cleaners alter the lipid composition of the skin and damage the skin barrier. However, little is known about the effects of acids used in cleaners on the skin. Here, we investigated the effects of acidic pH on the skin and evaluated the skin irritation of acids commonly used in cleaners with a 3D-reconstructed human epidermis model, KeraSkinTM, according to OECD TG439. First, to examine the effects of acidic pH, we evaluated the skin irritation of citrate buffers (0.1 M, McIlvaine buffer) prepared in a wide pH range (pH 1.5–6.0). Surprisingly, cell viability was not significantly affected even at pH 1.5, reflecting that the acidity alone may not be sufficient to induce skin irritation. Even after longer exposure (180 min), the cell viability was not reduced below 50%, a cutoff to determine an irritant. To examine the effect of the anionic part, several organic acids used in cleaners (citric acid, glycolic acid, lactic acid, malic acid, and succinic acid) were examined. These organic acids also failed to reduce viability at 0.1 M. However, at 1 M, most of the acids tested, except lactic acid, were determined to be skin irritants. Histology further supported the skin irritancy of acids at 1 M. Similarly, inorganic acids (hydrogen bromide, hydrogen chloride, nitric acid, and sulfuric acid) were determined to be irritants only at 1 M. In the case of alkaline agents, pH and concentrations were also important factors to determine the skin irritancy, although the epidermal structure and lipids were more damaged than acids. Collectively, we demonstrated that both the pH and concentration are important factors for the skin irritancy of acids, shedding an important insight into the mechanism of skin irritation. Full article
Show Figures

Figure 1

Article
Arsenic Metabolism, Toxicity and Accumulation in the White Button Mushroom Agaricus bisporus
Toxics 2022, 10(10), 554; https://doi.org/10.3390/toxics10100554 - 22 Sep 2022
Viewed by 836
Abstract
Mushrooms have unique properties in arsenic metabolism. In many commercial and wild-grown mushrooms, arsenobetaine (AsB), a non-toxic arsenical, was found as the dominant arsenic species. The AsB biosynthesis remains unknown, so we designed experiments to study conditions for AsB formation in the white [...] Read more.
Mushrooms have unique properties in arsenic metabolism. In many commercial and wild-grown mushrooms, arsenobetaine (AsB), a non-toxic arsenical, was found as the dominant arsenic species. The AsB biosynthesis remains unknown, so we designed experiments to study conditions for AsB formation in the white button mushroom, Agaricus bisporus. The mushrooms were treated with various arsenic species including arsenite (As(III)), arsenate (As(V)), methylarsenate (MAs(V)), dimethylarsenate (DMAs(V)) and trimethylarsine oxide (TMAsO), and their accumulation and metabolism were determined using inductively coupled mass spectrometer (ICP-MS) and high-pressure liquid chromatography coupled with ICP-MS (HPLC-ICP-MS), respectively. Our results showed that mycelia have a higher accumulation for inorganic arsenicals while fruiting bodies showed higher accumulation for methylated arsenic species. Two major arsenic metabolites were produced in fruiting bodies: DMAs(V) and AsB. Among tested arsenicals, only MAs(V) was methylated to DMAs(V). Surprisingly, AsB was only detected as the major arsenic product when TMAsO was supplied. Additionally, AsB was only detected in the fruiting body, but not mycelium, suggesting that methylated products were transported to the fruiting body for arsenobetaine formation. Overall, our results support that methylation and AsB formation are two connected pathways where trimethylated arsenic is the optimal precursor for AsB formation. Full article
(This article belongs to the Special Issue Environmental and Health Effects of Heavy Metal)
Show Figures

Graphical abstract

Article
Evaluation of Bisphenol A in Pregnant Women from 10 Caribbean Countries
Toxics 2022, 10(10), 556; https://doi.org/10.3390/toxics10100556 - 22 Sep 2022
Viewed by 697
Abstract
Bisphenol A (BPA), a phenolic chemical incorporated into many plastic products, has been found to act as an endocrine disruptor that potentially is linked to adverse neurodevelopmental outcomes. Prenatal BPA concentration levels were assessed in 10 English-speaking Caribbean countries by randomly selecting 15 [...] Read more.
Bisphenol A (BPA), a phenolic chemical incorporated into many plastic products, has been found to act as an endocrine disruptor that potentially is linked to adverse neurodevelopmental outcomes. Prenatal BPA concentration levels were assessed in 10 English-speaking Caribbean countries by randomly selecting 15 maternal urine samples from approximately 50 pregnant women samples collected in each island and then comparing the findings with comparable data from Canada and the U.S. BPA was detected in all samples ranging from a low geometric mean of 1.46 μg/L (St. Lucia) to a high of 4.88 μg/L (St. Kitts & Nevis). All of the Caribbean islands sampled had geometric mean concentration levels that were higher than those recorded in two Canadian biomonitoring surveys (1.26 μg/L and 0.80 μg/L) and the U.S. NHANES survey (1.39 μg/L). This first biomonitoring survey of BPA concentration levels in maternal urine samples taken from Caribbean countries clearly points to the need for Caribbean governments and public health officials to first engage in legislative and regulatory efforts to ban or minimize the importation and use of BPA products used the Caribbean and, second, to continue to conduct biomonitoring surveys so as to ensure that these laws and regulations are indeed leading to a decrease of BPA concentrations in Caribbean populations. Full article
Show Figures

Figure 1

Article
Emission Characteristics of Air Pollutants and CO2 from 11 Cities with Different Economic Development around the Bohai Sea in China from 2008–2017
Toxics 2022, 10(9), 547; https://doi.org/10.3390/toxics10090547 - 19 Sep 2022
Viewed by 707
Abstract
Cities around the Bohai Sea are one of the main population cluster areas in China, which are characterized by high levels of sustainability performance and human capital, as well as resource-intensive industries. In this study, levels of economic development metrics and emissions of [...] Read more.
Cities around the Bohai Sea are one of the main population cluster areas in China, which are characterized by high levels of sustainability performance and human capital, as well as resource-intensive industries. In this study, levels of economic development metrics and emissions of air pollutants (BC, CO, NH3, NOx, OC, PM2.5, PM10, and SO2) and CO2 across eleven cities around the Bohai Sea from 2008 to 2017 were compared to illustrate the potential relationships between air pollutants/carbon emissions and socioeconomic developments. Meanwhile, the associations between the levels of economic development metrics (GDP per capita), emissions, and energy use per GDP have also been examined. Large differences across these 11 cities presenting different economic development levels and energy consumption characteristics have been observed. Cities with development dependable on the consumption of fossil fuels and the development of resource-intensive industries have emitted large amounts of air pollutants and CO2. Furthermore, the emissions and energy use per GDP for all the cities follow environmental Kuznets curves. The comparison results suggested that the developing cities dependable on resource-intensive industries around the Bohai Sea would obtain greater socioeconomic benefits owing to the interregional cooperation policies under top-down socioeconomic development plans and bottom-up technology development, accompanied by reduced emissions of air pollutants and CO2. Full article
Show Figures

Figure 1

Article
Healthier Lifestyles Attenuated Association of Single or Mixture Exposure to Air Pollutants with Cardiometabolic Risk in Rural Chinese Adults
Toxics 2022, 10(9), 541; https://doi.org/10.3390/toxics10090541 - 17 Sep 2022
Viewed by 822
Abstract
There is little research on how long-term exposure to independent and multiple air pollutants changes cardiometabolic risk in adults. In addition, previous studies focused on only the effect of one or two lifestyles on cardiometabolic risk. The evidence on the interactive effects of [...] Read more.
There is little research on how long-term exposure to independent and multiple air pollutants changes cardiometabolic risk in adults. In addition, previous studies focused on only the effect of one or two lifestyles on cardiometabolic risk. The evidence on the interactive effects of the lifestyle score and exposure to independent and mixtures of air pollutants on cardiometabolic risk is lacking. A total of 33,638 rural residents were included in the cross-sectional study. The three-year average concentrations of air pollutants for participants were predicted by using a satellite-based prediction. The air pollution score was created to assess the combined exposure of four air pollutants (PM1, PM2.5, PM10, and NO2). A gender−age-specific cardiometabolic risk score was calculated. Multivariable-adjusted linear regression and quantile g-computation were used to investigate the associations between air pollutants and cardiometabolic risk. Interaction plots were applied to describe the interactive effects of air pollution and the healthy lifestyle score on cardiometabolic risk. Per interquartile range (IQR) unit increases in PM1, PM2.5, PM10, or NO2 were associated with 0.162 (95% CI: 0.091, 0.233), 0.473 (95% CI: 0.388, 0.559), 0.718 (95% CI: 0.627, 0.810), and 0.795 (95% CI: 0.691, 0.898) unit increases in cardiometabolic risk score (all p < 0.05), respectively. A 0.854 (95% CI: 0.768, 0.940) unit increase in cardiometabolic risk was associated with each IQR increase in air pollution score. Furthermore, the strengths of associations of PM1, PM2.5, PM10, NO2, and the air pollution score on cardiometabolic risk score were attenuated with the healthy lifestyle score increase. In addition, there was no statistical significance after the lifestyle score equal to four scores for the effect of PM1 on the cardiometabolic risk score. In conclusions, individual or joint air pollutants were associated with an increased cardiometabolic risk. Improving the healthy lifestyle may be an effective method to improve cardiometabolic health in highly polluted rural regions. Full article
Show Figures

Graphical abstract

Article
Deoxynivalenol Induces Apoptosis via FOXO3a-Signaling Pathway in Small-Intestinal Cells in Pig
Toxics 2022, 10(9), 535; https://doi.org/10.3390/toxics10090535 - 13 Sep 2022
Viewed by 832
Abstract
Deoxynivalenol (DON) is a mycotoxin that is found in feed ingredients derived from grains such as corn and wheat. Consumption of DON-contaminated feed has been shown to cause damage to the intestine, kidneys, and liver. However, the molecular mechanism by which DON exerts [...] Read more.
Deoxynivalenol (DON) is a mycotoxin that is found in feed ingredients derived from grains such as corn and wheat. Consumption of DON-contaminated feed has been shown to cause damage to the intestine, kidneys, and liver. However, the molecular mechanism by which DON exerts its effect in the small intestine is not completely understood. As a result, we profiled gene expression in intestinal epithelial cells treated with DON and examined the molecular function in vitro. We hypothesized that DON could induce apoptosis via the FOXO3a-signaling pathway in intestinal epithelial cells based on these findings. DON induced the apoptosis and the translocation of FOXO3a into the nucleus. Moreover, the inhibiting of FOXO3a alleviated the apoptosis and expression of apoptosis-related genes (TRAL, BCL-6, CASP8, and CASP3). ERK1/2 inhibitor treatment suppressed the translocation of FOXO3a into the nucleus. Our discovery suggests that DON induces apoptosis in intestinal epithelial cells through the FOXO3a-signaling pathway. Full article
(This article belongs to the Section Toxicology)
Show Figures

Figure 1

Article
Harmful Effects of Pyraclostrobin on the Fat Body and Pericardial Cells of Foragers of Africanized Honey Bee
Toxics 2022, 10(9), 530; https://doi.org/10.3390/toxics10090530 - 09 Sep 2022
Viewed by 1086
Abstract
Managed honey bees are daily exposed in agricultural settings or wild environments to multiple stressors. Currently, fungicide residues are increasingly present in bees’ pollen and nectar and can harm colonies’ production and survival. Therefore, our study aimed to evaluate the effects of the [...] Read more.
Managed honey bees are daily exposed in agricultural settings or wild environments to multiple stressors. Currently, fungicide residues are increasingly present in bees’ pollen and nectar and can harm colonies’ production and survival. Therefore, our study aimed to evaluate the effects of the fungicide pyraclostrobin on the fat body and pericardial cells of Africanized honey bees. The foragers were divided into three experimental treatment groups and two controls: pyraclostrobin 0.125 ng/µL (FG1), 0.025 ng/µL (FG2), 0.005 ng/µL (FG3), untreated control (CTL), and acetone control (CAC). After five days of oral exposure (ad libitum), the bees were dissected and prepared for histopathological and morphometric analysis. The FG1-treated bees showed extensive cytoarchitecture changes in the fat body and pericardial cells, inducing cell death. Bees from the FG2 group showed disarranged oenocytes, peripheral vacuolization, and pyknotic nuclei of pericardial cells, but the cytoarchitecture was not compromised as observed in FG1. Additionally, immune system cells were observed through the fat body in the FG1 group. Bees exposed to FG3 demonstrated only oenocytes vacuolization. A significant decrease in the oenocyte’s surface area for bees exposed to all pyraclostrobin concentrations was observed compared to the CTL and CAC groups. The bees from the FG1 and FG2 treatment groups presented a reduced surface area of pericardial cells compared to the controls and the FG3 group. This study highlighted the harmful effects of fungicide pyraclostrobin concentrations at the individual bee cellular level, potentially harming the colony level on continuous exposure. Full article
(This article belongs to the Section Toxicology)
Show Figures

Figure 1

Article
Cerium Oxide Enhances the Toxicity of Zinc Oxide Nanoparticles in Human Lung Epithelial Cell Cultures
Toxics 2022, 10(9), 522; https://doi.org/10.3390/toxics10090522 - 01 Sep 2022
Cited by 1 | Viewed by 1022
Abstract
Recently, many approaches have been developed to improve the performance of nanomaterials. Combining more than one nanomaterial is one such approach that achieves superior results. However, during the fabrication of nanomaterials or formulation of end products, materials can be released into the ambient [...] Read more.
Recently, many approaches have been developed to improve the performance of nanomaterials. Combining more than one nanomaterial is one such approach that achieves superior results. However, during the fabrication of nanomaterials or formulation of end products, materials can be released into the ambient air and be inhaled by workers. The adverse health outcomes of inhaling such compounds are unknown. In this study, we examined such effects in combining two of the most utilized nanomaterials in several industrial sectors: zinc oxide (ZnO) and cerium oxide (CeO2). These materials can be found together in sunscreens, polyvinyl alcohol (PVA) films, and construction products. The aim of this study was to assess the adverse biological outcomes of CeO2–ZnO nano-mixtures in human lung epithelial cells. A549 human lung epithelial cells were treated with increasing concentrations of ZnO or CeO2 NPs alone, or as a mixture of both, under submerged conditions for 24 h. After treatment, cell viability, reactive oxygen species (ROS) formation, cell membrane integrity, and cytokine production were examined. ZnO NPs showed a dose-dependent trend for all endpoints. CeO2 NPs did not exhibit any toxic effect in any individual concentrations. When higher doses of ZnO were combined with increasing doses of CeO2, loss of cell viability and an elevation in cell membrane leakage were observed. Interleukin 8 (IL-8) and ROS generation were higher when ZnO NPs were combined with CeO2 NPs, compared to cells that were treated with ZnO alone. The release of monocyte chemoattractant protein-1 (MCP-1) was reduced in the cells that were treated with higher doses of ZnO and CeO2. Thus, the presence of CeO2 enhanced the toxicity of ZnO in A549 cells at non-toxic levels of CeO2. This suggests an additive toxicity of these two nanomaterials. Full article
(This article belongs to the Special Issue Toxicity Assessment of Ambient Nanoparticles)
Show Figures

Graphical abstract

Article
Do Neighborhood Factors Modify the Effects of Lead Exposure on Child Behavior?
Toxics 2022, 10(9), 517; https://doi.org/10.3390/toxics10090517 - 31 Aug 2022
Viewed by 2549
Abstract
Lead exposure and neighborhoods can affect children’s behavior, but it is unclear if neighborhood characteristics modify the effects of lead on behavior. Understanding these modifications has important intervention implications. Blood lead levels (BLLs) in children (~7 years) from Montevideo, Uruguay, were categorized at [...] Read more.
Lead exposure and neighborhoods can affect children’s behavior, but it is unclear if neighborhood characteristics modify the effects of lead on behavior. Understanding these modifications has important intervention implications. Blood lead levels (BLLs) in children (~7 years) from Montevideo, Uruguay, were categorized at 2 µg/dL. Teachers completed two behavior rating scales (n = 455). At one-year follow-up (n = 380), caregivers reported child tantrums and parenting conflicts. Multilevel generalized linear models tested associations between BLLs and behavior, with neighborhood disadvantage, normalized difference vegetation index (NDVI), and distance to nearest greenspace as effect modifiers. No effect modification was noted for neighborhood disadvantage or NDVI. Children living nearest to greenspace with BLLs < 2 µg/dL were lower on behavior problem scales compared to children with BLLs ≥ 2 µg/dL. When furthest from greenspace, children were similar on behavior problems regardless of BLL. The probability of daily tantrums and conflicts was ~20% among children with BLLs < 2 µg/dL compared to ~45% among children with BLLs ≥ 2 µg/dL when closest to greenspace. Furthest from greenspace, BLLs were not associated with tantrums and conflicts. Effect modification of BLL on child behavior by distance to greenspace suggests that interventions should consider both greenspace access and lead exposure prevention. Full article
Show Figures

Figure 1

Article
Determination of the Oxidative Stress Biomarkers of 8-Hydroxydeoxyguanosine and Dityrosine in the Gills, Skin, Dorsal Fin, and Liver Tissue of Atlantic Salmon (Salmo salar) Parr
Toxics 2022, 10(9), 509; https://doi.org/10.3390/toxics10090509 - 29 Aug 2022
Viewed by 810
Abstract
Oxidative stress is a condition caused by an imbalance in the occurrence of reactive oxygen species in the cells and tissues of organisms. An ultra-performance liquid chromatography–electrospray ionization tandem mass spectrometry (UPLC–ESI–MS/MS) method was developed for the simultaneous determination of two oxidative stress [...] Read more.
Oxidative stress is a condition caused by an imbalance in the occurrence of reactive oxygen species in the cells and tissues of organisms. An ultra-performance liquid chromatography–electrospray ionization tandem mass spectrometry (UPLC–ESI–MS/MS) method was developed for the simultaneous determination of two oxidative stress biomarkers, 8-hydroxydeoxyguanosine (8OHDG) and dityrosine (DIY), in the gills, skin, dorsal fin, and liver tissue of Atlantic salmon (Salmo salar) parr. The use of target analyte-specific 13C and 15N internal standards allowed quantification of each target analyte to be performed through the standard solvent calibration curve. The relative recoveries [mean ± (relative standard deviation%)] of 8OHDG and DIY were 101 ± 11 and 104 ± 13% at a fortified concentration of 10 ng/mL (8OHDG) and 500 ng/mL (DIY), respectively, ensuring the accuracy of the extraction and quantification. The chromatographic separation was carried out using a gradient elution program with a total run time of 5 min. The limits of detection (LODs) were 0.11 and 1.37 ng/g wet weight (w.w.) for 8OHDG and DIY, respectively. To demonstrate the applicability of the developed method, it was applied in 907 tissue samples that were collected from Atlantic salmon parr individuals reared in an experimental land-based recirculating aquaculture system (RAS) treated with peracetic acid. Moreover, the possibility of using the dorsal fin as an alternative matrix for the minimally invasive assessment of oxidative stress in Atlantic salmon parr was introduced. To our knowledge, 8OHDG and DIY were used for the first time as biomarkers for biomonitoring the fish health (oxidative stress) of Atlantic salmon parr in RAS. Full article
(This article belongs to the Section Toxicology)
Show Figures

Graphical abstract

Article
Hematological Effects and Benchmark Doses of Long-Term Co-Exposure to Benzene, Toluene, and Xylenes in a Follow-Up Study on Petrochemical Workers
Toxics 2022, 10(9), 502; https://doi.org/10.3390/toxics10090502 - 28 Aug 2022
Cited by 1 | Viewed by 773
Abstract
Benzene, toluene, and xylenes (BTX) commonly co-exist. Exposure to individual components and BTX-rich mixtures can induce hematological effects. However, the hematological effects of long-term exposure to BTX are still unclear, and respective reference levels based on empirical evidence should be developed. We conducted [...] Read more.
Benzene, toluene, and xylenes (BTX) commonly co-exist. Exposure to individual components and BTX-rich mixtures can induce hematological effects. However, the hematological effects of long-term exposure to BTX are still unclear, and respective reference levels based on empirical evidence should be developed. We conducted a follow-up study in BTX-exposed petrochemical workers. Long-term exposure levels were quantified by measuring cumulative exposure (CE). Generalized weighted quantile sum (WQS) regression models and Benchmark Dose (BMD) Software were used to evaluate their combined effects and calculate their BMDs, respectively. Many hematologic parameters were significantly decreased at the four-year follow-up (p < 0.05). We found positive associations of CE levels of benzene, toluene, and xylene with the decline in monocyte counts, lymphocyte counts, and hematocrit, respectively (β > 0.010, Ptrend < 0.05). These associations were stronger in subjects with higher baseline parameters, males, drinkers, or overweight subjects (Pinteraction < 0.05). BTX had positive combined effects on the decline in monocyte counts, red-blood-cell counts, and hemoglobin concentrations (Ptrend for WQS indices < 0.05). The estimated BMDs for CE levels of benzene, toluene, and xylene were 2.138, 1.449, and 2.937 mg/m3 × year, respectively. Our study demonstrated the hematological effects of long-term BTX co-exposure and developed 8h-RELs of about 0.01 ppm based on their hematological effects. Full article
Article
Perfluorooctane Sulfonate Induces Dysfunction of Human Umbilical Vein Endothelial Cells via Ferroptosis Pathway
Toxics 2022, 10(9), 503; https://doi.org/10.3390/toxics10090503 - 28 Aug 2022
Viewed by 1142
Abstract
(1) Background: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant, and it is receiving increasing attention regarding its human health risks due to its extensive use. Endothelial dysfunction is a mark of cardiovascular disease, but the basic mechanism of PFOS-induced endothelial dysfunction is [...] Read more.
(1) Background: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant, and it is receiving increasing attention regarding its human health risks due to its extensive use. Endothelial dysfunction is a mark of cardiovascular disease, but the basic mechanism of PFOS-induced endothelial dysfunction is still not fully understood. Ferroptosis is a newly defined regulatory cell death driven by cellular metabolism and iron-dependent lipid peroxidation. Although ferroptosis has been shown to be involved in the pathogenesis of cardiovascular diseases, the involvement of ferroptosis in the pathogenesis of endothelial dysfunction caused by PFOS remains unclear. (2) Purpose: To explore the role of ferroptosis in the dysfunction of endothelial cells and underlying mechanisms. (3) Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to PFOS or PFOS and Fer-1. The viability, morphology change under electronic microscope, lipid-reactive oxygen species (lipid-ROS), and production of nitric oxide (NO) were determined. The expression of glutathione peroxidase 4(GPX4), ferritin heavy chain protein 1 (FTH1), heme oxygenase 1 (HO-1) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) were analyzed via Western blot analysis. (4) Results: PFOS was shown to cause a decrease in viability and morphological changes of mitochondria, and well as an increase in lipid droplets. The expression of GPX4, FTH1 and HO-1 was decreased, and that of ACSL4 was increased after exposure to PFOS. In addition to the above-mentioned ferroptosis-related manifestations, there was also a reduction in NO content. (5) Conclusions: PFOS induces ferroptosis by regulating the GPX4 and ACSL4 pathways, which leads to HUVEC dysfunction. Full article
(This article belongs to the Topic Hazard Assessment of Endocrine Disrupting Chemicals)
Show Figures

Figure 1

Article
Measuring TiO2N and AgHEC Airborne Particle Density during a Spray Coating Process
Toxics 2022, 10(9), 498; https://doi.org/10.3390/toxics10090498 - 27 Aug 2022
Viewed by 664
Abstract
Effective particle density is a key parameter for assessing inhalation exposure of engineered NPs in occupational environments. In this paper, particle density measurements were carried out using two different techniques: one based on the ratio between mass and volumetric particle concentrations; the other [...] Read more.
Effective particle density is a key parameter for assessing inhalation exposure of engineered NPs in occupational environments. In this paper, particle density measurements were carried out using two different techniques: one based on the ratio between mass and volumetric particle concentrations; the other one based on the ratio between aerodynamic and geometric particle diameter. These different approaches were applied to both field- and laboratory-scale atomization processes where the two target NPs (N-doped TiO2, TiO2N and AgNPs capped with a quaternized hydroxyethylcellulose, AgHEC) were generated. Spray tests using TiO2N were observed to release more and bigger particles than tests with AgHEC, as indicated by the measured particle mass concentrations and volumes. Our findings give an effective density of TiO2N particle to be in a similar range between field and laboratory measurements (1.8 ± 0.5 g/cm3); while AgHEC particle density showed wide variations (3.0 ± 0.5 g/cm3 and 1.2 + 0.1 g/cm3 for field and laboratory campaigns, respectively). This finding leads to speculation regarding the composition of particles emitted because atomized particle fragments may contain different Ag-to-HEC ratios, leading to different density values. A further uncertainty factor is probably related to low process emissions, making the subtraction of background concentrations from AgHEC process emissions unreliable. Full article
(This article belongs to the Special Issue Nano and Ultrafine Particle Toxicology and Exposure Assessment)
Show Figures

Figure 1

Article
Incorporation of Metabolic Activation in the HPTLC-SOS-Umu-C Bioassay to Detect Low Levels of Genotoxic Chemicals in Food Contact Materials
Toxics 2022, 10(9), 501; https://doi.org/10.3390/toxics10090501 - 27 Aug 2022
Cited by 2 | Viewed by 731
Abstract
The safety evaluation of food contact materials requires excluding mutagenicity and genotoxicity in migrates. Testing the migrates using in vitro bioassays has been proposed to address this challenge. To be fit for that purpose, bioassays must be capable of detecting very low, safety [...] Read more.
The safety evaluation of food contact materials requires excluding mutagenicity and genotoxicity in migrates. Testing the migrates using in vitro bioassays has been proposed to address this challenge. To be fit for that purpose, bioassays must be capable of detecting very low, safety relevant concentrations of DNA-damaging substances. There is currently no bioassay compatible with such qualifications. High-performance thin-layer chromatography (HPTLC), coupled with the planar SOS Umu-C (p-Umu-C) bioassay, was suggested as a promising rapid test (~6 h) to detect the presence of low levels of mutagens/genotoxins in complex mixtures. The current study aimed at incorporating metabolic activation in this assay and testing it with a set of standard mutagens (4-nitroquinoline-N-oxide, aflatoxin B1, mitomycin C, benzo(a)pyrene, N-ethyl nitrourea, 2-nitrofluorene, 7,12-dimethylbenzanthracene, 2-aminoanthracene and methyl methanesulfonate). An effective bioactivation protocol was developed. All tested mutagens could be detected at low concentrations (0.016 to 230 ng/band, according to substances). The calculated limits of biological detection were found to be up to 1400-fold lower than those obtained with the Ames assay. These limits are lower than the values calculated to ensure a negligeable carcinogenic risk of 10−5. They are all compatible with the threshold of toxicological concern for chemicals with alerts for mutagenicity (150 ng/person). They cannot be achieved by any other currently available test procedures. The p-Umu-C bioassay may become instrumental in the genotoxicity testing of complex mixtures such as food packaging, foods, and environmental samples. Full article
(This article belongs to the Special Issue Risk Assessment of Food Contact Materials/Articles)
Show Figures

Graphical abstract

Article
Lipidomics Profiles and Lipid Metabolite Biomarkers in Serum of Coal Workers’ Pneumoconiosis
Toxics 2022, 10(9), 496; https://doi.org/10.3390/toxics10090496 - 26 Aug 2022
Viewed by 869
Abstract
As a serious occupational pulmonary fibrosis disease, pneumoconiosis still lacks effective biomarkers. Previous studies suggest that pneumoconiosis may affect the body’s lipid metabolism. The purpose of this study was to explore lipidomics profiles and lipid metabolite biomarkers in the serum of coal workers’ [...] Read more.
As a serious occupational pulmonary fibrosis disease, pneumoconiosis still lacks effective biomarkers. Previous studies suggest that pneumoconiosis may affect the body’s lipid metabolism. The purpose of this study was to explore lipidomics profiles and lipid metabolite biomarkers in the serum of coal workers’ pneumoconiosis (CWP) by a population case-control study. A total of 150 CWP cases and 120 healthy controls from Beijing, China were included. Blood lipids were detected in serum biochemistry. Lipidomics was performed in serum samples for high-throughput detection of lipophilic metabolites. Serum high density lipoprotein cholesterol (HDL-C) decreased significantly in CWP cases. Lipidomics data found 131 differential lipid metabolites between the CWP case and control groups. Further, the top eight most important differential lipid metabolites were screened. They all belonged to differential metabolites of CWP at different stages. However, adjusting for potential confounding factors, only three of them were significantly related to CWP, including acylhexosylceramide (AHEXCER 43:5), diacylglycerol (DG 34:8) and dimethyl-phosphatidylethanolamine (DMPE 36:0|DMPE 18:0_18:0), of which good sensitivity and specificity were proven. The present study demonstrated that lipidomics profiles could change significantly in the serum of CWP patients and that the lipid metabolites represented by AHEXCER, DG and DMPE may be good biomarkers of CWP. Full article
Show Figures

Graphical abstract

Article
A Metabolomic Approach to Assess the Toxicity of the Olive Tree Endophyte Bacillus sp. PTA13 Lipopeptides to the Aquatic Macrophyte Lemna minor L.
Toxics 2022, 10(9), 494; https://doi.org/10.3390/toxics10090494 - 25 Aug 2022
Viewed by 804
Abstract
Pesticides represent a major human input into the ecosystem, posing a serious risk to non-target organisms. Therefore, there is pressure toward the reduction in their use and the discovery of alternative sources of bioactivity. Endophytic microorganisms represent a source of bioactivity, whose potential [...] Read more.
Pesticides represent a major human input into the ecosystem, posing a serious risk to non-target organisms. Therefore, there is pressure toward the reduction in their use and the discovery of alternative sources of bioactivity. Endophytic microorganisms represent a source of bioactivity, whose potential for plant protection has been recently established. In this context, an olive tree endophytic Bacillus sp. was isolated, exhibiting superior antifungal activity, mainly attributed to its major surfactin, iturin, and fengycin and the minor gageotetrin and bacilotetrin groups of lipopeptides (LP). Based on the potential of LP and the lack of information on their toxicity to aquatic organisms, we have investigated the toxicity of an LP extract to the model macrophyte Lemna minor L. The extract exhibited low phytotoxicity (EC50 = 419 μg·mL−1), and for the investigation of its effect on the plant, GC/EI/MS metabolomics was applied following exposure to sub-lethal doses (EC25 and EC50). Results revealed a general disturbance of plants’ biosynthetic capacity in response to LP treatments, with substantial effect on the amino acid pool and the defense mechanism regulated by jasmonate. There are no previous reports on the phytotoxicity of LP to L. minor, with evidence supporting their improved toxicological profile and potential in plant protection. Full article
(This article belongs to the Special Issue Toxicity of Contaminants on Aquatic Organisms)
Show Figures

Figure 1

Article
Commercial Fungicide Toxic Effects on Terrestrial Non-Target Species Might Be Underestimated When Based Solely on Active Ingredient Toxicity and Standard Earthworm Tests
Toxics 2022, 10(9), 488; https://doi.org/10.3390/toxics10090488 - 23 Aug 2022
Viewed by 830
Abstract
The ecosystem services provided by earthworms are lost when land management reduces their populations, hence, the importance of thorough assessments of management effects on this group. The present study aimed to: (1) review the possible influence of other ingredients within the formulations of [...] Read more.
The ecosystem services provided by earthworms are lost when land management reduces their populations, hence, the importance of thorough assessments of management effects on this group. The present study aimed to: (1) review the possible influence of other ingredients within the formulations of two commercial fungicides; (2) assess the sublethal effects of these commercial fungicides on Eisenia fetida; and (3) assess the acute lethal effects of one commercial fungicide on both Glossoscolex rione and E. fetida. Examining all components of the studied commercial formulations revealed that alongside the toxic active ingredients are other ingredients that are equally as or more toxic than the former and may even be in higher concentrations. The inhibition concentration of 10% of E. fetida’s progeny (IC10) was estimated at 133 mg kg−1 for PROSARO® and 1544 mg kg−1 for SWING PLUS®. Both fungicides showed an effect of hormesis on the progeny. In this first toxicity study with G. rione, it was found that this species is more sensitive to PROSARO® than E. fetida, with preliminary 14 day-lethal concentrations of 285 mg kg−1 for the former and >1000 mg kg−1 for the latter. Full article
(This article belongs to the Special Issue Current Developments in Soil Ecotoxicology)
Show Figures

Graphical abstract

Article
Insights into the Seasonal Olfactory Mechanism of Geosmin in Raw Water of Huangpu River
Toxics 2022, 10(8), 485; https://doi.org/10.3390/toxics10080485 - 19 Aug 2022
Viewed by 543
Abstract
Since the 1990s, the raw water of Huangpu River in Shanghai, China, has intermittently encountered off-flavor contamination. In this work, the concentrations of typical odor, geosmin, in raw water of Huangpu River are found to shift along with the seasons. However, microbes recognized [...] Read more.
Since the 1990s, the raw water of Huangpu River in Shanghai, China, has intermittently encountered off-flavor contamination. In this work, the concentrations of typical odor, geosmin, in raw water of Huangpu River are found to shift along with the seasons. However, microbes recognized as the producer of geosmin such as Cyanobacteria and Actinobacteria are not consistent with the shift of geosmin. Cyanobacteria blooms in summer rather than winter, whereas Actinobacteria thrives in winter. Representational difference analysis (RDA) reveals that microbes associated with blooming algae have positive co-occurrence correlations with the concentrations of geosmin and nutrients in winter, whereas those within Cyanobacteria and Planctomycete are in a positive correlation with temperature and thrive in summer. This causes the concentration of geosmin in raw water to appear to depend on the abundance of Actinobacteria rather than that of Cyanobacteria. However, combining with the synthesis and storage properties of geosmin in algae, as well as the decomposition properties of algae with Actinobacteria, geosmin might be synthesized by Cyanobacteria in summer, which is stored in cells of Cyanobacteria and released only via the decomposition of Actinobacteria in winter. This potential olfactory mechanism of geosmin is quite different from that derived from pure culture of odor producers or correlation analysis of bacteria and odors; thus, providing insights into the mechanism of practical off-flavor events. Full article
(This article belongs to the Special Issue Biodegradation and Hazards of Environmental Emerging Pollutants)
Show Figures

Figure 1

Article
Ecotoxicity of Polyvinylidene Difluoride (PVDF) and Polylactic Acid (PLA) Microplastics in Marine Zooplankton
Toxics 2022, 10(8), 479; https://doi.org/10.3390/toxics10080479 - 17 Aug 2022
Cited by 2 | Viewed by 1525
Abstract
The aim of this study was to investigate the ecotoxicity of polyvinylidene difluoride (PVDF) and polylactic acid (PLA) microplastics (MPs) in two marine zooplankton: the crustacean Artemia franciscana and the cnidarian Aurelia sp. (common jellyfish). To achieve this goal, (i) MP uptake, (ii) [...] Read more.
The aim of this study was to investigate the ecotoxicity of polyvinylidene difluoride (PVDF) and polylactic acid (PLA) microplastics (MPs) in two marine zooplankton: the crustacean Artemia franciscana and the cnidarian Aurelia sp. (common jellyfish). To achieve this goal, (i) MP uptake, (ii) immobility, and (iii) behavior (swimming speed, pulsation mode) of crustacean larval stages and jellyfish ephyrae exposed to MPs concentrations (1, 10, 100 mg/L) were assessed for 24 h. Using traditional and novel techniques, i.e., epifluorescence microscopy and 3D holotomography (HT), PVDF and PLA MPs were found in the digestive systems of the crustaceans and in the gelatinous tissue of jellyfish. Immobility was not affected in either organism, while a significant behavioral alteration in terms of pulsation mode was found in jellyfish after exposure to both PVDF and PLA MPs. Moreover, PLA MPs exposure in jellyfish induced a toxic effect (EC50: 77.43 mg/L) on the behavioral response. This study provides new insights into PLA and PVDF toxicity with the potential for a large impact on the marine ecosystem, since jellyfish play a key role in the marine food chain. However, further investigations incorporating additional species belonging to other trophic levels are paramount to better understand and clarify the impact of such polymers at micro scale in the marine environment. These findings suggest that although PVDF and PLA have been recently proposed as innovative and, in the case of PLA, biodegradable polymers, their effects on marine biota should not be underestimated. Full article
Show Figures

Figure 1

Article
Post-Mortem Analysis of Heroin Biomarkers, Morphine and Codeine in Stomach Wall Tissue in Heroin-Related Deaths
Toxics 2022, 10(8), 473; https://doi.org/10.3390/toxics10080473 - 14 Aug 2022
Viewed by 1241
Abstract
Toxicological analysis of some cases can be complicated by poor sample quality caused by decomposition. Although heroin-related deaths have been researched extensively, the interpretation of toxicology findings in these cases is challenging, especially in instances where blood samples are unavailable. Thus, it is [...] Read more.
Toxicological analysis of some cases can be complicated by poor sample quality caused by decomposition. Although heroin-related deaths have been researched extensively, the interpretation of toxicology findings in these cases is challenging, especially in instances where blood samples are unavailable. Thus, it is important to develop analytical methods for different sample types. In this study. a method for the quantification of 6-monoacetylmorphine, 6-acetylcodeine, morphine, and codeine in postmortem stomach wall tissue using liquid chromatography coupled with tandem mass spectrometry was developed and validated. All calibration curves prepared with the stomach wall tissue were linear and ranged from 0.5–1000 ng/g with determination coefficients of >0.99 and a lower limit of quantification of 1.0 ng/g. The coefficients of variation for within-run precision and between-run precision were <9%. Matrix effects of stomach wall tissues and their extraction recoveries were investigated and ranged from −19% to +17% and 76% to 80%, respectively. Among the 16 analyzed heroin-related death cases, 6-monoacetylmorphine, 6-acetylcodeine, morphine, and codeine were detected in 75%, 31%, 100%, and 94% of all stomach wall tissues with median concentrations of 90 ng/g, 20 ng/g, 140 ng/g, and 30 ng/g, respectively. This study provides new data on the distribution of 6-monoacetylmorphine, 6-Acetylcodeine, morphine, and codeine in postmortem stomach wall tissue and suggests the usefulness of alternative matrices for investigating heroin-related fatalities when blood samples are unavailable. In addition, the prevalence of 6-monoacetylmorphine in the stomach wall tissue was higher than that in the liver and kidney tissues. Full article
(This article belongs to the Special Issue Forensic Toxicology: A New Scientific Contribution)
Show Figures

Figure 1

Article
Glyphosate and AMPA in Human Urine of HBM4EU Aligned Studies: Part A Children
Toxics 2022, 10(8), 470; https://doi.org/10.3390/toxics10080470 - 12 Aug 2022
Cited by 3 | Viewed by 1225
Abstract
Few data are available on the exposure of children to glyphosate (Gly) in Europe. Within HBM4EU, new HBM exposure data were collected from aligned studies at five sampling sites distributed over Europe (studies: SLO CRP (SI); ORGANIKO (CY); GerES V-sub (DE); 3XG (BE); [...] Read more.
Few data are available on the exposure of children to glyphosate (Gly) in Europe. Within HBM4EU, new HBM exposure data were collected from aligned studies at five sampling sites distributed over Europe (studies: SLO CRP (SI); ORGANIKO (CY); GerES V-sub (DE); 3XG (BE); ESTEBAN (FR)). Median Gly concentrations in urine were below or around the detection limit (0.1 µg/L). The 95th percentiles ranged between 0.18 and 1.03 µg Gly/L. The ratio of AMPA (aminomethylphosphonic acid; main metabolite of Gly) to Gly at molar basis was on average 2.2 and the ratio decreased with higher Gly concentrations, suggesting that other sources of AMPA, independent of metabolism of Gly to AMPA in the monitored participants, may concurrently operate. Using reverse dosimetry and HBM exposure data from five European countries (east, west and south Europe) combined with the proposed ADI (acceptable daily intake) of EFSA for Gly of 0.1 mg/kg bw/day (based on histopathological findings in the salivary gland of rats) indicated no human health risks for Gly in the studied populations at the moment. However, the absence of a group ADI for Gly+AMPA and ongoing discussions on e.g., endocrine disrupting effects cast some uncertainty in relation to the current single substance ADI for Gly. The carcinogenic effects of Gly are still debated in the scientific community. These outcomes would influence the risk conclusions presented here. Finally, regression analyses did not find clear associations between urinary exposure biomarkers and analyzed potential exposure determinants. More information from questionnaires targeting exposure-related behavior just before the sampling is needed. Full article
Show Figures

Figure 1

Article
Phytoremediation of Soil Contaminated by Organochlorine Pesticides and Toxic Trace Elements: Prospects and Limitations of Paulownia tomentosa
Toxics 2022, 10(8), 465; https://doi.org/10.3390/toxics10080465 - 11 Aug 2022
Viewed by 747
Abstract
Paulownia tomentosa (Thunb.) Steud is a drought-resistant, low-maintenance and fast-growing energy crop that can withstand a wide range of climatic conditions, provides a high biomass yield (approximately 50 t DM ha−1 yr−1), and develops successfully in contaminated sites. In Kazakhstan, [...] Read more.
Paulownia tomentosa (Thunb.) Steud is a drought-resistant, low-maintenance and fast-growing energy crop that can withstand a wide range of climatic conditions, provides a high biomass yield (approximately 50 t DM ha−1 yr−1), and develops successfully in contaminated sites. In Kazakhstan, there are many historically contaminated sites polluted by a mixture of xenobiotics of organic and inorganic origin that need to be revitalised. Pilot-scale research evaluated the potential of P. tomentosa for the phytoremediation of soils historically contaminated with organochlorine pesticides (OCPs) and toxic trace elements (TTEs) to minimise their impact on the environment. Targeted soils from the obsolete pesticide stockpiles located in three villages of Talgar district, Almaty region, Kazakhstan, i.e., Amangeldy (soil A), Beskainar (soil B), and Kyzylkairat (soil K), were subjected to research. Twenty OCPs and eight TTEs (As, Cr, Co, Ni, Cu, Zn, Cd, and Pb) were detected in the soils. The phytoremediation potential of P. tomentosa was investigated for OCPs whose concentrations in the soils were significantly different (aldrin, endosulfans, endrin aldehyde, HCB, heptachlor, hexabromobenzene, keltan, methoxychlor, and γ-HCH) and for TTEs (Cu, Zn, and Cd) whose concentrations exceeded maximum permissible concentrations. Bioconcentration (BCF) and translocation (TLF) factors were used as indicators of the phytoremediation process. It was ensured that the uptake and translocation of contaminants by P. tomentosa was highly variable and depended on their properties and concentrations in soil. Besides the ability to bioconcentrate Cr, Ni, and Cu, P. tomentosa demonstrated very encouraging results in the accumulation of endosulfans, keltan, and methoxychlor and the phytoextraction of γ-HCH (TLFs of 1.9–9.9) and HCB (BCFs of 197–571). The results of the pilot trials support the need to further investigate the potential of P. tomentosa for phytoremediation on a field scale. Full article
(This article belongs to the Section Toxicity Reduction and Environmental Remediation)
Show Figures

Graphical abstract

Article
Spatial Distribution, Contamination Levels, and Health Risk Assessment of Potentially Toxic Elements in Household Dust in Cairo City, Egypt
Toxics 2022, 10(8), 466; https://doi.org/10.3390/toxics10080466 - 11 Aug 2022
Cited by 2 | Viewed by 780
Abstract
Urban areas’ pollution, which is owing to rapid urbanization and industrialization, is one of the most critical issues in densely populated cities such as Cairo. The concentrations and the spatial distribution of fourteen potentially toxic elements (PTEs) in household dust were investigated in [...] Read more.
Urban areas’ pollution, which is owing to rapid urbanization and industrialization, is one of the most critical issues in densely populated cities such as Cairo. The concentrations and the spatial distribution of fourteen potentially toxic elements (PTEs) in household dust were investigated in Cairo City, Egypt. PTE exposure and human health risk were assessed using the USEPA’s exposure model and guidelines. The levels of As, Cd, Cr, Cu, Hg, Mo, Ni, Pb, and Zn surpassed the background values. Contamination factor index revealed that contamination levels are in the sequence Cd > Hg > Zn > Pb > Cu > As > Mo > Ni > Cr > Co > V > Mn > Fe > Al. The degree of contamination ranges from considerably to very high pollution. Elevated PTE concentrations in Cairo’s household dust may be due to heavy traffic emissions and industrial activities. The calculated noncarcinogenic risk for adults falls within the safe limit, while those for children exceed that limit in some sites. Cairo residents are at cancer risk owing to prolonged exposure to the indoor dust in their homes. A quick and targeted plan must be implemented to mitigate these risks. Full article
Show Figures

Figure 1

Article
Acute Rubigine® Poisoning in Martinique a French Overseas Department of America: Clinical Characteristics and Prognostic Factors
Toxics 2022, 10(8), 453; https://doi.org/10.3390/toxics10080453 - 05 Aug 2022
Viewed by 696
Abstract
Rubigine® is an anti-rust stain remover containing fluorides which is believed to have been the cause of many deaths in Martinique. However, after the modification of its composition in 2006, serious poisoning from old formulas containing fluorides persisted. Our main objective was [...] Read more.
Rubigine® is an anti-rust stain remover containing fluorides which is believed to have been the cause of many deaths in Martinique. However, after the modification of its composition in 2006, serious poisoning from old formulas containing fluorides persisted. Our main objective was to determine the clinical characteristics and prognostic factors of these intoxications. Methods: Any patient admitted to the Martinique University Hospital for acute Rubigine® poisoning was included from 1 January 2000 to 31 December 2016. Usual demographic and clinical data were collected and comparisons between surviving and deceased patients made using a univariate analysis and logistic regression. Results: Fifty-five patients were included (mean age: 43 years; sex ratio M/F: 1.1), and the main clinical characteristics were: changes in electrocardiogram (ECG) (80%), digestive system disorders (75%), and neurological disorders (12%). The main features linked to death were the presence of hydrofluoric acid (p < 0.0001), age over 55 years (p = 0.01), hypocalcemia after the initial intravenous calcium supplementation (p = 0.0003), diarrhea (p < 0.0001), hypersialorrhea (p < 0.0001), myocardial excitability (p < 0.0001), and state of shock (p < 0.0001). Three patients required circulatory support by venous-arterial ECMO. Mortality was 10.9%. Conclusions: Rubigine® poisoning is responsible for significant morbidity and mortality. Fortunately, its incidence as well as mortality has sharply decreased in Martinique thanks to the measures taken by the French state. This retrospective work nevertheless shows that acute intoxication by the old formula of Rubigine® remains the main factor of poor prognosis. Full article
(This article belongs to the Section Toxicology)
Show Figures

Figure 1

Article
Characterization of Potential Adverse Outcome Pathways Related to Metabolic Outcomes and Exposure to Per- and Polyfluoroalkyl Substances Using Artificial Intelligence
Toxics 2022, 10(8), 449; https://doi.org/10.3390/toxics10080449 - 04 Aug 2022
Cited by 1 | Viewed by 1485
Abstract
Human exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with numerous adverse health effects, depending on various factors such as the conditions of exposure (dose/concentration, duration, route of exposure, etc.) and characteristics associated with the exposed target (e.g., age, sex, ethnicity, [...] Read more.
Human exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with numerous adverse health effects, depending on various factors such as the conditions of exposure (dose/concentration, duration, route of exposure, etc.) and characteristics associated with the exposed target (e.g., age, sex, ethnicity, health status, and genetic predisposition). The biological mechanisms by which PFAS might affect systems are largely unknown. To support the risk assessment process, AOP-helpFinder, a new artificial intelligence tool, was used to rapidly and systematically explore all available published information in the PubMed database. The aim was to identify existing associations between PFAS and metabolic health outcomes that may be relevant to support building adverse outcome pathways (AOPs). The collected information was manually organized to investigate linkages between PFAS exposures and metabolic health outcomes, including dyslipidemia, hypertension, insulin resistance, and obesity. Links between PFAS exposure and events from the existing metabolic-related AOPs were also retrieved. In conclusion, by analyzing dispersed information from the literature, we could identify some associations between PFAS exposure and components of existing AOPs. Additionally, we identified some linkages between PFAS exposure and metabolic outcomes for which only sparse information is available or which are not yet present in the AOP-wiki database that could be addressed in future research. Full article
Show Figures

Figure 1

Article
Alleviation of Ammonium Toxicity in Salvia splendens ‘Vista Red’ with Silicon Supplementation
Toxics 2022, 10(8), 446; https://doi.org/10.3390/toxics10080446 - 03 Aug 2022
Cited by 3 | Viewed by 869
Abstract
Ammonium (NH4+) toxicity seriously hampers the yield and quality of salvia plants because most varieties or sub-species are highly sensitive to NH4+. Silicon (Si) is an alternative that is used to minimize these disturbances and maintain better [...] Read more.
Ammonium (NH4+) toxicity seriously hampers the yield and quality of salvia plants because most varieties or sub-species are highly sensitive to NH4+. Silicon (Si) is an alternative that is used to minimize these disturbances and maintain better growth under NH4+ toxicity. Nevertheless, the mitigatory effects of Si on NH4+-stressed salvia are unknown. Therefore, this study was carried out to determine how Si assists to alleviate the NH4+ toxicity degree in salvia. To this end, salvia plants were cultivated in a controlled environment supplied with a constant N (nitrogen) level (13 meq·L−1) in the form of three NH4+:NO3 ratios (0:100, 50:50, 100:0), each with (1.0 meq·L−1) or without Si. Physiological disorders and typical NH4+ toxicity symptoms, as well as interrupted photosynthesis, were observed in the 100% NH4+-treated plants. Furthermore, cation uptake inhibition and oxidative damage were also imposed by the 100% NH4+ supply. In contrast, in the presence of Si, the NH4+ toxicity degree was attenuated and plant growth was ensured. Accordingly, the NH4+ toxicity appearance ratio decreased significantly. Furthermore, Si-treated plants showed an ameliorated photosynthetic ability, elevated internal K and Ca levels, and enhanced antioxidative capacity, as reflected by improved major antioxidant enzyme activities, as well as diminished accumulation of ROS (reactive oxygen species) and MDA (malondialdehyde). Our findings enlightened the agronomic importance of additional Si to nutrient solutions, especially pertaining to bedding plants at risk of NH4+ toxicity. Full article
(This article belongs to the Special Issue Heavy Metal Toxicity Effects on Plants)
Show Figures

Figure 1

Article
Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000–2021)
Toxics 2022, 10(8), 443; https://doi.org/10.3390/toxics10080443 - 02 Aug 2022
Cited by 1 | Viewed by 1196
Abstract
Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it [...] Read more.
Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014–2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000–2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years. Full article
Show Figures

Figure 1

Article
A Population-Based Human In Vitro Approach to Quantify Inter-Individual Variability in Responses to Chemical Mixtures
Toxics 2022, 10(8), 441; https://doi.org/10.3390/toxics10080441 - 01 Aug 2022
Cited by 2 | Viewed by 1120
Abstract
Human cell-based population-wide in vitro models have been proposed as a strategy to derive chemical-specific estimates of inter-individual variability; however, the utility of this approach has not yet been tested for cumulative exposures in mixtures. This study aimed to test defined mixtures and [...] Read more.
Human cell-based population-wide in vitro models have been proposed as a strategy to derive chemical-specific estimates of inter-individual variability; however, the utility of this approach has not yet been tested for cumulative exposures in mixtures. This study aimed to test defined mixtures and their individual components and determine whether adverse effects of the mixtures were likely to be more variable in a population than those of the individual chemicals. The in vitro model comprised 146 human lymphoblastoid cell lines from four diverse subpopulations of European and African descent. Cells were exposed, in concentration–response, to 42 chemicals from diverse classes of environmental pollutants; in addition, eight defined mixtures were prepared from these chemicals using several exposure- or hazard-based scenarios. Points of departure for cytotoxicity were derived using Bayesian concentration–response modeling and population variability was quantified in the form of a toxicodynamic variability factor (TDVF). We found that 28 chemicals and all mixtures exhibited concentration–response cytotoxicity, enabling calculation of the TDVF. The median TDVF across test substances, for both individual chemicals or defined mixtures, ranged from a default assumption (101/2) of toxicodynamic variability in human population to >10. The data also provide a proof of principle for single-variant genome-wide association mapping for toxicity of the chemicals and mixtures, although replication would be necessary due to statistical power limitations with the current sample size. This study demonstrates the feasibility of using a set of human lymphoblastoid cell lines as an in vitro model to quantify the extent of inter-individual variability in hazardous properties of both individual chemicals and mixtures. The data show that population variability of the mixtures is unlikely to exceed that of the most variable component, and that similarity in genome-wide associations among components may be used to accrue additional evidence for grouping of constituents in a mixture for cumulative assessments. Full article
(This article belongs to the Special Issue Computational Toxicology: Expanding Frontiers in Risk Assessment)
Show Figures

Figure 1

Article
The Role of Ferroptosis in the Damage of Human Proximal Tubule Epithelial Cells Caused by Perfluorooctane Sulfonate
Toxics 2022, 10(8), 436; https://doi.org/10.3390/toxics10080436 - 29 Jul 2022
Cited by 1 | Viewed by 1128
Abstract
Perfluorooctane sulfonate (PFOS) is a typical persistent organic pollutant and environmental endocrine disruptor that has been shown to be associated with the development of many diseases; it poses a considerable threat to the ecological environment and to human health. PFOS is known to [...] Read more.
Perfluorooctane sulfonate (PFOS) is a typical persistent organic pollutant and environmental endocrine disruptor that has been shown to be associated with the development of many diseases; it poses a considerable threat to the ecological environment and to human health. PFOS is known to cause damage to renal cells; however, studies of PFOS-induced ferroptosis in cells have not been reported. We used the CCK-8 method to detect cell viability, flow cytometry and immunofluorescence methods to detect ROS levels and Western blot to detect ferroptosis, endoplasmic reticulum stress, antioxidant and apoptosis-related proteins. In our study, we found that PFOS could induce the onset of ferroptosis in HK-2 cells with decreased GPx4 expression and elevated ACSL4 and FTH1 expression, which are hallmarks for the development of ferroptosis. In addition, PFOS-induced ferroptosis in HK-2 cells could be reversed by Fer-1. We also found that endoplasmic reticulum stress and its mediated apoptotic mechanism and P53-mediated antioxidant mechanism are involved in the toxic damage of cells by PFOS. In this paper, we demonstrated for the first time that PFOS can induce ferroptosis in HK-2 cells. In addition, we preliminarily explored other mechanisms of cytotoxic damage by PFOS, which provides a new idea to study the toxicity of PFOS as well as the damage to the kidney and its mechanism. Full article
(This article belongs to the Topic Hazard Assessment of Endocrine Disrupting Chemicals)
Show Figures

Graphical abstract

Article
Helium Suicide, a Rapid and Painless Asphyxia: Toxicological Findings
Toxics 2022, 10(8), 424; https://doi.org/10.3390/toxics10080424 - 28 Jul 2022
Viewed by 45324
Abstract
Suicide by helium inhalation has become increasingly common in the last few decades in Europe and the US because it produces a quick and painless death. Inhaled-gas suicides can easily be assessed through death scene investigation and autopsy. However, helium is a colorless [...] Read more.
Suicide by helium inhalation has become increasingly common in the last few decades in Europe and the US because it produces a quick and painless death. Inhaled-gas suicides can easily be assessed through death scene investigation and autopsy. However, helium is a colorless and odorless inert gas that unfortunately cannot be detected using standard toxicological analysis. A successful gas analysis was performed following the suicide of a 17-year-old female. For the detection of helium, central/peripheral blood samples and gaseous samples from the esophagus, stomach, and upper and lower respiratory airways (from the trachea and the primary left and right bronchia) were collected with a gastight syringe, ensuring minimal dilution. Qualitative analyses were positive in all gaseous samples. Quantitative analyses were performed using a special gas-inlet system with a vacuum by which the sample can be transferred to a mass spectrometer, reducing the risk of contamination. Helium concentrations were 20.16% from the trachea, 12.33% from the right lung, and 1.5% from the stomach. Based on the high levels of helium, the cause and manner of death were assessed as asphyxia suicide by inhalation of helium. Therefore, toxicological analyses should always be applied in order to gain evidence of inhaled gas in gaseous samples. Full article
(This article belongs to the Special Issue The Identification of Drug Abuse)
Show Figures

Figure 1

Article
Effects of Discarded Masks on the Offshore Microorganisms during the COVID-19 Pandemic
Toxics 2022, 10(8), 426; https://doi.org/10.3390/toxics10080426 - 28 Jul 2022
Cited by 1 | Viewed by 1028
Abstract
Numerous disposable plastic masks had been produced and used for preventing the worldwide COVID-19 pandemic effectively. Discarded masks are a potential source of microplastic pollution in marine ecosystems. The effect of discarded masks on offshore microorganisms is still unclear. Herein, we profiled the [...] Read more.
Numerous disposable plastic masks had been produced and used for preventing the worldwide COVID-19 pandemic effectively. Discarded masks are a potential source of microplastic pollution in marine ecosystems. The effect of discarded masks on offshore microorganisms is still unclear. Herein, we profiled the interaction between the microplastics released by discarded masks and marine microbes. The effects of mask quantity, time, and environment on the microplastic-related communities were determined. We characterized the bacterial communities of each group using 16S rRNA gene sequencing and metagenomic sequencing and correlated the community diversity to the physicochemical properties of seawater. We found that the diversity and richness of microflora on the surface of microplastics with different quantity and time varied significantly. Proteobacteria are the main bacteria on microplastics, and the KEGG metabolic pathway prediction shows that amino acid metabolism and carbohydrate metabolism were abundant. In addition, there was a correlation between bacterial communities and Antibiotic Resistance Ontology (ARO). We used scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR) techniques to evaluate the plastic polymer characteristics of disposable medical masks. Our research shows that disposable medical masks immersed in seawater can alter the microbial community. This study provides the most recent data and insights into the contamination of discarded masks in the marine environment. Full article
(This article belongs to the Special Issue Occurrence, Fate and Transport of Marine Pollutants)
Show Figures

Graphical abstract

Article
Indoor Air Quality Monitoring and Characterization of Airborne Workstations Pollutants within Detergent Production Plant
Toxics 2022, 10(8), 419; https://doi.org/10.3390/toxics10080419 - 26 Jul 2022
Viewed by 766
Abstract
The indoor air quality (IAQ) of five workstations within a detergent production unit was monitored. Particulate matter (PM) was measured using a gravitational settlement method, and later characterized. To ascertain the quality of indoor air within the workstations, which could directly or indirectly [...] Read more.
The indoor air quality (IAQ) of five workstations within a detergent production unit was monitored. Particulate matter (PM) was measured using a gravitational settlement method, and later characterized. To ascertain the quality of indoor air within the workstations, which could directly or indirectly affect the health and performance of the workers, a physical inspection of the plant premises was undertaken. The mean value of the following air-quality parameters; particulate matter(PM2.5), particulate matter (PM10), formaldehyde (HCHO), volatile organic compounds (VOCs), carbon dioxide (CO2), temperature (T) and percent relative humidity (%RH) were obtained within the range of 24.5–48.5 µg/m3, 26.75–61.75 µg/m3, 0.0–0.012 mg/m3, 0.09–1.35 mg/m3, 1137–1265 ppm, 25.65–28.15 °C and 20.13–23.8%, respectively. Of the particulate matter components characterized, sodium oxide (Na2O)—25.30 mg/m3, aluminum oxide (Al2O3)—22.93 mg/m3, silicon dioxide (SiO2)—34.17 mg/m3, sulfur trioxide (SO3)—41.57 mg/m3, calcium oxide (CaO)—10.94 mg/m3 and iron III oxide (Fe2O3)—19.23 mg/m3, were of significance. These results, compared with international standards for industrial indoor air quality, suggest that indoor air contamination emanating from the chemicals used in production workstations is traced to the design of the plant structures and the activities carried out within the workstations. Full article
Show Figures

Figure 1

Article
Is Mixtures’ Additivity Supported by Empirical Data? A Case Study of Developmental Toxicity of PFOS and 6:2 FTS in Wildtype Zebrafish Embryos
Toxics 2022, 10(8), 418; https://doi.org/10.3390/toxics10080418 - 25 Jul 2022
Viewed by 1018
Abstract
Per- and polyfluoroalkyl substances (PFASs) are a major priority for many federal and state regulatory agencies charged with monitoring levels of emerging contaminants in environmental media and setting health-protective benchmarks to guide risk assessments. While screening levels and toxicity reference values have been [...] Read more.
Per- and polyfluoroalkyl substances (PFASs) are a major priority for many federal and state regulatory agencies charged with monitoring levels of emerging contaminants in environmental media and setting health-protective benchmarks to guide risk assessments. While screening levels and toxicity reference values have been developed for numerous individual PFAS compounds, there remain important data gaps regarding the mode of action for toxicity of PFAS mixtures. The present study aims to contribute whole-mixture toxicity data and advance the methods for evaluating mixtures of two key components of aqueous film-forming foams: perfluorooctanesulfonic acid (PFOS), and 6:2 fluorotelomer sulfonic acid (6:2 FTS). Wildtype (AB) zebrafish embryos were exposed to PFOS and 6:2 FTS, both as individual components and as binary mixtures, from 2 to 122 h post-fertilization. Five treatment levels were selected to encompass environmentally relevant exposure levels. Experimental endpoints consisted of mortality, hatching, and developmental endpoints, including swim bladder inflation, yolk sac area, and larval body length. Results from dose–response analysis indicate that the assumption of additivity using conventional points of departure (e.g., NOAEL, LOAEL) is not supported for critical effect endpoints with these PFAS mixtures, and that the interactions vary as a function of the dose range. Alternative methods for quantifying relative potency are proposed, and recommendations for additional investigations are provided to further advance assessments of the toxicity of PFAS mixtures to aquatic organisms. Full article
Show Figures

Figure 1

Article
Morphometrical, Morphological, and Immunocytochemical Characterization of a Tool for Cytotoxicity Research: 3D Cultures of Breast Cell Lines Grown in Ultra-Low Attachment Plates
Toxics 2022, 10(8), 415; https://doi.org/10.3390/toxics10080415 - 24 Jul 2022
Viewed by 923
Abstract
Three-dimensional cell cultures may better mimic avascular tumors. Yet, they still lack characterization and standardization. Therefore, this study aimed to (a) generate multicellular aggregates (MCAs) of four breast cell lines: MCF7, MDA-MB-231, and SKBR3 (tumoral) and MCF12A (non-tumoral) using ultra-low attachment (ULA) plates, [...] Read more.
Three-dimensional cell cultures may better mimic avascular tumors. Yet, they still lack characterization and standardization. Therefore, this study aimed to (a) generate multicellular aggregates (MCAs) of four breast cell lines: MCF7, MDA-MB-231, and SKBR3 (tumoral) and MCF12A (non-tumoral) using ultra-low attachment (ULA) plates, (b) detail the methodology used for their formation and analysis, providing technical tips, and (c) characterize the MCAs using morphometry, qualitative cytology (at light and electron microscopy), and quantitative immunocytochemistry (ICC) analysis. Each cell line generated uniform MCAs with structural differences among cell lines: MCF7 and MDA-MB-231 MCAs showed an ellipsoid/discoid shape and compact structure, while MCF12A and SKBR3 MCAs were loose, more flattened, and presented bigger areas. MCF7 MCAs revealed glandular breast differentiation features. ICC showed a random distribution of the proliferating and apoptotic cells throughout the MCAs, not fitting in the traditional spheroid model. ICC for cytokeratin, vimentin, and E-cadherin showed different results according to the cell lines. Estrogen (ER) and progesterone (PR) receptors were positive only in MCF7 and human epidermal growth factor receptor 2 (HER-2) in SKBR3. The presented characterization of the MCAs in non-exposed conditions provided a good baseline to evaluate the cytotoxic effects of potential anticancer compounds. Full article
(This article belongs to the Section Toxicology)
Show Figures

Figure 1

Article
Antiseizure and Neuroprotective Efficacy of Midazolam in Comparison with Tezampanel (LY293558) against Soman-Induced Status Epilepticus
Toxics 2022, 10(8), 409; https://doi.org/10.3390/toxics10080409 - 22 Jul 2022
Cited by 1 | Viewed by 590
Abstract
Acute exposure to nerve agents induces status epilepticus (SE), which can cause death or long-term brain damage. Diazepam is approved by the FDA for the treatment of nerve agent-induced SE, and midazolam (MDZ) is currently under consideration to replace diazepam. However, animal studies [...] Read more.
Acute exposure to nerve agents induces status epilepticus (SE), which can cause death or long-term brain damage. Diazepam is approved by the FDA for the treatment of nerve agent-induced SE, and midazolam (MDZ) is currently under consideration to replace diazepam. However, animal studies have raised questions about the neuroprotective efficacy of benzodiazepines. Here, we compared the antiseizure and neuroprotective efficacy of MDZ (5 mg/kg) with that of tezampanel (LY293558; 10 mg/kg), an AMPA/GluK1 receptor antagonist, administered 1 h after injection of the nerve agent, soman (1.2 × LD50), in adult male rats. Both of the anticonvulsants promptly stopped SE, with MDZ having a more rapid effect. However, SE reoccurred to a greater extent in the MDZ-treated group, resulting in a significantly longer total duration of SE within 24 h post-exposure compared with the LY293558-treated group. The neuroprotective efficacy of the two drugs was studied in the basolateral amygdala, 30 days post-exposure. Significant neuronal and inter-neuronal loss, reduced ratio of interneurons to the total number of neurons, and reduction in spontaneous inhibitory postsynaptic currents accompanied by increased anxiety were found in the MDZ-treated group. The rats treated with LY293558 did not differ from the control rats (not exposed to soman) in any of these measurements. Thus, LY293558 has significantly greater efficacy than midazolam in protecting against prolonged seizures and brain damage caused by acute nerve agent exposure. Full article
(This article belongs to the Special Issue Chemical and Biological Threats, Hazard Potential and Countermeasures)
Show Figures

Figure 1

Article
Effects of Amendments and Indigenous Microorganisms on the Growth and Cd and Pb Uptake of Coriander (Coriandrum sativum L.) in Heavy Metal-Contaminated Soils
Toxics 2022, 10(8), 408; https://doi.org/10.3390/toxics10080408 - 22 Jul 2022
Cited by 1 | Viewed by 695
Abstract
Heavy metal (HM) contamination of soils is a worldwide problem with adverse consequences to the environment and human health. For the safe production of vegetables in contaminated soil, efficient soil amendments need to be applied such as nano-hydroxyapatite (n-HAP) and poly γ-glutamic acid [...] Read more.
Heavy metal (HM) contamination of soils is a worldwide problem with adverse consequences to the environment and human health. For the safe production of vegetables in contaminated soil, efficient soil amendments need to be applied such as nano-hydroxyapatite (n-HAP) and poly γ-glutamic acid (γ-PGA), which can mitigate heavy metal uptake and enhance crop yield. However, the combined effects of soil amendments and indigenous microorganisms (IMOs) on HMs immobilisation and accumulation by crops have received little attention. We established a pot experiment to investigate the effects of IMOs combined with n-HAP and γ-PGA on coriander (Coriandrum sativum L.) growth and its Cd and Pb uptake in two acidic soils contaminated with HMs. The study demonstrated that applying n-HAP, with and without IMOs, significantly increased shoot dry biomass and reduced plant Cd and Pb uptake and diethylenetriaminepentaacetic acid (DTPA) extractable Cd and Pb concentrations in most cases. However, γ-PGA, with and without IMOs, only reduced soil DTPA-extractable Pb concentrations in slightly contaminated soil with 0.29 mg/kg Cd and 50.9 mg/kg Pb. Regardless of amendments, IMOs independently increased shoot dry biomass and soil DTPA-extractable Cd concentrations in moderately contaminated soil with 1.08 mg/kg Cd and 100.0 mg/kg Pb. A synergistic effect was observed with a combined IMOs and n-HAP treatment, where DTPA-extractable Cd and Pb concentrations decreased in slightly contaminated soil compared with the independent IMOs and n-HAP treatments. The combined treatment of γ-PGA and IMOs substantially increased shoot dry biomass in moderately contaminated soil. These results indicate that solo n-HAP enhanced plant growth and soil Cd and Pb immobilisation, and mitigated Cd and Pb accumulation in shoots. However, the combination of n-HAP and IMOs was optimal for stabilising and reducing HMs’ uptake and promoting plant growth in contaminated soil, suggesting its potential for safe crop production. Full article
(This article belongs to the Section Toxicity Reduction and Environmental Remediation)
Show Figures

Figure 1

Communication
Development and Applications of a Zebrafish (Danio rerio) CYP1A-Targeted Monoclonal Antibody (CRC4) with Reactivity across Vertebrate Taxa: Evidence for a Conserved CYP1A Epitope
Toxics 2022, 10(7), 404; https://doi.org/10.3390/toxics10070404 - 20 Jul 2022
Viewed by 957
Abstract
CYP1A is a heme-thiolate enzyme associated with the cytochrome P4501A1 monooxygenase system and is inducible by a wide variety of xenobiotics and endogenous ligands that bind and activate the aryl hydrocarbon receptor (AHR). The AHR-CYP1A axis is important for detoxification of certain xenobiotics [...] Read more.
CYP1A is a heme-thiolate enzyme associated with the cytochrome P4501A1 monooxygenase system and is inducible by a wide variety of xenobiotics and endogenous ligands that bind and activate the aryl hydrocarbon receptor (AHR). The AHR-CYP1A axis is important for detoxification of certain xenobiotics and for homeostatic balance of endogenous sex hormones, amine hormones, vitamins, fatty acids, and phospholipids. Herein, we generated and described applications of a zebrafish CYP1A-targeted monoclonal antibody (mAb CRC4) that fortuitously recognizes induced CYP1A across vertebrate taxa, including fish, chicken, mouse, rat, and human. We then demonstrated that mAb CRC4 targets a highly conserved epitope signature of vertebrate CYP1A. The unique complimentary determining region (CDR) sequences of heavy and light chains were determined, and these Ig sequences will allow for the expression of recombinant mAb CRC4, thus superseding the need for long-term hybridoma maintenance. This antibody works well for immunohistochemistry (IHC), as well as whole-mounted IHC in zebrafish embryos. Monoclonal antibody CRC4 may be particularly useful for studying the AHR-CYP1A axis in multiple vertebrate species and within the context of Oceans and Human Health research. By using archived samples, when possible, we actively promoted efforts to reduce, replace, and refine studies involving live animals. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
Show Figures

Figure 1

Article
Mobilization of Unexploded Ordnance on the Seabed
Toxics 2022, 10(7), 389; https://doi.org/10.3390/toxics10070389 - 13 Jul 2022
Viewed by 1348
Abstract
Unexploded ordnance devices (UXO) pose a potential threat to human life and material during offshore construction activities. Extensive survey activities are conducted to locate, identify, and clear these objects as necessary. For the period thereafter, it is necessary to investigate whether areas that [...] Read more.
Unexploded ordnance devices (UXO) pose a potential threat to human life and material during offshore construction activities. Extensive survey activities are conducted to locate, identify, and clear these objects as necessary. For the period thereafter, it is necessary to investigate whether areas that have already been cleared, or even objects that remain in place, may be affected by mobilization under tidal currents or waves, and could thus have an impact on operation and maintenance during the lifetime of the offshore installation. In this study, model simulations based on fluid mechanics are described to derive the loads on the objects caused by currents and waves and combined with knowledge of the known burial condition of the objects. Within the model, the hydrodynamic and hydrostatic loads on the object caused by waves and currents are balanced with inertia and rolling resistance. Thus, the critical current velocity and critical wave conditions for the mobilization of different objects are calculated and compared with the environmental conditions prevailing in the North Sea. As a result, a recurrence interval for the potential mobilization of objects on the seafloor is given, which can now be used to optimize route surveys and thus help accelerate offshore construction work. It is shown that currents are not able to mobilize the objects investigated in the study in almost all regions of the North Sea. Waves can mobilize certain objects in very shallow and extreme conditions. Full article
Show Figures

Figure 1

Article
Environmental Impact of Pharmaceutical Pollutants: Synergistic Toxicity of Ivermectin and Cypermethrin
Toxics 2022, 10(7), 388; https://doi.org/10.3390/toxics10070388 - 12 Jul 2022
Cited by 1 | Viewed by 1171
Abstract
Veterinary antiparasitic pharmaceuticals as well as pesticides have been detected in surface waters, and they may cause several toxic effects in this environmental compartment. In the present study, we evaluated the toxicity after exposure of different concentration of ivermectin (IVM; 50, 100, and [...] Read more.
Veterinary antiparasitic pharmaceuticals as well as pesticides have been detected in surface waters, and they may cause several toxic effects in this environmental compartment. In the present study, we evaluated the toxicity after exposure of different concentration of ivermectin (IVM; 50, 100, and 200 μg L−1) and cypermethrin (CYP; 5, 10, and 25 μg L−1) and the combination of these two compounds at non-toxic concentration (IVM 100 + CYP 5 μg L−1) in zebrafish embryos. Combination of IVM at 100 μg L−1 with CYP at 5 μg L−1 exposure induced hatching delay and malformations at 96 hpf in zebrafish larvae as well as significant induction of cell death in zebrafish larvae. At the same time, the two single concentrations of IVM and CYP did not show a toxic effect on zebrafish development. In conclusion, our study suggests that IVM and CYP show a synergistic effect at common, ineffective concentrations, promoting malformation and cell death in fish development. Full article
(This article belongs to the Special Issue Zebrafish as a Model for Pharmacological and Toxicological Research)
Show Figures

Figure 1

Article
Environmental and Health Risks Posed by Heavy Metal Contamination of Groundwater in the Sunan Coal Mine, China
Toxics 2022, 10(7), 390; https://doi.org/10.3390/toxics10070390 - 12 Jul 2022
Cited by 3 | Viewed by 754
Abstract
Groundwater is often used for domestic and irrigation purposes, even in mining areas. Mine drainage, rainfall, and infiltration cause heavy metal enrichment, adversely affecting the groundwater and harming human health. In this study, water samples (October 2021) in the Suzhou southern coal mining [...] Read more.
Groundwater is often used for domestic and irrigation purposes, even in mining areas. Mine drainage, rainfall, and infiltration cause heavy metal enrichment, adversely affecting the groundwater and harming human health. In this study, water samples (October 2021) in the Suzhou southern coal mining area were analyzed for the heavy metals As, Cr, Cu, Fe, Mn, Pb, and Zn to determine potential effects of heavy metal contamination on environmental quality and human health. It was found that 22% and 31% of the sampling sites had “excellent” and “good” water quality, respectively. Excessive concentrations of Fe and Mn were detected in 47% and 72% of the samples, respectively. The non-carcinogenic health risk values of As, Cr, Cu, Fe, Mn, Pb, and Zn were below the negligible levels of health risk set by various environmental agencies. Content ranking was as follows: Fe > Mn > Cr > Cu > Pb > Zn > As, with Fe accounting for 43%. All sampling points exceeded the maximum acceptable level of Cr recommended by the agencies. Chromium, the major carcinogenic factor in the study area, contributed to 95.45% of the total health risk. Therefore, the authorities in this region must closely monitor three heavy metal elements—Fe, Mn, and Cr. Full article
(This article belongs to the Section Human Toxicology and Epidemiology)
Show Figures

Figure 1

Article
Assessment of Soil-Heavy Metal Pollution and the Health Risks in a Mining Area from Southern Shaanxi Province, China
Toxics 2022, 10(7), 385; https://doi.org/10.3390/toxics10070385 - 11 Jul 2022
Cited by 3 | Viewed by 952
Abstract
Soil-heavy metal pollution in mining areas is one of the problems in the comprehensive treatment of soil environmental pollution. To explore the degree of soil-heavy metal pollution and the human health risk in mining areas, the contents of soil As, Cd, Cu, Cr, [...] Read more.
Soil-heavy metal pollution in mining areas is one of the problems in the comprehensive treatment of soil environmental pollution. To explore the degree of soil-heavy metal pollution and the human health risk in mining areas, the contents of soil As, Cd, Cu, Cr, Hg, Ni, Pb, and Cr(VI) in an abandoned gold mining area were determined. The geoaccumulation index (Igeo), single-factor pollution index (SPI), Nemerow comprehensive pollution index (NCPI), potential ecological risk index (PERI), and the human health risk assessment model were used to assess the pollution degree and the risk of soil-heavy metal pollution. Finally, the assessment results were used to provide remediation guidance. The results showed that (1) the average contents of As, Cd, Cr, Cu, Hg, and Ni in the mining area exceeded the background values of the soil elements. (2) The mining area was polluted by heavy metals to different degrees and had strong potential ecological hazards. (3) The total carcinogenic risk of heavy metals exceeded the health risk standard. The main components of pollution in the mining area were As, Cd, Cr, and Hg. Results from this study are expected to play a positive role in pollution treatment and the balance between humans and ecology. Full article
(This article belongs to the Special Issue Heavy Metal Contamination in Soil and Health Risks)
Show Figures

Figure 1

Article
In Vitro Assessment of Pesticides Toxicity and Data Correlation with Pesticides Physicochemical Properties for Prediction of Toxicity in Gastrointestinal and Skin Contact Exposure
Toxics 2022, 10(7), 378; https://doi.org/10.3390/toxics10070378 - 08 Jul 2022
Cited by 2 | Viewed by 971
Abstract
In this work, three pesticides of different physicochemical properties, namely, glyphosate (herbicide), imidacloprid (insecticide) and imazalil (fungicide), were selected to assess their cytotoxicity against distinct cell models (Caco-2, HepG2, A431, HaCaT, SK-MEL-5 and RAW 264.7 cells) to mimic gastrointestinal and skin exposure with [...] Read more.
In this work, three pesticides of different physicochemical properties, namely, glyphosate (herbicide), imidacloprid (insecticide) and imazalil (fungicide), were selected to assess their cytotoxicity against distinct cell models (Caco-2, HepG2, A431, HaCaT, SK-MEL-5 and RAW 264.7 cells) to mimic gastrointestinal and skin exposure with potential systemic effect. Cells were subjected to different concentrations of selected pesticides for 24 h or 48 h. Cell viability was assessed by Alamar Blue assay, morphological changes by bright-field microscopy and the IC50 values were calculated. Cytotoxic profiles were analysed using the physico-chemical parameters of the pesticides, namely: molecular weight, water solubility, the partition coefficient in the n-octanol/water (Log Pow) system, the topological polar surface area (TPSA), and number of hydrogen-bonds (donor/acceptor) and rotatable bonds. Results showed that glyphosate did not reduce cell viability (up to 1 mM), imidacloprid induced moderate toxicity (IC50 > 1 mM for Caco-2 cells while IC50 = 305.9 ± 22.4 μM for RAW 264.7 cells) and imazalil was highly cytotoxic (IC50 > 253.5 ± 3.37 for Caco-2 cells while IC50 = 31.3 ± 2.7 μM for RAW 264.7 cells) after 24 h exposure. Toxicity was time-dependent as IC50 values at 48 h exposure were lower, and decrease in cell viability was accompanied by changes in cell morphology. Pesticides toxicity was found to be directly proportional with their Log Pow, indicating that the affinity to a lipophilic environment such as the cell membranes governs their toxicity. Toxicity is inverse to pesticides TPSA, but lower TPSA favours membrane permeation. The lower toxicity against Caco-2 cells was attributed to the physiology and metabolism of cell barriers equipped with various ABC transporters. In conclusion, physicochemical factors such as Log Pow, TPSA and H-bond are likely to be directly correlated with pesticide-induced toxicity, thus being key factors to potentially predict the toxicity of other compounds. Full article
(This article belongs to the Section Toxicology)
Show Figures

Figure 1

Article
Application of an Ecotoxicological Battery Test to the Paddy Field Soils of the Albufera Natural Park
Toxics 2022, 10(7), 375; https://doi.org/10.3390/toxics10070375 - 05 Jul 2022
Viewed by 697
Abstract
Albufera Natural Park (ANP) (Valencia, Spain) is one of the most important wetland areas of the Mediterranean coast subject to high anthropogenic pressure, on whose soils a battery of bioassays has never been applied to evaluate the ecotoxicological risk. The present study determined [...] Read more.
Albufera Natural Park (ANP) (Valencia, Spain) is one of the most important wetland areas of the Mediterranean coast subject to high anthropogenic pressure, on whose soils a battery of bioassays has never been applied to evaluate the ecotoxicological risk. The present study determined available and water-soluble heavy metal content in four paddy soils used in the ANP, and the ecotoxicological effect on these soils was evaluated by performing the bioassays regulated in Spanish Royal Decree 9/2005. Soil properties and extractable Co, Cr, Cu, Ni, Pb and Zn (EDTA pH = 7) were analyzed in soils. These elements and macro- and micronutrients were also assessed in soil leachate. A test battery covering the following was needed: acute toxicity test in Eisenia foetida (OECD TG 207); mineralization tests of nitrogen (OECD TG 2016) and carbon (OECD TG 217); growth inhibition test in Raphidocelis subcapitata (OECD TG 201); mobility inhibition test in Daphnia magna (OECD TG 202). The soils found in the most anthropized areas to the north of the ANP (Massanassa and Alfafar) demonstrated a higher concentration of available heavy metals than in the southern ones (Sueca and Sollana). The aqueous leachate of the studied soils contained very low concentrations, which would be related to soil properties. Despite the high concentration of available potentially toxic elements (PTEs) in the Massanassa and Alfafar soils, the studied soils showed no toxicity during the performed battery bioassays. Therefore, soils can be considered non-toxic despite the obtained PTEs available concentration. Full article
(This article belongs to the Special Issue Toxicity and Bioaccumulation of Contaminants in Soil and Wastewater)
Show Figures

Figure 1

Article
Dietary Perfluorohexanoic Acid (PFHxA) Exposures in Juvenile Zebrafish Produce Subtle Behavioral Effects across Generations
Toxics 2022, 10(7), 372; https://doi.org/10.3390/toxics10070372 - 04 Jul 2022
Viewed by 1034
Abstract
Ubiquitous anthropogenic contaminants of concern, per- and polyfluoroalkyl substances (PFAS) are frequently detected in the environment and human populations around the world. Diet is a predominate route of human exposure, and PFAS are frequently measured in food. Manufacturing trends have shifted from legacy [...] Read more.
Ubiquitous anthropogenic contaminants of concern, per- and polyfluoroalkyl substances (PFAS) are frequently detected in the environment and human populations around the world. Diet is a predominate route of human exposure, and PFAS are frequently measured in food. Manufacturing trends have shifted from legacy PFAS to shorter-chain alternatives that are suggested to be safer, such as perfluorohexanoic acid (PFHxA). However, the current amount of data to support safety assessments of these alternatives is not yet sufficient. The present study investigated the effects of a 42-day dietary exposure to 1, 10, or 100 ng/g PFHxA in juvenile zebrafish. The zebrafish model was leveraged to interrogate morphometrics, fecundity, and numerous behavior endpoints across multiple generations. Dietary PFHxA exposure did not result in measurable body burden and did not affect growth, fecundity, adult social perception behavior, or associative learning. PFHxA exposure did induce abnormal adult anxiety behaviors in the F0 generation that persisted transgenerationally in the F1 and F2. Abnormal larval and juvenile behavior was observed in the F1 generation, but not in the F2. PFHxA juvenile dietary exposure induced subtle and multigenerational behavior effects that warrant further investigation of this and other alternative short-chain PFAS. Full article
Show Figures

Graphical abstract

Article
Ecological Integrity Impairment and Habitat Fragmentation for Neotropical Macroinvertebrate Communities in an Agricultural Stream
Toxics 2022, 10(7), 346; https://doi.org/10.3390/toxics10070346 - 22 Jun 2022
Cited by 1 | Viewed by 977
Abstract
The Volcán River watershed in the south Pacific of Costa Rica comprises forests, small urban settlements, cattle fields, and intensive agriculture (mostly pineapple and sugarcane). The ecological integrity and quality of its waters was assessed from 2011–2013 and 2018–2019 by means of physical–chemical [...] Read more.
The Volcán River watershed in the south Pacific of Costa Rica comprises forests, small urban settlements, cattle fields, and intensive agriculture (mostly pineapple and sugarcane). The ecological integrity and quality of its waters was assessed from 2011–2013 and 2018–2019 by means of physical–chemical parameters (pH, conductivity, temperature, DO, DBO, nitrate, total phosphorus, and pesticide residues) and benthic macroinvertebrate (MI) sampling in eight sites (Volcán, Cañas, and Ángel Rivers, and Peje and Maura streams), resulting in high ecological integrity in all sites except the Peje stream, which is polluted with nitrates and pesticides. Only in this stream was there a marked seasonal variation in the abundance of 16 MI families including Leptohyphidae, Leptophlebiidae, Philopotamidae, Glossossomatidae, and Corydalidae, among others, whose presence was limited exclusively to the dry season (December to April), disappearing from the stream in the rainy season, with corresponding peaks in nitrate (max 20.3 mg/L) and pesticides (mainly herbicides and organophosphate insecticides). The characteristics of the watershed, with large areas of forest and excellent water quality, allow for the re-colonization of organisms into the Peje stream; however, those organisms are incapable of development and growth, providing evidence of a contaminant-driven habitat fragmentation in this stream during the rainy season. Full article
Show Figures

Figure 1

Article
Pharmacokinetics and the Dermal Absorption of Bromochlorophene, a Cosmetic Preservative Ingredient, in Rats
Toxics 2022, 10(6), 329; https://doi.org/10.3390/toxics10060329 - 16 Jun 2022
Cited by 2 | Viewed by 1089
Abstract
The cosmetic industry has flourished in recent years. Accordingly, the safety of cosmetic ingredients is increasing. Bromochlorophene (BCP) is a commonly used cosmetic preservative. To evaluate the effects of BCP exposure, in vitro dermal absorption and in vivo pharmacokinetic (PK) studies were conducted [...] Read more.
The cosmetic industry has flourished in recent years. Accordingly, the safety of cosmetic ingredients is increasing. Bromochlorophene (BCP) is a commonly used cosmetic preservative. To evaluate the effects of BCP exposure, in vitro dermal absorption and in vivo pharmacokinetic (PK) studies were conducted using gel and cream formulations. The Franz diffusion cell system and rat dorsal skin were used for tests according to the Korea Ministry of Food and Drug Safety guidelines for in vitro skin absorption methods. After the dermal application (1.13 mg/cm2) of BCP in the gel and cream formulations, liquid chromatography–mass spectrometry (LC–MS/MS) was used to evaluate the amount of BCP that remained unabsorbed on the skin (WASH), and that was present in the receptor fluid (RF), stratum corneum (SC), and (epi)dermis (SKIN). The total dermal absorption rate of BCP was 7.42 ± 0.74% for the gel formulation and 1.5 ± 0.9% for the cream formulation. Total recovery in an in vitro dermal absorption study was 109.12 ± 8.79% and 105.43 ± 11.07% for the gel and cream formulations, respectively. In vivo PK and dermal absorption studies of BCP were performed following the Organization for Economic Cooperation and Development guidelines 417 and 427, respectively. When intravenous (i.v.) pharmacokinetics was performed, BCP was dissolved in glycerol formal and injected into the tail vein (n = 3) of the rats at doses of 1 and 0.2 mg/kg. Dermal PK parameters were estimated by the application of the gel and cream formulations (2.34 mg/kg of BCP as an active ingredient) to the dorsal skin of the rats. Intravenous and dermal PK parameters were analyzed using a non-compartmental method. The dermal bioavailability of BCP was determined as 12.20 ± 2.63% and 4.65 ± 0.60% for the gel and cream formulations, respectively. The representative dermal absorption of BCP was evaluated to be 12.20 ± 2.63% based on the results of the in vivo PK study. Full article
(This article belongs to the Special Issue Toxicokinetics of Chemicals in Consumer Products)
Show Figures

Figure 1

Article
“It’s Like Jogging Next to the Highway”: A Qualitative Analysis of the Motivations and Experiences of Single-, Dual-, and Ex-Users of IQOS in The Netherlands
Toxics 2022, 10(6), 283; https://doi.org/10.3390/toxics10060283 - 26 May 2022
Viewed by 1741
Abstract
The popularity of heated tobacco products (HTPs) is of concern, as most users are dual users exposed to emissions of both HTPs and conventional cigarettes. Furthermore, HTPs may appeal to young people and non-smokers. This study aims to build intelligence on user experiences [...] Read more.
The popularity of heated tobacco products (HTPs) is of concern, as most users are dual users exposed to emissions of both HTPs and conventional cigarettes. Furthermore, HTPs may appeal to young people and non-smokers. This study aims to build intelligence on user experiences in order to inform policy development. We conducted five semi-structured focus group interviews with single-, dual-, and ex-users of the HTP IQOS. The discussions focused on initiation and use, experiences and perception, and knowledge and information needs. We performed a thematic analysis of the transcripts. All users smoked cigarettes and/or roll your own (RYO) tobacco before using HTP. We found that almost all users started using IQOS after being introduced to it by others. Single users successfully quit smoking cigarettes using the IQOS, liked the taste, and experienced physical benefits. Dual users experienced more satisfaction from smoking cigarettes and used the IQOS for specific occasions, such as social situations or in places with smoking bans. All IQOS users described themselves as smokers and considered using the IQOS as an alternative way of smoking. Regulators may consider providing reliable and easily accessible information and regulating points of sale, promotional activities, and product properties such as flavors and devices in order to reduce product attractiveness and discourage use. Full article
(This article belongs to the Special Issue Assessing Novel Tobacco Products)
Article
Development of a 96-Well Electrophilic Allergen Screening Assay for Skin Sensitization Using a Measurement Science Approach
Toxics 2022, 10(5), 257; https://doi.org/10.3390/toxics10050257 - 17 May 2022
Cited by 2 | Viewed by 2798
Abstract
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 [...] Read more.
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
(This article belongs to the Section Toxicology)
Show Figures

Graphical abstract

Back to TopTop