Toxics

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5 pages, 224 KiB

Open AccessEditorial

The 10th Anniversary of Toxics: Recent Advances in Toxicology Research

by Demetrio Raldúa and Xiaojun Luo

Toxics 2024, 12(8), 538; https://doi.org/10.3390/toxics12080538 - 26 Jul 2024

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Abstract

Last year (2023) was the tenth anniversary of Toxics [...] Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

Research

Jump to: Editorial, Review

15 pages, 329 KiB

Open AccessArticle

First Report of the Joint Exposure to Glyphosate and Glufosinate of a Male Population in the Province of Córdoba (Argentina)

by Iohanna Filippi, Rocío I. Bonansea, Mariana Butinof, Ricardo A. Fernández, Marta Llorca, Marinella Farré, Sonia E. Muñoz and María V. Amé

Toxics 2023, 11(12), 1020; https://doi.org/10.3390/toxics11121020 - 14 Dec 2023

Cited by 2 | Viewed by 1428

Abstract

Despite potential health implications, data on the presence of Glyphosate (GLY) and other non-GLY herbicides in human matrices remain scarce. This study aimed to develop a simple and cost-effective methodology for detecting and quantifying GLY, its primary biodegradation product; aminomethylphosphonic acid (AMPA); and [...] Read more.

Despite potential health implications, data on the presence of Glyphosate (GLY) and other non-GLY herbicides in human matrices remain scarce. This study aimed to develop a simple and cost-effective methodology for detecting and quantifying GLY, its primary biodegradation product; aminomethylphosphonic acid (AMPA); and glufosinate (GLU) in plasma and urine of environmentally and occupationally exposed populations from the province of Córdoba (Argentina). Different alternatives of pre-treatment, derivatization with FMOC-Cl, solid phase extraction, and final sample conditioning steps were evaluated to improve the quantification of the herbicides by a high-performance liquid chromatography system coupled to a triple-quadrupole mass spectrometer. Recoveries ranged from 39 to 84% in both matrices, while limits of quantification were 3, 1, and 0.3 ng/mL and 3.6, 5.1, and 0.3 ng/mL for AMPA, GLY, and GLU in plasma and urine, respectively. In plasma samples, GLY was the most frequently detected analyte (32%), followed by GLU (10%). In urine samples, GLU was the most frequently detected herbicide (13%), followed by GLY (6%). No differences between group or matrix correlations were found. This study is the first report of GLU in human biological matrices and should be used to establish baseline values for future surveillance systems. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

16 pages, 1917 KiB

Open AccessArticle

Titanium Dioxide (TiO₂) Nanoparticle Toxicity in a Caenorhabditis elegans Model

by Sen-Ting Huang, Jian-He Lu, Sherwin M. Jualo, Lemmuel L. Tayo, Wan-Nurdiyana-Wan Mansor, Yi-Chieh Lai, Chih-Lung Wang and How-Ran Chao

Toxics 2023, 11(12), 989; https://doi.org/10.3390/toxics11120989 - 5 Dec 2023

Cited by 1 | Viewed by 1718

Abstract

Titanium dioxide is a compound that is used in the food, cosmetic, and paint industries; however, it is still toxic to humans and the environment. This study determined the toxicities of titanium dioxide nanoparticles (TiO₂ NPs) in a Caenorhabditis elegans (C. [...] Read more.

Titanium dioxide is a compound that is used in the food, cosmetic, and paint industries; however, it is still toxic to humans and the environment. This study determined the toxicities of titanium dioxide nanoparticles (TiO₂ NPs) in a Caenorhabditis elegans (C. elegans) model. The effects of commercially available (C-TiO₂) and synthetically (S-TiO₂) prepared TiO₂ NP solutions on lethality, lifespan, growth, reproduction, locomotion, and gene expression were studied in C. elegans. Exposure to TiO₂ NPs (0.0, 0.01, 0.1, 1.0, and 10 mg/L) did not result in any change to the survival rate or body length of the nematodes, regardless of the concentration. However, there was a decrease in the reproduction (brood size) and locomotion (body bending and head thrashing) of the nematodes as the TiO₂ NP concentration increased. The longevity of the nematodes was shortened following TiO₂ NP exposure. The gene expression of sod-1, sod-3, ctl-1, ctl-2, cyp35A2, mlt-1, and mlt-2 in the nematodes showed that there was an overexpression of all genes when the worms were exposed to 1 mg/L C-TiO₂ or 10 mg/L S-TiO₂. It was therefore concluded that compared with S-TiO₂, C-TiO₂ possibly causes more toxicity or genotoxicity in the C. elegans model. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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10 pages, 1200 KiB

Open AccessEditor’s ChoiceArticle

Per- and Polyfluoroalkyl Substances (PFAS) in Community Water Systems (CWS) and the Risk of Thyroid Cancer: An Ecological Study

by Mathilda Alsen, Angela M. Leung and Maaike van Gerwen

Toxics 2023, 11(9), 786; https://doi.org/10.3390/toxics11090786 - 16 Sep 2023

Cited by 5 | Viewed by 2339

Abstract

Thyroid cancer incidence has been steadily increasing over the past decade in the United States (US). A discussion exists regarding the potential contribution of exposure to endocrine-disrupting chemicals, encompassing certain per- and poly-fluoroalkyl substances (PFASs). This ecological study evaluated the potential correlation between [...] Read more.

Thyroid cancer incidence has been steadily increasing over the past decade in the United States (US). A discussion exists regarding the potential contribution of exposure to endocrine-disrupting chemicals, encompassing certain per- and poly-fluoroalkyl substances (PFASs). This ecological study evaluated the potential correlation between PFAS levels in drinking water and thyroid cancer incidence in the US. Data on age-adjusted thyroid cancer incidence rate (per 100,000 persons) by county were obtained from the Centers for Disease Control and Prevention (CDC) for US counties with available data in 2015–2019. Data on PFAS concentrations in the drinking water of selected community water systems (CWSs) were obtained from the CDC National Environmental Public Health Tracking Network in 2013–2015. The correlation between PFASs in CWSs and thyroid cancer incidence was calculated using Spearman correlation. A statistically significant correlation was found between perfluorooctanoic acid (PFOA) (r = 0.031; p = 0.043), perfluorononanoic acid (PFNA) (r = 0.058; p ≤ 0.001), and thyroid cancer incidence. The results suggest a potential link between certain PFAS exposures and thyroid cancer risk. However, due to the nature of an ecological study, no conclusions can be drawn at the individual level or causality. More research is needed, particularly on an individual level to allow for more detailed exposure assessment. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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20 pages, 2952 KiB

Open AccessArticle

Differential Susceptibility to Benzo[a]pyrene Exposure during Gestation and Lactation in Mice with Genetic Variations in the Aryl Hydrocarbon Receptor and Cyp1 Genes

by Mackenzie Feltner, Patrick M. Hare, Asia Good, Emma G. Foster, Katelyn Clough, Jade Perry, Amanda Honaker, Angela Kyntchev, Mickayla Kowalski and Christine Perdan Curran

Toxics 2023, 11(9), 778; https://doi.org/10.3390/toxics11090778 - 13 Sep 2023

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Abstract

Polycyclic aromatic hydrocarbons are ubiquitous air pollutants, with additional widespread exposure in the diet. PAH exposure has been linked to adverse birth outcomes and long-term neurological consequences. To understand genetic differences that could affect susceptibility following developmental exposure to polycyclic aromatic hydrocarbons, we [...] Read more.

Polycyclic aromatic hydrocarbons are ubiquitous air pollutants, with additional widespread exposure in the diet. PAH exposure has been linked to adverse birth outcomes and long-term neurological consequences. To understand genetic differences that could affect susceptibility following developmental exposure to polycyclic aromatic hydrocarbons, we exposed mice with variations in the aryl hydrocarbon receptor and the three CYP1 enzymes from gestational day 10 (G10) to weaning at postnatal day 25 (P25). We found unexpectedly high neonatal lethality in high-affinity Ahr^bCyp1b1(-/-) knockout mice compared with all other genotypes. Over 60% of BaP-exposed pups died within their first 5 days of life. There was a significant effect of BaP on growth rates in surviving pups, with lower weights observed from P7 to P21. Again, Ahr^bCyp1b1(-/-) knockout mice were the most susceptible to growth retardation. Independent of treatment, this line of mice also had impaired development of the surface righting reflex. We used high-resolution mass spectrometry to measure BaP and metabolites in tissues from both dams and pups. We found the highest BaP levels in adipose from poor-affinity Ahr^dCyp1a2(-/-) dams and identified three major BaP metabolites (BaP-7-OH, BaP-9-OH, and BaP-4,5-diol), but our measurements were limited to a single time point. Future work is needed to understand BaP pharmacokinetics in the contexts of gestation and lactation and how differential metabolism leads to adverse developmental outcomes. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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12 pages, 5893 KiB

Open AccessArticle

Third-Hand Exposure to E-Cigarette Vapour Induces Pulmonary Effects in Mice

by Andrew E. Thorpe, Chantal Donovan, Richard Y. Kim, Howard J. Vindin, Razia Zakarya, Hanna Miyai, Yik L. Chan, David van Reyk, Hui Chen and Brian G. Oliver

Toxics 2023, 11(9), 749; https://doi.org/10.3390/toxics11090749 - 4 Sep 2023

Cited by 3 | Viewed by 5792

Abstract

In the last decade, e-cigarette usage has increased, with an estimated 82 million e-cigarette users globally. This is, in part, due to the common opinion that they are “healthier” than tobacco cigarettes or simply “water vapour”. Third-hand e-vapour exposure is the chemical residue [...] Read more.

In the last decade, e-cigarette usage has increased, with an estimated 82 million e-cigarette users globally. This is, in part, due to the common opinion that they are “healthier” than tobacco cigarettes or simply “water vapour”. Third-hand e-vapour exposure is the chemical residue left behind from e-cigarette aerosols, which is of concern due to its invisible nature, especially among young children. However, there is limited information surrounding third-hand e-vapour exposure. This study aimed to investigate the pulmonary effects of sub-chronic third-hand e-vapour exposure in a murine model. BALB/c mice (4 weeks of age) were exposed to a towel containing nicotine free (0 mg) e-vapour, nicotine (18 mg) e-vapour, or no e-vapour (sham) and replaced daily for 4 weeks. At the endpoint, lung function was assessed, and bronchoalveolar lavage fluid and lungs were collected to measure inflammation and fibrosis. Mice exposed to third-hand e-vapour without nicotine had alveolar enlargement compared to sham exposed controls. Mice exposed to third-hand e-vapour with nicotine had reduced bronchial responsiveness to provocation, increased epithelial thickening in large airways, increased epithelial layers in small airways, alveolar enlargement, and increased small airway collagen deposition, compared to sham exposed controls. In conclusion, our study shows that third-hand e-vapour exposure, particularly in the presence of nicotine, negatively affects the lung health of mice and highlights the need for greater public awareness surrounding the dangers of third-hand exposure to e-cigarette vapour. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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20 pages, 2994 KiB

Open AccessArticle

Association of Per- and Polyfluoroalkyl Substances with Allostatic Load Stratified by Herpes Simplex Virus 1 and 2 Exposure

by Yvonne S. Boafo, Sayed Mostafa and Emmanuel Obeng-Gyasi

Toxics 2023, 11(9), 745; https://doi.org/10.3390/toxics11090745 - 1 Sep 2023

Cited by 3 | Viewed by 2101

Abstract

Herpes Simplex Virus (HSV) 1 and 2 are persistent infections that affect a significant percentage of United States (US) adults, with 48% having HSV-1 and 12% having HSV-2. Using data stratified by HSV-1 and HSV-2 exposures, this study investigated the association of per- [...] Read more.

Herpes Simplex Virus (HSV) 1 and 2 are persistent infections that affect a significant percentage of United States (US) adults, with 48% having HSV-1 and 12% having HSV-2. Using data stratified by HSV-1 and HSV-2 exposures, this study investigated the association of per- and polyfluoroalkyl substances (PFAS), a group of toxic synthetic organofluorine chemical compounds found in environmental, occupational, and home settings, with allostatic load (AL), an index of chronic physiological stress. Descriptive statistics, multivariable logistic regression, and Bayesian Kernel Machine Regression (BKMR) modeling were used to assess the effects of multi-PFAS exposures on AL using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2014. Results indicated participants not exposed to PFAS exhibited 77% to 97% lower odds of higher AL (p < 0.001). For example, PFOS per unit increase brought forth a 2% odds increase in higher AL (OR: 1.02; 95% CI: 1.00, 1.05; p < 0.05). Participants exposed to PFAS had reduced odds of higher AL (77%–79%), regardless of their HSV-1 and HSV-2 status. PFAS exposure was more prevalent in those with HSV-1 (60%) than in those with HSV-2 (20%) infection, while AL levels were comparable in both groups (17%). BKMR revealed a nonlinear PFAS-AL association and confirmed interactions among PFAS. In summary, PFAS exposure increased the likelihood of higher AL among those with persistent HSV infections. Our study enhances the current understanding of the complex dynamics involving PFAS, persistent infections, and AL, which hold significant implications for public health and clinical intervention strategies. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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16 pages, 6644 KiB

Open AccessArticle

Internal Defense System of Mytilus galloprovincialis (Lamarck, 1819): Ecological Role of Hemocytes as Biomarkers for Thiacloprid and Benzo[a]Pyrene Pollution

by Alessio Alesci, Davide Di Paola, Angelo Fumia, Sebastian Marino, Claudio D’Iglio, Sergio Famulari, Marco Albano, Nunziacarla Spanò and Eugenia Rita Lauriano

Toxics 2023, 11(9), 731; https://doi.org/10.3390/toxics11090731 - 25 Aug 2023

Cited by 4 | Viewed by 1525

Abstract

The introduction of pollutants, such as thiacloprid and benzo[a]pyrene (B[a]P), into the waters of urbanized coastal and estuarine areas through fossil fuel spills, domestic and industrial waste discharges, atmospheric inputs, and continental runoff poses a major threat to the fauna and flora of [...] Read more.

The introduction of pollutants, such as thiacloprid and benzo[a]pyrene (B[a]P), into the waters of urbanized coastal and estuarine areas through fossil fuel spills, domestic and industrial waste discharges, atmospheric inputs, and continental runoff poses a major threat to the fauna and flora of the aquatic environment and can have a significant impact on the internal defense system of invertebrates such as mussels. Using monoclonal and polyclonal anti-Toll-like receptor 2 (TLR2) and anti-inducible nitric oxide synthetase (iNOS) antibodies for the first time, this work aims to examine hemocytes in the mantle and gills of M. galloprovincialis as biomarkers of thiacloprid and B[a]P pollution and analyze their potential synergistic effect. To pursue this objective, samples were exposed to the pollutants, both individually and simultaneously. Subsequently, oxidative stress biomarkers were evaluated by enzymatic analysis, while tissue changes and the number of hemocytes in the different contaminated groups were assessed via histomorphological and immunohistochemical analyses. Our findings revealed that in comparison to a single exposure, the two pollutants together significantly elevated oxidative stress. Moreover, our data may potentially enhance knowledge on how TLR2 and iNOS work as part of the internal defense system of bivalves. This would help in creating new technologies and strategies, such as biosensors, that are more suitable for managing water pollution, and garnering new details on the condition of the marine ecosystem. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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13 pages, 2270 KiB

Open AccessArticle

Modeling the Greenhouse Gases Data Series in Europe during 1990–2021

by Alina Bărbulescu

Toxics 2023, 11(9), 726; https://doi.org/10.3390/toxics11090726 - 24 Aug 2023

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Abstract

Nowadays, climate change and atmospheric pollution are two of humanity's most significant challenges. Greenhouse gases (GHGs) are responsible for climate change, and they create effects that are mostly irreversible. Therefore, monitoring and reducing such emissions are compulsory for the preservation of the environment [...] Read more.

Nowadays, climate change and atmospheric pollution are two of humanity's most significant challenges. Greenhouse gases (GHGs) are responsible for climate change, and they create effects that are mostly irreversible. Therefore, monitoring and reducing such emissions are compulsory for the preservation of the environment for future generations. The European Union took action in this direction. The article presents the evolution of the total GHGs trend, from 1990 to 2021, in the EU countries and their associates. Trend analysis and grouping of the countries using different clustering techniques are performed. The analysis of the existence of greenhouse gases (GHGs) series’ trend, in 30 countries from Europe, showed that the GHG emissions decreased from 1990 to 2021 in only 17 countries. The annual series, built using the data reported by each country each year, does not present a specific trend. After grouping the countries in clusters by k-means and hierarchical clustering, the representative series for the annual recorded values in the 30 studied countries, called Regional series (RegS), is built using series selected from the cluster with the highest number of elements. The same algorithm provides the Representative Temporal series (TempS), which selects specific years after clustering the annual GHG series. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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18 pages, 2244 KiB

Open AccessArticle

Investigation of Metal Toxicity on Microalgae Phaeodactylum tricornutum, Hipersaline Zooplankter Artemia salina, and Jellyfish Aurelia aurita

by Borja Mercado, Nuria Valero, Luis Roca-Pérez, Elena Bernabeu-Berni and Oscar Andreu-Sánchez

Toxics 2023, 11(8), 716; https://doi.org/10.3390/toxics11080716 - 20 Aug 2023

Cited by 4 | Viewed by 1889

Abstract

The escalating global anthropogenic activities associated with industrial development have led to the increased introduction of heavy metals (HMs) into marine environments through effluents. This study aimed to assess the toxicity of three HMs (Cr, Cu, and Cd) on organisms spanning different trophic [...] Read more.

The escalating global anthropogenic activities associated with industrial development have led to the increased introduction of heavy metals (HMs) into marine environments through effluents. This study aimed to assess the toxicity of three HMs (Cr, Cu, and Cd) on organisms spanning different trophic levels: Phaeodactylum tricornutum (a primary producer), Artemia salina (a primary consumer), and Aurelia aurita (a secondary consumer). The EC₅₀ values obtained revealed varying relative toxicities for the tested organisms. Phaeodactylum tricornutum exhibited the highest sensitivity to Cu, followed by Cd and Cr, while Artemia salina displayed the highest sensitivity to Cr, followed by Cu and Cd. A. aurita, on the other hand, demonstrated the highest sensitivity to Cu, followed by Cr and Cd. This experimental investigation further supported previous studies that have suggested A. aurita as a suitable model organism for ecotoxicity testing. Our experiments encompassed sublethal endpoints, such as pulsation frequency, acute effects, and mortality, highlighting different levels of sensitivity among the organisms. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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14 pages, 1464 KiB

Open AccessArticle

Metal Levels in Delaware Bay Horseshoe Crab Eggs from the Surface Reflect Metals in Egg Clutches Laid beneath the Sand

by Joanna Burger

Toxics 2023, 11(7), 614; https://doi.org/10.3390/toxics11070614 - 14 Jul 2023

Cited by 3 | Viewed by 1488

Abstract

Understanding variations in metal levels in biota geographically and under different environmental conditions is essential to determining risk to organisms themselves and to their predators. It is often difficult to determine food chain relationships because predators may eat several different prey types. Horseshoe [...] Read more.

Understanding variations in metal levels in biota geographically and under different environmental conditions is essential to determining risk to organisms themselves and to their predators. It is often difficult to determine food chain relationships because predators may eat several different prey types. Horseshoe crab (Limulus polyphemus) eggs form the basis for a complex food web in Delaware Bay, New Jersey, USA. Female horseshoe crabs lay thumb-sized clutches of eggs, several cm below the surface, and often dislodge previously laid eggs that are brought to the surface by wave action, where they are accessible and critical food for migrant shorebirds. This paper compares metal and metalloid (chromium [Cr], cadmium [Cd], lead [Pb], mercury [Hg], arsenic [As] and selenium [Se]) concentrations in horseshoe crab eggs collected on the surface with concentrations in eggs from clutches excavated from below the sand surface, as well as examining metals in eggs from different parts of the Bay. The eggs were all collected in May 2019, corresponding to the presence of the four main species of shorebirds migrating through Delaware Bay. These migrating birds eat almost entirely horseshoe crab eggs during their stopover in Delaware Bay, and there are differences in the levels of metals in blood of different shorebirds. These differences could be due to whether they have access to egg clutches below sand (ruddy turnstones, Arenaria interpres) or only to eggs on the surface (the threatened red knot [Calidris canutus rufa] and other species of shorebirds). Correlations between metals in clutches were also examined. Except for As and Cd, there were no significant differences between the metals in crab egg clutches and eggs on the surface that shorebirds, gulls, and other predators eat. There were significant locational differences in metal levels in horseshoe crab eggs (except for Pb), with most metals being highest in the sites on the lower portion of Delaware Bay. Most metals in crab eggs have declined since studies were conducted in the mid-1990s but were similar to levels in horseshoe crab eggs in 2012. The data continue to provide important monitoring and assessment information for a keystone species in an ecosystem that supports many species, including threatened and declining shorebird species during spring migration. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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19 pages, 4306 KiB

Open AccessArticle

Polychlorinated Biphenyls (PCBs) Impact Prostatic Collagen Density and Bladder Volume in Young Adult Mice Exposed during in Utero and Lactational Development

by Audrey Spiegelhoff, Kathy Wang, Monica Ridlon, Thomas Lavery, Conner L. Kennedy, Serena George and Kimberly P. Keil Stietz

Toxics 2023, 11(7), 609; https://doi.org/10.3390/toxics11070609 - 13 Jul 2023

Cited by 1 | Viewed by 1513

Abstract

Polychlorinated biphenyls (PCBs) are persistent organic pollutants linked to deleterious health outcomes, including voiding dysfunction in developmentally exposed mice. Changes in prostate volume and/or extracellular matrix composition are associated with voiding dysfunction in men and animal models. Whether PCB-induced changes in voiding function [...] Read more.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants linked to deleterious health outcomes, including voiding dysfunction in developmentally exposed mice. Changes in prostate volume and/or extracellular matrix composition are associated with voiding dysfunction in men and animal models. Whether PCB-induced changes in voiding function in male mice occur in part via alterations to the prostate or an alternate mechanism is unclear. Therefore, we tested whether developmental exposure to the MARBLES PCB mixture altered prostate morphology in young adult offspring. C57Bl/6J female mice were dosed daily with the MARBLES PCB mixture at 0, 0.1, 1 or 6 mg/kg/d for two weeks prior to mating and through gestation and lactation, offspring were collected at 6 weeks of age. Ventral prostate mass was decreased in the 1 mg/kg/d PCB group compared to other PCB groups. There were no PCB-induced changes in prostate smooth muscle thickness, apoptosis, proliferation, or testes mass. PCBs impacted the prostate extracellular matrix; anterior prostate collagen density was decreased in the 1 mg/kg/d PCB group compared to all other groups. Normalized bladder volume was increased in male and female offspring in the 6 mg/kg/d PCB group compared to control. No change in water consumption, bladder mass or bladder smooth muscle thickness accompanied changes in bladder volume. Urine and serum creatinine concentrations were elevated but only in male mice. Together, these results suggest that developmental exposure to PCBs can influence prostate wet weight and prostate/bladder morphology, but PCBs do not promote prostate enlargement. Whether these changes persist throughout adult life and how they contribute to voiding function in animal models and humans is of future interest. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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28 pages, 3597 KiB

Open AccessEditor’s ChoiceArticle

Predicting Dose-Dependent Carcinogenicity of Chemical Mixtures Using a Novel Hybrid Neural Network Framework and Mathematical Approach

by Sarita Limbu and Sivanesan Dakshanamurthy

Toxics 2023, 11(7), 605; https://doi.org/10.3390/toxics11070605 - 12 Jul 2023

Cited by 3 | Viewed by 1680

Abstract

This study addresses the challenge of assessing the carcinogenic potential of hazardous chemical mixtures, such as per- and polyfluorinated substances (PFASs), which are known to contribute significantly to cancer development. Here, we propose a novel framework called HNN_MixCancer that utilizes a hybrid [...] Read more.

This study addresses the challenge of assessing the carcinogenic potential of hazardous chemical mixtures, such as per- and polyfluorinated substances (PFASs), which are known to contribute significantly to cancer development. Here, we propose a novel framework called HNN_MixCancer that utilizes a hybrid neural network (HNN) integrated into a machine-learning framework. This framework incorporates a mathematical model to simulate chemical mixtures, enabling the creation of classification models for binary (carcinogenic or noncarcinogenic) and multiclass classification (categorical carcinogenicity) and regression (carcinogenic potency). Through extensive experimentation, we demonstrate that our HNN model outperforms other methodologies, including random forest, bootstrap aggregating, adaptive boosting, support vector regressor, gradient boosting, kernel ridge, decision tree with AdaBoost, and KNeighbors, achieving a superior accuracy of 92.7% in binary classification. To address the limited availability of experimental data and enrich the training data, we generate an assumption-based virtual library of chemical mixtures using a known carcinogenic and noncarcinogenic single chemical for all the classification models. Remarkably, in this case, all methods achieve accuracies exceeding 98% for binary classification. In external validation tests, our HNN method achieves the highest accuracy of 80.5%. Furthermore, in multiclass classification, the HNN demonstrates an overall accuracy of 96.3%, outperforming RF, Bagging, and AdaBoost, which achieved 91.4%, 91.7%, and 80.2%, respectively. In regression models, HNN, RF, SVR, GB, KR, DT with AdaBoost, and KN achieved average R² values of 0.96, 0.90, 0.77, 0.94, 0.96, 0.96, and 0.97, respectively, showcasing their effectiveness in predicting the concentration at which a chemical mixture becomes carcinogenic. Our method exhibits exceptional predictive power in prioritizing carcinogenic chemical mixtures, even when relying on assumption-based mixtures. This capability is particularly valuable for toxicology studies that lack experimental data on the carcinogenicity and toxicity of chemical mixtures. To our knowledge, this study introduces the first method for predicting the carcinogenic potential of chemical mixtures. The HNN_MixCancer framework offers a novel alternative for dose-dependent carcinogen prediction. Ongoing efforts involve implementing the HNN method to predict mixture toxicity and expanding the application of HNN_MixCancer to include multiple mixtures such as PFAS mixtures and co-occurring chemicals. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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16 pages, 4556 KiB

Open AccessArticle

Antitumor Profile of Combined Matricaria recutita Flower Extract and 5-Fluorouracil Chemotherapy in Sarcoma 180 In Vivo Model

by Sara A. Santos, Ricardo G. Amaral, Ariel S. Graça, Silvana V. F. Gomes, Fabrício P. Santana, Iza B. de Oliveira, Luciana N. Andrade, Patrícia Severino, Ricardo L. C. de Albuquerque-Júnior, Sandra L. Santos, Eliana B. Souto and Adriana A. Carvalho

Toxics 2023, 11(4), 375; https://doi.org/10.3390/toxics11040375 - 14 Apr 2023

Cited by 2 | Viewed by 2143

Abstract

Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract [...] Read more.

Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with a reduction in white pulp, leukopenia and thrombocytopenia, was observed in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day did not interfere in myelosuppressive action of 5-FU. In hematological analysis, body and visceral mass variation and biochemical parameters related to renal (urea and creatinine) and cardiac (CK-MB) function, no alteration was observed. In biochemical parameters related to liver function enzymes, there was a reduction in aspartate transaminase (AST) values in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day does not appear to influence enzyme reduction. The results of this study suggest that the association between the 5-FU+MRFE 200 can positively interfere with the antitumor activity, promoting the antineoplastic-induced reduction in body mass, while minimizing the toxicity of chemotherapy. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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Review

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29 pages, 980 KiB

Open AccessEditor’s ChoiceReview

Interaction between Per- and Polyfluorinated Substances (PFAS) and Acetaminophen in Disease Exacerbation—Focusing on Autism and the Gut–Liver–Brain Axis

by Danielle Qiu Yun Jiang and Tai Liang Guo

Toxics 2024, 12(1), 39; https://doi.org/10.3390/toxics12010039 - 3 Jan 2024

Cited by 1 | Viewed by 3855

Abstract

This review presents a new perspective on the exacerbation of autism spectrum disorder (ASD) by per- and polyfluoroalkyl substances (PFAS) through the gut–liver–brain axis. We have summarized evidence reported on the involvement of the gut microbiome and liver inflammation that led to the [...] Read more.

This review presents a new perspective on the exacerbation of autism spectrum disorder (ASD) by per- and polyfluoroalkyl substances (PFAS) through the gut–liver–brain axis. We have summarized evidence reported on the involvement of the gut microbiome and liver inflammation that led to the onset and exacerbation of ASD symptoms. As PFAS are toxicants that particularly target liver, this review has comprehensively explored the possible interaction between PFAS and acetaminophen, another liver toxicant, as the chemicals of interest for future toxicology research. Our hypothesis is that, at acute dosages, acetaminophen has the ability to aggravate the impaired conditions of the PFAS-exposed liver, which would further exacerbate neurological symptoms such as lack of social communication and interest, and repetitive behaviors using mechanisms related to the gut–liver–brain axis. This review discusses their potential interactions in terms of the gut–liver–brain axis and signaling pathways that may contribute to neurological diseases. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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12 pages, 1809 KiB

Open AccessEditor’s ChoiceReview

(Micro)Plastics Are Toxic Pollutants

by Judith S. Weis and Juan José Alava

Toxics 2023, 11(11), 935; https://doi.org/10.3390/toxics11110935 - 17 Nov 2023

Cited by 14 | Viewed by 3473

Abstract

Plastics, including microplastics, have generally been regarded as harmful to organisms because of their physical characteristics. There has recently been a call to understand and regard them as persistent, bioaccumulative, and toxic. This review elaborates on the reasons that microplastics in particular should [...] Read more.

Plastics, including microplastics, have generally been regarded as harmful to organisms because of their physical characteristics. There has recently been a call to understand and regard them as persistent, bioaccumulative, and toxic. This review elaborates on the reasons that microplastics in particular should be considered as “toxic pollutants”. This view is supported by research demonstrating that they contain toxic chemicals within their structure and also adsorb additional chemicals, including polychlorinated biphenyls (PCBs), pesticides, metals, and polycyclic aromatic hydrocarbons (PAHs), from the environment. Furthermore, these chemicals can be released into tissues of animals that consume microplastics and can be responsible for the harmful effects observed on biological processes such as development, physiology, gene expression, and behavior. Leachates, weathering, and biofilm play important roles in the interactions between microplastics and biota. Global policy efforts by the United Nations Environmental Assembly via the international legally binding treaty to address global plastic pollution should consider the designation of harmful plastics (e.g., microplastics) with associated hazardous chemicals as toxic pollutants. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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40 pages, 1890 KiB

Open AccessEditor’s ChoiceReview

Insights in Pharmaceutical Pollution: The Prospective Role of eDNA Metabarcoding

by Charikleia Papaioannou, George Geladakis, Vasiliki Kommata, Costas Batargias and George Lagoumintzis

Toxics 2023, 11(11), 903; https://doi.org/10.3390/toxics11110903 - 5 Nov 2023

Cited by 5 | Viewed by 6663

Abstract

Environmental pollution is a growing threat to natural ecosystems and one of the world’s most pressing concerns. The increasing worldwide use of pharmaceuticals has elevated their status as significant emerging contaminants. Pharmaceuticals enter aquatic environments through multiple pathways related to anthropogenic activity. Their [...] Read more.

Environmental pollution is a growing threat to natural ecosystems and one of the world’s most pressing concerns. The increasing worldwide use of pharmaceuticals has elevated their status as significant emerging contaminants. Pharmaceuticals enter aquatic environments through multiple pathways related to anthropogenic activity. Their high consumption, insufficient waste treatment, and the incapacity of organisms to completely metabolize them contribute to their accumulation in aquatic environments, posing a threat to all life forms. Various analytical methods have been used to quantify pharmaceuticals. Biotechnology advancements based on next-generation sequencing (NGS) techniques, like eDNA metabarcoding, have enabled the development of new methods for assessing and monitoring the ecotoxicological effects of pharmaceuticals. eDNA metabarcoding is a valuable biomonitoring tool for pharmaceutical pollution because it (a) provides an efficient method to assess and predict pollution status, (b) identifies pollution sources, (c) tracks changes in pharmaceutical pollution levels over time, (d) assesses the ecological impact of pharmaceutical pollution, (e) helps prioritize cleanup and mitigation efforts, and (f) offers insights into the diversity and composition of microbial and other bioindicator communities. This review highlights the issue of aquatic pharmaceutical pollution while emphasizing the importance of using modern NGS-based biomonitoring actions to assess its environmental effects more consistently and effectively. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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28 pages, 2683 KiB

Open AccessReview

Dithiocarbamates: Properties, Methodological Approaches and Challenges to Their Control

by Claudia Campanale, Mariangela Triozzi, Annamaria Ragonese, Daniela Losacco and Carmine Massarelli

Toxics 2023, 11(10), 851; https://doi.org/10.3390/toxics11100851 - 11 Oct 2023

Cited by 11 | Viewed by 5113

Abstract

Dithiocarbamates (DTCs) are a group of chemicals used primarily as fungicides, although they are exploited for various other applications. DTCs represent one of the oldest classes of broad-spectrum fungicides employed worldwide to control fungal diseases on many crops. Due to their ease of [...] Read more.

Dithiocarbamates (DTCs) are a group of chemicals used primarily as fungicides, although they are exploited for various other applications. DTCs represent one of the oldest classes of broad-spectrum fungicides employed worldwide to control fungal diseases on many crops. Due to their ease of synthesis, low production costs (cheap and readily available starting materials) and a fungicidal activity with a multi-site mode of action, they are still among modern agriculture’s most extensively used pesticides. Although the environmental degradation in air, water, and soil is relatively rapid due to photolysis and/or hydrolysis, they are among the most frequently detected pesticides in the European Union (EU), also with a high frequency of maximum residue level (MRL) exceedances. The current review aims to comprehensively survey all aspects of DTCs, including the environmental fate, toxicity and analytical methods for determining parental compounds and degradation products in environmental and food samples. Furthermore, the accumulation of carbamate and dithiocarbamate pesticides in vegetables, fruits, bioindicator organisms and human biological samples, as well as their health effects on humans, are also considered in this study. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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13 pages, 870 KiB

Open AccessReview

Survey on the Environmental Risks of Bisphenol A and Its Relevant Regulations in Taiwan: An Environmental Endocrine-Disrupting Chemical of Increasing Concern

by Wen-Tien Tsai

Toxics 2023, 11(9), 722; https://doi.org/10.3390/toxics11090722 - 23 Aug 2023

Cited by 3 | Viewed by 2398

Abstract

Bisphenol A (BPA) has been identified as one of the endocrine disruptors or endocrine disrupting chemicals (EDCs). Due to its massive production (over 700,000 tons per year) and the extensive use of BPA-based plastics (i.e., polycarbonate and epoxy resin) in Taiwan, it was [...] Read more.

Bisphenol A (BPA) has been identified as one of the endocrine disruptors or endocrine disrupting chemicals (EDCs). Due to its massive production (over 700,000 tons per year) and the extensive use of BPA-based plastics (i.e., polycarbonate and epoxy resin) in Taiwan, it was thus included as a toxic substance by the Ministry of Environment. This work surveyed the updated information about the production of BPA and its environmental distribution in Taiwan over the past decade. Furthermore, the regulatory strategies and countermeasures for managing the environmental risks of BPA by the Taiwan government were summarized to show the cross-ministerial efforts under the relevant acts, including the Toxic and Concerned Chemical Substances Control Act (TCCSCA), the Food Sanitation Management Act (FSMA) and the Commodity Inspection Act (CIA). The findings showed that most monitoring data were far below the acceptable risks. However, people may pose an adverse threat to the aquatic environment and human health via ecological and food chains. In addition, some countermeasures were further recommended to echo the international actions on environmental endocrine disruptors in recent years. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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29 pages, 2029 KiB

Open AccessReview

Association between Heavy Metals, Metalloids and Metabolic Syndrome: New Insights and Approaches

by Airton C. Martins, Beatriz Ferrer, Alexey A. Tinkov, Samuel Caito, Romina Deza-Ponzio, Anatoly V. Skalny, Aaron B. Bowman and Michael Aschner

Toxics 2023, 11(8), 670; https://doi.org/10.3390/toxics11080670 - 3 Aug 2023

Cited by 9 | Viewed by 3810

Abstract

Metabolic syndrome (MetS) is an important public health issue that affects millions of people around the world and is growing to pandemic-like proportions. This syndrome is defined by the World Health Organization (WHO) as a pathologic condition characterized by abdominal obesity, insulin resistance, [...] Read more.

Metabolic syndrome (MetS) is an important public health issue that affects millions of people around the world and is growing to pandemic-like proportions. This syndrome is defined by the World Health Organization (WHO) as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Moreover, the etiology of MetS is multifactorial, involving many environmental factors, including toxicant exposures. Several studies have associated MetS with heavy metals exposure, which is the focus of this review. Environmental and/or occupational exposure to heavy metals are a major risk, contributing to the development of chronic diseases. Of particular note, toxic metals such as mercury, lead, and cadmium may contribute to the development of MetS by altering oxidative stress, IL-6 signaling, apoptosis, altered lipoprotein metabolism, fluid shear stress and atherosclerosis, and other mechanisms. In this review, we discuss the known and potential roles of heavy metals in MetS etiology as well as potential targeted pathways that are associated with MetS. Furthermore, we describe how new approaches involving proteomic and transcriptome analysis, as well as bioinformatic tools, may help bring about an understanding of the involvement of heavy metals and metalloids in MetS. Full article

(This article belongs to the Special Issue The 10th Anniversary of Toxics)

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