Toxics

38 pages, 5753 KiB

Open AccessEditor’s ChoiceArticle

A Machine-Learning-Driven Pathophysiology-Based New Approach Method for the Dose-Dependent Assessment of Hazardous Chemical Mixtures and Experimental Validations

by Sarita Limbu, Eric Glasgow, Tessa Block and Sivanesan Dakshanamurthy

Toxics 2024, 12(7), 481; https://doi.org/10.3390/toxics12070481 - 30 Jun 2024

Cited by 1 | Viewed by 1384

Abstract

Environmental chemicals, such as PFAS, exist as mixtures and are frequently encountered at varying concentrations, which can lead to serious health effects, such as cancer. Therefore, understanding the dose-dependent toxicity of chemical mixtures is essential for health risk assessment. However, comprehensive methods to [...] Read more.

Environmental chemicals, such as PFAS, exist as mixtures and are frequently encountered at varying concentrations, which can lead to serious health effects, such as cancer. Therefore, understanding the dose-dependent toxicity of chemical mixtures is essential for health risk assessment. However, comprehensive methods to assess toxicity and identify the mechanisms of these harmful mixtures are currently absent. In this study, the dose-dependent toxicity assessments of chemical mixtures are performed in three methodologically distinct phases. In the first phase, we evaluated our machine-learning method (AI-HNN) and pathophysiology method (CPTM) for predicting toxicity. In the second phase, we integrated AI-HNN and CPTM to establish a comprehensive new approach method (NAM) framework called AI-CPTM that is targeted at refining prediction accuracy and providing a comprehensive understanding of toxicity mechanisms. The third phase involved experimental validations of the AI-CPTM predictions. Initially, we developed binary, multiclass classification, and regression models to predict binary, categorical toxicity, and toxic potencies using nearly a thousand experimental mixtures. This empirical dataset was expanded with assumption-based virtual mixtures, compensating for the lack of experimental data and broadening the scope of the dataset. For comparison, we also developed machine-learning models based on RF, Bagging, AdaBoost, SVR, GB, KR, DT, KN, and Consensus methods. The AI-HNN achieved overall accuracies of over 80%, with the AUC exceeding 90%. In the final phase, we demonstrated the superior performance and predictive capability of AI-CPTM, including for PFAS mixtures and their interaction effects, through rigorous literature and statistical validations, along with experimental dose-response zebrafish-embryo toxicity assays. Overall, the AI-CPTM approach significantly improves upon the limitations of standalone AI models, showing extensive enhancements in identifying toxic chemicals and mixtures and their mechanisms. This study is the first to develop a hybrid NAM that integrates AI with a pathophysiology method to comprehensively predict chemical-mixture toxicity, carcinogenicity, and mechanisms. Full article

(This article belongs to the Section Novel Methods in Toxicology Research)

► Show Figures

Figure 1

14 pages, 2954 KiB

Open AccessEditor’s ChoiceArticle

Prenatal Arsenic Exposure on DNA Methylation of C18ORF8 and ADAMTS9 Genes of Newborns from the POSGRAD Birth Cohort Study

by Carolina Lerma-Treviño, Leticia Hernández-Cadena, Jorge Octavio Acosta-Montes, Georgina Hernández-Montes, Isabel Alvarado-Cruz, Isabelle Romieu and Albino Barraza-Villarreal

Toxics 2024, 12(7), 476; https://doi.org/10.3390/toxics12070476 - 30 Jun 2024

Viewed by 1546

Abstract

Exposure to arsenic (As) is a public health problem associated with cancer (skin and colon) and it has been reported that epigenetic changes may be a potential mechanism of As carcinogenesis. It is pertinent to evaluate this process in genes that have been [...] Read more.

Exposure to arsenic (As) is a public health problem associated with cancer (skin and colon) and it has been reported that epigenetic changes may be a potential mechanism of As carcinogenesis. It is pertinent to evaluate this process in genes that have been associated with cancer, such as ADAMTS9 and C18ORF8. Gestation and delivery data were obtained from the POSGRAD study. Exposure to As was measured in urine during pregnancy. Gene methylation was performed by sodium bisulfite sequencing; 26 CpG sites for the C18ORF8 gene and 21 for ADAMTS9 were analyzed. These sites are located on the CpG islands near the start of transcription. Sociodemographic characteristics were obtained by a questionnaire. The statistical analysis was performed using multiple linear regression models adjusted for potential confounders. Newborns with an As exposure above 49.4 μg g⁻¹ showed a decrease of 0.21% on the methylation rate in the sites CpG15, CpG19, and CpG21 of the C18ORF8 gene (adjusted ß = −0.21, p-value = 0.02). No statistically significant association was found between prenatal exposure to As and methylation of the ADAMTS9 gene. Prenatal exposure to As was associated with decreased DNA methylation at the CpG15, CpG19, and CpG21 sites of the C18ORF8 gene. These sites can provide information to elucidate epigenetic mechanisms associated with prenatal exposure to As and cancer. Full article

(This article belongs to the Section Human Toxicology and Epidemiology)

► Show Figures

Figure 1

16 pages, 3457 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

The Flavoring Agent Ethyl Vanillin Induces Cellular Stress Responses in HK-2 Cells

by Ashley J. Cox, Kathleen C. Brown and Monica A. Valentovic

Toxics 2024, 12(7), 472; https://doi.org/10.3390/toxics12070472 - 29 Jun 2024

Viewed by 994

Abstract

Flavored e-cigarettes are a popular alternative to cigarette smoking; unfortunately, the extrapulmonary effects are not well-characterized. Human proximal tubule cells were cultured for 24 or 48 h with 0–1000 µM ethyl vanillin (ETH VAN) and cytotoxicity evaluated. Mitochondrial health was significantly diminished following [...] Read more.

Flavored e-cigarettes are a popular alternative to cigarette smoking; unfortunately, the extrapulmonary effects are not well-characterized. Human proximal tubule cells were cultured for 24 or 48 h with 0–1000 µM ethyl vanillin (ETH VAN) and cytotoxicity evaluated. Mitochondrial health was significantly diminished following 48 h of exposure, accompanied by significantly decreased spare capacity, coupling efficiency, and ATP synthase expression. ETH VAN at 24 h inhibited glycolysis. The endoplasmic reticulum (ER) stress marker C/EBP homologous protein (CHOP) was increased at 100 μM relative to 500–1000 μM. The downstream proapoptotic marker cleaved caspase-3 subsequently showed a decreasing trend in expression after 48 h of exposure. The autophagy biomarkers microtubule-associated proteins 1A/1B light chain 3 (LC3B-I and LC3B-II) were measured by Western blot. LC3B-II levels and the LC3B-II/LC3B-I ratio increased at 24 h, which suggested activation of autophagy. In contrast, by 48 h, the autophagy biomarker LC3B-II decreased, resulting in no change in the LC3B-II/LC3B-I ratio. Mitophagy biomarker PTEN-induced putative kinase 1 (PINK1) expression decreased after 48 h of exposure. The downstream marker Parkin was not significantly changed after 24 or 48 h. These findings indicate that the flavoring ETH VAN can induce energy pathway dysfunction and cellular stress responses in a renal model. Full article

(This article belongs to the Special Issue Nephrotoxicity Induced by Drugs and Chemicals in the Environment)

► Show Figures

Figure 1

21 pages, 1562 KiB

Open AccessEditor’s ChoiceArticle

Toxic Elements in Sheep Milk, Whey, and Cheese from the Environmentally Burdened Area in Eastern Slovakia and Health Risk Assessment with Different Scenarios of Their Consumption

by Simona Almášiová, Róbert Toman, Martina Pšenková, Vladimír Tančin and Ivona Jančo

Toxics 2024, 12(7), 467; https://doi.org/10.3390/toxics12070467 - 27 Jun 2024

Cited by 1 | Viewed by 867

Abstract

The study aimed to determine the content of 17 elements (Al, As, Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Sb, Se, Sr, and Zn) in samples of sheep milk, cheese, and whey (36 samples in total) collected from a [...] Read more.

The study aimed to determine the content of 17 elements (Al, As, Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Sb, Se, Sr, and Zn) in samples of sheep milk, cheese, and whey (36 samples in total) collected from a farm in an environmentally burdened area due to the long-term mining and industrial activity in Slovakia as well as to determine the possible risk of consumption via health risk assessment calculations. Consumption of 120 g of milk, 500 g of milk, 20 g of cheese, and 100 g of cheese were used in calculations for children and adults, respectively. According to the results, concentrations of four elements are controversial. Lead concentrations in all types of samples exceeded the maximum permissible lead limit in milk set by European Union legislation. The content of Se and As is problematic for children’s consumption, and the target hazard quotient for As and Al is higher than one (considered potentially not safe) in all scenarios. According to the target system approach, lead concentrations in milk and cheese could adversely influence the nervous system and kidneys of adults’ and children’s developmental and reproductive systems. Considering the worst-case scenario, consuming sheep milk and cheese from the monitored areas could represent a risk and be potentially harmful to human health, mainly for children. However, further monitoring of the levels of elements and concentrations in environmentally burdened areas and more robust data on consumption are needed. Full article

(This article belongs to the Section Agrochemicals and Food Toxicology)

► Show Figures

Figure 1

35 pages, 3754 KiB

Open AccessEditor’s ChoiceArticle

Pharmaceutical and Trace Metal Interaction within the Water–Soil–Plant Continuum: Implications for Human and Soil Health

by Lesly Ayala Cabana, Ana de Santiago-Martín, Raffaella Meffe, Isabel López-Heras and Irene de Bustamante

Toxics 2024, 12(7), 457; https://doi.org/10.3390/toxics12070457 - 25 Jun 2024

Cited by 1 | Viewed by 1332

Abstract

Unplanned water reuse for crop irrigation may pose a global health risk due to the entry of contaminants into the food chain, undesirable effects on crop quality, and impact on soil health. In this study, we evaluate the impact derived from the co-occurrence [...] Read more.

Unplanned water reuse for crop irrigation may pose a global health risk due to the entry of contaminants into the food chain, undesirable effects on crop quality, and impact on soil health. In this study, we evaluate the impact derived from the co-occurrence of pharmaceuticals (Phs), trace metals (TMs), and one metalloid within the water–soil–plant continuum through bioassay experiments with Lactuca sativa L. Results indicate that the co-occurrence of Phs and TMs has synergistic or antagonistic effects, depending on target contaminants and environmental compartments. Complex formations between drugs and TMs may be responsible for enhanced sorption onto the soil of several Phs and TMs. Concerning plant uptake, the co-occurrence of Phs and TMs exerts antagonistic and synergistic effects on carbamazepine and diazepam, respectively. With the exception of Cd, drugs exert an antagonistic effect on TMs, negatively affecting their uptake and translocation. Drug contents in lettuce edible parts do not pose any threat to human health, but Cd levels exceed the maximum limits set for leafy vegetable foodstuffs. Under Ph-TM conditions, lettuce biomass decreases, and a nutrient imbalance is observed. Soil enzyme activity is stimulated under Ph-TM conditions (β-galactosidase) and Ph and Ph-TM conditions (urease and arylsulfatase), or it is not affected (phosphatase). Full article

(This article belongs to the Special Issue New Strategies for Detection and Bioremediation of Contaminated Water and Soil)

► Show Figures

Figure 1

29 pages, 867 KiB

Open AccessEditor’s ChoiceReview

Effects of Per- and Polyfluoroalkylated Substances on Female Reproduction

by María Estefanía González-Alvarez, Collins Antwi-Boasiako and Aileen F. Keating

Toxics 2024, 12(7), 455; https://doi.org/10.3390/toxics12070455 - 25 Jun 2024

Cited by 2 | Viewed by 1297

Abstract

Per- and poly-fluoroalkylated substances (PFAS) are a large group of chemicals that persist both in the environment and in the body. Legacy PFAS, e.g., perfluorooctanoic acid and perfluorooctane sulfonic acid, are implicated as endocrine disruptors and reproductive and developmental toxicants in epidemiological and [...] Read more.

Per- and poly-fluoroalkylated substances (PFAS) are a large group of chemicals that persist both in the environment and in the body. Legacy PFAS, e.g., perfluorooctanoic acid and perfluorooctane sulfonic acid, are implicated as endocrine disruptors and reproductive and developmental toxicants in epidemiological and animal model studies. This review describes female reproductive outcomes of reported studies and includes where associative relationships between PFAS exposures and female reproductive outcomes have been observed as well as where those are absent. In animal models, studies in which PFAS are documented to cause toxicity and where effects are lacking are described. Discrepancies exist in both human and animal studies and are likely attributable to human geographical contamination, developmental status, duration of exposure, and PFAS chemical identity. Similarly, in animal investigations, the model used, exposure paradigm, and developmental status of the female are important and vary widely in documented studies. Taken together, support for PFAS as reproductive and developmental toxicants exists, although the disparity in study conditions and human exposures contribute to the variation in effects noted. Full article

(This article belongs to the Special Issue Per- and Polyfluoroalkyl Substances in the Environment: Sources, Fate and Risk Assessments)

► Show Figures

Graphical abstract

18 pages, 1170 KiB

Open AccessEditor’s ChoiceReview

Potential Early Effect Biomarkers for Ambient Air Pollution Related Mental Disorders

by Lijun Bai, Kai Wang, Dandan Liu and Shaowei Wu

Toxics 2024, 12(7), 454; https://doi.org/10.3390/toxics12070454 - 24 Jun 2024

Viewed by 1386

Abstract

Air pollution is one of the greatest environmental risks to health, with 99% of the world’s population living where the World Health Organization’s air quality guidelines were not met. In addition to the respiratory and cardiovascular systems, the brain is another potential target [...] Read more.

Air pollution is one of the greatest environmental risks to health, with 99% of the world’s population living where the World Health Organization’s air quality guidelines were not met. In addition to the respiratory and cardiovascular systems, the brain is another potential target of air pollution. Population- and experiment-based studies have shown that air pollution may affect mental health through direct or indirect biological pathways. The evidence for mental hazards associated with air pollution has been well documented. However, previous reviews mainly focused on epidemiological associations of air pollution with some specific mental disorders or possible biological mechanisms. A systematic review is absent for early effect biomarkers for characterizing mental health hazards associated with ambient air pollution, which can be used for early warning of related mental disorders and identifying susceptible populations at high risk. This review summarizes possible biomarkers involved in oxidative stress, inflammation, and epigenetic changes linking air pollution and mental disorders, as well as genetic susceptibility biomarkers. These biomarkers may provide a better understanding of air pollution’s adverse effects on mental disorders and provide future research direction in this arena. Full article

(This article belongs to the Section Air Pollution and Health)

► Show Figures

Figure 1

14 pages, 3123 KiB

Open AccessEditor’s ChoiceArticle

Removal of Aqueous Antimony and Arsenic by Iron-Loaded Coal Gasification Slag Composite

by Zheng Leng, Changzhi Zhou, Hong Hou and Junhuan Wang

Toxics 2024, 12(6), 440; https://doi.org/10.3390/toxics12060440 - 19 Jun 2024

Viewed by 953

Abstract

The adsorption of Sb(V) and As(V) onto iron-loaded gasification slag composite material (Fe-GFS), as well as the possible mechanisms, was investigated. Batch experiments showed that in a single system, Fe-GFS sorbed As(V) to a greater extent than Sb(V) with the maximum adsorption capacity [...] Read more.

The adsorption of Sb(V) and As(V) onto iron-loaded gasification slag composite material (Fe-GFS), as well as the possible mechanisms, was investigated. Batch experiments showed that in a single system, Fe-GFS sorbed As(V) to a greater extent than Sb(V) with the maximum adsorption capacity (pH 3.0) of 34.99 mg/g (0.47 mmol/g), while that of Sb(V) was 27.61 mg/g (0.23 mmol/g). In the composite system, the presence of low concentrations of Sb(V) reduced the adsorption efficiency of Fe-GFS for As(V), while the presence of high concentrations of Sb(V) actually promoted the adsorption of As(V). The presence of As(V) consistently inhibited the adsorption of Sb(V) by Fe-GFS. Compared to Fe-GFS, new peaks appeared in the FTIR spectra after adsorption, indicating the presence of Sb-O and As-O bonds on the surface after adsorption. XPS results showed that the adsorption of As(V) and Sb(V) led to a decrease in Fe-OH bonds, with a more significant decrease in Fe-OH bonds observed after the adsorption of As(V), indicating a stronger affinity of Fe-GFS for As(V) compared to Sb(V). Our results suggest that Fe-GFS is an efficient adsorbent with great potential for applications in water containing As(V) and Sb(V). Full article

(This article belongs to the Section Toxicity Reduction and Environmental Remediation)

► Show Figures

Figure 1

26 pages, 2730 KiB

Open AccessEditor’s ChoiceArticle

Integrated Approach for Testing and Assessment for Developmental Neurotoxicity (DNT) to Prioritize Aromatic Organophosphorus Flame Retardants

by Anna Kreutz, Oluwakemi B. Oyetade, Xiaoqing Chang, Jui-Hua Hsieh, Mamta Behl, David G. Allen, Nicole C. Kleinstreuer and Helena T. Hogberg

Toxics 2024, 12(6), 437; https://doi.org/10.3390/toxics12060437 - 18 Jun 2024

Viewed by 1655

Abstract

Organophosphorus flame retardants (OPFRs) are abundant and persistent in the environment but have limited toxicity information. Their similarity in structure to organophosphate pesticides presents great concern for developmental neurotoxicity (DNT). However, current in vivo testing is not suitable to provide DNT information on [...] Read more.

Organophosphorus flame retardants (OPFRs) are abundant and persistent in the environment but have limited toxicity information. Their similarity in structure to organophosphate pesticides presents great concern for developmental neurotoxicity (DNT). However, current in vivo testing is not suitable to provide DNT information on the amount of OPFRs that lack data. Over the past decade, an in vitro battery was developed to enhance DNT assessment, consisting of assays that evaluate cellular processes in neurodevelopment and function. In this study, behavioral data of small model organisms were also included. To assess if these assays provide sufficient mechanistic coverage to prioritize chemicals for further testing and/or identify hazards, an integrated approach to testing and assessment (IATA) was developed with additional information from the Integrated Chemical Environment (ICE) and the literature. Human biomonitoring and exposure data were identified and physiologically-based toxicokinetic models were applied to relate in vitro toxicity data to human exposure based on maximum plasma concentration. Eight OPFRs were evaluated, including aromatic OPFRs (triphenyl phosphate (TPHP), isopropylated phenyl phosphate (IPP), 2-ethylhexyl diphenyl phosphate (EHDP), tricresyl phosphate (TMPP), isodecyl diphenyl phosphate (IDDP), tert-butylphenyl diphenyl phosphate (BPDP)) and halogenated FRs ((Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(2-chloroethyl) phosphate (TCEP)). Two representative brominated flame retardants (BFRs) (2,2′4,4′-tetrabromodiphenyl ether (BDE-47) and 3,3′,5,5′-tetrabromobisphenol A (TBBPA)) with known DNT potential were selected for toxicity benchmarking. Data from the DNT battery indicate that the aromatic OPFRs have activity at similar concentrations as the BFRs and should therefore be evaluated further. However, these assays provide limited information on the mechanism of the compounds. By integrating information from ICE and the literature, endocrine disruption was identified as a potential mechanism. This IATA case study indicates that human exposure to some OPFRs could lead to a plasma concentration similar to those exerting in vitro activities, indicating potential concern for human health. Full article

(This article belongs to the Special Issue Risk Assessment of Flame Retardants in Consumer Products)

► Show Figures

Figure 1

15 pages, 2925 KiB

Open AccessEditor’s ChoiceArticle

Association between Volatile Organic Compound Exposure and Sex Hormones in Adolescents: The Mediating Role of Serum Albumin

by Xinyao Lian, Jianhui Guo, Yaqi Wang, Shaoguan Wang and Jing Li

Toxics 2024, 12(6), 438; https://doi.org/10.3390/toxics12060438 - 18 Jun 2024

Cited by 1 | Viewed by 1144

Abstract

The associations between VOCs and sex hormones in adolescents remain unclear, and the role of serum albumin in these associations deserves to be explored. We conducted cross-sectional analyses using generalized linear models (GLMs), weighted quantile sum (WQS) regression, and mediation analysis, based on [...] Read more.

The associations between VOCs and sex hormones in adolescents remain unclear, and the role of serum albumin in these associations deserves to be explored. We conducted cross-sectional analyses using generalized linear models (GLMs), weighted quantile sum (WQS) regression, and mediation analysis, based on data from 584 adolescents from the National Health and Nutrition Examination Survey (NHANES). The GLM analyses revealed that seven kinds of mVOCs potentially affected sex hormone levels. According to the WQS regression results, 2-aminothiazoline-4-carboxylic acid (ATCA) was the major contributor to the significant associations of mixed mVOC exposure with testosterone, estradiol, and free androgen index in males; N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) was the major contributor to the significant associations of mixed mVOC exposure with sex hormone-binding globulin in males; and N-acetyl-S-(benzyl)-L-cysteine (BMA) was the major contributor to the significant associations of mixed mVOC exposure with the ratio of testosterone to estradiol in females. Moreover, serum albumin could mediate up to 9.2% of the associations between mixed exposure to mVOCs and sex hormones. Our findings could provide a reference for studies on the mechanisms underlying the effects of VOCs on sex hormones in adolescents and emphasize the necessity of reducing exposure to ATCA, AMCC, BMA, and their parent compounds. Full article

(This article belongs to the Special Issue Environmental and Health Effects of Volatile Organic Compounds)

► Show Figures

Graphical abstract

14 pages, 21149 KiB

Open AccessEditor’s ChoiceArticle

The Legacy of Hg Contamination in a Past Mining Area (Tuscany, Italy): Hg Speciation and Health Risk Assessment

by Simone Arrighi, Fabrizio Franceschini, Riccardo Petrini, Silvia Fornasaro and Lisa Ghezzi

Toxics 2024, 12(6), 436; https://doi.org/10.3390/toxics12060436 - 16 Jun 2024

Viewed by 1699

Abstract

The mercury cell manufacturing process, which has been extensively used in chlor-alkali plants to produce chlorine and caustic soda by electrolysis, represents a major source of Hg environmental pollution. At Saline di Volterra (Tuscany, Italy), solution mining by pumping water into halite deposits [...] Read more.

The mercury cell manufacturing process, which has been extensively used in chlor-alkali plants to produce chlorine and caustic soda by electrolysis, represents a major source of Hg environmental pollution. At Saline di Volterra (Tuscany, Italy), solution mining by pumping water into halite deposits was applied to produce brines for a mercury-cell chlor-alkali plant. The Hg-contaminated, exhausted brines were pumped back at depth into the rock salt field in order to renew the available resources. Activities ceased in 1994, following the leakage dispersion of highly contaminated Hg(0)-bearing brines into the environment. The mercury content in the soil, measured during a survey conducted in 2000, reached 334 mg/kg, highlighting diffuse contamination in the floodplain. By 2009, the Hg concentration had generally decreased and was mostly confined to the topsoil layer. In order to evaluate the present Hg soil pollution, a geochemical survey was carried out in 2023, almost thirty years after the contamination event. The obtained data indicated the occurrence of legacy Hg, which reached 25.5 mg/kg in some soil samples. Speciation analysis for the most contaminated soil revealed that Hg(0) represented about 17.3% of the total Hg and that water-soluble and organic Hg fractions were negligible. These results suggest that the originally released metallic mercury has volatilized and likely oxidized, becoming practically immobile in the soil. A risk assessment, performed by applying Hg speciation analysis, indicated that the mercury in the soil does not carry a risk of non-cancerous effects for different exposure routes in case of subsequent use of the site and that the formerly contaminated area can now be converted into a leisure area. Full article

(This article belongs to the Special Issue Monitoring and Assessment of Mercury Pollution)

► Show Figures

Figure 1

17 pages, 3145 KiB

Open AccessEditor’s ChoiceArticle

Citric Acid Inhibits Cd Absorption and Transportation by Improving the Antagonism of Essential Elements in Rice Organs

by Kexin Chen, Bozhen Yu, Weijie Xue, Yuebing Sun, Changbo Zhang, Xusheng Gao, Xiaojia Zhou, Yun Deng, Jiarun Yang and Boqian Zhang

Toxics 2024, 12(6), 431; https://doi.org/10.3390/toxics12060431 - 14 Jun 2024

Cited by 1 | Viewed by 1062

Abstract

Excessive cadmium (Cd) in rice is a global environmental problem. Therefore, reducing Cd content in rice is of great significance for ensuring food security and human health. A field experiment was conducted to study the effects of foliar application of citric acid (CA) [...] Read more.

Excessive cadmium (Cd) in rice is a global environmental problem. Therefore, reducing Cd content in rice is of great significance for ensuring food security and human health. A field experiment was conducted to study the effects of foliar application of citric acid (CA) on Cd absorption and transportation in rice under high Cd-contaminated soils (2.04 mg·kg⁻¹). This study revealed that there was a negative correlation between Cd content in vegetative organs and CA content, and that foliar spraying of CA (1 mM and 5 mM) significantly increased CA content and reduced Cd content in vegetative organs. The Cd reduction effect of 5 mM CA was better than that of 1 mM, and 5 mM CA reduced Cd content in grains and spikes by 52% and 37%, respectively. CA significantly increased Mn content in vegetative organs and increased Ca/Mn ratios in spikes, flag leaves, and roots. CA significantly reduced soluble Cd content in vegetative organs and promoted the transformation of Cd into insoluble Cd, thus inhibiting the transport of Cd from vegetative organs to grains. The foliar field application of 1 mM and 5 mM CA could inhibit Cd absorption and transportation by reducing Cd bioactivity and increasing the antagonistic of essential elements in rice vegetative organs. These results provide technical support and a theoretical basis for solving the problem of excessive Cd in rice. Full article

(This article belongs to the Special Issue Transformation Process and Toxic Effects of Pollutants in Agricultural Environment)

► Show Figures

Figure 1

26 pages, 5196 KiB

Open AccessEditor’s ChoiceArticle

Using the Multicomponent Aerosol FORmation Model (MAFOR) to Determine Improved VOC Emission Factors in Ship Plumes

by Lea Fink, Matthias Karl, Volker Matthias, Andreas Weigelt, Matti Irjala and Pauli Simonen

Toxics 2024, 12(6), 432; https://doi.org/10.3390/toxics12060432 - 14 Jun 2024

Viewed by 1126

Abstract

International shipping’s particulate matter primary emissions have a share in global anthropogenic emissions of between 3% and 4%. Ship emissions of volatile organic compounds (VOCs) can play an important role in the formation of fine particulate matter. Using an aerosol box model for [...] Read more.

International shipping’s particulate matter primary emissions have a share in global anthropogenic emissions of between 3% and 4%. Ship emissions of volatile organic compounds (VOCs) can play an important role in the formation of fine particulate matter. Using an aerosol box model for the near-plume scale, this study investigated how the changing VOC emission factor (EF) for ship engines impacts the formation of secondary PM_2.5 in ship exhaust plumes that were detected during a measurement campaign. The agreement between measured and modeled particle number size distribution was improved by adjusting VOC emissions, in particular of intermediate-, low-, and extremely low-volatility compounds. The scaling of the VOC emission factor showed that the initial emission factor, based on literature data, had to be multiplied by 3.6 for all VOCs. Information obtained from the box model was integrated into a regional-scale chemistry transport model (CTM) to study the influence of changed VOC ship emissions over the Mediterranean Sea. The regional-scale CTM run with adjusted ship emissions indicated a change in PM_2.5 of up to 5% at the main shipping routes and harbor cities in summer. Nevertheless, overall changes due to a change in the VOC EF were rather small, indicating that the size of grid cells in CTMs leads to a fast dilution. Full article

(This article belongs to the Section Air Pollution and Health)

► Show Figures

Figure 1

11 pages, 308 KiB

Open AccessEditor’s ChoiceArticle

Biogas Digestate and Sewage Sludge as Suitable Feeds for Black Soldier Fly (Hermetia illucens) Larvae

by Jana Kofroňová, Abir Melliti and Radek Vurm

Toxics 2024, 12(6), 414; https://doi.org/10.3390/toxics12060414 - 5 Jun 2024

Cited by 1 | Viewed by 1379

Abstract

Hermetia illucens larvae can use organic wastes as a substrate, which makes them an interesting potential feed. However, waste may contain heavy metals, which are limited in feed. Here, we investigated the ability of H. illucens to grow on organic wastes and measured [...] Read more.

Hermetia illucens larvae can use organic wastes as a substrate, which makes them an interesting potential feed. However, waste may contain heavy metals, which are limited in feed. Here, we investigated the ability of H. illucens to grow on organic wastes and measured their heavy metal bioaccumulation. The larvae were fed with food waste, biogas digestates, and sewage sludge. When the first adult fly was visible, the tests were stopped and the larvae immediately processed. The samples (wastes before use, larvae after feeding) were analysed for mineral nutrient and heavy metal content using AAS and ICP-OES, respectively. The results show that the weight of the larvae fed with food waste increased sevenfold, which was broadly in line with expectations. Those fed with sewage sludge and digestate from biogas station increased threefold. While the larvae fed with sewage sludge exceeded the limits for heavy metals, particularly Cd and Pb, in feedstock, those fed with biogas digestate and food waste did not. These findings add to the literature showing the suitability of different wastes as H. illucens feed, and the importance of excluding waste contaminated with heavy metals from larvae intended for use as animal feed, or else diverting these larvae to non-feed uses. Full article

(This article belongs to the Special Issue Bioremediation of Pollutants in Sewage Sludge)

29 pages, 1627 KiB

Open AccessEditor’s ChoiceReview

Non-Steroidal Anti-Inflammatory Drugs in the Aquatic Environment and Bivalves: The State of the Art

by Pedro Pires, André M. P. T. Pereira, Angelina Pena and Liliana J. G. Silva

Toxics 2024, 12(6), 415; https://doi.org/10.3390/toxics12060415 - 5 Jun 2024

Cited by 2 | Viewed by 945

Abstract

In recent years, contaminants of emerging concern have been reported in several environmental matrices due to advances in analytical methodologies. These anthropogenic micropollutants are detected at residual levels, representing an ecotoxicological threat to aquatic ecosystems. In particular, the pharmacotherapeutic group of non-steroidal anti-inflammatories [...] Read more.

In recent years, contaminants of emerging concern have been reported in several environmental matrices due to advances in analytical methodologies. These anthropogenic micropollutants are detected at residual levels, representing an ecotoxicological threat to aquatic ecosystems. In particular, the pharmacotherapeutic group of non-steroidal anti-inflammatories (NSAIDs) is one of the most prescribed and used, as well as one of the most frequently detected in the aquatic environment. Bivalves have several benefits as a foodstuff, and also as an environment bioindicator species. Therefore, they are regarded as an ideal tool to assess this issue from both ecotoxicological and food safety perspectives. Thus, the control of these residues in bivalves is extremely important to safeguard environmental health, also ensuring food safety and public health. This paper aims to review NSAIDs in bivalves, observing their consumption, physicochemical characteristics, and mechanisms of action; their environmental occurrence in the aquatic environment and aquatic biota; and their effects on the ecosystem and the existent legal framework. A review of the analytical methodologies for the determination of NSAIDs in bivalves is also presented. Full article

(This article belongs to the Special Issue Pharmaceuticals in the Aquatic Environment: Monitoring, Impacts and Ecological Risk)

16 pages, 20893 KiB

Open AccessEditor’s ChoiceArticle

Degradation of Sodium Acetate by Catalytic Ozonation Coupled with MnOx/NiOOH-Modified Fly Ash

by Ruifu Chen, Hao Zhang, Shengyu Shao, Huajun Xu, Kaicheng Zhou, Yinzhi Jiang and Pengfei Sun

Toxics 2024, 12(6), 412; https://doi.org/10.3390/toxics12060412 - 4 Jun 2024

Viewed by 868

Abstract

Fly ash, a type of solid waste generated in power plants, can be utilized as a catalyst carrier to enhance its value-added potential. Common methods often involve using a large amount of alkali for preprocessing, resulting in stable quartz and mullite forming silicate [...] Read more.

Fly ash, a type of solid waste generated in power plants, can be utilized as a catalyst carrier to enhance its value-added potential. Common methods often involve using a large amount of alkali for preprocessing, resulting in stable quartz and mullite forming silicate dissolution. This leads to an increased specific surface area and pore structure. In this study, we produced a catalyst composed of MnO_x/NiOOH supported on fly ash by directly employing nickel hydroxide and potassium permanganate to generate metal active sites over the fly ash surface while simultaneously creating a larger specific surface area and pore structure. The ozone catalytic oxidation performance of this catalyst was evaluated using sodium acetate as the target organic matter. The experimental results demonstrated that an optimal removal efficiency of 57.5% for sodium acetate was achieved, surpassing even that of MnO_x/NiOOH supported catalyst by using γ-Al₂O₃. After loading of MnO_x/NiOOH, an oxygen vacancy is formed on the surface of fly ash, which plays an indirect oxidation effect on sodium acetate due to the transformation of ozone to •O₂⁻ and •OH over this oxygen vacancy. The reaction process parameters, including varying concentrations of ozone, sodium acetate, and catalyst dosage, as well as pH value and the quantitative analysis of formed free radicals, were examined in detail. This work demonstrated that fly ash could be used as a viable catalytic material for wastewater treatment and provided a new solution to the added value of fly ash. Full article

(This article belongs to the Special Issue Effective Catalytic Processes for Water and Wastewater Treatment)

► Show Figures

Figure 1

24 pages, 6232 KiB

Open AccessEditor’s ChoiceArticle

Advanced Photocatalytic Degradation of Cytarabine from Pharmaceutical Wastewaters

by Alexandra Berbentea, Mihaela Ciopec, Narcis Duteanu, Adina Negrea, Petru Negrea, Nicoleta Sorina Nemeş, Bogdan Pascu, Paula Svera (m. Ianasi), Cătălin Ianăşi, Daniel Marius Duda Seiman, Delia Muntean and Estera Boeriu

Toxics 2024, 12(6), 405; https://doi.org/10.3390/toxics12060405 - 31 May 2024

Cited by 1 | Viewed by 995

Abstract

The need to develop advanced wastewater treatment techniques and their use has become a priority, the main goal being the efficient removal of pollutants, especially those of organic origin. This study presents the photo-degradation of a pharmaceutical wastewater containing Kabi cytarabine, using ultraviolet [...] Read more.

The need to develop advanced wastewater treatment techniques and their use has become a priority, the main goal being the efficient removal of pollutants, especially those of organic origin. This study presents the photo-degradation of a pharmaceutical wastewater containing Kabi cytarabine, using ultraviolet (UV) radiation, and a synthesized catalyst, a composite based on bismuth and iron oxides (BFO). The size of the bandgap was determined by UV spectroscopy, having a value of 2.27 eV. The specific surface was determined using the BET method, having a value of 0.7 m² g⁻¹. The material studied for the photo-degradation of cytarabine presents a remarkable photo-degradation efficiency of 97.9% for an initial concentration 0f 10 mg/L cytarabine Kabi when 0.15 g of material was used, during 120 min of interaction with UV radiation at 3 cm from the irradiation source. The material withstands five photo-degradation cycles with good results. At the same time, through this study, it was possible to establish that pyrimidine derivatives could be able to combat infections caused by Escherichia coli and Candida parapsilosis. Full article

(This article belongs to the Special Issue Techniques and Methods for Toxic Agent Analysis and Removal)

► Show Figures

Figure 1

20 pages, 12157 KiB

Open AccessEditor’s ChoiceReview

Global Trends and Hotspots in Research on the Health Risks of Organophosphate Flame Retardants: A Bibliometric and Visual Analysis

by Zhiyuan Du, Yuanyuan Ruan, Jiabin Chen, Jian Fang, Shuo Xiao, Yewen Shi and Weiwei Zheng

Toxics 2024, 12(6), 391; https://doi.org/10.3390/toxics12060391 - 27 May 2024

Viewed by 1663

Abstract

Background: Organophosphate flame retardants (OPFRs) are compounds with a wide range of industrial and commercial applications and are mainly used as flame retardants and plasticizers. The global consumption of OPFRs has risen rapidly in recent decades, and they have been widely detected in [...] Read more.

Background: Organophosphate flame retardants (OPFRs) are compounds with a wide range of industrial and commercial applications and are mainly used as flame retardants and plasticizers. The global consumption of OPFRs has risen rapidly in recent decades, and they have been widely detected in environmental media. Unfortunately, OPFRs have been associated with many adverse health outcomes. The issue of the health risks of OPFRs is attracting increasing attention. Therefore, there is a need to review the current state of research and trends in this field to help researchers and policymakers quickly understand the field, identify new research directions, and allocate appropriate resources for further development of the OPFR health risk research field. Methods: This study statistically analyzed 1162 relevant publications included in the Web of Science Core Collection from 2003–2023. The internal and external features of the literature, such as publication trends, countries, authors, journals, and keywords, were quantitatively analyzed and visually presented to identify the research hotspots, compositions, and paradigms of the field and to horizontally and vertically analyze the development trends and structural evolution of the field. Results: The development of the field can be divided into three stages, and the field entered a period of rapid development in 2016. China (649 papers) is the most prolific country, followed by the United States (188 papers). The authors STAPLETON HM and WANG Y have the highest combined impact. International collaboration between countries and researchers still needs to be strengthened. Science of The Total Environment is the most frequently published journal (162 papers), and Environmental Science and Technology is the most frequently cited journal (5285 citations). Endocrine disruption, developmental toxicity, and neurotoxicity are the health effects of greatest interest. Conclusions: Future research is expected to be multidisciplinary, and research hotspots may involve a comprehensive assessment of OPFR exposure in the population, exploration of the mechanisms of endocrine-disrupting effects and in vivo metabolic processes, and examination of the health effects of OPFR metabolites. Full article

(This article belongs to the Special Issue Toxic Mode of Action, Toxicity Testing, and Health Risks of Environmental Pollutants)

► Show Figures

Figure 1

15 pages, 1791 KiB

Open AccessEditor’s ChoiceReview

Cadmium Exposure: Mechanisms and Pathways of Toxicity and Implications for Human Health

by Fei Qu and Weiwei Zheng

Toxics 2024, 12(6), 388; https://doi.org/10.3390/toxics12060388 - 26 May 2024

Cited by 11 | Viewed by 5684

Abstract

Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca²⁺ signaling, interference with cellular signaling [...] Read more.

Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca²⁺ signaling, interference with cellular signaling pathways, and epigenetic modifications. By detailing the absorption, distribution, metabolism, and excretion (ADME) of Cd, alongside its interactions with cellular components such as mitochondria and DNA, this paper highlights the extensive damage caused by Cd²⁺ at the cellular and tissue levels. The role of Cd in inducing oxidative stress—a pivotal mechanism behind its toxicity—is discussed with emphasis on how it disrupts the balance between oxidants and antioxidants, leading to cellular damage and apoptosis. Additionally, the review covers Cd’s impact on signaling pathways like Mitogen-Activated Protein Kinase (MAPK), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor Protein 53 (p53) pathways, illustrating how its interference with these pathways contributes to pathological conditions and carcinogenesis. The epigenetic effects of Cd, including DNA methylation and histone modifications, are also explored to explain its long-term impact on gene expression and disease manifestation. This comprehensive analysis not only elucidates the mechanisms of Cd toxicity but also underscores the critical need for enhanced strategies to mitigate its public health implications. Full article

(This article belongs to the Special Issue Toxic Mode of Action, Toxicity Testing, and Health Risks of Environmental Pollutants)

► Show Figures

Graphical abstract

12 pages, 3044 KiB

Open AccessEditor’s ChoiceArticle

Machine Learning to Predict Drug-Induced Liver Injury and Its Validation on Failed Drug Candidates in Development

by Fahad Mostafa, Victoria Howle and Minjun Chen

Toxics 2024, 12(6), 385; https://doi.org/10.3390/toxics12060385 - 24 May 2024

Viewed by 1197

Abstract

Drug-induced liver injury (DILI) poses a significant challenge for the pharmaceutical industry and regulatory bodies. Despite extensive toxicological research aimed at mitigating DILI risk, the effectiveness of these techniques in predicting DILI in humans remains limited. Consequently, researchers have explored novel approaches and [...] Read more.

Drug-induced liver injury (DILI) poses a significant challenge for the pharmaceutical industry and regulatory bodies. Despite extensive toxicological research aimed at mitigating DILI risk, the effectiveness of these techniques in predicting DILI in humans remains limited. Consequently, researchers have explored novel approaches and procedures to enhance the accuracy of DILI risk prediction for drug candidates under development. In this study, we leveraged a large human dataset to develop machine learning models for assessing DILI risk. The performance of these prediction models was rigorously evaluated using a 10-fold cross-validation approach and an external test set. Notably, the random forest (RF) and multilayer perceptron (MLP) models emerged as the most effective in predicting DILI. During cross-validation, RF achieved an average prediction accuracy of 0.631, while MLP achieved the highest Matthews Correlation Coefficient (MCC) of 0.245. To validate the models externally, we applied them to a set of drug candidates that had failed in clinical development due to hepatotoxicity. Both RF and MLP accurately predicted the toxic drug candidates in this external validation. Our findings suggest that in silico machine learning approaches hold promise for identifying DILI liabilities associated with drug candidates during development. Full article

(This article belongs to the Collection Predictive Toxicology)

► Show Figures

Figure 1

18 pages, 6218 KiB

Open AccessEditor’s ChoiceArticle

Utilization of Peptidoglycans from Lactic Acid Bacterial Cell Walls for the Mitigation of Acrylamide and 5-Hydroxymethylfurfural

by Hui Yang, Xue Zhang, Yadong Zhu, Bo Zhang, Junfeng Fan, Hongfei Zhao and Bolin Zhang

Toxics 2024, 12(6), 380; https://doi.org/10.3390/toxics12060380 - 23 May 2024

Viewed by 979

Abstract

Acrylamide (AA) and 5-hydroxymethylfurfural (HMF), which are potentially carcinogenic to humans, are often produced during the hot processing of foods. This study first used a molecular docking model to simulate the binding behavior of four lactic acid bacteria peptidoglycans (PGNs) to AA/HMF, and [...] Read more.

Acrylamide (AA) and 5-hydroxymethylfurfural (HMF), which are potentially carcinogenic to humans, are often produced during the hot processing of foods. This study first used a molecular docking model to simulate the binding behavior of four lactic acid bacteria peptidoglycans (PGNs) to AA/HMF, and the binding rate of LAB-based PGNs to AA/HMF was evaluated in vitro. In silico results show that interaction energy is the driving force responsible for the adsorption of LAB-derived PGNs to AA/HMF. In vitro results showed that the PGN of B. lactis B1-04 bound the most AA (28.7%) and HMF (48.0%), followed by L. acidophilus NCFM, B. breve CICC 6079, and L. plantarum CICC 22135. Moreover, an AA/HMF-bound layer on the cell surface of B. lactis B1-04 was observed via AFM and SEM due to adsorption. XPS analysis indicated the removal rate of AA/HMF by selected strains was positively correlated with the proportion of C-O, C=O, and N-H groups of PGNs. The atoms O1, O2, O3, O4, N1, N2, N3, H1, and H2 are involved in the adsorption of LAB-based PGNs to AA/HMF. Thus, the PGNs derived from these four Lactobacillus strains can be regarded as natural adsorbents for the binding of AA/HMF. Full article

(This article belongs to the Section Agrochemicals and Food Toxicology)

► Show Figures

Figure 1

17 pages, 7667 KiB

Open AccessEditor’s ChoiceArticle

The Protective Effects of Ganoderma lucidum Active Peptide GLP4 on Lung Injury Induced by Cadmium Poisoning in Mice

by Shirong Zhu, Xiaoling Wang and Gaoqiang Liu

Toxics 2024, 12(6), 378; https://doi.org/10.3390/toxics12060378 - 22 May 2024

Cited by 1 | Viewed by 1211

Abstract

Ganoderma triterpenes and spore powder have shown promising results in mitigating cadmium-induced renal and hepatic injuries. Ganoderma lucidum active peptide GLP4 is a natural protein with dual antioxidant activities derived from the mycelium of Ganoderma lucidum. However, its efficacy in alleviating cadmium-induced [...] Read more.

Ganoderma triterpenes and spore powder have shown promising results in mitigating cadmium-induced renal and hepatic injuries. Ganoderma lucidum active peptide GLP4 is a natural protein with dual antioxidant activities derived from the mycelium of Ganoderma lucidum. However, its efficacy in alleviating cadmium-induced lung injury remains unexplored. This study aims to investigate the protective effects of GLP4 against cadmium-induced lung injury in mice. Mice were exposed to cadmium chloride via nebulization to induce lung injury. The protective effect of GLP4 was assessed by measuring the total cell count in BALF, levels of inflammatory cytokines, and the expression of NLRP3 in lung tissues a through histopathological examination of lung tissue changes. The results showed that GLP4 significantly mitigated histopathological damage in lung tissues, decreased the secretion of inflammatory cytokines, and reduced the expression of NLRP3, which was elevated in cadmium-exposed mice. In vitro studies further revealed that GLP4 inhibited the cadmium-induced activation of the NLRP3 inflammasome. Notably, acute cadmium exposure by the respiratory tract did not affect the liver and kidneys of the mice. The findings suggest that GLP4 reduces cadmium-induced lung injury in mice by inhibiting the activation of the NLRP3 inflammasome, which provides a theoretical foundation for using Ganoderma lucidum as a preventive and therapeutic agent against cadmium poisoning. Full article

(This article belongs to the Section Human Toxicology and Epidemiology)

► Show Figures

Figure 1

15 pages, 8550 KiB

Open AccessEditor’s ChoiceArticle

Effects of 17β-Estradiol Pollution on Microbial Communities and Methane Emissions in Aerobic Water Bodies

by Zihao Gao, Yu Zheng, Zhendong Li and Aidong Ruan

Toxics 2024, 12(5), 373; https://doi.org/10.3390/toxics12050373 - 19 May 2024

Viewed by 1034

Abstract

17β-Estradiol (E2) is a widely present trace pollutant in aquatic environments. However, its impact on microbial communities in aerobic lake waters, which are crucial for methane (CH₄) production, remains unclear. This study conducted an E2 contamination experiment by constructing laboratory-simulated aerobic [...] Read more.

17β-Estradiol (E2) is a widely present trace pollutant in aquatic environments. However, its impact on microbial communities in aerobic lake waters, which are crucial for methane (CH₄) production, remains unclear. This study conducted an E2 contamination experiment by constructing laboratory-simulated aerobic microecosystems. Using 16S rRNA high-throughput sequencing, the effects of E2 on bacterial and archaeal communities were systematically examined. Combined with gas chromatography, the patterns and mechanisms of E2’s impact on CH₄ emissions in aerobic aquatic systems were uncovered for the first time. Generally, E2 contamination increased the randomness of bacterial and archaeal community assemblies and weakened microbial interactions. Furthermore, changes occurred in the composition and ecological functions of bacterial and archaeal communities under E2 pollution. Specifically, two days after exposure to E2, the relative abundance of Proteobacteria in the low-concentration (L) and high-concentration (H) groups decreased by 6.99% and 4.01%, respectively, compared to the control group (C). Conversely, the relative abundance of Planctomycetota was 1.81% and 1.60% higher in the L and H groups, respectively. E2 contamination led to an increase in the relative abundance of the methanogenesis functional group and a decrease in that of the methanotrophy functional group. These changes led to an increase in CH₄ emissions. This study comprehensively investigated the ecotoxicological effects of E2 pollution on microbial communities in aerobic water bodies and filled the knowledge gap regarding aerobic methane production under E2 contamination. Full article

(This article belongs to the Special Issue Occurrence, Accumulation, and Impacts of Environmental Pollutants in Aquatic Systems)

► Show Figures

Figure 1

17 pages, 4489 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Segmentation of Renal Thyroid Follicle Colloid in Common Carp: Insights into Perfluorooctanoic Acid-Induced Morphometric Alterations

by Maurizio Manera and Luisa Giari

Toxics 2024, 12(5), 369; https://doi.org/10.3390/toxics12050369 - 17 May 2024

Viewed by 1170

Abstract

Perfluorooctanoic acid (PFOA) is a globally prevalent contaminant of concern recognised for its persistence and detrimental effects on both wildlife and humans. While PFOA has been established as a disruptor of thyroid function, limited data exist regarding its impact on thyroid morphology. The [...] Read more.

Perfluorooctanoic acid (PFOA) is a globally prevalent contaminant of concern recognised for its persistence and detrimental effects on both wildlife and humans. While PFOA has been established as a disruptor of thyroid function, limited data exist regarding its impact on thyroid morphology. The kidney of the common carp (Cyprinus carpio) harbours numerous thyroid follicles, rendering it a valuable biomarker organ for investigating PFOA-induced thyroid alterations. Renal tissue slides, stained with the Alcian blue/PAS method, were examined from carp in three experimental groups: unexposed, exposed to 200 ng L⁻¹, and exposed to 2 mg L⁻¹ of PFOA over 56 days. Thyroid follicle colloids were segmented, and related morphometric parameters, including perimeter, area, and shape descriptors, were obtained. Statistical analyses revealed significant reductions in thyroid follicle colloid perimeter and area in the 200 ng L⁻¹ PFOA group compared to the unexposed and 2 mg L⁻¹ PFOA groups. Additionally, the fish exposed to PFOA exhibited a significantly higher follicle count compared to the unexposed fish. These findings collectively suggest that PFOA induces thyroid folliculogenesis, emphasising its impact on thyroid morphology even at an environmentally relevant concentration (200 ng L⁻¹). Full article

(This article belongs to the Special Issue Impact of Per- and Polyfluoroalkyl Substances (PFAS) on Aquatic Animals: Immunotoxicity, Endocrine Disruption, and Beyond)

► Show Figures

Figure 1

14 pages, 12382 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Environmentally Relevant Concentrations of Triphenyl Phosphate (TPhP) Impact Development in Zebrafish

by Benjamin Schmandt, Mfon Diduff, Gabrielle Smart and Larissa M. Williams

Toxics 2024, 12(5), 368; https://doi.org/10.3390/toxics12050368 - 16 May 2024

Viewed by 2126

Abstract

A common flame-retardant and plasticizer, triphenyl phosphate (TPhP) is an aryl phosphate ester found in many aquatic environments at nM concentrations. Yet, most studies interrogating its toxicity have used µM concentrations. In this study, we used the model organism zebrafish (Danio rerio [...] Read more.

A common flame-retardant and plasticizer, triphenyl phosphate (TPhP) is an aryl phosphate ester found in many aquatic environments at nM concentrations. Yet, most studies interrogating its toxicity have used µM concentrations. In this study, we used the model organism zebrafish (Danio rerio) to uncover the developmental impact of nM exposures to TPhP at the phenotypic and molecular levels. At concentrations of 1.5–15 nM (0.5 µg/L–5 µg/L), chronically dosed 5dpf larvae were shorter in length and had pericardial edema phenotypes that had been previously reported for exposures in the µM range. Cardiotoxicity was observed but did not present as cardiac looping defects as previously reported for µM concentrations. The RXR pathway does not seem to be involved at nM concentrations, but the tbx5a transcription factor cascade including natriuretic peptides (nppa and nppb) and bone morphogenetic protein 4 (bmp4) were dysregulated and could be contributing to the cardiac phenotypes. We also demonstrate that TPhP is a weak pro-oxidant, as it increases the oxidative stress response within hours of exposure. Overall, our data indicate that TPhP can affect animal development at environmentally relevant concentrations and its mode of action involves multiple pathways. Full article

(This article belongs to the Special Issue Environmental Pollutants Toxicity Mechanism and Safety Testing: Zebrafish as a Model Organism)

► Show Figures

Graphical abstract

11 pages, 1303 KiB

Open AccessEditor’s ChoicePerspective

Food Plants and Environmental Contamination: An Update

by Nicoletta Guerrieri, Stefania Mazzini and Gigliola Borgonovo

Toxics 2024, 12(5), 365; https://doi.org/10.3390/toxics12050365 - 15 May 2024

Cited by 2 | Viewed by 1970

Abstract

Food plants are the basis of human nutrition, but, in contaminated places, they can uptake contaminants. Environmental contamination and climate change can modify food quality; generally, they have a negative impact on and imply risks to human health. Heavy metals, like lead, arsenic, [...] Read more.

Food plants are the basis of human nutrition, but, in contaminated places, they can uptake contaminants. Environmental contamination and climate change can modify food quality; generally, they have a negative impact on and imply risks to human health. Heavy metals, like lead, arsenic, cadmium, and chromium, can be present at various environmental levels (soil, water, and atmosphere), and they are widely distributed in the world. Food plants can carry out heavy metal bioaccumulation, a defense pathway for plants, which is different for every plant species. Accumulation is frequent in the roots and the leaves, and heavy metals can be present in fruits and seeds; As and Cd are always present. In addition, other contaminants can bioaccumulate in food plants, including emerging contaminants, like persistent organic pollutants (POPs), pesticides, and microplastics. In food plants, these are present in the roots but also in the leaves and fruits, depending on their chemical structure. The literature published in recent years was examined to understand the distribution of contaminants among food plants. In the literature, old agronomical practices and new integrated technology to clean the water, control the soil, and monitor the crops have been proposed to mitigate contamination and produce high food quality and high food safety. Full article

(This article belongs to the Special Issue Environmental Pollution and Food Safety)

► Show Figures

Figure 1

13 pages, 1218 KiB

Open AccessEditor’s ChoicePerspective

Inhalation of Microplastics—A Toxicological Complexity

by Myriam Borgatta and Florian Breider

Toxics 2024, 12(5), 358; https://doi.org/10.3390/toxics12050358 - 11 May 2024

Cited by 4 | Viewed by 1684

Abstract

Humans are chronically exposed to airborne microplastics (MPs) by inhalation. Various types of polymer particles have been detected in lung samples, which could pose a threat to human health. Inhalation toxicological studies are crucial for assessing the effects of airborne MPs and for [...] Read more.

Humans are chronically exposed to airborne microplastics (MPs) by inhalation. Various types of polymer particles have been detected in lung samples, which could pose a threat to human health. Inhalation toxicological studies are crucial for assessing the effects of airborne MPs and for exposure-reduction measures. This communication paper addresses important health concerns related to MPs, taking into consideration three levels of complexity, i.e., the particles themselves, the additives present in the plastics, and the exogenous substances adsorbed onto them. This approach aims to obtain a comprehensive toxicological profile of deposited MPs in the lungs, encompassing local and systemic effects. The physicochemical characteristics of MPs may play a pivotal role in lung toxicity. Although evidence suggests toxic effects of MPs in animal and cell models, no established causal link with pulmonary or systemic diseases in humans has been established. The transfer of MPs and associated chemicals from the lungs into the bloodstream and/or pulmonary circulation remains to be confirmed in humans. Understanding the toxicity of MPs requires a multidisciplinary investigation using a One Health approach. Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

► Show Figures

Figure 1

22 pages, 4680 KiB

Open AccessEditor’s ChoiceArticle

Exposure to a PFOA, PFOS and PFHxS Mixture during Gestation and Lactation Alters the Liver Proteome in Offspring of CD-1 Mice

by Emily Kaye, Emily Marques, Juliana Agudelo Areiza, Seyed Mohamad Sadegh Modaresi and Angela Slitt

Toxics 2024, 12(5), 348; https://doi.org/10.3390/toxics12050348 - 9 May 2024

Cited by 1 | Viewed by 1783

Abstract

Perfluroalkyl substances (PFASs) are persistent man-made chemicals considered to be emerging pollutants, with Perfluorooctanoic acid (PFOA), Perfluorooctanesulfonic acid (PFOS), and Perfluorohexanesulphonic acid (PFHxS) being linked to hepatotoxicity and steatosis. PFOA, PFOS, and PFHxS can undergo placental and lactational transfer, which results in PFOA, [...] Read more.

Perfluroalkyl substances (PFASs) are persistent man-made chemicals considered to be emerging pollutants, with Perfluorooctanoic acid (PFOA), Perfluorooctanesulfonic acid (PFOS), and Perfluorohexanesulphonic acid (PFHxS) being linked to hepatotoxicity and steatosis. PFOA, PFOS, and PFHxS can undergo placental and lactational transfer, which results in PFOA, PFOS, and PFHxS distribution to the neonatal liver. Moreover, in pregnant dams, exposure to a PFAS mixture, in combination with a high fat diet, increased hepatic steatosis in offspring at postnatal day 21, but the mechanisms have not been elucidated. It was hypothesized that gestational/lactational PFAS exposure would alter the pup liver proteome and biochemical/signaling pathways. Timed-pregnant CD-1 dams were fed a standard chow or 60% kcal high-fat diet. From GD1 until PND20, dams were dosed via oral gavage with vehicle (0.5% Tween 20), individual doses of PFOA, PFOS, PFHxS at 1 mg/kg, or a mixture (1 mg/kg each, totaling 3 mg/kg). Livers were collected from PND21 offspring and SWATH-MS proteomics was performed. IPA analysis revealed PFAS exposure modified disease and biological function pathways involved in liver damage, xenobiotics, and lipid regulation in the PND21 liver. These pathways included lipid and fatty acid transport, storage, oxidation, and synthesis, as well as xenobiotic metabolism and transport, and liver damage and inflammation. This indicates the pup liver proteome is altered via maternal exposure and predisposes the pup to metabolic dysfunctions. Full article

(This article belongs to the Special Issue PFAS Toxicology and Metabolism)

► Show Figures

Figure 1

13 pages, 578 KiB

Open AccessEditor’s ChoiceArticle

Association between Prenatal Dietary Toxicants and Infant Neurodevelopment: The Role of Fish

by Xiruo Kou, Nerea Becerra-Tomás, Josefa Canals, Monica Bulló and Victoria Arija

Toxics 2024, 12(5), 338; https://doi.org/10.3390/toxics12050338 - 6 May 2024

Viewed by 1470

Abstract

More research is needed to understand how the maternal consumption of fish and fish-borne toxicants impacts infant neurodevelopment. The present analysis was conducted over 460 mother–infant pairs within the ECLIPSES study. Dietary intake of metals and persistent organic pollutants from fish (including white [...] Read more.

More research is needed to understand how the maternal consumption of fish and fish-borne toxicants impacts infant neurodevelopment. The present analysis was conducted over 460 mother–infant pairs within the ECLIPSES study. Dietary intake of metals and persistent organic pollutants from fish (including white fish, blue fish, and seafood) was estimated in pregnant women. The infants underwent cognitive, language, and motor function assessments using the Bayley Scales of Infant Development-III at the 40-day postpartum. Associations between dietary toxicants and outcomes were assessed using multivariable linear regression models. Estimated prenatal exposure to fish-borne toxicants, such as arsenic, inorganic arsenic, methylmercury, dioxin-like polychlorinated biphenyls (DL-PCBs), and non-DL-PCBs, was associated with poorer language functions in infants, whereas no significant associations were found with motor or cognitive functions. Maternal fish consumption exceeding the Spanish recommendation of no more than 71 g per day was linked to these adverse effects on language abilities without affecting motor or cognitive development. This highlights the importance of vigilant monitoring of environmental toxicants and the provision of dietary guidance for pregnant women, with potential implications for public health and child development. Full article

(This article belongs to the Special Issue Toxicology Research of Foodborne Contaminants)

► Show Figures

Figure 1

13 pages, 1021 KiB

Open AccessEditor’s ChoiceArticle

Spatial Variation in Mercury Accumulation in Bottlenose Dolphins (Tursiops spp.) in Southeastern U.S.A.

by Mackenzie L. Griffin, Colleen E. Bryan, Tara M. Cox, Brian C. Balmer, Russell D. Day, Laura Garcia Barcia, Antoinette M. Gorgone, Jeremy J. Kiszka, Jenny A. Litz, Robin M. Perrtree, Teri K. Rowles, Lori H. Schwacke, Randall S. Wells and Eric Zolman

Toxics 2024, 12(5), 327; https://doi.org/10.3390/toxics12050327 - 30 Apr 2024

Viewed by 2816

Abstract

Bottlenose dolphins (Tursiops spp.) inhabit bays, sounds, and estuaries (BSEs) throughout the southeast region of the U.S.A. and are sentinel species for human and ecosystem-level health. Dolphins are vulnerable to the bioaccumulation of contaminants through the coastal food chain because they are [...] Read more.

Bottlenose dolphins (Tursiops spp.) inhabit bays, sounds, and estuaries (BSEs) throughout the southeast region of the U.S.A. and are sentinel species for human and ecosystem-level health. Dolphins are vulnerable to the bioaccumulation of contaminants through the coastal food chain because they are high-level predators. Currently, there is limited information on the spatial dynamics of mercury accumulation in these dolphins. Total mercury (THg) was measured in dolphin skin from multiple populations across the U.S. Southeast Atlantic and Gulf of Mexico coasts, and the influence of geographic origin, sex, and age class was investigated. Mercury varied significantly among sampling sites and was greatest in dolphins in St. Joseph Bay, Florida Everglades, and Choctawhatchee Bay (14,193 ng/g ± 2196 ng/g, 10,916 ng/g ± 1532 ng/g, and 7333 ng/g ± 1405 ng/g wet mass (wm), respectively) and lowest in dolphins in Charleston and Skidaway River Estuary (509 ng/g ± 32.1 ng/g and 530 ng/g ± 58.4 ng/g wm, respectively). Spatial mercury patterns were consistent regardless of sex or age class. Bottlenose dolphin mercury exposure can effectively represent regional trends and reflect large-scale atmospheric mercury input and local biogeochemical processes. As a sentinel species, the bottlenose dolphin data presented here can direct future studies to evaluate mercury exposure to human residents in St. Joseph Bay, Choctawhatchee Bay, and Florida Coastal Everglades, as well as additional sites with similar geographical, oceanographic, or anthropogenic parameters. These data may also inform state and federal authorities that establish fish consumption advisories to determine if residents in these locales are at heightened risk for mercury toxicity. Full article

(This article belongs to the Special Issue The Impact of Heavy Metals on Aquatic Ecosystems)

► Show Figures

Figure 1

18 pages, 3898 KiB

Open AccessEditor’s ChoiceArticle

Identification and Visualization of Polystyrene Microplastics/Nanoplastics in Flavored Yogurt by Raman Imaging

by Xin Ling, Jun Cheng, Weirong Yao, He Qian, Dazhi Ding, Zhilong Yu, Yunfei Xie and Fangwei Yang

Toxics 2024, 12(5), 330; https://doi.org/10.3390/toxics12050330 - 30 Apr 2024

Viewed by 2002

Abstract

The contamination of food by microplastics has garnered widespread attention, particularly concerning the health risks associated with small-sized microplastics. However, detecting these smaller microplastics in food poses challenges attributed to the complexity of food matrices and instrumental and method limitations. Here, we employed [...] Read more.

The contamination of food by microplastics has garnered widespread attention, particularly concerning the health risks associated with small-sized microplastics. However, detecting these smaller microplastics in food poses challenges attributed to the complexity of food matrices and instrumental and method limitations. Here, we employed Raman imaging for visualization and identification of polystyrene particles synthesized in polymerization reactions, ranging from 400 to 2600 nm. We successfully developed a quantitative model of particle size and concentration for polystyrene, exhibiting excellent fit (R² of 0.9946). We established procedures for spiked flavored yogurt using synthesized polystyrene, providing fresh insights into microplastic extraction efficiency. Recovery rates calculated from models validated the method’s feasibility. In practical applications, the assessment of the size, type, shape, and quantity of microplastics in unspiked flavored yogurt was conducted. The most common polymers found were polystyrene, polypropylene, and polyethylene, with the smallest polystyrene sizes ranging from 1 to 10 μm. Additionally, we conducted exposure assessments of microplastics in branded flavored yogurt. This study established a foundation for developing a universal method to quantify microplastics in food, covering synthesis of standards, method development, validation, and application. Full article

(This article belongs to the Special Issue Detection and Risk Assessment of Undesirable Chemical Residues in Food)

► Show Figures

Graphical abstract

22 pages, 2261 KiB

Open AccessEditor’s ChoiceReview

Potential Effects of Environmental and Occupational Exposure to Microplastics: An Overview of Air Contamination

by Priscilla Boccia, Simona Mondellini, Simona Mauro, Miriam Zanellato, Marco Parolini and Elena Sturchio

Toxics 2024, 12(5), 320; https://doi.org/10.3390/toxics12050320 - 28 Apr 2024

Cited by 3 | Viewed by 1877

Abstract

Microplastics (MPs) are now ubiquitous environmental contaminants that lead to unavoidable human exposure; they have received increasing attention in recent years and have become an emerging area of research. The greatest concern is the negative impacts of MPs on marine, fresh-water, and terrestrial [...] Read more.

Microplastics (MPs) are now ubiquitous environmental contaminants that lead to unavoidable human exposure; they have received increasing attention in recent years and have become an emerging area of research. The greatest concern is the negative impacts of MPs on marine, fresh-water, and terrestrial ecosystems, as well as human health, to the extent that the World Health Organization (WHO) calls for increased research and standardized methods to assess exposure to MPs. Many countries and international organizations are implementing or proposing legislation in this regard. This review aims to summarize the current state of legislation, indoor and outdoor contamination, and potential human health risk due to exposure to airborne MPs, considering that occupational exposure to MPs is also becoming a growing area of concern. Even though research regarding MPs has continuously increased in the last twenty years, the effects of MPs on human health have been scarcely investigated, and toxicity studies are still limited and not directly comparable, due to the lack of standardized studies in this field. Full article

(This article belongs to the Special Issue Microplastic Pollution and Impact on Aquatic and Terrestrial Ecosystems)

► Show Figures

Figure 1

13 pages, 282 KiB

Open AccessEditor’s ChoiceArticle

Lead Levels in the Most Consumed Mexican Foods: First Monitoring Effort

by Alejandra Cantoral, Larissa Betanzos-Robledo, Sonia Collado-López, Betzabeth A. García-Martínez, Héctor Lamadrid-Figueroa, Rosa M. Mariscal-Moreno, Araceli Díaz-Ruiz, Camilo Ríos and Martha María Téllez-Rojo

Toxics 2024, 12(5), 318; https://doi.org/10.3390/toxics12050318 - 28 Apr 2024

Viewed by 1697

Abstract

Globally, there is growing concern over the presence of lead (Pb) in foods because it is a heavy metal with several toxic effects on human health. However, monitoring studies have not been conducted in Mexico. In this study, we estimated the concentrations of [...] Read more.

Globally, there is growing concern over the presence of lead (Pb) in foods because it is a heavy metal with several toxic effects on human health. However, monitoring studies have not been conducted in Mexico. In this study, we estimated the concentrations of Pb in the most consumed foods and identified those that exceeded the maximum limits (MLs) for Pb in foods established by the International Standards. Based on the Mexican National Health and Nutrition Survey, 103 foods and beverages were selected and purchased in Mexico City retail stores and markets. Samples were analyzed twice using atomic absorption spectrophotometry. Values above the limit of quantification (0.0025 mg/kg) were considered to be detected. The percentage of detected values was 18%. The highest concentration was found in infant rice cereal (1.005 mg/kg), whole wheat bread (0.447 mg/kg), pre-cooked rice (0.276 mg/kg), black pepper (0.239 mg/kg), and turmeric (0.176 mg/kg). Among the foods with detected Pb, the levels in infant rice cereal, whole wheat bread, pre-cooked rice, and soy infant formula exceeded the MLs. The food groups with the highest percentages of exceeded MLs were baby foods (18%) and cereals (11%). Monitoring the concentration of contaminants in foods is essential for implementing food safety policies and protecting consumer health. Full article

(This article belongs to the Section Metals and Radioactive Substances)

17 pages, 5234 KiB

Open AccessEditor’s ChoiceArticle

Analysis of Binding Modes between Three Perfluorosulfonates and GPER Based on Computational Simulation and Multiple Spectral Methods

by Wenhui Liang, Yanting Chen, Yuchen Wei, Zeyu Song, Cancan Li, Yanhong Zheng and Zhongsheng Yi

Toxics 2024, 12(5), 315; https://doi.org/10.3390/toxics12050315 - 26 Apr 2024

Viewed by 1462

Abstract

Perfluorinated compounds (PFCs) belong to a significant category of global environmental pollutants. Investigating the toxicological effects of PFCs within biological systems is of critical significance in various disciplines such as life sciences, environmental science, chemistry, and ecotoxicology. In this study, under simulated human [...] Read more.

Perfluorinated compounds (PFCs) belong to a significant category of global environmental pollutants. Investigating the toxicological effects of PFCs within biological systems is of critical significance in various disciplines such as life sciences, environmental science, chemistry, and ecotoxicology. In this study, under simulated human physiological conditions (pH = 7.4), a combination of multiple spectroscopic techniques and computational simulations was employed to investigate the impact of perfluorinated compounds (PFCs) on the G protein-coupled estrogen receptor (GPER). Additionally, the research focused on exploring the binding modes and toxicological mechanisms between PFCs and GPER at the molecular level. All three perfluorinated sulfonic acids (PFSAs) can induce quenching of GPER fluorescence through static quenching and non-radiative energy transfer. Steady-state fluorescence calculations at different temperatures revealed apparent binding constants in the order of 10⁶, confirming a strong binding affinity between the three PFSAs and GPER. Molecular docking studies indicated that the binding sites of PFSAs are located within the largest hydrophobic cavity in the head region of GPER, where they can engage in hydrogen bonding and hydrophobic interactions with amino acid residues within the cavity. Fourier transform infrared spectroscopy, three-dimensional fluorescence, and molecular dynamics simulations collectively indicate that proteins become more stable upon binding with small molecules. There is an overall increase in hydrophobicity, and alterations in the secondary structure of the protein are observed. This study deepens the comprehension of the effects of PFCs on the endocrine system, aiding in evaluating their potential impact on human health. It provides a basis for policy-making and environmental management while also offering insights for developing new pollution monitoring methods and drug therapies. Full article

(This article belongs to the Special Issue Computational Toxicology for Environmental Criteria/Benchmarks of Emerging Contaminants)

► Show Figures

Figure 1

16 pages, 2293 KiB

Open AccessEditor’s ChoiceArticle

Perinatal Tetrahydrocannabinol Compromises Maternal Care and Increases Litter Attrition in the Long–Evans Rat

by Emma Carlson, Eric Teboul, Charlene Canale, Harper Coleman, Christina Angeliu, Karissa Garbarini and Vincent P. Markowski

Toxics 2024, 12(5), 311; https://doi.org/10.3390/toxics12050311 - 26 Apr 2024

Viewed by 2803

Abstract

The marijuana legalization trend in the U.S. will likely lead to increased use by younger adults during gestation and postpartum. The current study examined the hypothesis that delta-9-tetrahydrocannabinol (THC) would disrupt voluntary maternal care behaviors and negatively impact offspring development. Rat dams were [...] Read more.

The marijuana legalization trend in the U.S. will likely lead to increased use by younger adults during gestation and postpartum. The current study examined the hypothesis that delta-9-tetrahydrocannabinol (THC) would disrupt voluntary maternal care behaviors and negatively impact offspring development. Rat dams were gavaged with 0, 2, 5, or 10 mg/kg THC from the 1st day of gestation through the 21st postnatal day. Somatic growth and developmental milestones were measured in the offspring, and maternal pup retrieval tests were conducted on postnatal days 1, 3, and 5. THC did not affect body growth but produced transient delays in the righting reflex and eye opening in offspring. However, there was significant pup mortality due to impaired maternal care. Dams in all THC groups took significantly longer to retrieve their pups to the nest and often failed to retrieve any pups. Serum levels of THC and metabolites measured at this time were comparable to those in breastfeeding women who are chronic users. Benchmark doses associated with a 10% reduction of pup retrieval or increased pup mortality were 0.383 (BMDL 0.228) and 0.794 (BMDL 0.442) mg/kg THC, respectively. The current findings indicate that maternal care is an important and heretofore overlooked index of THC behavioral toxicity and should be included in future assessments of THC’s health risks. Full article

(This article belongs to the Section Drugs Toxicity)

► Show Figures

Figure 1

18 pages, 2503 KiB

Open AccessEditor’s ChoiceArticle

Reproductive and Developmental Effects of Sex-Specific Chronic Exposure to Dietary Arsenic in Zebrafish (Danio rerio)

by Mahesh Rachamalla, Arash Salahinejad, Vladimir Kodzhahinchev and Som Niyogi

Toxics 2024, 12(4), 302; https://doi.org/10.3390/toxics12040302 - 19 Apr 2024

Cited by 1 | Viewed by 1567

Abstract

The present study investigated the reproductive and developmental effects of sex-specific chronic exposure to dietary arsenic in zebrafish. Adult zebrafish (Danio rerio) were exposed to environmentally realistic doses of arsenic via diet [0 (control; no added arsenic), 30 (low), 60 (medium), [...] Read more.

The present study investigated the reproductive and developmental effects of sex-specific chronic exposure to dietary arsenic in zebrafish. Adult zebrafish (Danio rerio) were exposed to environmentally realistic doses of arsenic via diet [0 (control; no added arsenic), 30 (low), 60 (medium), and 100 (high) μg/g dry weight, as arsenite] for 90 days. Following exposure, arsenic-exposed females from each dietary treatment were mated with control males, and similarly, arsenic-exposed males from each dietary treatment were mated with control females. In females, arsenic exposure resulted in a dose-dependent decrease in reproductive performance (fecundity, fertilization success, and hatching success). Moreover, a dose-dependent increase in developmental toxicity (larval deformities and larval mortality) was observed with maternal exposure to arsenic. In contrast, in males, arsenic exposure also induced similar reproductive and developmental toxicity; however, the adverse effects were mainly evident only in the medium and high dietary arsenic treatment groups. We also examined the sex-specific effects of dietary arsenic exposure on the expression of genes that regulate the hypothalamus–pituitary–gonadal–liver (HPG-L) axis in fish. The gene expression results indicated the downregulation of HPG-L axis genes in females irrespective of the arsenic treatment dose; however, the reduced expression of HPG-L axis genes in males was recorded only in the medium and high arsenic treatment groups. These observations suggest that chronic arsenic exposure in either females or males causes reproductive and developmental toxicity in zebrafish. However, these toxic effects are markedly higher in females than in males. Our results also suggest that arsenic can act as an endocrine disruptor and mediate reproductive and developmental toxicity by disrupting the HPG-L axis in zebrafish. Full article

(This article belongs to the Special Issue Endocrine-Disrupting Chemicals and Reproductive Toxicology)

► Show Figures

Figure 1

17 pages, 1668 KiB

Open AccessEditor’s ChoiceArticle

Lipid Dysregulation Induced by Gasoline and Diesel Exhaust Exposure and the Interaction with Age

by Yutong Gao, Xinzhuo Zhang, Xinting Li, Jinsheng Zhang, Zongyan Lv, Dongping Guo, Hongjun Mao and Ting Wang

Toxics 2024, 12(4), 303; https://doi.org/10.3390/toxics12040303 - 19 Apr 2024

Viewed by 1667

Abstract

Limited knowledge exists regarding gasoline and diesel exhaust effects on lipid metabolism. This study collected gasoline and diesel exhaust under actual driving conditions and conducted inhalation exposure on male young and middle-aged C57BL/6J mice for 4 h/day for 5 days to simulate commuting [...] Read more.

Limited knowledge exists regarding gasoline and diesel exhaust effects on lipid metabolism. This study collected gasoline and diesel exhaust under actual driving conditions and conducted inhalation exposure on male young and middle-aged C57BL/6J mice for 4 h/day for 5 days to simulate commuting exposure intensity. Additionally, PM_2.5 from actual roadways, representing gasoline and diesel vehicles, was generated for exposure to human umbilical vein endothelial cells (HUVECs) and normal liver cells (LO2) for 24, 48, and 72 h to further investigate exhaust particle toxicity. Results showed that diesel exhaust reduced total cholesterol and low-density lipoprotein cholesterol levels in young mice, indicating disrupted lipid metabolism. Aspartate aminotransferase and alanine aminotransferase levels increased by 53.7% and 21.7%, respectively, suggesting potential liver injury. Diesel exhaust exposure decreased superoxide dismutase and increased glutathione peroxidase levels. Cell viability decreased, and reactive oxygen species levels increased in HUVECs and LO2 following exposure to exhaust particles, with dose- and time-dependent effects. Diesel exhaust particles exhibited more severe inhibition of cell proliferation and oxidative damage compared to gasoline exhaust particles. These findings provide novel evidence of the risk of disrupted lipid metabolism due to gasoline and diesel exhaust, emphasizing the toxicity of diesel exhaust. Full article

(This article belongs to the Special Issue Toxicity and Human Health Assessment of Air Pollutants)

► Show Figures

Graphical abstract

14 pages, 3474 KiB

Open AccessEditor’s ChoiceArticle

Oleanolic Acid Acetate Alleviates Cisplatin-Induced Nephrotoxicity via Inhibition of Apoptosis and Necroptosis In Vitro and In Vivo

by Bori Lee, Yeon-Yong Kim, Seungwon Jeong, Seung Woong Lee, Seung-Jae Lee, Mun-Chual Rho, Sang-Hyun Kim and Soyoung Lee

Toxics 2024, 12(4), 301; https://doi.org/10.3390/toxics12040301 - 18 Apr 2024

Cited by 1 | Viewed by 2160

Abstract

Cisplatin is a widely used anti-cancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. [...] Read more.

Cisplatin is a widely used anti-cancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas it increased Bcl-2 expression. Moreover, in a cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor-interacting protein kinase (RIPK) and mixed lineage kinase domain-like (MLKL) were identified. In an in vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted via co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anti-cancer adjuvant. Full article

(This article belongs to the Section Drugs Toxicity)

► Show Figures

Figure 1

14 pages, 276 KiB

Open AccessEditor’s ChoiceArticle

Monitoring and Risk Assessment of Pesticide Residues in Fishery Products Using GC–MS/MS in South Korea

by Myungheon Kim, Mihyun Cho, Seo-Hong Kim, Yoonmi Lee, Mi-Ra Jo, Yong-Sun Moon and Moo-Hyeog Im

Toxics 2024, 12(4), 299; https://doi.org/10.3390/toxics12040299 - 18 Apr 2024

Cited by 3 | Viewed by 2181

Abstract

The aim of this study was to assess the risk of pesticide contamination in aquaculture and its impact on fishery products. We conducted an assessment of 300 samples collected from nine regions in South Korea, including various types of seafood, such as freshwater [...] Read more.

The aim of this study was to assess the risk of pesticide contamination in aquaculture and its impact on fishery products. We conducted an assessment of 300 samples collected from nine regions in South Korea, including various types of seafood, such as freshwater fish, marine fish, crustaceans, and shellfish. Pesticide residues in seafood were analyzed using GC–MS/MS after sample preparation using a modified QuEChERS method, revealing the presence of eight pesticides (4,4′-DDE, 4,4′-DDT, boscalid, isoprothiolane, oxadiazon, pendimethalin, thifluzamide, and trifluralin) across seven fish species (carp, far eastern catfish, crucian carp, eel, Chinese muddy loach, mirror carp, and sea bass). Following the grouping of DDE with DDT, a risk assessment of fishery products was conducted. After the estimated daily intake (EDI) of fish was calculated and compared with the acceptable daily intake (ADI), the health risk index (HI, %ADI) of the detected pesticides was evaluated and found to be 1.07% or lower. The results suggest that the consumption of domestically farmed fish products in South Korea poses minimal health risks associated with pesticide residues. Full article

(This article belongs to the Special Issue Detection and Risk Assessment of Undesirable Chemical Residues in Food)

14 pages, 3892 KiB

Open AccessEditor’s ChoiceArticle

Decreased Ubiquitination and Acetylation of Histones 3 and 4 Are Associated with Obesity-Induced Disorders of Spermatogenesis in Mice

by Mahamadou Fofana, Zhenyang Li, Han Li, Wenqi Li, Lu Wu, Lu Lu and Qizhan Liu

Toxics 2024, 12(4), 296; https://doi.org/10.3390/toxics12040296 - 17 Apr 2024

Viewed by 1901

Abstract

Background: Obesity, a chronic metabolic disorder, is related to cardiovascular diseases, diabetes, cancer, and reproductive disorders. The relationship between obesity and male infertility is now well recognized, but the mechanisms involved are unclear. We aimed to observe the effect of obesity on spermatogenesis [...] Read more.

Background: Obesity, a chronic metabolic disorder, is related to cardiovascular diseases, diabetes, cancer, and reproductive disorders. The relationship between obesity and male infertility is now well recognized, but the mechanisms involved are unclear. We aimed to observe the effect of obesity on spermatogenesis and to investigate the role of histone ubiquitination and acetylation modifications in obesity-induced spermatogenesis disorders. Methods: Thirty male C57BL/6J mice were randomly divided into two groups. The control group was fed with a general maintenance diet (12% fat), while a high-fat diet (HFD) group was fed with 40% fat for 10 weeks; then, they were mated with normal females. The fertility of male mice was calculated, testicular and sperm morphology were observed, and the expression levels of key genes and the levels of histone acetylation and ubiquitination modification during spermatogenesis were detected. Results: The number of sperm was decreased, as well as the sperm motility, while the number of sperm with malformations was increased. In the testes, the mRNA and protein expression levels of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), chromosome region maintenance-1 protein (CRM1), high-mobility group B2 (HMGB2), phosphoglycerate kinase 2 (PGK2), and testicular angiotensin-converting enzyme (tACE) were decreased. Furthermore, obesity led to a decrease in ubiquitinated H2A (ubH2A) and reduced levels of histone H3 acetylation K18 (H3AcK18) and histone H4 acetylation K5, K8, K12, and K16 (H4tetraAck), which disrupted protamine 1 (Prm1) deposition in testis tissue. Conclusion: These results suggest that low levels of histone ubiquitination and acetylation are linked with obesity-induced disorders during spermatogenesis, contributing to a better understanding of obesity-induced damage to male reproduction. Full article

(This article belongs to the Section Reproductive and Developmental Toxicity)

► Show Figures

Graphical abstract

23 pages, 3242 KiB

Open AccessEditor’s ChoiceArticle

Concordance between In Vitro and In Vivo Relative Toxic Potencies of Diesel Exhaust Particles from Different Biodiesel Blends

by Subramanian Karthikeyan, Dalibor Breznan, Errol M. Thomson, Erica Blais, Renaud Vincent and Premkumari Kumarathasan

Toxics 2024, 12(4), 290; https://doi.org/10.3390/toxics12040290 - 16 Apr 2024

Cited by 1 | Viewed by 1618

Abstract

Diesel exhaust particles (DEPs) contribute to air pollution exposure-related adverse health impacts. Here, we examined in vitro, and in vivo toxicities of DEPs from a Caterpillar C11 heavy-duty diesel engine emissions using ultra-low-sulfur diesel (ULSD) and biodiesel blends (20% v/v) [...] Read more.

Diesel exhaust particles (DEPs) contribute to air pollution exposure-related adverse health impacts. Here, we examined in vitro, and in vivo toxicities of DEPs from a Caterpillar C11 heavy-duty diesel engine emissions using ultra-low-sulfur diesel (ULSD) and biodiesel blends (20% v/v) of canola (B20C), soy (B20S), or tallow–waste fry oil (B20T) in ULSD. The in vitro effects of DEPs (DEP_ULSD, DEP_B20C, DEP_B20S, and DEP_B20T) in exposed mouse monocyte/macrophage cells (J774A.1) were examined by analyzing the cellular cytotoxicity endpoints (CTB, LDH, and ATP) and secreted proteins. The in vivo effects were assessed in BALB/c mice (n = 6/group) exposed to DEPs (250 µg), carbon black (CB), or saline via intratracheal instillation 24 h post-exposure. Bronchoalveolar lavage fluid (BALF) cell counts, cytokines, lung/heart mRNA, and plasma markers were examined. In vitro cytotoxic potencies (e.g., ATP) and secreted TNF-α were positively correlated (p < 0.05) with in vivo inflammatory potency (BALF cytokines, lung/heart mRNA, and plasma markers). Overall, DEP_ULSD and DEP_B20C appeared to be more potent compared to DEP_B20S and DEP_B20T. These findings suggested that biodiesel blend-derived DEP potencies can be influenced by biodiesel sources, and inflammatory process- was one of the potential underlying toxicity mechanisms. These observations were consistent across in vitro and in vivo exposures, and this work adds value to the health risk analysis of cleaner fuel alternatives. Full article

(This article belongs to the Section Air Pollution and Health)

► Show Figures

Figure 1

15 pages, 2010 KiB

Open AccessEditor’s ChoiceArticle

Exposure to Molybdate Results in Metabolic Disorder: An Integrated Study of the Urine Elementome and Serum Metabolome in Mice

by Kun Zhou, Miaomiao Tang, Wei Zhang, Yanling Chen, Yusheng Guan, Rui Huang, Jiawei Duan, Zibo Liu, Xiaoming Ji, Yingtong Jiang, Yanhui Hu, Xiaoling Zhang, Jingjing Zhou and Minjian Chen

Toxics 2024, 12(4), 288; https://doi.org/10.3390/toxics12040288 - 14 Apr 2024

Viewed by 1805

Abstract

The increasing use of molybdate has raised concerns about its potential toxicity in humans. However, the potential toxicity of molybdate under the current level of human exposure remains largely unknown. Endogenous metabolic alterations that are caused in humans by environmental exposure to pollutants [...] Read more.

The increasing use of molybdate has raised concerns about its potential toxicity in humans. However, the potential toxicity of molybdate under the current level of human exposure remains largely unknown. Endogenous metabolic alterations that are caused in humans by environmental exposure to pollutants are associated with the occurrence and progression of many diseases. This study exposed eight-week-old male C57 mice to sodium molybdate at doses relevant to humans (0.01 and 1 mg/kg/day) for eight weeks. Inductively coupled plasma mass spectrometry (ICP-MS) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS) were utilized to assess changes in urine element levels and serum metabolites in mice, respectively. A total of 838 subjects from the NHANES 2017–2018 population database were also included in our study to verify the associations between molybdenum and cadmium found in mice. Analysis of the metabolome in mice revealed that four metabolites in blood serum exhibited significant changes, including 5-aminolevulinic acid, glycolic acid, l-acetylcarnitine, and 2,3-dihydroxypropyl octanoate. Analysis of the elementome revealed a significant increase in urine levels of cadmium after molybdate exposure in mice. Notably, molybdenum also showed a positive correlation with cadmium in humans from the NHANES database. Further analysis identified a positive correlation between cadmium and 2,3-dihydroxypropyl octanoate in mice. In conclusion, these findings suggest that molybdate exposure disrupted amino acid and lipid metabolism, which may be partially mediated by molybdate-altered cadmium levels. The integration of elementome and metabolome data provides sensitive information on molybdate-induced metabolic disorders and associated toxicities at levels relevant to human exposure. Full article

(This article belongs to the Special Issue State-of-the-Art Environmental Chemicals Exposomics and Metabolomics)

► Show Figures

Figure 1

15 pages, 6184 KiB

Open AccessEditor’s ChoiceArticle

Thyroid Hormone Receptor Agonistic and Antagonistic Activity of Newly Synthesized Dihydroxylated Polybrominated Diphenyl Ethers: An In Vitro and In Silico Coactivator Recruitment Study

by Mengtao Zhang, Jianghong Shi, Bing Li, Hui Ge, Huanyu Tao, Jiawei Zhang, Xiaoyan Li and Zongwei Cai

Toxics 2024, 12(4), 281; https://doi.org/10.3390/toxics12040281 - 11 Apr 2024

Viewed by 1292

Abstract

Dihydroxylated polybrominated diphenyl ethers (DiOH-PBDEs) could be the metabolites of PBDEs of some organisms or the natural products of certain marine bacteria and algae. OH-PBDEs may demonstrate binding affinity to thyroid hormone receptors (TRs) and can disrupt the functioning of the systems modulated [...] Read more.

Dihydroxylated polybrominated diphenyl ethers (DiOH-PBDEs) could be the metabolites of PBDEs of some organisms or the natural products of certain marine bacteria and algae. OH-PBDEs may demonstrate binding affinity to thyroid hormone receptors (TRs) and can disrupt the functioning of the systems modulated by TRs. However, the thyroid hormone disruption mechanism of diOH-PBDEs remains elusive due to the absence of diOH-PBDEs standards. This investigation explores the potential disruptive effects of OH/diOH-PBDEs on thyroid hormones via competitive binding and coactivator recruitment with TRα and TRβ. At levels of 5000 nM and 25,000 nM, 6-OH-BDE-47 demonstrated significant recruitment of steroid receptor coactivator (SRC), whereas none of the diOH-PBDEs exhibited SRC recruitment within the range of 0.32–25,000 nM. AutoDock CrankPep (ADCP) simulations suggest that the conformation of SRC and TR–ligand complexes, particularly their interaction with Helix 12, rather than binding affinity, plays a pivotal role in ligand agonistic activity. 6,6′-diOH-BDE-47 displayed antagonistic activity towards both TRα and TRβ, while the antagonism of 3,5-diOH-BDE-100 for TRα and TRβ was concentration-dependent. 3,5-diOH-BDE-17 and 3,5-diOH-BDE-51 exhibited no discernible agonistic or antagonistic activities. Molecular docking analysis revealed that the binding energy of 3,3′,5-triiodo-L-thyronine (T3) surpassed that of OH/diOH-PBDEs. 3,5-diOH-BDE-100 exhibited the highest binding energy, whereas 6,6′-diOH-BDE-47 displayed the lowest. These findings suggest that the structural determinants influencing the agonistic and antagonistic activities of halogen phenols may be more intricate than previously proposed, involving factors beyond high-brominated PBDEs or hydroxyl group and bromine substitutions. It is likely that the agonistic or antagonistic propensities of OH/diOH-PBDEs are instigated by protein conformational changes rather than considerations of binding energy. Full article

(This article belongs to the Section Emerging Contaminants)

► Show Figures

Figure 1

16 pages, 1526 KiB

Open AccessEditor’s ChoiceArticle

The Biosorption Capacity of the Marine Microalga Phaeodactylum tricornutum for the Removal of Toluidine Blue from Seawater

by David Fernández, Julio Abalde and Enrique Torres

Toxics 2024, 12(4), 277; https://doi.org/10.3390/toxics12040277 - 9 Apr 2024

Viewed by 1318

Abstract

A wide variety of dyes, such as toluidine blue (TB), are used daily for a multitude of purposes. After use, many of these compounds end up in aqueous effluents, reaching natural environments, including marine environments. The removal of these pollutants from marine environments [...] Read more.

A wide variety of dyes, such as toluidine blue (TB), are used daily for a multitude of purposes. After use, many of these compounds end up in aqueous effluents, reaching natural environments, including marine environments. The removal of these pollutants from marine environments must be considered a priority problem. The search for natural techniques, such as biosorption, is a preferred option to eliminate pollution from natural environments. However, biosorption studies in seawater are scarce. For this reason, the living biomass of the marine microalga Phaeodactylum tricornutum was studied to determine its ability to remove TB from seawater. The kinetics of the biosorption process, the isotherms, and the effect of light and pH were determined. This biomass showed a maximum TB removal capacity of 45 ± 2 mg g⁻¹ in the presence of light. Light had a positive effect on the TB removal capacity of this living biomass. The best fitting kinetics was the pseudo-second order kinetics. The efficiency of the removal process increased with increasing pH. This removal was more effective at alkaline pH values. The results demonstrated the efficacy of P. tricornutum living biomass for the efficient removal of toluidine blue dye from seawater both in the presence and absence of light. Full article

(This article belongs to the Section Toxicity Reduction and Environmental Remediation)

► Show Figures

Figure 1

25 pages, 721 KiB

Open AccessEditor’s ChoiceReview

Developmental Toxicity of Fine Particulate Matter: Multifaceted Exploration from Epidemiological and Laboratory Perspectives

by Ruifeng Yan, Danni Ma, Yutong Liu, Rui Wang, Lifan Fan, Qiqi Yan, Chen Chen, Wenhao Wang, Zhihua Ren, Tingting Ku, Xia Ning and Nan Sang

Toxics 2024, 12(4), 274; https://doi.org/10.3390/toxics12040274 - 6 Apr 2024

Cited by 3 | Viewed by 1861

Abstract

Particulate matter of size ≤ 2.5 μm (PM_2.5) is a critical environmental threat that considerably contributes to the global disease burden. However, accompanied by the rapid research progress in this field, the existing research on developmental toxicity is still constrained by [...] Read more.

Particulate matter of size ≤ 2.5 μm (PM_2.5) is a critical environmental threat that considerably contributes to the global disease burden. However, accompanied by the rapid research progress in this field, the existing research on developmental toxicity is still constrained by limited data sources, varying quality, and insufficient in-depth mechanistic analysis. This review includes the currently available epidemiological and laboratory evidence and comprehensively characterizes the adverse effects of PM_2.5 on developing individuals in different regions and various pollution sources. In addition, this review explores the effect of PM_2.5 exposure to individuals of different ethnicities, genders, and socioeconomic levels on adverse birth outcomes and cardiopulmonary and neurological development. Furthermore, the molecular mechanisms involved in the adverse health effects of PM_2.5 primarily encompass transcriptional and translational regulation, oxidative stress, inflammatory response, and epigenetic modulation. The primary findings and novel perspectives regarding the association between public health and PM_2.5 were examined, highlighting the need for future studies to explore its sources, composition, and sex-specific effects. Additionally, further research is required to delve deeper into the more intricate underlying mechanisms to effectively prevent or mitigate the harmful effects of air pollution on human health. Full article

(This article belongs to the Special Issue Toxicity and Human Health Assessment of Air Pollutants)

► Show Figures

Figure 1

14 pages, 3604 KiB

Open AccessEditor’s ChoiceArticle

Fe-CGS Effectively Inhibits the Dynamic Migration and Transformation of Cadmium and Arsenic in Soil

by Hongliang Yin, Changzhi Zhou, Junhuan Wang, Mengxue Yin, Zhihao Wu, Ningning Song, Xin Song, Yuxian Shangguan, Zaijin Sun, Quanli Zong and Hong Hou

Toxics 2024, 12(4), 273; https://doi.org/10.3390/toxics12040273 - 6 Apr 2024

Viewed by 1489

Abstract

The iron-modified coal gasification slag (Fe-CGS) material has excellent performance in purifying heavy-metal-contaminated water due to its good surface properties and adsorption capacities. However, it is unclear whether it can provide long-term simultaneous stabilization of Cd and As in composite-contaminated soils in extreme [...] Read more.

The iron-modified coal gasification slag (Fe-CGS) material has excellent performance in purifying heavy-metal-contaminated water due to its good surface properties and adsorption capacities. However, it is unclear whether it can provide long-term simultaneous stabilization of Cd and As in composite-contaminated soils in extreme environments. This study investigated the long-term stabilization of Cd and As in acidic (JLG) and alkaline (QD) soils by simulating prolonged heavy rainfall with the addition of Fe-CGS. Multiple extraction methods were used to analyze the immobilization mechanisms of Cd and As in soil and their effects on bioavailability. The results indicate that the stabilization efficiency was related to the dosage of Fe-CGS. The concentrations of Cd and As in the JLG soil leachate were reduced by 77.6% (2.0 wt%) and 87.8% (1.0 wt%), respectively. Additionally, the availability of Cd and As decreased by 46.7% (2.0 wt%) and 53.0% (1.0 wt%), respectively. In the QD soil leachate, the concentration of Cd did not significantly change, while the concentration of As decreased by 92.3% (2.0 wt%). Furthermore, the availability of Cd and As decreased by 22.1% (2.0 wt%) and 40.2% (1.0 wt%), respectively. Continuous extraction revealed that Fe-CGS facilitated the conversion of unstable, acid-soluble Cd into oxidizable Cd and acid-soluble Cd. Additionally, it promoted the transformation of both non-specifically and specifically adsorbed As into amorphous iron oxide-bound and residual As. Fe-CGS effectively improved the soil pH, reduced the bioavailability of Cd and As, and blocked the migration of Cd and As under extreme rainfall leaching conditions. It also promoted the transformation of Cd and As into more stable forms, exhibiting satisfactory long-term stabilization performance for Cd and As. Full article

(This article belongs to the Section Toxicity Reduction and Environmental Remediation)

► Show Figures

Figure 1

17 pages, 1616 KiB

Open AccessEditor’s ChoiceArticle

A Comparison of In Vitro Points of Departure with Human Blood Levels for Per- and Polyfluoroalkyl Substances (PFAS)

by Richard S. Judson, Doris Smith, Michael DeVito, John F. Wambaugh, Barbara A. Wetmore, Katie Paul Friedman, Grace Patlewicz, Russell S. Thomas, Risa R. Sayre, Jennifer H. Olker, Sigmund Degitz, Stephanie Padilla, Joshua A. Harrill, Timothy Shafer and Kelly E. Carstens

Toxics 2024, 12(4), 271; https://doi.org/10.3390/toxics12040271 - 5 Apr 2024

Cited by 1 | Viewed by 2127

Abstract

Per- and polyfluoroalkyl substances (PFAS) are widely used, and their fluorinated state contributes to unique uses and stability but also long half-lives in the environment and humans. PFAS have been shown to be toxic, leading to immunosuppression, cancer, and other adverse health outcomes. [...] Read more.

Per- and polyfluoroalkyl substances (PFAS) are widely used, and their fluorinated state contributes to unique uses and stability but also long half-lives in the environment and humans. PFAS have been shown to be toxic, leading to immunosuppression, cancer, and other adverse health outcomes. Only a small fraction of the PFAS in commerce have been evaluated for toxicity using in vivo tests, which leads to a need to prioritize which compounds to examine further. Here, we demonstrate a prioritization approach that combines human biomonitoring data (blood concentrations) with bioactivity data (concentrations at which bioactivity is observed in vitro) for 31 PFAS. The in vitro data are taken from a battery of cell-based assays, mostly run on human cells. The result is a Bioactive Concentration to Blood Concentration Ratio (BCBCR), similar to a margin of exposure (MoE). Chemicals with low BCBCR values could then be prioritized for further risk assessment. Using this method, two of the PFAS, PFOA (Perfluorooctanoic Acid) and PFOS (Perfluorooctane Sulfonic Acid), have BCBCR values < 1 for some populations. An additional 9 PFAS have BCBCR values < 100 for some populations. This study shows a promising approach to screening level risk assessments of compounds such as PFAS that are long-lived in humans and other species. Full article

(This article belongs to the Special Issue Human Exposure to per- and Polyfluoroalkyl Substances (PFASs): Toxicity, Health Effects, and Mitigation)

► Show Figures

Figure 1

111 pages, 4013 KiB

Open AccessEditor’s ChoiceReview

The Comet Assay as a Tool in Human Biomonitoring Studies of Environmental and Occupational Exposure to Chemicals—A Systematic Scoping Review

by Carina Ladeira, Peter Møller, Lisa Giovannelli, Goran Gajski, Anja Haveric, Ezgi Eyluel Bankoglu, Amaya Azqueta, Marko Gerić, Helga Stopper, José Cabêda, Fernanda S. Tonin and Andrew Collins

Toxics 2024, 12(4), 270; https://doi.org/10.3390/toxics12040270 - 5 Apr 2024

Cited by 4 | Viewed by 3294

Abstract

Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease prevention. In recent years, the comet assay has become an important tool for assessing DNA damage, both in [...] Read more.

Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease prevention. In recent years, the comet assay has become an important tool for assessing DNA damage, both in environmental and occupational exposure contexts. To evidence the role of the comet assay in human biomonitoring, we have analysed original research studies of environmental or occupational exposure that used the comet assay in their assessments, following the PRISMA-ScR method (preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews). Groups of chemicals were designated according to a broad classification, and the results obtained from over 300 original studies (n = 123 on air pollutants, n = 14 on anaesthetics, n = 18 on antineoplastic drugs, n = 57 on heavy metals, n = 59 on pesticides, and n = 49 on solvents) showed overall higher values of DNA strand breaks in the exposed subjects in comparison with the unexposed. In summary, our systematic scoping review strengthens the relevance of the use of the comet assay in assessing DNA damage in human biomonitoring studies. Full article

(This article belongs to the Special Issue Environmental and Occupational Exposure to Chemical Agents and Health Challenges)

► Show Figures

Figure 1

15 pages, 2345 KiB

Open AccessEditor’s ChoiceArticle

Crop Contamination and Human Exposure to Per- and Polyfluoroalkyl Substances around a Fluorochemical Industrial Park in China

by Kairan Xu, Jian Huang, Yufeng Zhang, Xilong Wu, Dan Cai, Guocheng Hu, Yu Li, Zhuobiao Ni, Qingqi Lin, Shizhong Wang and Rongliang Qiu

Toxics 2024, 12(4), 269; https://doi.org/10.3390/toxics12040269 - 4 Apr 2024

Cited by 1 | Viewed by 2393

Abstract

Due to their significant environmental impact, there has been a gradual restriction of the production and utilization of legacy per- and polyfluoroalkyl substances (PFAS), leading to continuous development and adoption of novel alternatives. To effectively identify the potential environmental risks from crop consumption, [...] Read more.

Due to their significant environmental impact, there has been a gradual restriction of the production and utilization of legacy per- and polyfluoroalkyl substances (PFAS), leading to continuous development and adoption of novel alternatives. To effectively identify the potential environmental risks from crop consumption, the levels of 25 PFAS, including fourteen perfluoroalkyl acids (PFAAs), two precursor substances and nine novel alternatives, in agricultural soils and edible parts of various crops around a fluoride industrial park (FIP) in Changshu city, China, were measured. The concentration of ΣPFAS in the edible parts of all crops ranged from 11.64 to 299.5 ng/g, with perfluorobutanoic acid (PFBA) being the dominant compound, accounting for an average of 71% of ΣPFAS. The precursor substance, N-methylperfluoro-octanesulfonamidoacetic acid (N-MeFOSAA), was detected in all crop samples. Different types of crops showed distinguishing accumulation profiles for the PFAS. Solanaceae and leafy vegetables showed higher levels of PFAS contamination, with the highest ΣPFAS concentrations reaching 190.91 and 175.29 ng/g, respectively. The highest ΣAlternative was detected in leafy vegetables at 15.21 ng/g. The levels of human exposure to PFAS through crop consumption for various aged groups were also evaluated. The maximum exposure to PFOA for urban toddlers reached 109.8% of the standard value set by the European Food Safety Authority (EFSA). In addition, short-chained PFAAs and novel alternatives may pose potential risks to human health via crop consumption. Full article

(This article belongs to the Topic Advances in Environmental Behaviors of Persistent Contaminants: Fate, Distribution, Risk, and Challenges)

► Show Figures

Figure 1

13 pages, 1725 KiB

Open AccessEditor’s ChoiceArticle

Effects of Temperature and Salinity on Perfluorooctane Sulfonate (PFOS) Toxicity in Larval Estuarine Organisms

by Katy W. Chung, Peter B. Key, Philip Tanabe and Marie E. DeLorenzo

Toxics 2024, 12(4), 267; https://doi.org/10.3390/toxics12040267 - 2 Apr 2024

Cited by 1 | Viewed by 1711

Abstract

Perfluorooctane sulfonate (PFOS) is a persistent contaminant that has been found globally within the environment. Key data gaps exist in the toxicity of PFOS to marine organisms, especially estuarine species that are crucial to the food web: fish, shrimp, and mollusks. This study [...] Read more.

Perfluorooctane sulfonate (PFOS) is a persistent contaminant that has been found globally within the environment. Key data gaps exist in the toxicity of PFOS to marine organisms, especially estuarine species that are crucial to the food web: fish, shrimp, and mollusks. This study developed toxicity thresholds for larval estuarine species, including grass shrimp (Palaemon pugio), sheepshead minnows (Cyprinodon variegatus), mysids (Americamysis bahia), and Eastern mud snails (Tritia obsoleta). Multiple abiotic stressors (salinity and temperature) were included as variables in testing the toxicity of PFOS. Acute 96 h toxicity testing under standard test conditions of 25 °C and 20 ppt seawater yielded LC₅₀ values of 0.919 mg/L for C. variegatus, 1.375 mg/L for A. bahia, 1.559 mg/L for T. obsoleta, and 2.011 mg/L for P. pugio. The effects of increased temperature (32 °C) and decreased salinity (10 ppt) varied with test species. PFOS toxicity for the sheepshead minnows increased with temperature but was not altered by decreased salinity. For grass shrimp and mud snails, PFOS toxicity was greater under lower salinity. The combination of higher temperature and lower salinity was observed to lower the toxicity thresholds for all species. These data demonstrate that expanding toxicity testing to include a wider range of parameters will improve the environmental risk assessment of chemical contaminants, especially for species inhabiting dynamic estuarine ecosystems. Full article

(This article belongs to the Special Issue PFAS Toxicology and Metabolism)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI