Toxics

23 pages, 1269 KiB

Open AccessEditor’s ChoiceReview

Contaminants of Emerging Concern (CECs) and Male Reproductive Health: Challenging the Future with a Double-Edged Sword

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Toxics 2023, 11(4), 330; https://doi.org/10.3390/toxics11040330 - 30 Mar 2023

Cited by 1 | Viewed by 2822

Abstract

Approximately 9% of couples are infertile, with half of these cases relating to male factors. While many cases of male infertility are associated with genetic and lifestyle factors, approximately 30% of cases are still idiopathic. Contaminants of emerging concern (CECs) denote substances identified [...] Read more.

Approximately 9% of couples are infertile, with half of these cases relating to male factors. While many cases of male infertility are associated with genetic and lifestyle factors, approximately 30% of cases are still idiopathic. Contaminants of emerging concern (CECs) denote substances identified in the environment for the first time or detected at low concentrations during water quality analysis. Since CEC production and use have increased in recent decades, CECs are now ubiquitous in surface and groundwater. CECs are increasingly observed in human tissues, and parallel reports indicate that semen quality is continuously declining, supporting the notion that CECs may play a role in infertility. This narrative review focuses on several CECs (including pesticides and pharmaceuticals) detected in the nearshore marine environment of False Bay, Cape Town, South Africa, and deliberates their potential effects on male fertility and the offspring of exposed parents, as well as the use of spermatozoa in toxicological studies. Collective findings report that chronic in vivo exposure to pesticides, including atrazine, simazine, and chlorpyrifos, is likely to be detrimental to the reproduction of many organisms, as well as to sperm performance in vitro. Similarly, exposure to pharmaceuticals such as diclofenac and naproxen impairs sperm motility both in vivo and in vitro. These contaminants are also likely to play a key role in health and disease in offspring sired by parents exposed to CECs. On the other side of the double-edged sword, we propose that due to its sensitivity to environmental conditions, spermatozoa could be used as a bioindicator in eco- and repro-toxicology studies. Full article

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

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19 pages, 5393 KiB

Open AccessEditor’s ChoiceArticle

Polystyrene Microplastics Induced Ovarian Toxicity in Juvenile Rats Associated with Oxidative Stress and Activation of the PERK-eIF2α-ATF4-CHOP Signaling Pathway

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Toxics 2023, 11(3), 225; https://doi.org/10.3390/toxics11030225 - 27 Feb 2023

Cited by 4 | Viewed by 1611

Abstract

Numerous reports confirm that microplastics exposure could induce reproductive toxicity in mammals. However, the effects of microplastics exposure during juveniles on ovarian apoptosis through oxidative and endoplasmic reticulum (ER) stresses remains unclear, which is the focus of our study. In the present study, [...] Read more.

Numerous reports confirm that microplastics exposure could induce reproductive toxicity in mammals. However, the effects of microplastics exposure during juveniles on ovarian apoptosis through oxidative and endoplasmic reticulum (ER) stresses remains unclear, which is the focus of our study. In the present study, female rats (4 weeks old) were exposed to polystyrene microplastics (PS-MPs, 1 μm) at different dosages (0, 0.5, and 2.0 mg/kg) for 28 days. Findings revealed that 2.0 mg/kg of PS-MPs distinctly increased the atretic follicle ratio in the ovary and dramatically reduced the serum levels of estrogen and progesterone. Additionally, the oxidative stress indicators declined, including the activity of superoxide dismutase and catalase, whereas the malondialdehyde content in the ovary was considerably enhanced in the 2.0 mg/kg PS-MPs group. Furthermore, the expressions of genes related to ER stress (PERK, eIF2α, ATF4, and CHOP) and apoptosis were remarkably elevated in the 2.0 mg/kg PS-MPs group compared with those in the control group. We found that PS-MPs induced oxidative stress and activated the PERK-eIF2α-ATF4-CHOP signaling pathway in juvenile rats. Moreover, with the oxidative stress inhibitor N-acetyl-cysteine and eIF2α dephosphorylation blocker Salubrinal treatment, ovarian damage induced by PS-MPs was repaired and associated enzyme activities were improved. Overall, our results indicated that PS-MPs exposure induced ovarian injury associated with oxidative stress and activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in juvenile rats, providing new prospects for assessing the health risks of children exposed to microplastics. Full article

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

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28 pages, 2658 KiB

Open AccessEditor’s ChoiceReview

Pancreas–Liver–Adipose Axis: Target of Environmental Cadmium Exposure Linked to Metabolic Diseases

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Diana Moroni-González

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Victor Enrique Sarmiento-Ortega

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Alfonso Diaz

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Eduardo Brambila

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Samuel Treviño

Toxics 2023, 11(3), 223; https://doi.org/10.3390/toxics11030223 - 26 Feb 2023

Cited by 1 | Viewed by 1800

Abstract

Cadmium has been well recognized as a critical toxic agent in acute and chronic poisoning cases in occupational and nonoccupational settings and environmental exposure situations. Cadmium is released into the environment after natural and anthropogenic activities, particularly in contaminated and industrial areas, causing [...] Read more.

Cadmium has been well recognized as a critical toxic agent in acute and chronic poisoning cases in occupational and nonoccupational settings and environmental exposure situations. Cadmium is released into the environment after natural and anthropogenic activities, particularly in contaminated and industrial areas, causing food pollution. In the body, cadmium has no biological activity, but it accumulates primarily in the liver and kidney, which are considered the main targets of its toxicity, through oxidative stress and inflammation. However, in the last few years, this metal has been linked to metabolic diseases. The pancreas–liver–adipose axis is largely affected by cadmium accumulation. Therefore, this review aims to collect bibliographic information that establishes the basis for understanding the molecular and cellular mechanisms linked to cadmium with carbohydrate, lipids, and endocrine impairments that contribute to developing insulin resistance, metabolic syndrome, prediabetes, and diabetes. Full article

(This article belongs to the Special Issue Endocrine Disruptors Exposure, Toxicity and Health Risk Assessment)

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15 pages, 1678 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Associations with Blood Lead and Urinary Cadmium Concentrations in Relation to Mortality in the US Population: A Causal Survival Analysis with G-Computation

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Toxics 2023, 11(2), 133; https://doi.org/10.3390/toxics11020133 - 29 Jan 2023

Cited by 2 | Viewed by 1684

Abstract

Using the parametric g-formula, we estimated the 27-year risk of all-cause and specific causes of mortality under different potential interventions for blood lead (BLLs) and urinary cadmium (UCd) levels. We used data on 14,311 adults aged ≥20 years enrolled in the NHANES-III between [...] Read more.

Using the parametric g-formula, we estimated the 27-year risk of all-cause and specific causes of mortality under different potential interventions for blood lead (BLLs) and urinary cadmium (UCd) levels. We used data on 14,311 adults aged ≥20 years enrolled in the NHANES-III between 1988 and 1994 and followed up through 31 Dec 31 2015. Time and cause of death were determined from the National Death Index records. We used the parametric g-formula with pooled logistic regression models to estimate the relative and absolute risk of all-cause, cardiovascular, and cancer mortality under different potential threshold interventions for BLLs and UCd concentrations. Median follow-up was 22.5 years. A total of 5167 (36%) participants died by the end of the study, including 1550 from cardiovascular diseases and 1135 from cancer. Increases in BLLs and creatinine-corrected UCd levels from the 5th to the 95th percentiles were associated with risk differences of 4.17% (1.54 to 8.77) and 6.22% (4.51 to 12.00) for all-cause mortality, 1.52% (0.09 to 3.74) and 1.06% (−0.57 to 3.50) for cardiovascular disease mortality, and 1.32% (−0.09 to 3.67) and 0.64% (−0.98 to 2.80) for cancer mortality, respectively. Interventions to reduce historical exposures to lead and cadmium may have prevented premature deaths, especially from cardiovascular disease. Full article

(This article belongs to the Special Issue Feature Papers in Environmental Epidemiology)

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18 pages, 5446 KiB

Open AccessEditor’s ChoiceArticle

Gestational Exposure to Phthalates and Phthalate Replacements in Relation to Neurodevelopmental Delays in Early Childhood

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Seonyoung Park

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Emily Zimmerman

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Gredia Huerta-Montañez

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Toxics 2023, 11(1), 65; https://doi.org/10.3390/toxics11010065 - 11 Jan 2023

Cited by 3 | Viewed by 1524

Abstract

Phthalates have been linked to changes in child neurodevelopment. However, sex-specificity has been reported inconsistently, and little is known about the impact of recent phthalate replacement chemicals. Our analysis included mother–child pairs (N = 274) from the PROTECT birth cohort in Puerto Rico. [...] Read more.

Phthalates have been linked to changes in child neurodevelopment. However, sex-specificity has been reported inconsistently, and little is known about the impact of recent phthalate replacement chemicals. Our analysis included mother–child pairs (N = 274) from the PROTECT birth cohort in Puerto Rico. Phthalate metabolites were measured in multiple maternal urine collected during pregnancy. Neurodevelopment was measured at 6, 12, and 24 months of age using the Battelle Developmental Inventory-2nd edition (BDI), which provides scores for adaptive, personal-social, communication, motor, and cognitive domains. Multivariable linear regression was used to examine associations between phthalate metabolite concentrations and BDI scores, adjusting for maternal age, maternal education, child age, and specific gravity. Sex-specificity was assessed with sex X exposure interaction terms and stratified models. Results show that all five domains were significantly associated with mono-3-carboxypropyl phthalate (MCPP) at age 24 months, suggesting a holistic developmental delay related to this metabolite. Sex-specificity existed for all timepoints (p-interaction < 0.2), in general, showing stronger associations among boys. For example, metabolites of a recent phthalate replacement, di-2-ethylhexyl terephthalate (DEHTP), were differentially associated with the adaptive domain (boys −7.53%/IQR, 95% CI: −14.58, −0.48 vs. girls −0.85%/IQR, 95% CI: −5.08, 3.37), and the cognitive domain (boys −6.05%/IQR, 95% CI: −10.88, −1.22 vs. girls −1.93%/IQR, 95%CI: −4.14, 0.28) at 6 months. To conclude, gestational exposure to phthalates and phthalate replacements was associated with neurodevelopmental delay across multiple domains, with differences by sex and child age. Full article

(This article belongs to the Special Issue Insights of Perinatal Endocrine Disruptors Exposure Influencing Maternal and Child Health)

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20 pages, 1584 KiB

Open AccessEditor’s ChoiceArticle

Adverse Outcome Pathway ‘Footprinting’: A Novel Approach to the Integration of 21st Century Toxicology Information into Chemical Mixtures Risk Assessment

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Jason C. Lambert

Toxics 2023, 11(1), 37; https://doi.org/10.3390/toxics11010037 - 30 Dec 2022

Cited by 1 | Viewed by 1770

Abstract

For over a decade, New Approach Methodologies (NAMs) such as structure-activity/read-across, -omics technologies, and Adverse Outcome Pathway (AOP), have been considered within regulatory communities as alternative sources of chemical and biological information potentially relevant to human health risk assessment. Integration of NAMs into [...] Read more.

For over a decade, New Approach Methodologies (NAMs) such as structure-activity/read-across, -omics technologies, and Adverse Outcome Pathway (AOP), have been considered within regulatory communities as alternative sources of chemical and biological information potentially relevant to human health risk assessment. Integration of NAMs into applications such as chemical mixtures risk assessment has been limited due to the lack of validation of qualitative and quantitative application to adverse health outcomes in vivo, and acceptance by risk assessors. However, leveraging existent hazard and dose–response information, including NAM-based data, for mixture component chemicals across one or more levels of biological organization using novel approaches such as AOP ‘footprinting’ proposed herein, may significantly advance mixtures risk assessment. AOP footprinting entails the systematic stepwise profiling and comparison of all known or suspected AOPs involved in a toxicological effect at the level of key event (KE). The goal is to identify key event(s) most proximal to an adverse outcome within each AOP suspected of contributing to a given health outcome at which similarity between mixture chemicals can be confidently determined. These key events are identified as the ‘footprint’ for a given AOP. This work presents the general concept, and a hypothetical example application, of AOP footprinting as a key methodology for the integration of NAM data into mixtures risk assessment. Full article

(This article belongs to the Special Issue Evaluating Chemical Exposures and Toxicity of Complex Mixtures and Multiple Stressors)

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25 pages, 1007 KiB

Open AccessEditor’s ChoiceReview

Alternative Methods for Skin-Sensitization Assessment

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Toxics 2022, 10(12), 740; https://doi.org/10.3390/toxics10120740 - 29 Nov 2022

Cited by 6 | Viewed by 2284

Abstract

Skin sensitization is a term used to refer to the regulatory hazard known as allergic contact dermatitis (ACD) in humans or contact hypersensitivity in rodents, an important health endpoint considered in chemical hazard and risk assessments. Information on skin sensitization potential is required [...] Read more.

Skin sensitization is a term used to refer to the regulatory hazard known as allergic contact dermatitis (ACD) in humans or contact hypersensitivity in rodents, an important health endpoint considered in chemical hazard and risk assessments. Information on skin sensitization potential is required in various regulatory frameworks, such as the Directive of the European Parliament and the Council on Registration, Evaluation and Authorization of Chemicals (REACH). The identification of skin-sensitizing chemicals previously required the use of animal testing, which is now being replaced by alternative methods. Alternative methods in the field of skin sensitization are based on the measurement or prediction of key events (KE), i.e., (i) the molecular triggering event, i.e., the covalent binding of electrophilic substances to nucleophilic centers in skin proteins; (ii) the activation of keratinocytes; (iii) the activation of dendritic cells; (iv) the proliferation of T cells. This review article focuses on the current state of knowledge regarding the methods corresponding to each of the key events in skin sensitization and considers the latest trends in the development and modification of these methods. Full article

(This article belongs to the Section Exposome Analysis and Risk Assessment)

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32 pages, 5946 KiB

Open AccessEditor’s ChoiceReview

Characterization of the Toxicological Impact of Heavy Metals on Human Health in Conjunction with Modern Analytical Methods

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Dana Claudia Filipoiu

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Simona Gabriela Bungau

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Alexandra Georgiana Tarce

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Mihaela Alexandra Bogdan

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Tapan Behl

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Aurelia Cristina Nechifor

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Syed Shams ul Hassan

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Delia Mirela Tit

Toxics 2022, 10(12), 716; https://doi.org/10.3390/toxics10120716 - 23 Nov 2022

Cited by 17 | Viewed by 4061

Abstract

Increased environmental pollution, urbanization, and a wide variety of anthropogenic activities have led to the release of toxic pollutants into the environment, including heavy metals (HMs). It has been found that increasing concentrations of HMs lead to toxicity, mineral imbalances, and serious diseases, [...] Read more.

Increased environmental pollution, urbanization, and a wide variety of anthropogenic activities have led to the release of toxic pollutants into the environment, including heavy metals (HMs). It has been found that increasing concentrations of HMs lead to toxicity, mineral imbalances, and serious diseases, which are occurring more and more frequently. Therefore, testing has become imperative to detect these deficiencies in a timely manner. The detection of traces of HMs, especially toxic ones, in human tissues, various biological fluids, or hair is a complex, high-precision analysis that enables early diagnosis, addressing people under constant stress or exposed to a toxic environment; the test also targets people who have died in suspicious circumstances. Tissue mineral analysis (TMA) determines the concentration of toxic minerals/metals at the intracellular level and can therefore determine correlations between measured concentrations and imbalances in the body. Framing the already-published information on the topic, this review aimed to explore the toxicity of HMs to human health, the harmful effects of their accumulation, the advantages vs. the disadvantages of choosing different biological fluids/tissues/organs necessary for the quantitative measurement of HM in the human body, as well as the choice of the optimal method, correlated with the purpose of the analysis. Full article

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

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16 pages, 850 KiB

Open AccessEditor’s ChoiceArticle

Prenatal Metal Exposures and Associations with Kidney Injury Biomarkers in Children

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Chitra Amarasiriwardena

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Ivan Pantic

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Mari Cruz Tolentino

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Guadalupe Estrada-Gutierrez

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Jason H. Greenberg

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Martha M. Téllez-Rojo

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Robert O. Wright

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Alison P. Sanders

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Maria José Rosa

Toxics 2022, 10(11), 692; https://doi.org/10.3390/toxics10110692 - 16 Nov 2022

Cited by 3 | Viewed by 1683

Abstract

Prenatal exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) may be nephrotoxic, yet limited studies have examined subclinical kidney injury biomarkers in children. We assessed whether metal exposure in the second trimester (2T), a crucial time of kidney development, is [...] Read more.

Prenatal exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) may be nephrotoxic, yet limited studies have examined subclinical kidney injury biomarkers in children. We assessed whether metal exposure in the second trimester (2T), a crucial time of kidney development, is associated with altered urine kidney injury and function biomarkers in preadolescent children. Analyses included 494 children participating in a birth cohort study in Mexico City. Concentrations of As, Cd, and Pb were measured from pregnant women in 2T blood and urine, and Hg in urine only. Kidney biomarkers were measured from children in urine at age 8–12 years. We assessed the associations between individual metals and (1) kidney biomarkers using linear regression and (2) a multi-protein kidney mixture using weighted quantile sum (WQS) regression. Associations of separate urine and blood metal mixtures with individual kidney biomarkers were assessed via WQS. Within the multi-protein mixture, the association with increased urinary As was predominated by urine alpha-1-microglobulin (A1M), interferon gamma-induced protein 10 (IP10), and fatty acid binding protein 1; the association with increased urinary Cd was predominated by A1M, clusterin, and albumin. The urine metal mixture was associated with increased albumin (0.23 ng/mL; 95% confidence interval (CI): 0.10, 0.37), IP10 (0.15 ng/mL; 95% CI: 0.02, 0.28), and cystatin C (0.17 ng/mL; 95% CI: 0.04, 0.31); these associations were mainly driven by urinary As and Cd. We observed null associations between prenatal blood or urine metal mixtures and estimated glomerular filtration rate. Higher prenatal urinary metals, individually and as a mixture were associated with altered kidney injury biomarkers in children. Further research and longer participant follow-up are required to ascertain the risk of kidney disease later in life. Full article

(This article belongs to the Special Issue Prenatal Exposure to Environmental Pollutants: Effects on Fetal Development, Birth Outcomes and Children’s Health)

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42 pages, 2669 KiB

Open AccessEditor’s ChoiceReview

Reduced Birth Weight and Exposure to Per- and Polyfluoroalkyl Substances: A Review of Possible Underlying Mechanisms Using the AOP-HelpFinder

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Thórhallur Ingi Halldórsson

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Maria Uhl

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Eva Cecilie Bonefeld-Jørgensen

Toxics 2022, 10(11), 684; https://doi.org/10.3390/toxics10110684 - 12 Nov 2022

Cited by 7 | Viewed by 2360

Abstract

Prenatal exposure to per- and polyfluorinated substances (PFAS) may impair fetal growth. Our knowledge of the underlying mechanisms is incomplete. We used the Adverse Outcome Pathway (AOP)-helpFinder tool to search PubMed for studies published until March 2021 that examined PFAS exposure in relation [...] Read more.

Prenatal exposure to per- and polyfluorinated substances (PFAS) may impair fetal growth. Our knowledge of the underlying mechanisms is incomplete. We used the Adverse Outcome Pathway (AOP)-helpFinder tool to search PubMed for studies published until March 2021 that examined PFAS exposure in relation to birth weight, oxidative stress, hormones/hormone receptors, or growth signaling pathways. Of these 1880 articles, 106 experimental studies remained after abstract screening. One clear finding is that PFAS are associated with oxidative stress in in vivo animal studies and in vitro studies. It appears that PFAS-induced reactive-oxygen species (ROS) generation triggers increased peroxisome proliferator-activated receptor (PPAR)γ expression and activation of growth signaling pathways, leading to hyperdifferentiation of pre-adipocytes. Fewer proliferating pre-adipocytes result in lower adipose tissue weight and in this way may reduce birth weight. PFAS may also impair fetal growth through endocrine effects. Estrogenic effects have been noted in in vivo and in vitro studies. Overall, data suggest thyroid-damaging effects of PFAS affecting thyroid hormones, thyroid hormone gene expression, and histology that are associated in animal studies with decreased body and organ weight. The effects of PFAS on the complex relationships between oxidative stress, endocrine system function, adipogenesis, and fetal growth should be further explored. Full article

(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)

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10 pages, 314 KiB

Open AccessEditor’s ChoiceArticle

Risk Assessment of Essential and Toxic Elements in Freshwater Fish Species from Lakes near Black Sea, Bulgaria

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Toxics 2022, 10(11), 675; https://doi.org/10.3390/toxics10110675 - 08 Nov 2022

Cited by 7 | Viewed by 1189

Abstract

The aims of this study were to measure the concentrations of selected toxic and essential elements in the muscle tissue of five common freshwater fish species (roach (Rutilus rutilus), freshwater bream (Abramis brama), prussian carp (Carassius gibelio), crucian carp (Carassius carassius) and common [...] Read more.

The aims of this study were to measure the concentrations of selected toxic and essential elements in the muscle tissue of five common freshwater fish species (roach (Rutilus rutilus), freshwater bream (Abramis brama), prussian carp (Carassius gibelio), crucian carp (Carassius carassius) and common carp (Cyprinus carpio)) from Lake Burgas and Lake Mandra (Bulgaria). In all samples the levels of Cd, Cr, Cu, Mn, Ni, Pb, Fe and Zn were under the maximum allowed concentrations for safe human consumption in Bulgaria and ranged as follows: Cd 0.02–0.05; Cr 0.03–0.06; Cu 0.11–0.20; Mn 0.05–0.71; Ni 0.06–0.11; Pb 0.15–0.27, Fe 1.68–5.86 and Zn 1.94–9.06 mg/kg wet weight. The concentration of As was under detection limit. An assessment of the human risk by calculation of the target hazard quotients (THQ), hazard index (HI) and target risk (TR) was performed. The target hazard quotient (THQ) for individual elements and HI for combined metals were lower than 1, indicating no health risk for consumers due to the intake of either individual or combined metals. The target risk for iAs, Pb and Ni was below 10⁻⁶, indicating no carcinogenic risk. According to these results, the consumption of these freshwater fish species is safe for human health. Full article

(This article belongs to the Section Exposome Analysis and Risk Assessment)

17 pages, 773 KiB

Open AccessEditor’s ChoiceReview

Exposure to Microplastics during Early Developmental Stage: Review of Current Evidence

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Nur Hanisah Amran

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Siti Sarah Mohamad Zaid

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Mohd Helmy Mokhtar

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Latifah Abd Manaf

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Shatrah Othman

Toxics 2022, 10(10), 597; https://doi.org/10.3390/toxics10100597 - 10 Oct 2022

Cited by 5 | Viewed by 4113

Abstract

In the last few decades, microplastics (MPs) have been among the emerging environmental pollutants that have received serious attention from scientists and the general population due to their wide range of potentially harmful effects on living organisms. MPs may originate from primary sources [...] Read more.

In the last few decades, microplastics (MPs) have been among the emerging environmental pollutants that have received serious attention from scientists and the general population due to their wide range of potentially harmful effects on living organisms. MPs may originate from primary sources (micro-sized plastics manufactured on purpose) and secondary sources (breakdown of large plastic items through physical, chemical, and biological processes). Consequently, serious concerns are escalating because MPs can be easily disseminated and contaminate environments, including terrestrial, air, groundwater, marine, and freshwater systems. Furthermore, an exposure to even low doses of MPs during the early developmental stage may induce long-term health effects, even later in life. Accordingly, this study aims to gather the current evidence regarding the effects of MPs exposure on vital body systems, including the digestive, reproductive, central nervous, immune, and circulatory systems, during the early developmental stage. In addition, this study provides essential information about the possible emergence of various diseases later in life (i.e., adulthood). Full article

(This article belongs to the Special Issue Toxicity and Health Effects of Environmental Nano-/Microparticle Exposure)

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32 pages, 2428 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Nanoplastics and Microplastics May Be Damaging Our Livers

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Toxics 2022, 10(10), 586; https://doi.org/10.3390/toxics10100586 - 04 Oct 2022

Cited by 11 | Viewed by 2954

Abstract

Plastics in the environment can be degraded and even broken into pieces under the action of natural factors, and the degraded products with a particle size of less than 5 mm are called microplastics (MPs). MPs exist in a variety of environmental media [...] Read more.

Plastics in the environment can be degraded and even broken into pieces under the action of natural factors, and the degraded products with a particle size of less than 5 mm are called microplastics (MPs). MPs exist in a variety of environmental media that come into contact with the human body. It can enter the body through environmental media and food chains. At present, there are many studies investigating the damage of MPs to marine organisms and mammals. The liver is the largest metabolizing organ and plays an important role in the metabolism of MPs in the body. However, there is no available systematic review on the toxic effects of MPs on the liver. This paper summarizes the adverse effects and mechanisms of MPs on the liver, by searching the literature and highlighting the studies that have been published to date, and provides a scenario for the liver toxicity caused by MPs. Full article

(This article belongs to the Special Issue Toxicity and Health Effects of Environmental Nano-/Microparticle Exposure)

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14 pages, 1115 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Predicting the Bioconcentration Factor in Fish from Molecular Structures

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Linda Bertato

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Nicola Chirico

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Ester Papa

Toxics 2022, 10(10), 581; https://doi.org/10.3390/toxics10100581 - 30 Sep 2022

Cited by 3 | Viewed by 1935

Abstract

The bioconcentration factor (BCF) is one of the metrics used to evaluate the potential of a substance to bioaccumulate into aquatic organisms. In this work, linear and non-linear regression QSARs were developed for the prediction of log BCF using different computational approaches, and [...] Read more.

The bioconcentration factor (BCF) is one of the metrics used to evaluate the potential of a substance to bioaccumulate into aquatic organisms. In this work, linear and non-linear regression QSARs were developed for the prediction of log BCF using different computational approaches, and starting from a large and structurally heterogeneous dataset. The new MLR-OLS and ANN regression models have good fitting with R² values of 0.62 and 0.70, respectively, and comparable external predictivity with R²_ext 0.64 and 0.65 (RMSE_ext of 0.78 and 0.76), respectively. Furthermore, linear and non-linear classification models were developed using the regulatory threshold BCF >2000. A class balanced subset was used to develop classification models which were applied to chemicals not used to create the QSARs. These classification models are characterized by external and internal accuracy up to 84% and 90%, respectively, and sensitivity and specificity up to 90% and 80%, respectively. QSARs presented in this work are validated according to regulatory requirements and their quality is in line with other tools available for the same endpoint and dataset, with the advantage of low complexity and easy application through the software QSAR-ME Profiler. These QSARs can be used as alternatives for, or in combination with, existing models to support bioaccumulation assessment procedures. Full article

(This article belongs to the Special Issue The Transformation Mechanism and Environmental Effects of Emerging Pollutants)

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13 pages, 1926 KiB

Open AccessEditor’s ChoiceArticle

Arbuscular Mycorrhizal Fungal Inoculation Increases Organic Selenium Accumulation in Soybean (Glycine max (Linn.) Merr.) Growing in Selenite-Spiked Soils

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Toxics 2022, 10(10), 565; https://doi.org/10.3390/toxics10100565 - 26 Sep 2022

Cited by 1 | Viewed by 1213

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Selenium (Se) is an essential trace element for humans. Arbuscular mycorrhizal fungi (AMF) play a crucial role in increasing plant micronutrient acquisition. Soybean (Glycine max (Linn.) Merr.) is a staple food for most people around the world and a source of Se. [...] Read more.

Selenium (Se) is an essential trace element for humans. Arbuscular mycorrhizal fungi (AMF) play a crucial role in increasing plant micronutrient acquisition. Soybean (Glycine max (Linn.) Merr.) is a staple food for most people around the world and a source of Se. Therefore, it is necessary to study the mechanism of Se intake in soybean under the influence of AMF. In this study, the effects of fertilization with selenite and inoculation with different AMF strains (Claroideoglomus etunicatum (Ce), Funneliformis mosseae (Fm)) on the accumulation and speciation of Se in common soybean plants were discussed. We carried out a pot experiment at the soil for 90 days to investigate the impact of fertilization with selenite and inoculation with Ce and Fm on the Se fractions in soil, soybean biomass, accumulation and speciation of Se in common soybean plants. The daily dietary intake of the Se (DDI) formula was used to estimate the risk threshold of human intake of Se from soybean seeds. The results showed that combined use of both AMF and Se fertilizer could boost total Se and organic Se amounts in soyabean seeds than that of single Se application and that it could increase the proportion of available Se in soil. Soybean inoculated with Fm and grown in soil fertilized with selenite had the highest organic Se. The results suggest that AMF inoculation could promote root growth, more soil water-soluble Se and higher Se uptake. The maximum Se intake of soybean for adults was 93.15 μg/d when treated with Se fertilizer and Fm, which satisfies the needs of Se intake recommended by the WHO. Combined use of AMF inoculation and Se fertilizer increases the bioavailable Se in soil and promotes the total Se concentration and organic Se accumulation in soybean. In conclusion, AMF inoculation combined with Se fertilization can be a promising strategy for Se biofortification in soybean. Full article

(This article belongs to the Special Issue Safety Utilization and Remediation of Heavy Metal Polluted Farmland)

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12 pages, 2108 KiB

Open AccessEditor’s ChoiceCommunication

Evaluation of Skin Irritation of Acids Commonly Used in Cleaners in 3D-Reconstructed Human Epidermis Model, KeraSkin^TM

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Toxics 2022, 10(10), 558; https://doi.org/10.3390/toxics10100558 - 24 Sep 2022

Cited by 4 | Viewed by 3590

Abstract

Cleaners such as dishwashing liquids contain various chemicals that cause skin damage. Alkaline agents used in cleaners alter the lipid composition of the skin and damage the skin barrier. However, little is known about the effects of acids used in cleaners on the [...] Read more.

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

(This article belongs to the Special Issue Exposure to Indoor Hazardous Chemicals and Harmful Impacts on Human Body)

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12 pages, 1458 KiB

Open AccessEditor’s ChoiceArticle

Arsenic Metabolism, Toxicity and Accumulation in the White Button Mushroom Agaricus bisporus

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Toxics 2022, 10(10), 554; https://doi.org/10.3390/toxics10100554 - 22 Sep 2022

Cited by 2 | Viewed by 2129

Abstract

Mushrooms have unique properties in arsenic metabolism. In many commercial and wild-grown mushrooms, arsenobetaine (AsB), a non-toxic arsenical, was found as the dominant arsenic species. The AsB biosynthesis remains unknown, so we designed experiments to study conditions for AsB formation in the white [...] Read more.

Mushrooms have unique properties in arsenic metabolism. In many commercial and wild-grown mushrooms, arsenobetaine (AsB), a non-toxic arsenical, was found as the dominant arsenic species. The AsB biosynthesis remains unknown, so we designed experiments to study conditions for AsB formation in the white button mushroom, Agaricus bisporus. The mushrooms were treated with various arsenic species including arsenite (As(III)), arsenate (As(V)), methylarsenate (MAs(V)), dimethylarsenate (DMAs(V)) and trimethylarsine oxide (TMAsO), and their accumulation and metabolism were determined using inductively coupled mass spectrometer (ICP-MS) and high-pressure liquid chromatography coupled with ICP-MS (HPLC-ICP-MS), respectively. Our results showed that mycelia have a higher accumulation for inorganic arsenicals while fruiting bodies showed higher accumulation for methylated arsenic species. Two major arsenic metabolites were produced in fruiting bodies: DMAs(V) and AsB. Among tested arsenicals, only MAs(V) was methylated to DMAs(V). Surprisingly, AsB was only detected as the major arsenic product when TMAsO was supplied. Additionally, AsB was only detected in the fruiting body, but not mycelium, suggesting that methylated products were transported to the fruiting body for arsenobetaine formation. Overall, our results support that methylation and AsB formation are two connected pathways where trimethylated arsenic is the optimal precursor for AsB formation. Full article

(This article belongs to the Special Issue Environmental and Health Effects of Heavy Metal)

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9 pages, 1244 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Bisphenol A in Pregnant Women from 10 Caribbean Countries

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Martin S. Forde

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Suzanne Côté

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Elhadji A. Laouan Sidi

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Éric Gaudreau

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Pierre Ayotte

Toxics 2022, 10(10), 556; https://doi.org/10.3390/toxics10100556 - 22 Sep 2022

Cited by 1 | Viewed by 1305

Abstract

Bisphenol A (BPA), a phenolic chemical incorporated into many plastic products, has been found to act as an endocrine disruptor that potentially is linked to adverse neurodevelopmental outcomes. Prenatal BPA concentration levels were assessed in 10 English-speaking Caribbean countries by randomly selecting 15 [...] Read more.

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

(This article belongs to the Special Issue Prenatal Exposure to Environmental Pollutants: Effects on Fetal Development, Birth Outcomes and Children’s Health)

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17 pages, 3290 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Emission Characteristics of Air Pollutants and CO₂ from 11 Cities with Different Economic Development around the Bohai Sea in China from 2008–2017

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Toxics 2022, 10(9), 547; https://doi.org/10.3390/toxics10090547 - 19 Sep 2022

Cited by 1 | Viewed by 1289

Abstract

Cities around the Bohai Sea are one of the main population cluster areas in China, which are characterized by high levels of sustainability performance and human capital, as well as resource-intensive industries. In this study, levels of economic development metrics and emissions of [...] Read more.

Cities around the Bohai Sea are one of the main population cluster areas in China, which are characterized by high levels of sustainability performance and human capital, as well as resource-intensive industries. In this study, levels of economic development metrics and emissions of air pollutants (BC, CO, NH₃, NO_x, OC, PM_2.5, PM₁₀, and SO₂) and CO₂ across eleven cities around the Bohai Sea from 2008 to 2017 were compared to illustrate the potential relationships between air pollutants/carbon emissions and socioeconomic developments. Meanwhile, the associations between the levels of economic development metrics (GDP per capita), emissions, and energy use per GDP have also been examined. Large differences across these 11 cities presenting different economic development levels and energy consumption characteristics have been observed. Cities with development dependable on the consumption of fossil fuels and the development of resource-intensive industries have emitted large amounts of air pollutants and CO₂. Furthermore, the emissions and energy use per GDP for all the cities follow environmental Kuznets curves. The comparison results suggested that the developing cities dependable on resource-intensive industries around the Bohai Sea would obtain greater socioeconomic benefits owing to the interregional cooperation policies under top-down socioeconomic development plans and bottom-up technology development, accompanied by reduced emissions of air pollutants and CO₂. Full article

(This article belongs to the Special Issue State-of-the-Art Techniques in Air Quality, Climate Change, and Pollutant Transport)

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13 pages, 801 KiB

Open AccessEditor’s ChoiceArticle

Healthier Lifestyles Attenuated Association of Single or Mixture Exposure to Air Pollutants with Cardiometabolic Risk in Rural Chinese Adults

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Toxics 2022, 10(9), 541; https://doi.org/10.3390/toxics10090541 - 17 Sep 2022

Viewed by 1364

Abstract

There is little research on how long-term exposure to independent and multiple air pollutants changes cardiometabolic risk in adults. In addition, previous studies focused on only the effect of one or two lifestyles on cardiometabolic risk. The evidence on the interactive effects of [...] Read more.

There is little research on how long-term exposure to independent and multiple air pollutants changes cardiometabolic risk in adults. In addition, previous studies focused on only the effect of one or two lifestyles on cardiometabolic risk. The evidence on the interactive effects of the lifestyle score and exposure to independent and mixtures of air pollutants on cardiometabolic risk is lacking. A total of 33,638 rural residents were included in the cross-sectional study. The three-year average concentrations of air pollutants for participants were predicted by using a satellite-based prediction. The air pollution score was created to assess the combined exposure of four air pollutants (PM₁, PM_2.5, PM₁₀, and NO₂). A gender−age-specific cardiometabolic risk score was calculated. Multivariable-adjusted linear regression and quantile g-computation were used to investigate the associations between air pollutants and cardiometabolic risk. Interaction plots were applied to describe the interactive effects of air pollution and the healthy lifestyle score on cardiometabolic risk. Per interquartile range (IQR) unit increases in PM₁, PM_2.5, PM₁₀, or NO₂ were associated with 0.162 (95% CI: 0.091, 0.233), 0.473 (95% CI: 0.388, 0.559), 0.718 (95% CI: 0.627, 0.810), and 0.795 (95% CI: 0.691, 0.898) unit increases in cardiometabolic risk score (all p < 0.05), respectively. A 0.854 (95% CI: 0.768, 0.940) unit increase in cardiometabolic risk was associated with each IQR increase in air pollution score. Furthermore, the strengths of associations of PM₁, PM_2.5, PM₁₀, NO₂, and the air pollution score on cardiometabolic risk score were attenuated with the healthy lifestyle score increase. In addition, there was no statistical significance after the lifestyle score equal to four scores for the effect of PM₁ on the cardiometabolic risk score. In conclusions, individual or joint air pollutants were associated with an increased cardiometabolic risk. Improving the healthy lifestyle may be an effective method to improve cardiometabolic health in highly polluted rural regions. Full article

(This article belongs to the Special Issue Integrated Effects of Air Pollutions and Climate Change on Human Health)

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14 pages, 2577 KiB

Open AccessEditor’s ChoiceArticle

Deoxynivalenol Induces Apoptosis via FOXO3a-Signaling Pathway in Small-Intestinal Cells in Pig

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Tae Hong Kang

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Kyung Soo Kang

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Sang In Lee

Toxics 2022, 10(9), 535; https://doi.org/10.3390/toxics10090535 - 13 Sep 2022

Cited by 6 | Viewed by 1500

Abstract

Deoxynivalenol (DON) is a mycotoxin that is found in feed ingredients derived from grains such as corn and wheat. Consumption of DON-contaminated feed has been shown to cause damage to the intestine, kidneys, and liver. However, the molecular mechanism by which DON exerts [...] Read more.

Deoxynivalenol (DON) is a mycotoxin that is found in feed ingredients derived from grains such as corn and wheat. Consumption of DON-contaminated feed has been shown to cause damage to the intestine, kidneys, and liver. However, the molecular mechanism by which DON exerts its effect in the small intestine is not completely understood. As a result, we profiled gene expression in intestinal epithelial cells treated with DON and examined the molecular function in vitro. We hypothesized that DON could induce apoptosis via the FOXO3a-signaling pathway in intestinal epithelial cells based on these findings. DON induced the apoptosis and the translocation of FOXO3a into the nucleus. Moreover, the inhibiting of FOXO3a alleviated the apoptosis and expression of apoptosis-related genes (TRAL, BCL-6, CASP8, and CASP3). ERK1/2 inhibitor treatment suppressed the translocation of FOXO3a into the nucleus. Our discovery suggests that DON induces apoptosis in intestinal epithelial cells through the FOXO3a-signaling pathway. Full article

(This article belongs to the Section Toxicology)

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14 pages, 8324 KiB

Open AccessEditor’s ChoiceArticle

Harmful Effects of Pyraclostrobin on the Fat Body and Pericardial Cells of Foragers of Africanized Honey Bee

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Lais V. B. Inoue

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Caio E. C. Domingues

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Aleš Gregorc

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Elaine C. M. Silva-Zacarin

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Osmar Malaspina

Toxics 2022, 10(9), 530; https://doi.org/10.3390/toxics10090530 - 09 Sep 2022

Cited by 4 | Viewed by 2164

Abstract

Managed honey bees are daily exposed in agricultural settings or wild environments to multiple stressors. Currently, fungicide residues are increasingly present in bees’ pollen and nectar and can harm colonies’ production and survival. Therefore, our study aimed to evaluate the effects of the [...] Read more.

Managed honey bees are daily exposed in agricultural settings or wild environments to multiple stressors. Currently, fungicide residues are increasingly present in bees’ pollen and nectar and can harm colonies’ production and survival. Therefore, our study aimed to evaluate the effects of the fungicide pyraclostrobin on the fat body and pericardial cells of Africanized honey bees. The foragers were divided into three experimental treatment groups and two controls: pyraclostrobin 0.125 ng/µL (FG1), 0.025 ng/µL (FG2), 0.005 ng/µL (FG3), untreated control (CTL), and acetone control (CAC). After five days of oral exposure (ad libitum), the bees were dissected and prepared for histopathological and morphometric analysis. The FG1-treated bees showed extensive cytoarchitecture changes in the fat body and pericardial cells, inducing cell death. Bees from the FG2 group showed disarranged oenocytes, peripheral vacuolization, and pyknotic nuclei of pericardial cells, but the cytoarchitecture was not compromised as observed in FG1. Additionally, immune system cells were observed through the fat body in the FG1 group. Bees exposed to FG3 demonstrated only oenocytes vacuolization. A significant decrease in the oenocyte’s surface area for bees exposed to all pyraclostrobin concentrations was observed compared to the CTL and CAC groups. The bees from the FG1 and FG2 treatment groups presented a reduced surface area of pericardial cells compared to the controls and the FG3 group. This study highlighted the harmful effects of fungicide pyraclostrobin concentrations at the individual bee cellular level, potentially harming the colony level on continuous exposure. Full article

(This article belongs to the Section Toxicology)

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14 pages, 1175 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Copper Effect on Microalgae: Toxicity and Bioremediation Strategies

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Elena Cavalletti

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Giovanna Romano

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Fortunato Palma Esposito

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Toxics 2022, 10(9), 527; https://doi.org/10.3390/toxics10090527 - 06 Sep 2022

Cited by 12 | Viewed by 3234

Abstract

Microalgae are increasingly recognised as suitable microorganisms for heavy metal (HM) removal, since they are able to adsorb them onto their cell wall and, in some cases, compartmentalise them inside organelles. However, at relatively high HM concentrations, they could also show signs of [...] Read more.

Microalgae are increasingly recognised as suitable microorganisms for heavy metal (HM) removal, since they are able to adsorb them onto their cell wall and, in some cases, compartmentalise them inside organelles. However, at relatively high HM concentrations, they could also show signs of stress, such as organelle impairments and increased activities of antioxidant enzymes. The main aim of this review is to report on the mechanisms adopted by microalgae to counteract detrimental effects of high copper (Cu) concentrations, and on the microalgal potential for Cu bioremediation of aquatic environments. Studying the delicate balance between beneficial and detrimental effects of Cu on microalgae is of particular relevance as this metal is widely present in aquatic environments facing industrial discharges. This metal often induces chloroplast functioning impairment, generation of reactive oxygen species (ROS) and growth rate reduction in a dose-dependent manner. However, microalgae also possess proteins and small molecules with protective role against Cu and, in general, metal stress, which increase their resistance towards these pollutants. Our critical literature analysis reveals that microalgae can be suitable indicators of Cu pollution in aquatic environments, and could also be considered as components of eco-sustainable devices for HM bioremediation in association with other organisms. Full article

(This article belongs to the Special Issue Insights on Ecotoxicological Effects of Anthropogenic Contaminants in Aquatic Organisms)

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15 pages, 2858 KiB

Open AccessEditor’s ChoiceArticle

Cerium Oxide Enhances the Toxicity of Zinc Oxide Nanoparticles in Human Lung Epithelial Cell Cultures

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Tasnim Al Rashaideh

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Nervana Metwali

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Sarah S. Perry

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Andrea Adamcakova-Dodd

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Peter S. Thorne

Toxics 2022, 10(9), 522; https://doi.org/10.3390/toxics10090522 - 01 Sep 2022

Cited by 3 | Viewed by 1757

Abstract

Recently, many approaches have been developed to improve the performance of nanomaterials. Combining more than one nanomaterial is one such approach that achieves superior results. However, during the fabrication of nanomaterials or formulation of end products, materials can be released into the ambient [...] Read more.

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

(This article belongs to the Special Issue Toxicity Assessment of Ambient Nanoparticles)

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19 pages, 949 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Do Neighborhood Factors Modify the Effects of Lead Exposure on Child Behavior?

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Toxics 2022, 10(9), 517; https://doi.org/10.3390/toxics10090517 - 31 Aug 2022

Viewed by 4718

Abstract

Lead exposure and neighborhoods can affect children’s behavior, but it is unclear if neighborhood characteristics modify the effects of lead on behavior. Understanding these modifications has important intervention implications. Blood lead levels (BLLs) in children (~7 years) from Montevideo, Uruguay, were categorized at [...] Read more.

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

(This article belongs to the Special Issue Interaction and Intersection: The Effects of Environmental Exposures on Children's Health)

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22 pages, 15449 KiB

Open AccessEditor’s ChoiceReview

Inflammation and Autophagy: A Convergent Point between Autism Spectrum Disorder (ASD)-Related Genetic and Environmental Factors: Focus on Aluminum Adjuvants

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Loïc Angrand

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Jean-Daniel Masson

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Alberto Rubio-Casillas

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Marika Nosten-Bertrand

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Guillemette Crépeaux

Toxics 2022, 10(9), 518; https://doi.org/10.3390/toxics10090518 - 31 Aug 2022

Cited by 4 | Viewed by 9239

Abstract

Autism spectrum disorder (ASD), schizophrenia, and bipolar disorder are genetically complex and heterogeneous neurodevelopmental disorders (NDDs) resulting from genetic factors and gene-environment (GxE) interactions for which onset occurs in early brain development. Recent progress highlights the link between ASD and (i) immunogenetics, neurodevelopment, [...] Read more.

Autism spectrum disorder (ASD), schizophrenia, and bipolar disorder are genetically complex and heterogeneous neurodevelopmental disorders (NDDs) resulting from genetic factors and gene-environment (GxE) interactions for which onset occurs in early brain development. Recent progress highlights the link between ASD and (i) immunogenetics, neurodevelopment, and inflammation, and (ii) impairments of autophagy, a crucial neurodevelopmental process involved in synaptic pruning. Among various environmental factors causing risk for ASD, aluminum (Al)-containing vaccines injected during critical periods have received special attention and triggered relevant scientific questions. The aim of this review is to discuss the current knowledge on the role of early inflammation, immune and autophagy dysfunction in ASD as well as preclinical studies which question Al adjuvant impacts on brain and immune maturation. We highlight the most recent breakthroughs and the lack of epidemiological, pharmacokinetic and pharmacodynamic data constituting a “scientific gap”. We propose additional research, such as genetic studies that could contribute to identify populations at genetic risk, improving diagnosis, and potentially the development of new therapeutic tools. Full article

(This article belongs to the Special Issue Early Life Exposure to Persistent Organic Pollutants, a Particularly Sensitive Period)

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13 pages, 1701 KiB

Open AccessEditor’s ChoiceArticle

Determination of the Oxidative Stress Biomarkers of 8-Hydroxydeoxyguanosine and Dityrosine in the Gills, Skin, Dorsal Fin, and Liver Tissue of Atlantic Salmon (Salmo salar) Parr

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Alexandros G. Asimakopoulos

Toxics 2022, 10(9), 509; https://doi.org/10.3390/toxics10090509 - 29 Aug 2022

Cited by 1 | Viewed by 1739

Abstract

Oxidative stress is a condition caused by an imbalance in the occurrence of reactive oxygen species in the cells and tissues of organisms. An ultra-performance liquid chromatography–electrospray ionization tandem mass spectrometry (UPLC–ESI–MS/MS) method was developed for the simultaneous determination of two oxidative stress [...] Read more.

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

(This article belongs to the Section Toxicology)

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13 pages, 314 KiB

Open AccessEditor’s ChoiceArticle

Hematological Effects and Benchmark Doses of Long-Term Co-Exposure to Benzene, Toluene, and Xylenes in a Follow-Up Study on Petrochemical Workers

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Toxics 2022, 10(9), 502; https://doi.org/10.3390/toxics10090502 - 28 Aug 2022

Cited by 5 | Viewed by 1531

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Benzene, toluene, and xylenes (BTX) commonly co-exist. Exposure to individual components and BTX-rich mixtures can induce hematological effects. However, the hematological effects of long-term exposure to BTX are still unclear, and respective reference levels based on empirical evidence should be developed. We conducted [...] Read more.

Benzene, toluene, and xylenes (BTX) commonly co-exist. Exposure to individual components and BTX-rich mixtures can induce hematological effects. However, the hematological effects of long-term exposure to BTX are still unclear, and respective reference levels based on empirical evidence should be developed. We conducted a follow-up study in BTX-exposed petrochemical workers. Long-term exposure levels were quantified by measuring cumulative exposure (CE). Generalized weighted quantile sum (WQS) regression models and Benchmark Dose (BMD) Software were used to evaluate their combined effects and calculate their BMDs, respectively. Many hematologic parameters were significantly decreased at the four-year follow-up (p < 0.05). We found positive associations of CE levels of benzene, toluene, and xylene with the decline in monocyte counts, lymphocyte counts, and hematocrit, respectively (β > 0.010, P_trend < 0.05). These associations were stronger in subjects with higher baseline parameters, males, drinkers, or overweight subjects (P_interaction < 0.05). BTX had positive combined effects on the decline in monocyte counts, red-blood-cell counts, and hemoglobin concentrations (P_trend for WQS indices < 0.05). The estimated BMDs for CE levels of benzene, toluene, and xylene were 2.138, 1.449, and 2.937 mg/m³ × year, respectively. Our study demonstrated the hematological effects of long-term BTX co-exposure and developed 8h-RELs of about 0.01 ppm based on their hematological effects. Full article

(This article belongs to the Special Issue Biomonitoring and Exposure Assessment of Multiple Occupational Hazards)

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Open AccessEditor’s ChoiceArticle

Perfluorooctane Sulfonate Induces Dysfunction of Human Umbilical Vein Endothelial Cells via Ferroptosis Pathway

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Toxics 2022, 10(9), 503; https://doi.org/10.3390/toxics10090503 - 28 Aug 2022

Cited by 1 | Viewed by 1819

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(1) Background: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant, and it is receiving increasing attention regarding its human health risks due to its extensive use. Endothelial dysfunction is a mark of cardiovascular disease, but the basic mechanism of PFOS-induced endothelial dysfunction is [...] Read more.

(1) Background: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant, and it is receiving increasing attention regarding its human health risks due to its extensive use. Endothelial dysfunction is a mark of cardiovascular disease, but the basic mechanism of PFOS-induced endothelial dysfunction is still not fully understood. Ferroptosis is a newly defined regulatory cell death driven by cellular metabolism and iron-dependent lipid peroxidation. Although ferroptosis has been shown to be involved in the pathogenesis of cardiovascular diseases, the involvement of ferroptosis in the pathogenesis of endothelial dysfunction caused by PFOS remains unclear. (2) Purpose: To explore the role of ferroptosis in the dysfunction of endothelial cells and underlying mechanisms. (3) Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to PFOS or PFOS and Fer-1. The viability, morphology change under electronic microscope, lipid-reactive oxygen species (lipid-ROS), and production of nitric oxide (NO) were determined. The expression of glutathione peroxidase 4(GPX4), ferritin heavy chain protein 1 (FTH1), heme oxygenase 1 (HO-1) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) were analyzed via Western blot analysis. (4) Results: PFOS was shown to cause a decrease in viability and morphological changes of mitochondria, and well as an increase in lipid droplets. The expression of GPX4, FTH1 and HO-1 was decreased, and that of ACSL4 was increased after exposure to PFOS. In addition to the above-mentioned ferroptosis-related manifestations, there was also a reduction in NO content. (5) Conclusions: PFOS induces ferroptosis by regulating the GPX4 and ACSL4 pathways, which leads to HUVEC dysfunction. Full article

(This article belongs to the Topic Hazard Assessment of Endocrine Disrupting Chemicals)

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14 pages, 2045 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Measuring TiO₂N and AgHEC Airborne Particle Density during a Spray Coating Process

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Sara Trabucco

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Antti Joonas Koivisto

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Toxics 2022, 10(9), 498; https://doi.org/10.3390/toxics10090498 - 27 Aug 2022

Cited by 2 | Viewed by 1180

Abstract

Effective particle density is a key parameter for assessing inhalation exposure of engineered NPs in occupational environments. In this paper, particle density measurements were carried out using two different techniques: one based on the ratio between mass and volumetric particle concentrations; the other [...] Read more.

Effective particle density is a key parameter for assessing inhalation exposure of engineered NPs in occupational environments. In this paper, particle density measurements were carried out using two different techniques: one based on the ratio between mass and volumetric particle concentrations; the other one based on the ratio between aerodynamic and geometric particle diameter. These different approaches were applied to both field- and laboratory-scale atomization processes where the two target NPs (N-doped TiO₂, TiO₂N and AgNPs capped with a quaternized hydroxyethylcellulose, AgHEC) were generated. Spray tests using TiO₂N were observed to release more and bigger particles than tests with AgHEC, as indicated by the measured particle mass concentrations and volumes. Our findings give an effective density of TiO₂N particle to be in a similar range between field and laboratory measurements (1.8 ± 0.5 g/cm³); while AgHEC particle density showed wide variations (3.0 ± 0.5 g/cm³ and 1.2 + 0.1 g/cm³ for field and laboratory campaigns, respectively). This finding leads to speculation regarding the composition of particles emitted because atomized particle fragments may contain different Ag-to-HEC ratios, leading to different density values. A further uncertainty factor is probably related to low process emissions, making the subtraction of background concentrations from AgHEC process emissions unreliable. Full article

(This article belongs to the Special Issue Nano and Ultrafine Particle Toxicology and Exposure Assessment)

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15 pages, 3919 KiB

Open AccessEditor’s ChoiceArticle

Incorporation of Metabolic Activation in the HPTLC-SOS-Umu-C Bioassay to Detect Low Levels of Genotoxic Chemicals in Food Contact Materials

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Claudine Cottet-Fontannaz

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Gabriele Scholz

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Benoît Schilter

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Maricel Marin-Kuan

Toxics 2022, 10(9), 501; https://doi.org/10.3390/toxics10090501 - 27 Aug 2022

Cited by 10 | Viewed by 1779

Abstract

The safety evaluation of food contact materials requires excluding mutagenicity and genotoxicity in migrates. Testing the migrates using in vitro bioassays has been proposed to address this challenge. To be fit for that purpose, bioassays must be capable of detecting very low, safety [...] Read more.

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

(This article belongs to the Special Issue Risk Assessment of Food Contact Materials/Articles)

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19 pages, 4523 KiB

Open AccessEditor’s ChoiceArticle

Lipidomics Profiles and Lipid Metabolite Biomarkers in Serum of Coal Workers’ Pneumoconiosis

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Toxics 2022, 10(9), 496; https://doi.org/10.3390/toxics10090496 - 26 Aug 2022

Cited by 6 | Viewed by 1763

Abstract

As a serious occupational pulmonary fibrosis disease, pneumoconiosis still lacks effective biomarkers. Previous studies suggest that pneumoconiosis may affect the body’s lipid metabolism. The purpose of this study was to explore lipidomics profiles and lipid metabolite biomarkers in the serum of coal workers’ [...] Read more.

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

(This article belongs to the Special Issue Biomonitoring and Exposure Assessment of Multiple Occupational Hazards)

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18 pages, 3446 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

A Metabolomic Approach to Assess the Toxicity of the Olive Tree Endophyte Bacillus sp. PTA13 Lipopeptides to the Aquatic Macrophyte Lemna minor L.

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Evgenia-Anna Papadopoulou

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Katerina Giaki

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Apostolis Angelis

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Alexios-Leandros Skaltsounis

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Konstantinos A. Aliferis

Toxics 2022, 10(9), 494; https://doi.org/10.3390/toxics10090494 - 25 Aug 2022

Cited by 3 | Viewed by 2089

Abstract

Pesticides represent a major human input into the ecosystem, posing a serious risk to non-target organisms. Therefore, there is pressure toward the reduction in their use and the discovery of alternative sources of bioactivity. Endophytic microorganisms represent a source of bioactivity, whose potential [...] Read more.

Pesticides represent a major human input into the ecosystem, posing a serious risk to non-target organisms. Therefore, there is pressure toward the reduction in their use and the discovery of alternative sources of bioactivity. Endophytic microorganisms represent a source of bioactivity, whose potential for plant protection has been recently established. In this context, an olive tree endophytic Bacillus sp. was isolated, exhibiting superior antifungal activity, mainly attributed to its major surfactin, iturin, and fengycin and the minor gageotetrin and bacilotetrin groups of lipopeptides (LP). Based on the potential of LP and the lack of information on their toxicity to aquatic organisms, we have investigated the toxicity of an LP extract to the model macrophyte Lemna minor L. The extract exhibited low phytotoxicity (EC₅₀ = 419 μg·mL⁻¹), and for the investigation of its effect on the plant, GC/EI/MS metabolomics was applied following exposure to sub-lethal doses (EC₂₅ and EC₅₀). Results revealed a general disturbance of plants’ biosynthetic capacity in response to LP treatments, with substantial effect on the amino acid pool and the defense mechanism regulated by jasmonate. There are no previous reports on the phytotoxicity of LP to L. minor, with evidence supporting their improved toxicological profile and potential in plant protection. Full article

(This article belongs to the Special Issue Toxicity of Contaminants on Aquatic Organisms)

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16 pages, 3943 KiB

Open AccessEditor’s ChoiceArticle

Commercial Fungicide Toxic Effects on Terrestrial Non-Target Species Might Be Underestimated When Based Solely on Active Ingredient Toxicity and Standard Earthworm Tests

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Gabriella Jorge-Escudero

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Mariana Pérez Polanco

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Jan Erland Lagerlöf

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Carlos Alberto Pérez

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Diana Míguez

Toxics 2022, 10(9), 488; https://doi.org/10.3390/toxics10090488 - 23 Aug 2022

Cited by 5 | Viewed by 1694

Abstract

The ecosystem services provided by earthworms are lost when land management reduces their populations, hence, the importance of thorough assessments of management effects on this group. The present study aimed to: (1) review the possible influence of other ingredients within the formulations of [...] Read more.

The ecosystem services provided by earthworms are lost when land management reduces their populations, hence, the importance of thorough assessments of management effects on this group. The present study aimed to: (1) review the possible influence of other ingredients within the formulations of two commercial fungicides; (2) assess the sublethal effects of these commercial fungicides on Eisenia fetida; and (3) assess the acute lethal effects of one commercial fungicide on both Glossoscolex rione and E. fetida. Examining all components of the studied commercial formulations revealed that alongside the toxic active ingredients are other ingredients that are equally as or more toxic than the former and may even be in higher concentrations. The inhibition concentration of 10% of E. fetida’s progeny (IC₁₀) was estimated at 133 mg kg⁻¹ for PROSARO^® and 1544 mg kg⁻¹ for SWING PLUS^®. Both fungicides showed an effect of hormesis on the progeny. In this first toxicity study with G. rione, it was found that this species is more sensitive to PROSARO^® than E. fetida, with preliminary 14 day-lethal concentrations of 285 mg kg⁻¹ for the former and >1000 mg kg⁻¹ for the latter. Full article

(This article belongs to the Special Issue Current Developments in Soil Ecotoxicology)

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12 pages, 1864 KiB

Open AccessEditor’s ChoiceArticle

Insights into the Seasonal Olfactory Mechanism of Geosmin in Raw Water of Huangpu River

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Toxics 2022, 10(8), 485; https://doi.org/10.3390/toxics10080485 - 19 Aug 2022

Viewed by 1031

Abstract

Since the 1990s, the raw water of Huangpu River in Shanghai, China, has intermittently encountered off-flavor contamination. In this work, the concentrations of typical odor, geosmin, in raw water of Huangpu River are found to shift along with the seasons. However, microbes recognized [...] Read more.

Since the 1990s, the raw water of Huangpu River in Shanghai, China, has intermittently encountered off-flavor contamination. In this work, the concentrations of typical odor, geosmin, in raw water of Huangpu River are found to shift along with the seasons. However, microbes recognized as the producer of geosmin such as Cyanobacteria and Actinobacteria are not consistent with the shift of geosmin. Cyanobacteria blooms in summer rather than winter, whereas Actinobacteria thrives in winter. Representational difference analysis (RDA) reveals that microbes associated with blooming algae have positive co-occurrence correlations with the concentrations of geosmin and nutrients in winter, whereas those within Cyanobacteria and Planctomycete are in a positive correlation with temperature and thrive in summer. This causes the concentration of geosmin in raw water to appear to depend on the abundance of Actinobacteria rather than that of Cyanobacteria. However, combining with the synthesis and storage properties of geosmin in algae, as well as the decomposition properties of algae with Actinobacteria, geosmin might be synthesized by Cyanobacteria in summer, which is stored in cells of Cyanobacteria and released only via the decomposition of Actinobacteria in winter. This potential olfactory mechanism of geosmin is quite different from that derived from pure culture of odor producers or correlation analysis of bacteria and odors; thus, providing insights into the mechanism of practical off-flavor events. Full article

(This article belongs to the Special Issue Biodegradation and Hazards of Environmental Emerging Pollutants)

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24 pages, 1283 KiB

Open AccessEditor’s ChoiceReview

Recent Strategies for Bioremediation of Emerging Pollutants: A Review for a Green and Sustainable Environment

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Saroj Bala

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Diksha Garg

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Banjagere Veerabhadrappa Thirumalesh

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Minaxi Sharma

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Kandi Sridhar

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Baskaran Stephen Inbaraj

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Manikant Tripathi

Toxics 2022, 10(8), 484; https://doi.org/10.3390/toxics10080484 - 19 Aug 2022

Cited by 59 | Viewed by 11655

Abstract

Environmental pollution brought on by xenobiotics and other related recalcitrant compounds have recently been identified as a major risk to both human health and the natural environment. Due to their toxicity and non-biodegradability, a wide range of pollutants, such as heavy metals, polychlorinated [...] Read more.

Environmental pollution brought on by xenobiotics and other related recalcitrant compounds have recently been identified as a major risk to both human health and the natural environment. Due to their toxicity and non-biodegradability, a wide range of pollutants, such as heavy metals, polychlorinated biphenyls, plastics, and various agrochemicals are present in the environment. Bioremediation is an effective cleaning technique for removing toxic waste from polluted environments that is gaining popularity. Various microorganisms, including aerobes and anaerobes, are used in bioremediation to treat contaminated sites. Microorganisms play a major role in bioremediation, given that it is a process in which hazardous wastes and pollutants are eliminated, degraded, detoxified, and immobilized. Pollutants are degraded and converted to less toxic forms, which is a primary goal of bioremediation. Ex situ or in situ bioremediation can be used, depending on a variety of factors, such as cost, pollutant types, and concentration. As a result, a suitable bioremediation method has been chosen. This review focuses on the most recent developments in bioremediation techniques, how microorganisms break down different pollutants, and what the future holds for bioremediation in order to reduce the amount of pollution in the world. Full article

(This article belongs to the Special Issue Bioremediation of Soils Contaminated with Pharmaceuticals, Pesticides, Petroleum and Other Organic Compounds)

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15 pages, 1314 KiB

Open AccessEditor’s ChoiceArticle

Ecotoxicity of Polyvinylidene Difluoride (PVDF) and Polylactic Acid (PLA) Microplastics in Marine Zooplankton

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Michela Di Giannantonio

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Toxics 2022, 10(8), 479; https://doi.org/10.3390/toxics10080479 - 17 Aug 2022

Cited by 10 | Viewed by 3292

Abstract

The aim of this study was to investigate the ecotoxicity of polyvinylidene difluoride (PVDF) and polylactic acid (PLA) microplastics (MPs) in two marine zooplankton: the crustacean Artemia franciscana and the cnidarian Aurelia sp. (common jellyfish). To achieve this goal, (i) MP uptake, (ii) [...] Read more.

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

(This article belongs to the Special Issue Insights on Ecotoxicological Effects of Anthropogenic Contaminants in Aquatic Organisms)

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30 pages, 960 KiB

Open AccessEditor’s ChoiceReview

The Use of Human Biomonitoring to Assess Occupational Exposure to PAHs in Europe: A Comprehensive Review

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Andromachi Katsonouri

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Christiana M. Neophytou

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Toxics 2022, 10(8), 480; https://doi.org/10.3390/toxics10080480 - 17 Aug 2022

Cited by 3 | Viewed by 2652

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers’ health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make [...] Read more.

Polycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers’ health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make them more usable by regulators and policymakers. This comprehensive review, developed under the Human Biomonitoring for Europe (HBM4EU) Initiative, was based on the literature available from 2008–2022, aiming to present and discuss the information on occupational exposure to PAHs, in order to identify the strengths and limitations of exposure and effect biomarkers and the knowledge needs for regulation in the workplace. The most frequently used exposure biomarker is urinary 1-hydroxypyrene (1-OH-PYR), a metabolite of pyrene. As effect biomarkers, those based on the measurement of oxidative stress (urinary 8-oxo-dG adducts) and genotoxicity (blood DNA strand-breaks) are the most common. Overall, a need to advance new harmonized approaches both in data and sample collection and in the use of appropriate biomarkers in occupational studies to obtain reliable and comparable data on PAH exposure in different industrial sectors, was noted. Moreover, the use of effect biomarkers can assist to identify work environments or activities of high risk, thus enabling preventive risk mitigation and management measures. Full article

(This article belongs to the Special Issue Biomonitoring of Human Exposure: From Individual to Group Exposure Assessment)

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21 pages, 1422 KiB

Open AccessEditor’s ChoiceArticle

Post-Mortem Analysis of Heroin Biomarkers, Morphine and Codeine in Stomach Wall Tissue in Heroin-Related Deaths

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Ahmed I. Al-Asmari

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Hassan Alharbi

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Torki A. Zughaibi

Toxics 2022, 10(8), 473; https://doi.org/10.3390/toxics10080473 - 14 Aug 2022

Cited by 1 | Viewed by 2772

Abstract

Toxicological analysis of some cases can be complicated by poor sample quality caused by decomposition. Although heroin-related deaths have been researched extensively, the interpretation of toxicology findings in these cases is challenging, especially in instances where blood samples are unavailable. Thus, it is [...] Read more.

Toxicological analysis of some cases can be complicated by poor sample quality caused by decomposition. Although heroin-related deaths have been researched extensively, the interpretation of toxicology findings in these cases is challenging, especially in instances where blood samples are unavailable. Thus, it is important to develop analytical methods for different sample types. In this study. a method for the quantification of 6-monoacetylmorphine, 6-acetylcodeine, morphine, and codeine in postmortem stomach wall tissue using liquid chromatography coupled with tandem mass spectrometry was developed and validated. All calibration curves prepared with the stomach wall tissue were linear and ranged from 0.5–1000 ng/g with determination coefficients of >0.99 and a lower limit of quantification of 1.0 ng/g. The coefficients of variation for within-run precision and between-run precision were <9%. Matrix effects of stomach wall tissues and their extraction recoveries were investigated and ranged from −19% to +17% and 76% to 80%, respectively. Among the 16 analyzed heroin-related death cases, 6-monoacetylmorphine, 6-acetylcodeine, morphine, and codeine were detected in 75%, 31%, 100%, and 94% of all stomach wall tissues with median concentrations of 90 ng/g, 20 ng/g, 140 ng/g, and 30 ng/g, respectively. This study provides new data on the distribution of 6-monoacetylmorphine, 6-Acetylcodeine, morphine, and codeine in postmortem stomach wall tissue and suggests the usefulness of alternative matrices for investigating heroin-related fatalities when blood samples are unavailable. In addition, the prevalence of 6-monoacetylmorphine in the stomach wall tissue was higher than that in the liver and kidney tissues. Full article

(This article belongs to the Special Issue Forensic Toxicology: A New Scientific Contribution)

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20 pages, 1331 KiB

Open AccessEditor’s ChoiceReview

Multiple Targets of Toxicity in Environmental Exposure to Low-Dose Cadmium

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Soisungwan Satarug

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Glenda C. Gobe

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David A. Vesey

Toxics 2022, 10(8), 472; https://doi.org/10.3390/toxics10080472 - 13 Aug 2022

Cited by 13 | Viewed by 2481

Abstract

Dietary assessment reports and population surveillance programs show that chronic exposure to low levels of environmental cadmium (Cd) is inevitable for most people, and adversely impacts the health of children and adults. Based on a risk assessment model that considers an increase in [...] Read more.

Dietary assessment reports and population surveillance programs show that chronic exposure to low levels of environmental cadmium (Cd) is inevitable for most people, and adversely impacts the health of children and adults. Based on a risk assessment model that considers an increase in the excretion of β₂-microglobulin (β₂M) above 300 μg/g creatinine to be the “critical” toxicity endpoint, the tolerable intake level of Cd was set at 0.83 µg/kg body weight/day, and a urinary Cd excretion rate of 5.24 µg/g creatinine was considered to be the toxicity threshold level. The aim of this review is to draw attention to the many other toxicity endpoints that are both clinically relevant and more appropriate to derive Cd exposure limits than a β₂M endpoint. In the present review, we focus on a reduction in the glomerular filtration rate and diminished fecundity because chronic exposure to low-dose Cd, reflected by its excretion levels as low as 0.5 µg/g creatinine, have been associated with dose-dependent increases in risk of these pathological symptoms. Some protective effects of the nutritionally essential elements selenium and zinc are highlighted. Cd-induced mitochondrial dysfunction is discussed as a potential mechanism underlying gonadal toxicities and infertility. Full article

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

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14 pages, 598 KiB

Open AccessEditor’s ChoiceArticle

Glyphosate and AMPA in Human Urine of HBM4EU Aligned Studies: Part A Children

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Andromachi Katsonouri

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Konstantinos C. Makris

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Annelies De Decker

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Bert Morrens

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Nina Vogel

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Marike Kolossa-Gehring

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Toxics 2022, 10(8), 470; https://doi.org/10.3390/toxics10080470 - 12 Aug 2022

Cited by 10 | Viewed by 2157

Abstract

Few data are available on the exposure of children to glyphosate (Gly) in Europe. Within HBM4EU, new HBM exposure data were collected from aligned studies at five sampling sites distributed over Europe (studies: SLO CRP (SI); ORGANIKO (CY); GerES V-sub (DE); 3XG (BE); [...] Read more.

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

(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)

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15 pages, 1366 KiB

Open AccessEditor’s ChoiceArticle

Phytoremediation of Soil Contaminated by Organochlorine Pesticides and Toxic Trace Elements: Prospects and Limitations of Paulownia tomentosa

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Toxics 2022, 10(8), 465; https://doi.org/10.3390/toxics10080465 - 11 Aug 2022

Cited by 3 | Viewed by 1601

Abstract

Paulownia tomentosa (Thunb.) Steud is a drought-resistant, low-maintenance and fast-growing energy crop that can withstand a wide range of climatic conditions, provides a high biomass yield (approximately 50 t DM ha⁻¹ yr⁻¹), and develops successfully in contaminated sites. In Kazakhstan, [...] Read more.

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

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

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22 pages, 8841 KiB

Open AccessEditor’s ChoiceArticle

Spatial Distribution, Contamination Levels, and Health Risk Assessment of Potentially Toxic Elements in Household Dust in Cairo City, Egypt

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Sahar M. Abd El Bakey

Toxics 2022, 10(8), 466; https://doi.org/10.3390/toxics10080466 - 11 Aug 2022

Cited by 5 | Viewed by 1538

Abstract

Urban areas’ pollution, which is owing to rapid urbanization and industrialization, is one of the most critical issues in densely populated cities such as Cairo. The concentrations and the spatial distribution of fourteen potentially toxic elements (PTEs) in household dust were investigated in [...] Read more.

Urban areas’ pollution, which is owing to rapid urbanization and industrialization, is one of the most critical issues in densely populated cities such as Cairo. The concentrations and the spatial distribution of fourteen potentially toxic elements (PTEs) in household dust were investigated in Cairo City, Egypt. PTE exposure and human health risk were assessed using the USEPA’s exposure model and guidelines. The levels of As, Cd, Cr, Cu, Hg, Mo, Ni, Pb, and Zn surpassed the background values. Contamination factor index revealed that contamination levels are in the sequence Cd > Hg > Zn > Pb > Cu > As > Mo > Ni > Cr > Co > V > Mn > Fe > Al. The degree of contamination ranges from considerably to very high pollution. Elevated PTE concentrations in Cairo’s household dust may be due to heavy traffic emissions and industrial activities. The calculated noncarcinogenic risk for adults falls within the safe limit, while those for children exceed that limit in some sites. Cairo residents are at cancer risk owing to prolonged exposure to the indoor dust in their homes. A quick and targeted plan must be implemented to mitigate these risks. Full article

(This article belongs to the Special Issue Potentially Toxic Elements Pollution in Urban and Suburban Environments)

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8 pages, 496 KiB

Open AccessEditor’s ChoiceArticle

Acute Rubigine^® Poisoning in Martinique a French Overseas Department of America: Clinical Characteristics and Prognostic Factors

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Toxics 2022, 10(8), 453; https://doi.org/10.3390/toxics10080453 - 05 Aug 2022

Viewed by 1082

Abstract

Rubigine^® is an anti-rust stain remover containing fluorides which is believed to have been the cause of many deaths in Martinique. However, after the modification of its composition in 2006, serious poisoning from old formulas containing fluorides persisted. Our main objective was [...] Read more.

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

(This article belongs to the Section Toxicology)

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14 pages, 1720 KiB

Open AccessEditor’s ChoiceArticle

Characterization of Potential Adverse Outcome Pathways Related to Metabolic Outcomes and Exposure to Per- and Polyfluoroalkyl Substances Using Artificial Intelligence

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Toxics 2022, 10(8), 449; https://doi.org/10.3390/toxics10080449 - 04 Aug 2022

Cited by 3 | Viewed by 2523

Abstract

Human exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with numerous adverse health effects, depending on various factors such as the conditions of exposure (dose/concentration, duration, route of exposure, etc.) and characteristics associated with the exposed target (e.g., age, sex, ethnicity, [...] Read more.

Human exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with numerous adverse health effects, depending on various factors such as the conditions of exposure (dose/concentration, duration, route of exposure, etc.) and characteristics associated with the exposed target (e.g., age, sex, ethnicity, health status, and genetic predisposition). The biological mechanisms by which PFAS might affect systems are largely unknown. To support the risk assessment process, AOP-helpFinder, a new artificial intelligence tool, was used to rapidly and systematically explore all available published information in the PubMed database. The aim was to identify existing associations between PFAS and metabolic health outcomes that may be relevant to support building adverse outcome pathways (AOPs). The collected information was manually organized to investigate linkages between PFAS exposures and metabolic health outcomes, including dyslipidemia, hypertension, insulin resistance, and obesity. Links between PFAS exposure and events from the existing metabolic-related AOPs were also retrieved. In conclusion, by analyzing dispersed information from the literature, we could identify some associations between PFAS exposure and components of existing AOPs. Additionally, we identified some linkages between PFAS exposure and metabolic outcomes for which only sparse information is available or which are not yet present in the AOP-wiki database that could be addressed in future research. Full article

(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)

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17 pages, 3502 KiB

Open AccessEditor’s ChoiceArticle

Alleviation of Ammonium Toxicity in Salvia splendens ‘Vista Red’ with Silicon Supplementation

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Jinnan Song

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Jingli Yang

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Byoung Ryong Jeong

Toxics 2022, 10(8), 446; https://doi.org/10.3390/toxics10080446 - 03 Aug 2022

Cited by 7 | Viewed by 1625

Abstract

Ammonium (NH₄⁺) toxicity seriously hampers the yield and quality of salvia plants because most varieties or sub-species are highly sensitive to NH₄⁺. Silicon (Si) is an alternative that is used to minimize these disturbances and maintain better [...] Read more.

Ammonium (NH₄⁺) toxicity seriously hampers the yield and quality of salvia plants because most varieties or sub-species are highly sensitive to NH₄⁺. Silicon (Si) is an alternative that is used to minimize these disturbances and maintain better growth under NH₄⁺ toxicity. Nevertheless, the mitigatory effects of Si on NH₄⁺-stressed salvia are unknown. Therefore, this study was carried out to determine how Si assists to alleviate the NH₄⁺ toxicity degree in salvia. To this end, salvia plants were cultivated in a controlled environment supplied with a constant N (nitrogen) level (13 meq·L⁻¹) in the form of three NH₄⁺:NO₃⁻ ratios (0:100, 50:50, 100:0), each with (1.0 meq·L⁻¹) or without Si. Physiological disorders and typical NH₄⁺ toxicity symptoms, as well as interrupted photosynthesis, were observed in the 100% NH₄⁺-treated plants. Furthermore, cation uptake inhibition and oxidative damage were also imposed by the 100% NH₄⁺ supply. In contrast, in the presence of Si, the NH₄⁺ toxicity degree was attenuated and plant growth was ensured. Accordingly, the NH₄⁺ toxicity appearance ratio decreased significantly. Furthermore, Si-treated plants showed an ameliorated photosynthetic ability, elevated internal K and Ca levels, and enhanced antioxidative capacity, as reflected by improved major antioxidant enzyme activities, as well as diminished accumulation of ROS (reactive oxygen species) and MDA (malondialdehyde). Our findings enlightened the agronomic importance of additional Si to nutrient solutions, especially pertaining to bedding plants at risk of NH₄⁺ toxicity. Full article

(This article belongs to the Special Issue Heavy Metal Toxicity Effects on Plants)

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21 pages, 1629 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000–2021)

Toxics 2022, 10(8), 443; https://doi.org/10.3390/toxics10080443 - 02 Aug 2022

Cited by 2 | Viewed by 2041

Abstract

Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it [...] Read more.

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

(This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?)

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20 pages, 5506 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

A Population-Based Human In Vitro Approach to Quantify Inter-Individual Variability in Responses to Chemical Mixtures

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Toxics 2022, 10(8), 441; https://doi.org/10.3390/toxics10080441 - 01 Aug 2022

Cited by 4 | Viewed by 1976

Abstract

Human cell-based population-wide in vitro models have been proposed as a strategy to derive chemical-specific estimates of inter-individual variability; however, the utility of this approach has not yet been tested for cumulative exposures in mixtures. This study aimed to test defined mixtures and [...] Read more.

Human cell-based population-wide in vitro models have been proposed as a strategy to derive chemical-specific estimates of inter-individual variability; however, the utility of this approach has not yet been tested for cumulative exposures in mixtures. This study aimed to test defined mixtures and their individual components and determine whether adverse effects of the mixtures were likely to be more variable in a population than those of the individual chemicals. The in vitro model comprised 146 human lymphoblastoid cell lines from four diverse subpopulations of European and African descent. Cells were exposed, in concentration–response, to 42 chemicals from diverse classes of environmental pollutants; in addition, eight defined mixtures were prepared from these chemicals using several exposure- or hazard-based scenarios. Points of departure for cytotoxicity were derived using Bayesian concentration–response modeling and population variability was quantified in the form of a toxicodynamic variability factor (TDVF). We found that 28 chemicals and all mixtures exhibited concentration–response cytotoxicity, enabling calculation of the TDVF. The median TDVF across test substances, for both individual chemicals or defined mixtures, ranged from a default assumption (10^1/2) of toxicodynamic variability in human population to >10. The data also provide a proof of principle for single-variant genome-wide association mapping for toxicity of the chemicals and mixtures, although replication would be necessary due to statistical power limitations with the current sample size. This study demonstrates the feasibility of using a set of human lymphoblastoid cell lines as an in vitro model to quantify the extent of inter-individual variability in hazardous properties of both individual chemicals and mixtures. The data show that population variability of the mixtures is unlikely to exceed that of the most variable component, and that similarity in genome-wide associations among components may be used to accrue additional evidence for grouping of constituents in a mixture for cumulative assessments. Full article

(This article belongs to the Special Issue Computational Toxicology: Expanding Frontiers in Risk Assessment)

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14 pages, 4715 KiB

Open AccessEditor’s ChoiceArticle

The Role of Ferroptosis in the Damage of Human Proximal Tubule Epithelial Cells Caused by Perfluorooctane Sulfonate

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Toxics 2022, 10(8), 436; https://doi.org/10.3390/toxics10080436 - 29 Jul 2022

Cited by 2 | Viewed by 2045

Abstract

Perfluorooctane sulfonate (PFOS) is a typical persistent organic pollutant and environmental endocrine disruptor that has been shown to be associated with the development of many diseases; it poses a considerable threat to the ecological environment and to human health. PFOS is known to [...] Read more.

Perfluorooctane sulfonate (PFOS) is a typical persistent organic pollutant and environmental endocrine disruptor that has been shown to be associated with the development of many diseases; it poses a considerable threat to the ecological environment and to human health. PFOS is known to cause damage to renal cells; however, studies of PFOS-induced ferroptosis in cells have not been reported. We used the CCK-8 method to detect cell viability, flow cytometry and immunofluorescence methods to detect ROS levels and Western blot to detect ferroptosis, endoplasmic reticulum stress, antioxidant and apoptosis-related proteins. In our study, we found that PFOS could induce the onset of ferroptosis in HK-2 cells with decreased GPx4 expression and elevated ACSL4 and FTH1 expression, which are hallmarks for the development of ferroptosis. In addition, PFOS-induced ferroptosis in HK-2 cells could be reversed by Fer-1. We also found that endoplasmic reticulum stress and its mediated apoptotic mechanism and P53-mediated antioxidant mechanism are involved in the toxic damage of cells by PFOS. In this paper, we demonstrated for the first time that PFOS can induce ferroptosis in HK-2 cells. In addition, we preliminarily explored other mechanisms of cytotoxic damage by PFOS, which provides a new idea to study the toxicity of PFOS as well as the damage to the kidney and its mechanism. Full article

(This article belongs to the Topic Hazard Assessment of Endocrine Disrupting Chemicals)

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20 pages, 998 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Occupational Exposure to Hexavalent Chromium, Nickel and PAHs: A Mixtures Risk Assessment Approach Based on Literature Exposure Data from European Countries

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Toxics 2022, 10(8), 431; https://doi.org/10.3390/toxics10080431 - 29 Jul 2022

Cited by 3 | Viewed by 1790

Abstract

Hexavalent chromium (Cr(VI)), nickel (Ni) and polycyclic aromatic hydrocarbons (PAHs) are genotoxic co-occurring lung carcinogens whose occupational health risk is still understudied. This study, conducted within the European Human Biomonitoring Initiative (HBM4EU), aimed at performing a mixtures risk assessment (MRA) based on published [...] Read more.

Hexavalent chromium (Cr(VI)), nickel (Ni) and polycyclic aromatic hydrocarbons (PAHs) are genotoxic co-occurring lung carcinogens whose occupational health risk is still understudied. This study, conducted within the European Human Biomonitoring Initiative (HBM4EU), aimed at performing a mixtures risk assessment (MRA) based on published human biomonitoring (HBM) data from Cr(VI), Ni and/or PAHs occupational co-exposure in Europe. After data extraction, Risk Quotient (RQ) and Sum of Risk Quotients (SRQ) were calculated for binary and ternary mixtures to characterise the risk. Most selected articles measured urinary levels of Cr and Ni and a SRQ > 1 was obtained for co-exposure levels in welding activities, showing that there is concern regarding co-exposure to these substances. Similarly, co-exposure to mixtures of Cr(VI), Ni and PAHs in waste incineration settings resulted in SRQ > 1. In some studies, a low risk was estimated based on the single substances’ exposure level (RQ < 1), but the mixture was considered of concern (SRQ > 1), highlighting the relevance of considering exposure to the mixture rather than to its single components. Overall, this study points out the need of using a MRA based on HBM data as a more realistic approach to assess and manage the risk at the workplace, in order to protect workers’ health. Full article

(This article belongs to the Special Issue Human Biomonitoring in Health Risk Assessment: Current Practices and Recommendations for the Future)

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