Hazard Assessment of Endocrine Disrupting Chemicals

Topic Information

Dear Colleagues,

The exponential growth in genome and transcriptome projects conducted over the past decade provides an unprecedented opportunity to informatively address the hazard assessment of endocrine-disrupting chemicals, both in invertebrate and vertebrate phyla. Several examples indisputably demonstrate that the genomic architecture of a given species is a key aspect in determining its response towards chemical insults. Therefore, disclosing the molecular landscape governing the physiological responses of different taxa is fundamental to understand the mode of action (MoA) of environmental pollutants and relate them with adversity. Understanding the MoA of environmental chemicals in a wide array of representative taxa allows for the building of a toxicant response at an ecosystem scale, thus becoming a central piece of hazard and risk assessment.

For this Topic, we invite high-quality original research papers, short communications, and reviews focusing on all aspects of hazard assessment of endocrine-disrupting chemicals. Studies may be in vivo, in vitro, and in silico studies including both field and laboratory approaches. Research on single chemicals, mixtures, and complex environmental samples are welcome. We also welcome computational or predictive studies.

Prof. Dr. Miguel Machado Santos
Dr. Davide Degli Esposti
Dr. Teresa Neuparth
Dr. Luís Filipe C. Castro
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Fishes fishes	2.3	1.9	2016	15.7 Days	CHF 2600
International Journal of Environmental Research and Public Health ijerph	-	5.4	2004	29.6 Days	CHF 2500
Journal of Xenobiotics jox	6.0	4.6	2011	21.7 Days	CHF 1600
Toxics toxics	4.6	3.4	2013	14.7 Days	CHF 2600

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Published Papers (15 papers)

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12 pages, 1399 KiB  

Open AccessArticle

Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression—Arguments for Preemptive Testing

by Sibylle Christine Roll and Martina Hahn

J. Xenobiot. 2022, 12(4), 317-328; https://doi.org/10.3390/jox12040022 - 28 Oct 2022

Cited by 2 | Viewed by 1813

Abstract

Background: The international drug agencies annotate pharmacogenes for many years. Pharmacogenetic testing is thus far only established in few settings, assuming that only few patients are actually affected by drug-gene interactions. Methods: 108 hospitalized patients with major depressive disorder were genotyped for CYP1A2 [...] Read more.

Background: The international drug agencies annotate pharmacogenes for many years. Pharmacogenetic testing is thus far only established in few settings, assuming that only few patients are actually affected by drug-gene interactions. Methods: 108 hospitalized patients with major depressive disorder were genotyped for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, NAT2, DPYD; VKORC1 and TMTP. Results: We found 583 (mean 5.4, median 5) divergent phenotypes (i.e., divergent from the common phenotypes considered normal, e.g., extensive metabolizer) in the 12 analyzed pharmacokinetic genes. The rate for at least one divergent phenotype was 100% in our cohort for CYP, but also for all 12 important pharmacogenes: patients had at least two divergent phenotypes. Compared to a large Danish cohort, CYP2C9 NM and IM status, CYP2C19 UM, CYP2D6 UM and DYPD (GAS 0, 1, 2) genotypes differed statistical significantly. For CYP2D6 and CYP2C19, 13% of the patients were normal metabolizers for both enzymes in our cohort, but this value was 27.3% in the Danish cohort, which is a highly significant difference (p < 0.0001). Conclusion: Divergent phenotypes in pharmacogenes are not the exception, but the rule. Patients with divergent phenotypes seem more prone for hospitalization, emphasizing the need for pre-emptive testing to avoid inefficacy and adverse drug effects in all patients. Full article

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

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10 pages, 2068 KiB  

Open AccessArticle

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

by Jiajing Cui, Pingwei Wang, Shuqi Yan, Yujun Liang, Dongge Liu and Shuping Ren

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

Cited by 3 | Viewed by 2123

Abstract

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

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

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

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14 pages, 4715 KiB  

Open AccessArticle

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

by Pingwei Wang, Dongge Liu, Shuqi Yan, Yujun Liang, Jiajing Cui, Li Guo, Shuping Ren and Peng Chen

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

Cited by 5 | Viewed by 2388

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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22 pages, 1945 KiB  

Open AccessArticle

Association of Serum Levels of Plasticizers Compounds, Phthalates and Bisphenols, in Patients and Survivors of Breast Cancer: A Real Connection?

by Mariana Segovia-Mendoza, Margarita Isabel Palacios-Arreola, Luz María Monroy-Escamilla, Alexandra Estela Soto-Piña, Karen Elizabeth Nava-Castro, Yizel Becerril-Alarcón, Roberto Camacho-Beiza, David Eduardo Aguirre-Quezada, Elías Cardoso-Peña, Omar Amador-Muñoz, José de Jesús Garduño-García and Jorge Morales-Montor

Int. J. Environ. Res. Public Health 2022, 19(13), 8040; https://doi.org/10.3390/ijerph19138040 - 30 Jun 2022

Cited by 5 | Viewed by 2345

Abstract

Phthalates and bisphenols are ubiquitous environmental pollutants with the ability to perturb different systems. Specifically, they can alter the endocrine system, and this is why they are also known as endocrine-disrupting compounds (EDCs). Interestingly, they are related to the development and progression of [...] Read more.

Phthalates and bisphenols are ubiquitous environmental pollutants with the ability to perturb different systems. Specifically, they can alter the endocrine system, and this is why they are also known as endocrine-disrupting compounds (EDCs). Interestingly, they are related to the development and progression of breast cancer (BC), but the threshold concentrations at which they trigger that are not well established. Objectives: The aim of this study was to compare the concentration measures of parent EDCs in three groups of women (without BC, with BC, and BC survivors) from two urban populations in Mexico, to establish a possible association between EDCs and this disease. We consider the measure of the parent compounds would reflect the individual’s exposure. Methods: The levels of di-ethyl-hexyl-phthalate (DEHP), butyl-benzyl-phthalate (BBP), di-n-butyl phthalate (DBP) and di-ethyl-phthalate (DEP), bisphenol A (BPA) and bisphenol S (BPS) were determined by gas chromatograph-mass spectrometry in 102 subjects, including 37 women without any pathological disease, 46 patients with BC and 19 women survivals of BC of Mexico and Toluca City. Results: All phthalates were detected in 100% of women, two of them were significantly higher in patients with different BC subtypes in Mexico City. Differential increases were observed mainly in the serum concentration of phthalates in women with BC compared to women without disease between Mexico and Toluca City. In addition, when performing an analysis of the concentrations of phthalates by molecular type of BC, DEP and BBP were found mainly in aggressive and poorly differentiated types of BC. It should be noted that female BC survivors treated with anti-hormonal therapy showed lower levels of BBP than patients with BC. BPA and BPS were found in most samples from Mexico City. However, BPS was undetectable in women from Toluca City. Discussion: The results of our study support the hypothesis of a positive association between exposure to phthalates and BC incidence. Full article

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

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13 pages, 381 KiB  

Open AccessArticle

Urine Di-(2-ethylhexyl) Phthalate Metabolites Are Independently Related to Body Fluid Status in Adults: Results from a U.S. Nationally Representative Survey

by Wei-Jie Wang, Chia-Sung Wang, Chi-Kang Wang, An-Ming Yang and Chien-Yu Lin

Int. J. Environ. Res. Public Health 2022, 19(12), 6964; https://doi.org/10.3390/ijerph19126964 - 07 Jun 2022

Cited by 3 | Viewed by 2074

Abstract

Purpose: Di-(2-ethylhexyl) phthalate (DEHP) has been utilized in many daily products for decades. Previous studies have reported that DEHP exposure could induce renin–angiotensin–aldosterone system activation and increase epithelial sodium channel (ENaC) activity, which contributes to extracellular fluid (ECF) volume expansion. However, there is [...] Read more.

Purpose: Di-(2-ethylhexyl) phthalate (DEHP) has been utilized in many daily products for decades. Previous studies have reported that DEHP exposure could induce renin–angiotensin–aldosterone system activation and increase epithelial sodium channel (ENaC) activity, which contributes to extracellular fluid (ECF) volume expansion. However, there is also no previous study to evaluate the association between DEHP exposure and body fluid status. Methods: We selected 1678 subjects (aged ≥18 years) from a National Health and Nutrition Examination Survey (NHANES) in 2003–2004 to determine the relationship between urine DEHP metabolites and body composition (body measures, bioelectrical impedance analysis (BIA)). Results: After weighing the sampling strategy in multiple linear regression analysis, we report that higher levels of DEHP metabolites are correlated with increases in body measures (body weight, body mass index (BMI), waist circumference), BIA parameters (estimated fat mass, percent body fat, ECF, and ECF/intracellular fluid (ICF) ratio) in multiple linear regression analysis. The relationship between DEHP metabolites and the ECF/ICF ratio was more evident in subjects of younger age (20–39 years old), women, non-Hispanic white ethnicity, and subjects who were not active smokers. Conclusion: In addition to being positively correlated with body measures and body fat, we found that urine DEHP metabolites were positively correlated with ECF and the ECF/ICF ratio in the US general adult population. The finding implies that DEHP exposures might increase ECF volume and the ECF/ICF ratio, which may have adverse health outcomes on the cardiovascular system. Further research is needed to clarify the causal relationship. Full article

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

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19 pages, 1837 KiB  

Open AccessReview

Adverse Effects of Perfluorooctane Sulfonate on the Liver and Relevant Mechanisms

by Pingwei Wang, Dongge Liu, Shuqi Yan, Jiajing Cui, Yujun Liang and Shuping Ren

Toxics 2022, 10(5), 265; https://doi.org/10.3390/toxics10050265 - 19 May 2022

Cited by 18 | Viewed by 4845

Abstract

Perfluorooctane sulfonate (PFOS) is a persistent, widely present organic pollutant. PFOS can enter the human body through drinking water, ingestion of food, contact with utensils containing PFOS, and occupational exposure to PFOS, and can have adverse effects on human health. Increasing research shows [...] Read more.

Perfluorooctane sulfonate (PFOS) is a persistent, widely present organic pollutant. PFOS can enter the human body through drinking water, ingestion of food, contact with utensils containing PFOS, and occupational exposure to PFOS, and can have adverse effects on human health. Increasing research shows that the liver is the major target of PFOS, and that PFOS can damage liver tissue and disrupt its function; however, the exact mechanisms remain unclear. In this study, we reviewed the adverse effects of PFOS on liver tissue and cells, as well as on liver function, to provide a reference for subsequent studies related to the toxicity of PFOS and liver injury caused by PFOS. Full article

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

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15 pages, 2256 KiB  

Open AccessArticle

Insights into the Endocrine Disrupting Activity of Emerging Non-Phthalate Alternate Plasticizers against Thyroid Hormone Receptor: A Structural Perspective

by Torki A. Zughaibi, Ishfaq Ahmad Sheikh and Mohd Amin Beg

Toxics 2022, 10(5), 263; https://doi.org/10.3390/toxics10050263 - 19 May 2022

Cited by 10 | Viewed by 3286

Abstract

Many endocrine-disrupting chemicals (EDCs) have a ubiquitous presence in our environment due to anthropogenic activity. These EDCs can disrupt hormone signaling in the human and animal body systems including the very important hypothalamic-pituitary-thyroid (HPT) axis causing adverse health effects. Thyroxine (T4) and triiodothyronine [...] Read more.

Many endocrine-disrupting chemicals (EDCs) have a ubiquitous presence in our environment due to anthropogenic activity. These EDCs can disrupt hormone signaling in the human and animal body systems including the very important hypothalamic-pituitary-thyroid (HPT) axis causing adverse health effects. Thyroxine (T4) and triiodothyronine (T3) are hormones of the HPT axis which are essential for regulation of metabolism, heart rate, body temperature, growth, development, etc. In this study, potential endocrine-disrupting activity of the most common phthalate plasticizer, DEHP, and emerging non-phthalate alternate plasticizers, DINCH, ATBC, and DEHA against thyroid hormone receptor (TRα) were characterized. The structural binding characterization of indicated ligands was performed against the TRα ligand binding site employing Schrodinger’s induced fit docking (IFD) approach. The molecular simulations of interactions of the ligands against the residues lining a TRα binding pocket, including bonding interactions, binding energy, docking score, and IFD score were analyzed. In addition, the structural binding characterization of TRα native ligand, T3, was also done for comparative analysis. The results revealed that all ligands were placed stably in the TRα ligand-binding pocket. The binding energy values were highest for DINCH, followed by ATBC, and were higher than the values estimated for TRα native ligand, T3, whereas the values for DEHA and DEHP were similar and comparable to that of T3. This study suggested that all the indicated plasticizers have the potential for thyroid hormone disruption with two alternate plasticizers, DINCH and ATBC, exhibiting higher potential for thyroid dysfunction compared to DEHA and DEHP. Full article

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

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Supplementary File 1 (ZIP, 641 KiB)

32 pages, 3734 KiB  

Open AccessArticle

Multi-Strategy Assessment of Different Uses of QSAR under REACH Analysis of Alternatives to Advance Information Transparency

by Kazue Chinen and Timothy Malloy

Int. J. Environ. Res. Public Health 2022, 19(7), 4338; https://doi.org/10.3390/ijerph19074338 - 04 Apr 2022

Cited by 5 | Viewed by 1793

Abstract

Under the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) analysis of alternatives (AoA) process, quantitative structure–activity relationship (QSAR) models play an important role in expanding information gathering and organizing frameworks. Increasingly recognized as an alternative to testing under registration. QSARs have become [...] Read more.

Under the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) analysis of alternatives (AoA) process, quantitative structure–activity relationship (QSAR) models play an important role in expanding information gathering and organizing frameworks. Increasingly recognized as an alternative to testing under registration. QSARs have become a relevant tool in bridging data gaps and supporting weight of evidence (WoE) when assessing alternative substances. Additionally, QSARs are growing in importance in integrated testing strategies (ITS). For example, the REACH ITS framework for specific endpoints directs registrants to consider non-testing results, including QSAR predictions, when deciding if further animal testing is needed. Despite the raised profile of QSARs in these frameworks, a gap exists in the evaluation of QSAR use and QSAR documentation under authorization. An assessment of the different uses (e.g., WoE and ITS) in which QSAR predictions play a role in evidence gathering and organizing remains unaddressed for AoA. This study approached the disparity in information for QSAR predictions by conducting a substantive review of 24 AoA through May 2017, which contained higher-tier endpoints under REACH. Understanding the manner in which applicants manage QSAR prediction information in AoA and assessing their potential within ITS will be valuable in promoting regulatory use of QSARs and building out future platforms in the face of rapidly evolving technology while advancing information transparency. Full article

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

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17 pages, 1037 KiB  

Open AccessArticle

Ecotoxicological Estimation of 4-Cumylphenol, 4-t-Octylphenol, Nonylphenol, and Volatile Leachate Phenol Degradation by the Microscopic Fungus Umbelopsis isabellina Using a Battery of Biotests

by Tomasz Janicki, Andrzej Długoński, Aleksandra Felczak, Jerzy Długoński and Mariusz Krupiński

Int. J. Environ. Res. Public Health 2022, 19(7), 4093; https://doi.org/10.3390/ijerph19074093 - 30 Mar 2022

Cited by 4 | Viewed by 1764

Abstract

The phenolic xenobiotics nonylphenol (NP), 4-tert-octylphenol (4-t-OP), and 4-cumylphenol (4-CP) have the potential to seriously disrupt the endocrine system. Volatile phenols (VPs), especially those present in landfill leachate, also adversely affect the health of numerous organisms. Microbial degradation of [...] Read more.

The phenolic xenobiotics nonylphenol (NP), 4-tert-octylphenol (4-t-OP), and 4-cumylphenol (4-CP) have the potential to seriously disrupt the endocrine system. Volatile phenols (VPs), especially those present in landfill leachate, also adversely affect the health of numerous organisms. Microbial degradation of xenobiotics can result in the formation of intermediates with higher toxicity than the precursor substrates. Therefore, the main aim of this study was to assess the changes in environmental ecotoxicity during the biotransformation of nonylphenol, 4-tert-octylphenol, 4-cumylphenol and volatile phenols by Umbelopsis isabellina using a battery of biotests. The application of bioindicators belonging to different taxonomic groups and diverse trophic levels (producers, consumers, and reducers) indicated a significant reduction in toxicity during the cultivation of fungus cultures both for nonylphenol, 4-tert-octylphenol, 4-cumylphenol and volatile phenols. The rate of toxicity decline was correlated with the degree of xenobiotic biotransformation. Removal of 4-cumylphenol and 4-tert-octylphenol also led to a decrease in the anti-androgenic potential. Moreover, this is the first report demonstrating the anti-androgenic properties of 4-cumylphenol. The results showed that U. isabellina is an attractive tool for the bioremediation and detoxification of contaminated environments. Full article

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

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12 pages, 2322 KiB  

Open AccessArticle

Human Exposure to Chlorinated Organophosphate Ester Flame Retardants and Plasticizers in an Industrial Area of Shenzhen, China

by Yunlang Liu, Tingting Zhu, Zuoming Xie, Chen Deng, Xiujuan Qi, Rong Hu, Jinglin Wang and Jianyi Chen

Int. J. Environ. Res. Public Health 2022, 19(5), 3126; https://doi.org/10.3390/ijerph19053126 - 07 Mar 2022

Cited by 4 | Viewed by 2445

Abstract

Human exposure to organophosphate esters (OPEs) is more pervasive in industrial areas manufacturing OPE-related products. OPE exposure is of great concern due to its associations with adverse health effects, while studies on OPE exposure in industrial districts are scarce. This study aimed to [...] Read more.

Human exposure to organophosphate esters (OPEs) is more pervasive in industrial areas manufacturing OPE-related products. OPE exposure is of great concern due to its associations with adverse health effects, while studies on OPE exposure in industrial districts are scarce. This study aimed to assess human exposure to OPEs in a typical industrial area producing large amounts of OPE-related products in Shenzhen, China. Tris (2-chloroethyl)-phosphate (TCEP), tris (2-chloroisopropyl) phosphate (TCPP) and other common OPEs were analyzed in urine (n = 30) and plasma (n = 21) samples. Moreover, we measured five OPE metabolites (mOPEs) in plasma samples (n = 21). The results show that TCPP and TCEP are dominant compounds, with moderate to high levels compared with those reported in urine and plasma samples from other regions. In addition, di-n-butyl phosphate (DnBP) and diethyl phosphite (DEP) were frequently detected in plasma samples and could be considered as biomarkers. Risk assessment revealed a moderate to high potential health risk from TCEP exposure. Our results provide basic data for human exposure to OPEs in industrial areas and call for the prevention and mitigation of industrial chlorinated OPE pollution. Full article

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

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13 pages, 7140 KiB  

Open AccessArticle

Effects of Cadmium Exposure on Leydig Cells and Blood Vessels in Mouse Testis

by Shi-Han Yang, Si-Ting Chen, Chen Liang, Yong-Hong Shi and Qiu-Sheng Chen

Int. J. Environ. Res. Public Health 2022, 19(4), 2416; https://doi.org/10.3390/ijerph19042416 - 19 Feb 2022

Cited by 5 | Viewed by 2038

Abstract

Environmental exposure to cadmium (Cd) contributes to a decline in the quality of human semen. Although the testis is sensitive to Cd exposure, the mechanism underlying how cadmium affects the testis remains to be defined. In this study, male mice were treated with [...] Read more.

Environmental exposure to cadmium (Cd) contributes to a decline in the quality of human semen. Although the testis is sensitive to Cd exposure, the mechanism underlying how cadmium affects the testis remains to be defined. In this study, male mice were treated with intraperitoneal injections of 0, 0.5, 1.5 and 2.5 mg CdCl₂/kg/day for 10 days, respectively. Both the testicular weight and the 3β-HSD activity of Leydig cells were significantly reduced with the administration of 2.5 mg CdCl₂/kg/day. The height of endothelial cells in the interstitial blood vessels significantly increased with the use of 2.5 mg CdCl₂/kg/day compared with the control. Western blot data showed that the protein levels of CD31, αSMA, caveolin and Ng2 increased with cadmium exposure, and this increase was particularly significant with the administration of 2.5 mg CdCl₂/kg/day. CD31, αSMA, caveolin and Ng2 are related to angiogenesis. Based on our data, cadmium exposure may stimulate the proliferation of the mural cells and endothelial cells of blood vessels, which may lead to abnormal function of the testis. Full article

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

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13 pages, 1677 KiB  

Open AccessArticle

Vanadium Toxicity Monitored by Fertilization Outcomes and Metal Related Proteolytic Activities in Paracentrotus lividus Embryos

by Roberto Chiarelli, Chiara Martino, Maria Carmela Roccheri and Fabiana Geraci

Toxics 2022, 10(2), 83; https://doi.org/10.3390/toxics10020083 - 10 Feb 2022

Cited by 4 | Viewed by 2183

Abstract

Metal pharmaceutical residues often represent emerging toxic pollutants of the aquatic environment, as wastewater treatment plants do not sufficiently remove these compounds. Recently, vanadium (V) derivatives have been considered as potential therapeutic factors in several diseases, however, only limited information is available about [...] Read more.

Metal pharmaceutical residues often represent emerging toxic pollutants of the aquatic environment, as wastewater treatment plants do not sufficiently remove these compounds. Recently, vanadium (V) derivatives have been considered as potential therapeutic factors in several diseases, however, only limited information is available about their impact on aquatic environments. This study used sea urchin embryos (Paracentrotus lividus) to test V toxicity, as it is known they are sensitive to V doses from environmentally relevant to very cytotoxic levels (50 nM; 100 nM; 500 nM; 1 µM; 50 µM; 100 µM; 500 µM; and 1 mM). We used two approaches: The fertilization test (FT) and a protease detection assay after 36 h of exposure. V affected the fertilization percentage and increased morphological abnormalities of both egg and fertilization envelope, in a dose-dependent manner. Moreover, a total of nine gelatinases (with apparent molecular masses ranging from 309 to 22 kDa) were detected, and their proteolytic activity depended on the V concentration. Biochemical characterization shows that some of them could be aspartate proteases, whereas substrate specificity and the Ca²⁺/Zn²⁺ requirement suggest that others are similar to mammalian matrix metalloproteinases (MMPs). Full article

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

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20 pages, 4893 KiB  

Open AccessFeature PaperArticle

Isolation of DiNP-Degrading Microbes from the Mouse Colon and the Influence DiNP Exposure Has on the Microbiota, Intestinal Integrity, and Immune Status of the Colon

by Karen K. Chiu, Shah Tauseef Bashir, Ahmed M. Abdel-Hamid, Lindsay V. Clark, Mary J. Laws, Isaac Cann, Romana A. Nowak and Jodi A. Flaws

Toxics 2022, 10(2), 75; https://doi.org/10.3390/toxics10020075 - 06 Feb 2022

Cited by 4 | Viewed by 3008

Abstract

Di-isononyl phthalate (DiNP) is a plasticizer used to impart flexibility or stability in a variety of products including polyvinyl chloride, cable coatings, artificial leather, and footwear. Previous studies have examined the impact of DiNP on gut integrity and the colonic immune microenvironment, but [...] Read more.

Di-isononyl phthalate (DiNP) is a plasticizer used to impart flexibility or stability in a variety of products including polyvinyl chloride, cable coatings, artificial leather, and footwear. Previous studies have examined the impact of DiNP on gut integrity and the colonic immune microenvironment, but this study further expands the research by examining whether DiNP exposure alters the colonic microbiota and various immune markers. Previous studies have also revealed that environmental microbes degrade various phthalates, but no studies have examined whether anaerobic gut bacteria can degrade DiNP. Thus, this study tested the hypothesis that DiNP exposure alters the gut microbiota and immune-related factors, and that anaerobic bacteria in the gut can utilize DiNP as the sole carbon source. To test this hypothesis, adult female mice were orally dosed with corn oil or various doses of DiNP for 10–14 consecutive days. After the treatment period, mice were euthanized during diestrus. Colonic contents were collected for full-length 16S rRNA gene sequencing to identify the bacteria in the colon contents. Sanger sequencing of the 16S rRNA gene was used to identify bacteria that were able to grow in Bacteroides minimal media with DiNP as the sole carbon source. Colon tissues were collected for immunohistochemistry of immune(-related) factors. An environmentally relevant dose of DiNP (200 µg/kg) significantly increased a Lachnoclostridium taxon and decreased Blautia compared to the control. Collectively, minimal changes in the colonic microbiota were observed as indicated by non-significant beta-diversities between DiNP treatments and control. Furthermore, three strains of anaerobic bacteria derived from the colon were identified to use DiNP as the sole carbon source. Interestingly, DiNP exposure did not alter protein levels of interleukin-6, tumor necrosis factor alpha, claudin-1, and mucin-1 compared to the control. Collectively, these findings show that DiNP exposure alters the gut microbiota and that the gut contains DiNP-degrading microbes. Full article

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

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Open AccessFeature PaperArticle

Prioritizing the Effects of Emerging Contaminants on Estuarine Production under Global Warming Scenarios

by Irene Martins, Joana Soares, Teresa Neuparth, Aldo F. Barreiro, Cândido Xavier, Carlos Antunes and Miguel M. Santos

Toxics 2022, 10(2), 46; https://doi.org/10.3390/toxics10020046 - 20 Jan 2022

Cited by 4 | Viewed by 3119

Abstract

Due to non-linear interactions, the effects of contaminant mixtures on aquatic ecosystems are difficult to assess, especially under temperature rise that will likely exacerbate the complexity of the responses. Yet, under the current climatic crisis, assessing the effects of water contaminants and temperature [...] Read more.

Due to non-linear interactions, the effects of contaminant mixtures on aquatic ecosystems are difficult to assess, especially under temperature rise that will likely exacerbate the complexity of the responses. Yet, under the current climatic crisis, assessing the effects of water contaminants and temperature is paramount to understanding the biological impacts of mixtures of stressors on aquatic ecosystems. Here, we use an ecosystem model followed by global sensitivity analysis (GSA) to prioritize the effects of four single emerging contaminants (ECs) and their mixture, combined with two temperature rise scenarios, on the biomass production of a NE Atlantic estuary. Scenarios ran for 10 years with a time-step of 0.1 days. The results indicate that macroinvertebrate biomass was significantly explained by the effect of each single EC and by their mixture but not by temperature. Globally, the most adverse effects were induced by two ECs and by the mixture of the four ECs, although the sensitivity of macroinvertebrates to the tested scenarios differed. Overall, the present approach is useful to prioritize the effects of stressors and assess the sensitivity of the different trophic groups within food webs, which may be of relevance to support decision making linked to the sustainable management of estuaries and other aquatic systems. Full article

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

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Open AccessFeature PaperCommunication

From Extrapolation to Precision Chemical Hazard Assessment: The Ecdysone Receptor Case Study

by Raquel Ruivo, João Sousa, Teresa Neuparth, Olivier Geffard, Arnaud Chaumot, L. Filipe C. Castro, Davide Degli-Esposti and Miguel M. Santos

Toxics 2022, 10(1), 6; https://doi.org/10.3390/toxics10010006 - 27 Dec 2021

Cited by 2 | Viewed by 2378

Abstract

Hazard assessment strategies are often supported by extrapolation of damage probabilities, regarding chemical action and species susceptibilities. Yet, growing evidence suggests that an adequate sampling of physiological responses across a representative taxonomic scope is of paramount importance. This is particularly relevant for Nuclear [...] Read more.

Hazard assessment strategies are often supported by extrapolation of damage probabilities, regarding chemical action and species susceptibilities. Yet, growing evidence suggests that an adequate sampling of physiological responses across a representative taxonomic scope is of paramount importance. This is particularly relevant for Nuclear Receptors (NR), a family of transcription factors, often triggered by ligands and thus, commonly exploited by environmental chemicals. Within NRs, the ligand-induced Ecdysone Receptor (EcR) provides a remarkable example. Long regarded as arthropod specific, this receptor has been extensively targeted by pesticides, seemingly innocuous to non-target organisms. Yet, current evidence clearly suggests a wider presence of EcR orthologues across metazoan lineages, with unknown physiological consequences. Here, we address the state-of-the-art regarding the phylogenetic distribution and functional characterization of metazoan EcRs and provide a critical analysis of the potential disruption of such EcRs by environmental chemical exposure. Using EcR as a case study, hazard assessment strategies are also discussed in view of the development of a novel “precision hazard assessment paradigm. Full article

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

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