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Environmental Toxicology – Toxic Effects, Mechanisms, and Risk Assessment of Endocrine Disrupting Chemicals

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A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Environmental Sciences".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 17495

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Special Issue Editors

Prof. Dr. Kyunghee Ji

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Guest Editor

Department of Occupational and Environmental Health, School of Environmental Science, Yongin University, Yongin 17092, Republic of Korea
Interests: alternative compounds; bisphenols; ecotoxicology; endocrine disrupting chemicals; mixture toxicity; molecular toxicology; reproduction; thyroid hormones; persistent organic pollutants; pharmaceuticals; risk assessment

Dr. Sunmi Kim

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Guest Editor

Chemical Safety Research Center, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea
Interests: environmental & human health risk assessment; exposure assessment; biomonitoring; persistent organic pollutants (POPs); phthalates; bisphenols; endocrine-disrupting chemicals; consumer products; environmental epidemiology; multiple chemical exposure; thyroid hormones; ecotoxicology

Special Issue Information

Dear Colleagues,

This Special Issue will describe the toxic effects, mechanisms, and risk assessment of endocrine-disrupting chemicals that have been detected in the environment recently. Endocrine-disrupting chemicals such as bisphenol A and its alternatives, flame retardants, perfluoroalkyl acids, pharmaceuticals, phthalates, and others have been frequently detected in the environment and biota. However, there is only limited information available on their toxicological effects and risk assessment. To fill these knowledge gaps, this Special Issue aims to include a range of topics with the goal of linking toxic effects and underlying mechanisms for various endocrine-disrupting chemicals and approaches critical to support risk assessment and management. Manuscripts will be considered in areas such as:

Hazard characterization of endocrine disrupting chemicals;
Toxic effects of individual chemicals or mixtures at different organizational levels;
Investigations of the toxicological mechanism of endocrine disrupting chemicals;
New strategies in risk assessment of endocrine disrupting chemicals including in vivo, in vitro, and in silico methods.

Prof. Kyunghee Ji
Dr. Sunmi Kim
Guest Editors

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Keywords

Bisphenol A and its alternatives
Ecotoxicity
Endocrine-disrupting chemicals
Flame retardants
Mixture toxicity
Perfluoroalkyl acids
Pharmaceuticals
Phthalates
Toxic effects and underlying mechanism
Risk assessment

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Published Papers (6 papers)

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Research

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11 pages, 1279 KiB

Open AccessArticle

Developmental Toxicity and Thyroid Endocrine Disruption of Polyhexamethylene Guanidine Hydrochloride and Humidifier Disinfectant in Zebrafish Larvae

by Suhyun Park, Hyojin Kim and Kyunghee Ji

Appl. Sci. 2021, 11(11), 4884; https://doi.org/10.3390/app11114884 - 26 May 2021

Viewed by 2360

Abstract

Polyhexamethylene guanidine (PHMG), a major component of humidifier disinfectants (HDs), is responsible for the outbreak of pulmonary diseases in pregnant women and children in South Korea. This study aims to characterize the developmental toxicity and thyroid endocrine disruption of Vegetable Home Cleanup HD and its main component, PHMG-hydrochloride (PHMG-H), in zebrafish embryo/larvae after a 7-d exposure. Acute lethality, development, whole-body thyroid hormones, and transcription of genes related to the hypothalamus-pituitary-thyroid axis were investigated. Zebrafish embryos exposed to the actual-use concentration (0.6%) of HD exhibited significant embryo coagulation and larval mortality. The concentration of triiodothyronine (T3) was significantly high in fish exposed to 0.4 mg/L PHMG-H, accompanied by the downregulation of the tshβ gene. These results suggest a feedback mechanism for the regulation of increased T3 levels. Significant decrease of thyroxine (T4) concentration, increase of T3/T4 ratio, and upregulation of the deio2 gene in fish exposed to PHMG-H suggested that there was an increase in the active T3 due to the catalysis of outer ring deiodination. Future research is required to determine the factors that contribute to the differences in toxicity between the two counter ions of PHMG. Full article

(This article belongs to the Special Issue Environmental Toxicology – Toxic Effects, Mechanisms, and Risk Assessment of Endocrine Disrupting Chemicals)

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12 pages, 597 KiB

Open AccessArticle

Exposure to Phthalates and Alternative Plasticizers Is Associated with Methylation Changes of ESR1 and PGR in Uterine Leiomyoma: The ELENA Study

by Yoon Hee Cho, Yeong Sook Yoon, Min Sun Koo, Wanseo Kim, Younglim Kho, Sunmi Kim, Yang Jee Kim, Haewon Choi, Eun Jeong Choi, Jae Whoan Koh, Kyoung Chul Chun and Young Ah Kim

Appl. Sci. 2021, 11(9), 4234; https://doi.org/10.3390/app11094234 - 7 May 2021

Cited by 1 | Viewed by 2371

Abstract

Uterine leiomyomas are estrogen-dependent benign tumors with unknown etiologies. Phthalates are endocrine-disrupting chemicals and ubiquitous in the environment; thus, it has been suggested that they play a role in the development of uterine leiomyoma. We aimed to investigate whether the pathogenesis of uterine leiomyoma is related to methylation changes in promoter regions of estrogen receptor α (ESR1) and progesterone receptor (PGR) genes in response to phthalates and alternative plasticizers exposure. Urinary concentrations of 20 phthalate metabolites and seven metabolites of di-2-ethylhexyl terephthalate (DEHTP) and di (isononyl) cyclohexane-1,2-dicarboxylate (DINCH) were measured by UHPLC-MS/MS in thirty leiomyoma patients, who provided both paired leiomyoma and myometrium tissues. Methylation levels of ESR1 and PGR were analyzed by pyrosequencing assay. A total of 12 phthalate metabolites and 5 alternative metabolites (3 DEHTP and 2 DINCH) were detected >70% among study participants. The methylation of ESR1 and PGR were significantly lower in leiomyoma tissues compared to those in myometrium (18.10 ± 4.41 vs. 28.72 ± 4.95; 2.32 ± 0.81 vs. 3.27 ± 0.56, respectively). ESR1 methylation in leiomyoma was negatively associated with mono-2-carboxylmethyl-hexyl phthalate (2cx-MMHP) and mono-3-carbocyl-propyl phthalate (MCPP) after adjusting for confounding factors. However, 1-mono-2-ethyl-5-oxohexyl-benzene-1,4-dicarboxylate (5OXO-MEHTP), one of the alternatives, showed positive association with ESR1 methylation in leiomyoma. PGR methylation in leiomyoma was significantly associated with mono butyl phthalate (MnBP), but negatively associated with cyclohexane-1,2-dicarboxylate-mono-7-hydroxy-4-methyl-heptyl ester (cx-MINCH). Our results suggest that phthalates exposure may contribute to leiomyoma pathogenesis via ESR1 and PGR methylation changes. Full article

(This article belongs to the Special Issue Environmental Toxicology – Toxic Effects, Mechanisms, and Risk Assessment of Endocrine Disrupting Chemicals)

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12 pages, 3298 KiB

Open AccessFeature PaperArticle

Investigation on Sex Hormone-Disruption Effects of Two Novel Brominated Flame Retardants (DBDPE and BTBPE) in Male Zebrafish (Danio rerio) and Two Human Cell Lines (H295R and MVLN)

by Jiwon Choi, Gowoon Lee, Sunmi Kim and Kyungho Choi

Appl. Sci. 2021, 11(9), 3837; https://doi.org/10.3390/app11093837 - 23 Apr 2021

Cited by 8 | Viewed by 2758

Abstract

Decabromodiphenyl ethane (DBDPE) and 1,2-bis(2,4,6-tribromo-phenoxy) ethane (BTBPE) are novel brominated flame retardants (NBFRs) and have been detected in variety of environment and biota. Although sex endocrine-disrupting potential has been suggested in experimental studies, their adverse effects on sex steroid hormones and underlying mechanisms are largely unclear. The purpose of the present study is to investigate the sex hormone-disrupting effects of two NBFRs using in vivo and in vitro models together. For this, male zebrafish (Danio rerio) along with human adrenocortical carcinoma (H295R) and breast carcinoma (MVLN) cell lines were employed. In male zebrafish, 14-day exposure to DBDPE significantly increased 17β-estradiol (E2) concentrations. Disruption of sex hormone regulation was also suggested after exposure to BTBPE, i.e., the increasing trend of E2 levels, E2/11-ketotestosterone (11-KT) ratio, and estrogen receptor-alpha (erα) and erβ gene expression levels. In H295R cells, an E2/T ratio showed an increasing trend by DBDPE exposure, but transcriptions of major genes in steroidogenesis pathway were not affected. Taken together, our observation implies that two NBFRs could cause the sex hormone disruption potential in male zebrafish and H295R cells but probably not through alteration of steroidogenesis pathway. Full article

(This article belongs to the Special Issue Environmental Toxicology – Toxic Effects, Mechanisms, and Risk Assessment of Endocrine Disrupting Chemicals)

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9 pages, 2954 KiB

Open AccessArticle

Effect of Chronic Exposure to Pesticide Methomyl on Antioxidant Defense System in Testis of Tilapia (Oreochromis niloticus) and Its Recovery Pattern

by Shunlong Meng, Xi Chen, Chao Song, Limin Fan, Liping Qiu, Yao Zheng, Jiazhang Chen and Pao Xu

Appl. Sci. 2021, 11(8), 3332; https://doi.org/10.3390/app11083332 - 8 Apr 2021

Cited by 10 | Viewed by 2415

Abstract

The chronic effect of environmental methomyl on the antioxidant system in testis of Nile tilapia (Oreochromis niloticus) and its recovery pattern was investigated. Tilapia were exposed to sublethal concentrations of 0.2, 2, 20 and 200 μgL⁻¹ methomyl for 30 days and thereafter moved to methomyl-free water for 18 days. Antioxidant levels in testis, including glutathione peroxidase, catalase, glutathione-S-transferase, glutathione reductase, superoxide dismutase, reduced glutathione, oxidized glutathione were measured every 6 days during the period of exposure, and at 18 days after being transferred to methomyl-free water. The results showed that lower methomyl concentration (0.2 μgL⁻¹) had no effect on the above antioxidants, thus 0.2 μgL⁻¹ could be seen as NOAEL for methomyl to tilapia. However, higher methomyl concentration of 2, 20 and 200 μgL⁻¹ could significantly influence the above antioxidants. Glutathione peroxidase and oxidized glutathione increased significantly. On the contrary, reduced glutathione decreased significantly. Catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase increased at lower methomyl (2 and 20 μgL⁻¹), but decreased at higher methomyl (200 μgL⁻¹). The recovery test showed that oxidative damage caused by lower methomyl of 2 and 20 μgL⁻¹ was reversible, and oxidative damage caused by higher methomyl of 200 μgL⁻¹ was irreversible within 18 days of recovery period. Full article

(This article belongs to the Special Issue Environmental Toxicology – Toxic Effects, Mechanisms, and Risk Assessment of Endocrine Disrupting Chemicals)

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14 pages, 2119 KiB

Open AccessArticle

Simulation of Chronic Intoxication in Rats Exposed to Cadmium and Mercury

by Iveta Cimboláková, Tatiana Kimáková, Henrieta Pavolová, Tomáš Bakalár, Dušan Kudelas and Andrea Seňová

Appl. Sci. 2020, 10(22), 8066; https://doi.org/10.3390/app10228066 - 13 Nov 2020

Cited by 2 | Viewed by 2000

Abstract

Cadmium and mercury are widespread and non-biodegradable pollutants of great concern to human and animal health. In this study, the influence of exposure to low doses of cadmium and mercury on Wistar rats was investigated. The experiments aimed to identify suitable markers of chronic intoxication with heavy metals in rats. The subjects were 48 naive young rats (24 females and 24 males), four weeks old, grouped randomly into three distinct groups—control group, group exposed to cadmium and group exposed to mercury. The control group received sham treatment—clean untreated water. Cd exposed group received water containing cadmium chloride dihydrate and Hg exposed group received water with mercury dichloride. Both cadmium and mercury were administered to experimental rats in drinking water in concentrations exceeding the maximum acceptable concentration of these metals 500 times, i.e., 0.5 mg Hg and 2.5 mg Cd per liter of water. The results were evaluated quarterly during the experiment (52 weeks). Selected physiological parameters (life span, body weight changes and intake of food and water), reproductive parameters (number of births (litters), number of born pups and number of raised pups) and toxicological parameters (average daily dose, total dose received and the amount of toxic metal received) were studied. The results of the experiments indicate differences between both individual groups and between males and females, which confirmed that these parameters are essential in such experiments of chronic exposure to subtoxic doses of heavy metals. Full article

(This article belongs to the Special Issue Environmental Toxicology – Toxic Effects, Mechanisms, and Risk Assessment of Endocrine Disrupting Chemicals)

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Review

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24 pages, 3849 KiB

Open AccessReview

Systematic Review of Exposure to Bisphenol A Alternatives and Its Effects on Reproduction and Thyroid Endocrine System in Zebrafish

by Jiyun Lee, Kyong Whan Moon and Kyunghee Ji

Appl. Sci. 2021, 11(4), 1837; https://doi.org/10.3390/app11041837 - 19 Feb 2021

Cited by 14 | Viewed by 4706

Abstract

Bisphenol A (BPA), which is widely used for manufacturing polycarbonate plastics and epoxy resins, has been banned from use in plastic baby bottles because of concerns regarding endocrine disruption. Substances with similar chemical structures have been used as BPA alternatives; however, limited information is available on their toxic effects. In the present study, we reviewed the endocrine disrupting potential in the gonad and thyroid endocrine system in zebrafish after exposure to BPA and its alternatives (i.e., bisphenol AF, bisphenol C, bisphenol F, bisphenol S, bisphenol SIP, and bisphenol Z). Most BPA alternatives disturbed the endocrine system by altering the levels of genes and hormones involved in reproduction, development, and growth in zebrafish. Changes in gene expression related to steroidogenesis and sex hormone production were more prevalent in males than in females. Vitellogenin, an egg yolk precursor produced in females, was also detected in males, confirming that it could induce estrogenicity. Exposure to bisphenols in the parental generation induced a decrease in the hatchability associated with offspring generation. In zebrafish exposed to bisphenols, significant decreases in thyroxine concentrations and increases in thyroid-stimulating hormone concentrations were commonly observed. Alternative compounds used to replace a chemical of concern are believed to be less toxic than the original compound; however, several BPA alternatives appear to have similar or greater effects on the endocrine system in zebrafish. Since endocrine systems interact with each other, further studies are needed to assess the primary target of BPA alternatives among the endocrine axes. Full article

(This article belongs to the Special Issue Environmental Toxicology – Toxic Effects, Mechanisms, and Risk Assessment of Endocrine Disrupting Chemicals)

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