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Toxics
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Health Effects Associated with Exposures to Endocrine Disrupting Chemicals
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Health Effects Associated with Exposures to Endocrine Disrupting Chemicals

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Human Toxicology and Epidemiology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 33879

Special Issue Editors

Dr. Zeyan Liew

E-Mail Website
Guest Editor
Department of Environmental Health Sciences, Yale School of Public Health, 1 Church Street, New Haven, CT 06510, USA
Interests: Acetaminophen; Attention Deficit Disorder with Hyperactivity; Child Development; Environmental Pollutants; Models, Statistical; Causality; Pharmacoepidemiology; Endocrine Disruptors; Pediatric Obesity; Autism Spectrum Disorder
Special Issues, Collections and Topics in MDPI journals
Dr. Gunnar Toft

E-Mail Website
Guest Editor
1. Steno Diabetes Center Aarhus, Aarhus University Hospital, 8200 Aarhus, Denmark
2. Department of Public Health, Aarhus University, Bartholins Allé 2-Building 1260, DK-8000 Aarhus, Denmark
Interests: epidemiology; biomarkers; reproductive toxicology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Accruing research shows that human exposures to a wide range of endocrine disrupting chemicals (EDCs) could increase the risk of disease across the lifespan by altering the homeostasis or action of endogenous hormones, or other signaling chemicals of the endocrine system. Commonly investigated EDCs include chemicals widely applied in commercial and industrial products, such as per and polyfluoralkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), bisphenol A (BPA), phthalates, and certain pesticides. Pharmaceutical agents, including analgesics and painkillers such as acetaminophen, have also been suggested to exhibit strong endocrine disrupting effects. Our understanding of human health risks associated with exposure to EDCs remains limited. The early development period (i.e. in-utero, infancy, and childhood) might be more vulnerable to exposures to EDCs, but depending on the outcomes, relevant exposure windows may include additional periods throughout the entire lifespan.

In this Special Issue, we invite epidemiological research (original articles, reviews, and communications) that addresses human health risks associated with exposures to EDCs. Of interest to this issue are:

  1. Studies that investigate the associations between exposures to EDCs and human health risks, including but not limited to neurological, reproductive, endocrine, cardiovascular, or immunological outcomes. We encourage studies addressing critical time windows of exposure. In addition to ‘classical’ EDCs, we also encourage studies focusing on less studied chemicals or newer types of compounds that might be classified as EDCs;
  2. Research addressing biological pathways or mechanisms of EDC exposure and adverse health outcomes, including genomic, epigenomic, metabolomic, and proteomic studies;
  3. Studies focusing on interacting or mixture effects of two or more types of EDCs. In addition to statistical modeling driven approaches, we encourage biologically driven approaches in which models also consider biological pathways and doses of exposures;
  4. Studies that characterize sources of exposures in a population-based setting;
  5. Studies that focus on minority health and health disparities relating to EDC exposures.

Dr. Zeyan Liew
Dr. Gunnar Toft
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • endocrine disrupting chemicals
  • epidemiology
  • adverse health impacts
  • critical time windows of exposure
  • mixture effects
  • sources of exposure
  • health disparities

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Published Papers (8 papers)

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Editorial

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3 pages, 191 KiB  
Editorial
Health Effects Associated with Exposures to Endocrine Disrupting Chemicals
by Gunnar Toft and Zeyan Liew
Toxics 2022, 10(8), 425; https://doi.org/10.3390/toxics10080425 - 28 Jul 2022
Cited by 1 | Viewed by 1911
Abstract
A number of recent studies have shown that human exposures to a wide range of endocrine-disrupting chemicals (EDCs) may increase the risk of disease across the lifespan by altering the homeostasis or action of endogenous hormones, or other signaling chemicals of the endocrine [...] Read more.
A number of recent studies have shown that human exposures to a wide range of endocrine-disrupting chemicals (EDCs) may increase the risk of disease across the lifespan by altering the homeostasis or action of endogenous hormones, or other signaling chemicals of the endocrine system [...] Full article
(This article belongs to the Special Issue Health Effects Associated with Exposures to Endocrine Disrupting Chemicals)

Research

Jump to: Editorial

11 pages, 767 KiB  
Article
The Confounder-Mediator Dilemma: Should We Control for Obesity to Estimate the Effect of Perfluoroalkyl Substances on Health Outcomes?
by Kosuke Inoue, Atsushi Goto, Takehiro Sugiyama, Cecilia Høst Ramlau-Hansen and Zeyan Liew
Toxics 2020, 8(4), 125; https://doi.org/10.3390/toxics8040125 - 20 Dec 2020
Cited by 26 | Viewed by 4636
Abstract
Confounding adjustment is important for observational studies to derive valid effect estimates for inference. Despite the theoretical advancement of confounding selection procedure, it is often challenging to distinguish between confounders and mediators due to the lack of information about the time-ordering and latency [...] Read more.
Confounding adjustment is important for observational studies to derive valid effect estimates for inference. Despite the theoretical advancement of confounding selection procedure, it is often challenging to distinguish between confounders and mediators due to the lack of information about the time-ordering and latency of each variable in the data. This is also the case for the studies of perfluoroalkyl substances (PFAS), a group of synthetic chemicals used in industry and consumer products that are persistent and have endocrine-disrupting properties on health outcomes. In this article, we used directed acyclic graphs to describe potential biases introduced by adjusting for or stratifying by the measure of obesity as an intermediate variable in PFAS exposure analyses. We compared results with or without adjusting for body mass index in two cross-sectional data analyses: (1) PFAS levels and maternal thyroid function during early pregnancy using the Danish National Birth Cohort and (2) PFAS levels and cardiovascular disease in adults using the National Health and Nutrition Examination Survey. In these examples, we showed that the potential heterogeneity observed in stratified analyses by overweight or obese status needs to be interpreted cautiously considering collider stratification bias. This article highlights the complexity of seemingly simple adjustment or stratification analyses, and the need for careful consideration of the confounding and/or mediating role of obesity in PFAS studies. Full article
(This article belongs to the Special Issue Health Effects Associated with Exposures to Endocrine Disrupting Chemicals)
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15 pages, 1970 KiB  
Article
Phthalates and Bisphenol A: Presence in Blood Serum and Follicular Fluid of Italian Women Undergoing Assisted Reproduction Techniques
by Donatella Paoli, Francesco Pallotti, Anna Pia Dima, Elena Albani, Carlo Alviggi, Franco Causio, Carola Conca Dioguardi, Alessandro Conforti, Rosanna Ciriminna, Gemma Fabozzi, Giuseppe Giuffrida, Roberto Gualtieri, Maria Giulia Minasi, Simona Ochetti, Valerio Pisaturo, Cinzia Racca, Laura Rienzi, Elena Sarcina, Catello Scarica, Giovanna Tomasi, Cristina Verlengia, Rita Villeggia, Federica Zullo, Andrea Lenzi, Francesco Botrè and Lucia De Santisadd Show full author list remove Hide full author list
Toxics 2020, 8(4), 91; https://doi.org/10.3390/toxics8040091 - 21 Oct 2020
Cited by 34 | Viewed by 4447
Abstract
Background: folliculogenesis is a strictly regulated process that may be affected by endocrine disrupting chemicals (EDCs) through sometimes not so clear molecular mechanisms. Methods: we conducted a multicentric observational study involving six fertility centers across Italy, prospectively recruiting 122 women attending a fertility [...] Read more.
Background: folliculogenesis is a strictly regulated process that may be affected by endocrine disrupting chemicals (EDCs) through sometimes not so clear molecular mechanisms. Methods: we conducted a multicentric observational study involving six fertility centers across Italy, prospectively recruiting 122 women attending a fertility treatment. Recruited women had age ≤42 years, and normal ovarian reserve. Blood and follicular fluid samples were taken for EDCs measurement using liquid chromatography tandem mass spectrometry and each woman completed an epidemiological questionnaire. Results: The main EDCs found were monobutyl phthalate (MBP) (median blood: 8.96 ng/mL, follicular fluid 6.43 ng/mL), monoethylhexyl phthalate (MEHP) (median blood: 9.16 ng/mL, follicular fluid 7.68 ng/mL) and bisphenol A (BPA) (median blood: 1.89 ng/mL, follicular fluid 1.86 ng/mL). We found that serum MBP concentration was significantly associated with the considered area (p < 0.001, adj. mean: 7.61 ng/mL, 14.40 ng/mL, 13.56 ng/mL; Area 1: Milan–Turin, Area 2: Rome–Naples; Area 3: Catania–Bari, respectively) but negatively with home plastic food packaging (p = 0.004). Follicular MBP was associated with irregular cycles (p = 0.019). No association was detected between EDCs and eating habits and other clinical and epidemiological features. Conclusions: This study represents the first Italian biomonitoring of plastic EDCs in follicular fluid, laying the basis for future prospective evaluation on oocyte quality before assisted reproduction techniques (ART). Full article
(This article belongs to the Special Issue Health Effects Associated with Exposures to Endocrine Disrupting Chemicals)
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15 pages, 557 KiB  
Article
Estimated Dietary Bisphenol-A Exposure and Adiposity in Samoan Mothers and Children
by Lacey W. Heinsberg, Christina N.N. Bui, Jennifer C. Hartle, Susan M. Sereika, Courtney C. Choy, Dongqing Wang, Christina Soti-Ulberg, Take Naseri, Muagututia Sefuiva Reupena, Rachel L. Duckham, Jennifer J. Park, Nicola L. Hawley and Nicole C. Deziel
Toxics 2020, 8(3), 67; https://doi.org/10.3390/toxics8030067 - 2 Sep 2020
Cited by 6 | Viewed by 3253
Abstract
The Pacific Island nation of Samoa is marked by prevalent obesity and an increasing dependence on packaged foods likely to contain the endocrine disruptor bisphenol-A (BPA). We evaluated participant- and household-level characteristics associated with estimated dietary BPA exposure in Samoan mothers and their [...] Read more.
The Pacific Island nation of Samoa is marked by prevalent obesity and an increasing dependence on packaged foods likely to contain the endocrine disruptor bisphenol-A (BPA). We evaluated participant- and household-level characteristics associated with estimated dietary BPA exposure in Samoan mothers and their children and examined associations between dietary BPA exposure and body mass index (BMI) and abdominal circumference (AC). Dietary BPA exposure indices were estimated for 399 mother–child pairs by combining information from dietary questionnaires and relative concentrations of BPA measured in foods/beverages. We observed moderate to strong correlation between mother–child daily BPA indices (Spearman’s rho = 0.7, p < 0.0001). In mothers, we observed lower daily BPA indices in those who were less physically active (p = 0.0004) and living in homes with higher income (p = 0.00001). In children, we observed lower daily BPA indices in those living in homes with higher income (p = 0.0003) and following a less modern dietary pattern (p = 0.002), and higher daily BPA indices in those who were less physically active (p = 0.02). No significant associations were observed between daily BPA indices and BMI or AC. Despite this, the application of the daily BPA index identified factors associated with dietary BPA exposure and warrants further examination in Samoa and other understudied populations. Full article
(This article belongs to the Special Issue Health Effects Associated with Exposures to Endocrine Disrupting Chemicals)
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13 pages, 500 KiB  
Article
Use of Personal Care Products and Semen Quality: A Cross-Sectional Study in Young Danish Men
by Kajsa Ugelvig Petersen, Ahmad Mahmoud Balkiss, Katia Keglberg Hærvig, Jens Peter Ellekilde Bonde, Karin Sørig Hougaard, Gunnar Toft, Cecilia Høst Ramlau-Hansen and Sandra Søgaard Tøttenborg
Toxics 2020, 8(3), 62; https://doi.org/10.3390/toxics8030062 - 22 Aug 2020
Cited by 4 | Viewed by 3933
Abstract
Personal care products (PCPs) may contain multiple chemicals capable of harming male reproductive function. The aim of this study was, therefore, to assess aggregated PCP exposure and potential associations with measures of semen quality in young men. Participants (n = 1058, age [...] Read more.
Personal care products (PCPs) may contain multiple chemicals capable of harming male reproductive function. The aim of this study was, therefore, to assess aggregated PCP exposure and potential associations with measures of semen quality in young men. Participants (n = 1058, age 18–21) were sampled among young men from the Danish National Birth Cohort (DNBC). Upon recruitment in 2017–2019, each man answered an online questionnaire and provided a semen sample. Exposure to 12 common types of PCPs was derived from the questionnaire, and the extent of use and co-use was analyzed. We applied a negative binomial regression model to estimate percentage differences in semen parameters between low, medium and high PCP exposure groups. All participants were exposed to at least one PCP more than once a week, resulting in a mean number (SD) of 5.3 (2.0) PCPs currently used. Most participants (92%) were also exposed to fragranced products on a weekly basis. Little association was observed between aggregated exposure to PCPs and sperm concentration, total sperm count, semen volume, sperm motility and morphology. Despite prevalent use of multiple PCPs, we found little indication of adverse effects of aggregated overall or fragranced PCP exposure on semen quality. Full article
(This article belongs to the Special Issue Health Effects Associated with Exposures to Endocrine Disrupting Chemicals)
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12 pages, 671 KiB  
Article
Phthalates, Para-Hydroxybenzoic Acids, Bisphenol-A, and Gonadal Hormones’ Effects on Susceptibility to Attention-Deficit/Hyperactivity Disorder
by Ching-Shu Tsai, Wen-Jiun Chou, Sheng-Yu Lee, Min-Jing Lee, Miao-Chun Chou and Liang-Jen Wang
Toxics 2020, 8(3), 57; https://doi.org/10.3390/toxics8030057 - 13 Aug 2020
Cited by 14 | Viewed by 3790
Abstract
This study aimed to examine whether endocrine-disrupting chemicals (EDCs), such as phthalates, para-hydroxybenzoic acids, and bisphenol-A (BPA), affect gonadal hormones and further link to the susceptibility to attention-deficit/hyperactivity disorder (ADHD). We recruited 98 boys with ADHD, 32 girls with ADHD, 42 boys without [...] Read more.
This study aimed to examine whether endocrine-disrupting chemicals (EDCs), such as phthalates, para-hydroxybenzoic acids, and bisphenol-A (BPA), affect gonadal hormones and further link to the susceptibility to attention-deficit/hyperactivity disorder (ADHD). We recruited 98 boys with ADHD, 32 girls with ADHD, 42 boys without ADHD and any other psychiatric disorders, and 26 girls without ADHD and any other psychiatric disorders. Urine levels of EDCs, including mono-methyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoethylhexyl phthalate (MEHP), methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), and bisphenol A (BPA), were examined. Endocrine systems were evaluated by using the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, free testosterone, estradiol, progesterone, sex hormone-binding globulin (SHBG), and prolactin. We found that boys with ADHD had higher levels of MnBP and EP than control boys. There were no significant differences regarding EDCs between the females with ADHD and control groups. No significant differences in testosterone, free testosterone, FSH, LH, estradiol, progesterone, or SHBG were found between the ADHD group and controls among either boys or girls. Among boys with ADHD, urine MBzP and MEHP levels were positively correlated with serum testosterone levels. Among girls, urine MEP levels were positively correlated with serum LH, testosterone, and free testosterone levels. The findings suggest that the possibility of an adverse impact of EDCs on gonadal hormones and neurodevelopment may exist. However, the results could be subject to potential selection bias, and the findings in this study should be interpreted with caution. Full article
(This article belongs to the Special Issue Health Effects Associated with Exposures to Endocrine Disrupting Chemicals)
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17 pages, 319 KiB  
Article
Ambient Exposure to Agricultural Pesticides during Pregnancy and Risk of Cerebral Palsy: A Population-Based Study in California
by Zeyan Liew, Ondine S. von Ehrenstein, Chenxiao Ling, Yuying Yuan, Qi Meng, Xin Cui, Andrew S. Park, Peter Uldall, Jørn Olsen, Myles Cockburn and Beate Ritz
Toxics 2020, 8(3), 52; https://doi.org/10.3390/toxics8030052 - 31 Jul 2020
Cited by 12 | Viewed by 7615
Abstract
Cerebral palsy (CP) is the most common neuro-motor disability in young children. Disruptions of maternal hormone function during pregnancy have been linked to CP risk. We investigated whether prenatal exposure to pesticide compounds with endocrine-disrupting action affect CP risk. We conducted a case-control [...] Read more.
Cerebral palsy (CP) is the most common neuro-motor disability in young children. Disruptions of maternal hormone function during pregnancy have been linked to CP risk. We investigated whether prenatal exposure to pesticide compounds with endocrine-disrupting action affect CP risk. We conducted a case-control study of 3905 CP cases and 39,377 controls born between 1998 and 2010 in California to mothers who lived in proximity (within 2 km) to any agricultural pesticide application recorded in the California Pesticide Use Reporting (PUR) system. We focused on 23 pesticides considered endocrine disruptors that are frequently used, and we found that exposure to any of the 23 pesticides in the first trimester was associated with elevated CP risks in female offspring (OR = 1.19; 95% CI: 1.05–1.35) but not males (OR = 0.99; 95% CI: 0.89–1.09) compared to the unexposed offspring. Positive associations were estimated for 15 pesticides suspected to affect the estrogen and 7 pesticides suspected to affect the thyroid hormone system. Our study suggests that first trimester exposure to pesticides that are suspected endocrine disruptors are associated with CP risk in female offspring. Pesticide exposures in early pregnancy may have sex-specific influences on the neuro-motor development of the fetus by interfering with endocrine systems. Full article
(This article belongs to the Special Issue Health Effects Associated with Exposures to Endocrine Disrupting Chemicals)
9 pages, 240 KiB  
Article
Per- and Polyfluoroalkyl Substances in Early Pregnancy and Risk for Preeclampsia: A Case-Control Study in Southern Sweden
by Lars Rylander, Christian H. Lindh, Stefan R. Hansson, Karin Broberg and Karin Källén
Toxics 2020, 8(2), 43; https://doi.org/10.3390/toxics8020043 - 16 Jun 2020
Cited by 33 | Viewed by 3429
Abstract
Preeclampsia is one of the most common causes of perinatal and maternal morbidity/mortality. One suggested environmental risk factor is exposure to endocrine-disrupting pollutants such as per- and polyfluoroalkyl substances (PFAS). The present case-control study in southern Sweden aims to investigate the hypothesized association [...] Read more.
Preeclampsia is one of the most common causes of perinatal and maternal morbidity/mortality. One suggested environmental risk factor is exposure to endocrine-disrupting pollutants such as per- and polyfluoroalkyl substances (PFAS). The present case-control study in southern Sweden aims to investigate the hypothesized association between serum concentrations of PFAS in early pregnancy and the risk of developing preeclampsia. The study included 296 women diagnosed with preeclampsia (cases) and 580 healthy pregnant women (controls). Maternal serum samples were obtained from a biobank of samples collected in early pregnancy in connection with screening for infections. Serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were analyzed using liquid chromatography-tandem-mass-spectrometry (LC/MS/MS). Among primiparous women, there were no differences in PFAS concentrations in early pregnancy between the cases and the controls whereas among multipara women, the cases had significantly higher concentrations of PFNA (median concentrations were 0.44 and 0.38 ng/mL, p = 0.04). When individual PFAS were categorized into quartiles and adjustment for potential confounders was performed, the women in the highest quartiles had no significant increased risks of developing preeclampsia as compared with women in the lowest category. In conclusion, the present study provides limited support for the hypothesized association between PFAS and preeclampsia in a population with relatively low exposure levels. Full article
(This article belongs to the Special Issue Health Effects Associated with Exposures to Endocrine Disrupting Chemicals)
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