Methods for the Determination of Endocrine-Disrupting Phthalate Esters

Qureshi, Munawar Saeed; Yusoff, Abdull Rahim bin Mohd; Wirzal, Mohd Dzul Hakim; Sirajuddin, Sirajuddin; Barek, Jiřı́; Afridi, Hassan Imran; Üstündağ, Zafer

doi:10.1080/10408347.2015.1004157

Cited by 41 publications

(17 citation statements)

References 145 publications

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“…Several phthalate esters have been the focus of evaluation for the risks to human reproduction by National Toxicology Program of the United States Environmental Protection Agency and the European Union [ 8 – 9 ]. These important phthalate EDCs are, dimethyl phthalate (DMP), dibutyl phthalate (DBP), di-iso-butyl phthalate (DIBP), butylbenzyl phthalate (BBP), di- n -hexyl phthalate (DNHP), di-2-ethylhexyl phthalate (DEHP), di- n -octyl phthalate (DNOP), di-iso-nonyl phthalate (DINP), and di-iso-decyl phthalate (DIDP).…”

Section: Introductionmentioning

confidence: 99%

Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers

et al. 2016

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Phthalates are a class of high volume production chemicals used as plasticizers for household and industrial use. Several members of this chemical family have endocrine disrupting activity. Owing to ubiquitous environmental distribution and exposure of human population at all stages of life, phthalate contamination is a continuous global public health problem. Clinical and experimental studies have indicated that several phthalates are associated with adverse effects on development and function of human and animal systems especially the reproductive system and exposures during pregnancy and early childhood are by far of utmost concern. Sex hormone-binding globulin (SHBG) is a plasma carrier protein that binds androgens and estrogens and represents a potential target for phthalate endocrine disruptor function in the body. In the present study, the binding mechanism of the nine phthalates i.e. DMP, DBP, DIBP, BBP, DNHP, DEHP, DNOP, DINP, DIDP with human SHBG was delineated by molecular docking simulation. Docking complexes of the nine phthalates displayed interactions with 15–31 amino acid residues of SHBG and a commonality of 55–95% interacting residues between natural ligand of SHBG, dihydrotestosterone, and the nine phthalate compounds was observed. The binding affinity values were more negative for long chain phthalates DEHP, DNOP, DINP, and DIDP compared to short chain phthalates such as DMP and DBP. The Dock score and Glide score values were also higher for long chain phthalates compared to short chain phthalates. Hence, overlapping of interacting amino acid residues between phthalate compounds and natural ligand, dihydrotestosterone, suggested potential disrupting activity of phthalates in the endocrine homeostasis function of SHBG, with long chain phthalates expected to be more potent than the short chain phthalates.

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Section: Introductionmentioning

confidence: 99%

Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers

et al. 2016

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“…In another study, a metabolite of DBP (monobutyl phthalate) was not associated with recurrent SA, although a metabolite of a structurally similar phthalate (mono-isobutyl phthalate) was associated with recurrent SA (Peng et al 2016). Phthalatess are well known endocrine disruptors (Qureshi et al 2016). Phthalates also generate oxidative stress (Tetz et al 2013; Wang et al 2010), inflammation (Wang et al 2010) and epigenetic changes (Grindler et al 2018; Strakovsky and Schantz 2018) in gestational tissues and cells in culture, suggesting several potential mechanisms to increase risk of SA.…”

Section: Discussionmentioning

confidence: 99%

Toxicants Associated with Spontaneous Abortion in the Comparative Toxicogenomics Database (CTD)

Harris

Yuan

Loch‐Caruso

et al. 2019

Preprint

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BackgroundUp to 70% of all pregnancies result in either implantation failure or spontaneous abortion (SA). Many events occur before women are aware of their pregnancy and we lack a comprehensive understanding of high-risk SA chemicals. In epidemiologic research, failure to account for a toxicant’s impact on SA can also bias toxicant-birth outcome associations. Our goal was to identify chemicals with a high number of interactions with SA genes, based on known toxicogenomic responses.MethodsWe used reference SA (MeSH: D000022) and chemical gene lists from the Comparative Toxicogenomics Database in three species (human, mouse, and rat). We prioritized chemicals (n=25) found in maternal blood/urine samples or in groundwater, tap water, or Superfund sites. For chemical-disease gene sets of sufficient size (n=13 chemicals, n=20 comparisons), chi-squared enrichment tests and proportional reporting ratios (PRR) were calculated. We then cross-validated enrichment results. Finally, among the SA genes, we assessed enrichment for gene ontology biological processes and for chemicals associated with SA in humans, we visualized specific gene-chemical interactions.ResultsThe number of unique genes annotated to a chemical ranged from 2 (bromacil) to 5,607 (atrazine), and 121 genes were annotated to SA. In humans, all chemicals tested were highly enriched for SA gene overlap (all p<0.001; parathion PRR=7, cadmium PRR=6.5, lead PRR=3.9, arsenic PRR=3.5, atrazine PRR=2.8). In mice, highest enrichment (p<0.001) was observed for naphthalene (PRR=16.1), cadmium (PRR=12.8), arsenic (PRR=11.6), and carbon tetrachloride (PRR=7.7). In rats, we observed highest enrichment (p<0.001) for cadmium (PRR=8.7), carbon tetrachloride (PRR=8.3), and dieldrin (PRR=5.3). Our findings were robust to 1,000 permutations each of gene sets ranging in size from 100 to 10,000. SA genes were overrepresented in biological processes: inflammatory response (q=0.001), collagen metabolic process (q=1×10−13), cell death (q=0.02), and vascular development (q=0.005).ConclusionWe observed chemical gene sets (parathion, cadmium, naphthalene, carbon tetrachloride, arsenic, lead, dieldrin, and atrazine) were highly enriched for SA genes. Exposures to chemicals linked to SA, thus linked to probability of live birth, may deplete fetuses susceptible to adverse birth outcomes. Our findings have critical public health implications for successful pregnancies as well as the interpretation of environmental pregnancy cohort analyses.

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“…Union have banned many phthalate compounds or classified them as potential toxicants because of their adverse effects (Miles-Richardson, 2004;Qureshi et al, 2015). Among the most common phthalates, longchain or high-molecular-weight phthalates, such as di-iso-butyl phthalate (DIBP), butylbenzyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP), di-n-hexyl phthalate (DnHP), di-iso-nonyl phthalate (DINP), di-n-octyl phthalate (DnOP) and di-iso-decyl phthalate (DIDP) have frequent use as plasticizers in polyvinyl chloride plastics, medical equipment, building materials, and household items like furniture, plastic toys, table cloths, etc.…”

Section: The United States Environmental Protection Agency and The Eumentioning

confidence: 99%

“…Phthalates are an important class of endocrine‐disrupting chemicals (EDCs) with very high usage in commercial industry as plasticizers and have adverse health effects, such as carcinogenicity, teratogenicity and mutagenicity (Heudorf, Mersch‐Sundermann, & Angerer, ). The United States Environmental Protection Agency and the European Union have banned many phthalate compounds or classified them as potential toxicants because of their adverse effects (Miles‐Richardson, ; Qureshi et al, ). Among the most common phthalates, long‐chain or high‐molecular‐weight phthalates, such as di‐iso‐butyl phthalate (DIBP), butylbenzyl phthalate (BBP), di‐2‐ethylhexyl phthalate (DEHP), di‐ n ‐hexyl phthalate (DnHP), di‐iso‐nonyl phthalate (DINP), di‐ n ‐octyl phthalate (DnOP) and di‐iso‐decyl phthalate (DIDP) have frequent use as plasticizers in polyvinyl chloride plastics, medical equipment, building materials, and household items like furniture, plastic toys, table cloths, etc.…”

Section: Introductionmentioning

confidence: 99%

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin

Sheikh

Beg

2017

J of Applied Toxicology

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Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis.

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Methods for the Determination of Endocrine-Disrupting Phthalate Esters

Cited by 41 publications

References 145 publications

Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers

Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers

Toxicants Associated with Spontaneous Abortion in the Comparative Toxicogenomics Database (CTD)

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin

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