Transcriptome profiling and pathway analysis of hepatotoxicity induced by tris (2-ethylhexyl) trimellitate (TOTM) in mice

Chen, Xianhua; Ma, Li; Hu, Yi-Xiang; Wang, Dan-Xian; Li, Fang; Li, Xue-Lai; Zhao, Jinchuan; Yu, Hairong; Ying, Hua‐Zhong; Yu, Chunjing

doi:10.1016/j.etap.2015.11.007

Cited by 16 publications

(7 citation statements)

References 74 publications

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“…In rats, TOTM induced hepatic vascular congestion, lipid globules in hepatocytes, with significantly decreased hepatocyte mitochondrial membrane antigen immune reaction indicating liver toxicity [ 28 ]. Intravenous injection of TOTM in mice induced upregulation of 694 genes and downregulation of 974 genes in liver [ 29 ]. Further analyses of 11 genes revealed that the functions of cell cycle pathway, oxidative process and lipid metabolism were affected during hepatotoxic effects of TOTM in mice.…”

Section: Introductionmentioning

confidence: 99%

Human sex hormone-binding globulin as a potential target of alternate plasticizers: an in silico study

et al. 2016

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BackgroundCurrently, alternate plasticizers are used to replace phthalate plasticizers in children’s toys, medical equipments and food packaging, due to the adverse effects of phthalate compounds on human health and laws prohibiting their use. Current information regarding the safety and potential adverse effects of alternate plasticizers is limited and recent studies have found alternate plasticizers to display similar characteristics to those observed in phthalate plasticizers. This study was undertaken to evaluate and predict the potential endocrine disrupting activity of the three most commonly used alternate plasticizers: di(2-ethylhexyl)terephthalate (DEHT), tris(2-ethylhexyl)trimellitate (TOTM), and diisononyl hexahydrophthalate (DINCH) against human sex hormone-binding globulin (SHBG) using in silico approaches.Materials and methodsThe crystal structure of human SHBG (Id: 1D2S) was retrieved from Protein Data Bank. PubChem database was searched for the structures of alternate plasticizers, DEHT, TOTM, and DINCH. Docking was performed using Glide (Schrodinger) Induced Fit Docking module.ResultsInduced Fit Docking of three alternate plasticizer compounds indicated that each of the three compounds fitted well into the steroid binding pocket of SHBG. Docking displays showed interactions of alternate plasticizers with 25–30 amino-acid residues of SHBG; 18–20 amino residues overlapped between the natural ligand, DHT, and the three compounds (commonality of 82–91 %). The hydrogen-bonding interaction of the amino-acid residue, Asn-82, of SHBG was also present in displays of DHT and all the three alternate phthalates. The binding affinity of all the three alternate phthalates was higher than DHT; maximum in DINCH followed by TOTM and DEHT.ConclusionOur results suggested that the three alternate plasticizers have potential to engage the important interacting residues of SHBG and thus interfere in its steroid homeostatic function.

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Section: Introductionmentioning

confidence: 99%

Human sex hormone-binding globulin as a potential target of alternate plasticizers: an in silico study

et al. 2016

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“…Intravenous administration of DINCH to rats did not affect their behavior (David et al, 2015). Importantly, lack of data on neurotoxicity of alternative plasticizers does not necessarily mean that these compounds are neurodevelopmentally safe and can be used safely, especially as several have been linked with adverse effects in other toxicity endpoints (Ghisari and Bonefeld-Jorgensen, 2009;Takeshita et al, 2011;Chen et al, 2016;A. Engel et al, 2018;Moche et al, 2021).…”

Section: Tablementioning

confidence: 99%

Phasing out DEHP from plastic indwelling medical devices used for intensive care: Does it reduce the long-term attention deficit of critically ill children?

Vanhorebeek

Malarvannan

Güiza

et al. 2022

Environment International

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“…For example, there is a lack of information regarding the toxicity of and the fate of the metabolites of alternative plasticizers (which is particularly important given that many of the negative health effects associated with DEHP are known to stem from its metabolites rather than the parent compound), including toxicological endpoints such as carcinogenicity and endocrine disruption [40]. As new concerns have been raised about some of these DEHP replacements, such as DINP [11,41,42,43,44,45], it is increasingly important to produce truly green replacement plasticizers, with the factors advancing hazard reduction playing a bigger role in plasticizer development. Furthermore, with hundreds of commercial plasticizers available today for numerous applications, it is important to ensure that these and new plasticizers are evaluated and designed systematically and thoroughly, to avoid the “regrettable substitution” of one problematic compound with another [35].…”

Section: Historical Perspectivementioning

confidence: 99%

How Green is Your Plasticizer?

et al. 2018

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Plasticizers are additives that are used to impart flexibility to polymer blends and improve their processability. Plasticizers are typically not covalently bound to the polymers, allowing them to leach out over time, which results in human exposure and environmental contamination. Phthalates, in particular, have been the subject of increasing concern due to their established ubiquity in the environment and their suspected negative health effects, including endocrine disrupting and anti-androgenic effects. As there is mounting pressure to find safe replacement compounds, this review addresses the design and experimental elements that should be considered in order for a new or existing plasticizer to be considered green. Specifically, a multi-disciplinary and holistic approach should be taken which includes toxicity testing (both in vitro and in vivo), biodegradation testing (with attention to metabolites), as well as leaching studies. Special consideration should also be given to the design stages of producing a new molecule and the synthetic and scale-up processes should also be optimized. Only by taking a multi-faceted approach can a plasticizer be considered truly green.

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Transcriptome profiling and pathway analysis of hepatotoxicity induced by tris (2-ethylhexyl) trimellitate (TOTM) in mice

Cited by 16 publications

References 74 publications

Human sex hormone-binding globulin as a potential target of alternate plasticizers: an in silico study

Human sex hormone-binding globulin as a potential target of alternate plasticizers: an in silico study

Phasing out DEHP from plastic indwelling medical devices used for intensive care: Does it reduce the long-term attention deficit of critically ill children?

How Green is Your Plasticizer?

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