Subacute effects of hexabromocyclododecane (HBCD) on hepatic gene expression profiles in rats

Cantón, Rocío F.; Peijnenburg, Ad; Hoogenboom, L.A.P.; Piersma, Aldert H.; Ven, Leo T.M. van der; Berg, Martin van den; Heneweer, Marjoke

doi:10.1016/j.taap.2008.04.013

Cited by 60 publications

(54 citation statements)

References 31 publications

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“…Induction of metabolic enzymes observed by Germer et al (2006) and Cantón et al (2008) are also consistent with CAR/PXR activation. Competition of T4 with TTR transport protein and potentiation of T3-receptor dependent cell proliferation in a rat pituitary cell line represent additional mechanisms for changes in thyroid hormone homeostasis and signalling.…”

Section: Consideration Of Critical Effects and Possibilities For Derisupporting

confidence: 67%

“…Studies in vivo, in rats, have shown that HBCDDs increase expression of a number of hepatic phase I and II biotransformation enzymes, including members of the CYP3A and CYP2B P450 sub-families, at the levels of mRNA, protein and enzyme activity, consistent with CAR/PXR activation (Germer et al, 2006;Cantón et al, 2008). In addition, evidence was obtained, at the mRNA levels for modulation of triacylglycerol and cholesterol metabolism (Cantón et al, 2008).…”

Section: Biochemical Effects and Molecular Mechanismsmentioning

confidence: 92%

See 1 more Smart Citation

Scientific Opinion on Hexabromocyclododecanes (HBCDDs) in Food

Alexander¹,

Benford²,

Boobis³

et al. 2011

EFS2

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EFSA was asked by the European Commission to deliver a scientific opinion on hexabromocyclododecanes (HBCDDs) in food. HBCDDs are additive flame retardants primarily used in expanded and extruded polystyrene applied as construction and packing materials, and in textiles. Technical HBCDD predominantly consists of three stereoisomers (α-, β-and γ-HBCDD). Also δ-and ε-HBCDD may be present but at very low concentrations. HBCDDs are present in the environment and likewise in biota and in food and feed. Data from the analysis of HBCDDs in 1,914 food samples were provided to EFSA by seven European countries, covering the period from 2000 to 2010. The Panel on Contaminants in the Food Chain (CONTAM Panel) selected α-, β-and γ-HBCDD to be of primary interest. Since all toxicity studies were carried out with technical HBCDD, a risk assessment of individual stereoisomers was not possible. Main targets were the liver, thyroid hormone homeostasis and the reproductive, nervous and immune systems. HBCDDs are not genotoxic. The CONTAM Panel identified neurodevelopmental effects on behaviour as the critical endpoint, and derived a benchmark dose lower confidence limit for a benchmark response of 10 % (BMDL 10 ) of 0.79 mg/kg body weight. Due to the limitations and uncertainties in the current data base, the CONTAM Panel concluded that it was inappropriate to use this BMDL to establish a health based guidance value, and instead used a margin of exposure (MOE) approach for the health risk assessment of HBCDDs. Since elimination characteristics of HBCDDs in animals and humans differ, the Panel used the body burden as starting point for the MOE approach. The CONTAM Panel concluded that current dietary exposure to HBCDDs in the European Union does not raise a health concern. Also additional exposure, particularly of young children, to HBCDDs from house dust is unlikely to raise a health concern. 4 The term "intra-individual" has been replaced by "individual" in the Summary and in Chapter 9.1. HBCDDs in FoodEFSA Journal 2011;9(7):2296 2 KEY WORDSHexabromocyclododecanes, HBCDDs, occurrence, food, toxicology, human exposure, risk assessment SUMMARYFollowing a request from the European Commission, the Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on hexabromocyclododecanes (HBCDDs) in food. HBCDDs are stereoisomers of 1,2,5,6,9,10-hexabromocyclododecane. Technical HBCDD predominantly consists of three stereoisomers (α-, β-and γ-HBCDD) present in relative amounts of 9-13 % α-HBCDD, <0.5-12 % β-HBCDD and 72-90 % γ-HBCDD. Also δ-and ε-HBCDD may be present in the technical product, although at very low concentrations. The HBCDD stereoisomers occur as enantiomer pairs.HBCDDs constitute an important and widely used group of additive flame retardants primarily used in expanded and extruded polystyrene applied as construction and packing materials, and also used in textiles. Concentrations in products are usually in the range between 0.7 % and 3.0 % by weight. As they are mixed into po...

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Section: Consideration Of Critical Effects and Possibilities For Derisupporting

confidence: 67%

Section: Biochemical Effects and Molecular Mechanismsmentioning

confidence: 92%

Scientific Opinion on Hexabromocyclododecanes (HBCDDs) in Food

Alexander¹,

Benford²,

Boobis³

et al. 2011

EFS2

View full text Add to dashboard Cite

show abstract

“…This study indicates that gene expression in zebrafish embryos/larvae provides a sensitive method of elucidating the toxicity mechanism, although only a few genes related to cell apoptosis pathway were selected for investigation. However, recent studies have shown that HBCD exposure may disrupt thyroid hormones in fish (Palace et al, 2008) and hepatic gene expression in rat liver (Cantón et al, 2008), and it may be that the use of DNA microarrays to carry out a large-scale genome screening for the induction by HBCD of other gene responses would provide more information on its toxicity in fish embryos. Nevertheless, as the post-hatched larval stage is more sensitive than the adult stage, sensitivity to the chemical could be increased with chronic exposure, and it is thus necessary to investigate the post-hatched stage in addition to the life-cycle exposure at environmentally relevant concentrations of HBCD to fully investigate its potential reproductive toxicity.…”

Section: Discussionmentioning

confidence: 99%

Hexabromocyclododecane-induced developmental toxicity and apoptosis in zebrafish embryos

et al. 2009

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“…However, subacute and chronic animal studies highlighted its perturbation in hepatic metabolism (Cantón et al 2008), the endocrine gland ), reproduction (Saegusa et al 2009), the central nerve (Eriksson et al 2006;Lilienthal et al 2009) and immunity (Koike et al 2013). The thyroid was reported to be disrupted by HBCD in both in vivo and in vitro animal models (Schriks et al 2007;van der Ven et al 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The liver was another deeply influenced organ, with downregulated lipid metabolismElectronic supplementary material The online version of this article (doi:10.1007/s11356-015-5940-2) contains supplementary material, which is available to authorized users. related gene expression in female rat liver (Cantón et al 2008). Though many studies based on conventional toxicology have been tried to understand the mechanisms underlying HBCD-induced subacute toxicity, it is not sufficient to provide a comprehensive information; systems toxicology approach such as metabolomics is considered as a powerful tool to further our understandings while complementing traditional approaches.…”

Section: Introductionmentioning

confidence: 99%

NMR- and LC–MS/MS-based urine metabolomic investigation of the subacute effects of hexabromocyclododecane in mice

Wang

Zhang

Wang

et al. 2016

Environ Sci Pollut Res

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In the present study, both untargeted and targeted metabolomics approaches were used to evaluate the subacute effects of hexabromocyclododecane (HBCD) on mice urine metabolome. Untargeted metabolomics based on (1)H NMR showed that HBCD exposure disturbed mice metabolism in both dosed groups, especially in high dosed group. The low-dose HBCD led to a decrease in alanine, malonic acid, and trimethylamine (TMA). High-dose HBCD-treated mice developed high levels of citric acid and 2-ketoglutarate, together with decreased alanine, acetate, formate, TMA, 3-hydroxybutyrate, and malonic acid. Targeted metabolomics for metabolic profiling of 20 amino acids identified alanine, lysine, and phenylalanine as significantly disturbed metabolites. These results indicated that subchronic exposure to HBCD caused a disturbance of mice metabolism, especially in TCA cycle, lipid metabolism, gut microbial metabolism, and homeostasis of amino acids, and the application of untargeted and targeted metabolomics combined with conventional toxicology approaches to evaluate the subacute effects of pollutants will provide more comprehensive information and aid in predicting health risk of these pollutants.

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Subacute effects of hexabromocyclododecane (HBCD) on hepatic gene expression profiles in rats

Cited by 60 publications

References 31 publications

Scientific Opinion on Hexabromocyclododecanes (HBCDDs) in Food

Scientific Opinion on Hexabromocyclododecanes (HBCDDs) in Food

Hexabromocyclododecane-induced developmental toxicity and apoptosis in zebrafish embryos

NMR- and LC–MS/MS-based urine metabolomic investigation of the subacute effects of hexabromocyclododecane in mice

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