Endocrine effects of hexabromocyclododecane (HBCD) in a one-generation reproduction study in Wistar rats

Ven, Leo T.M. van der; Kuil, Ton van de; Leonards, P.E.G.; Slob, Wout; Lilienthal, Hellmuth; Litens, Sabina; Herlin, Maria; Håkansson, Helen; Cantón, Rocío F.; Berg, Martin van den; Visser, Theo J.; Loveren, Henk Van; Vos, J.G.; Piersma, Aldert H.

doi:10.1016/j.toxlet.2008.12.003

Cited by 120 publications

(63 citation statements)

References 53 publications

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“…Consistent with these effects by NCM, perinatal exposure to TCDD also reduced bone geometrical parameters in young developing rats (Miettinen et al 2005). In contrast to the observation of similarity in response pattern between genders in the present study, results of a recent perinatal exposure study to the brominated flame retardant hexabromocyclododecane revealed gender-related differences, with bone geometrical parameters decreased in young males at PND77, while bone mineral density was decreased in young females at PND77 (van der Ven et al 2009). …”

Section: Discussionsupporting

confidence: 71%

“…Furthermore, alterations in bone quality were demonstrated for wildlife from organohalogencontaminated environments (Fox et al 2008;Johnson et al 2009;Lind et al 2003;Murtomaa et al 2007;RodriguezNavarro et al 2006;Roos et al 2010;Sonne et al 2004). Consistent with these observations, experimental studies with animal models revealed that single-chemical exposure to organohalogens induces changes in bone properties both in adult animals (Alvarez-Lloret et al 2009;Andrews et al 1990;Badraoui et al 2007;Herlin et al 2010;Jämsä et al 2001;Lind et al 2000a;2000b;van der Ven et al 2006) and in the offspring following maternal exposure (Hermsen et al 2008;van der Ven et al 2009). The most detailed toxicological bone studies were performed with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the organohalogen pollutant model compound, which exerts most of its effects through activation of the aryl hydrocarbon receptor (AhR) (Denison and Nagy 2003;Herlin et al 2010;Jämsä et al 2001).…”

Section: Perinatal Exposure To Environmental Contaminants Detected Inmentioning

confidence: 85%

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Perinatal Exposure to Environmental Contaminants Detected in Canadian Arctic Human Populations Changes Bone Geometry and Biomechanical Properties in Rat Offspring

Elabbas

Finnilä

Herlin

et al. 2011

Journal of Toxicology and Environmental Health, Part A

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Arctic inhabitants consume large proportions of fish and marine mammals, and are therefore continuously exposed to levels of environmental toxicants, which may produce adverse health effects. Fetuses and newborns are the most vulnerable groups. The aim of this study was to evaluate changes in bone geometry, mineral density, and biomechanical properties during development following perinatal exposure to a mixture of environmental contaminants corresponding to maternal blood levels in Canadian Arctic human populations. Sprague-Dawley rat dams were dosed with a Northern Contaminant Mixture (NCM) from gestational day 1 to postnatal day (PND) 23. NCM contains 27 contaminants comprising polychlorinated biphenyls, organochlorine pesticides, and methylmercury. Femurs were collected on PND 35, 77 and 350, and diaphysis was analyzed by peripheral quantitative computed tomography and three-point bending test, while femoral neck was assessed in an axial loading experiment. Dose-response modeling was performed to establish the benchmark dose (BMD) for the analyzed bone parameters. Exposure to the high dose of NMC resulted in short and thin femur with reduced mechanical strength in offspring at PND35. BMD of femur length, cortical area, and stiffness were 3.2, 1.6, and 0.8 mg/kg bw/d, respectively. At PND77 femur was still thin, but at PND350 no treatment-related bone differences were detected. This study provides new insights on environmental contaminants present in the maternal blood of Canadian Arctic populations, showing that perinatal exposure induces bone alterations in the young offspring. These findings could be significant from a health risk assessment point of view.

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Section: Discussionsupporting

confidence: 71%

Section: Perinatal Exposure To Environmental Contaminants Detected Inmentioning

confidence: 85%

Perinatal Exposure to Environmental Contaminants Detected in Canadian Arctic Human Populations Changes Bone Geometry and Biomechanical Properties in Rat Offspring

Elabbas

Finnilä

Herlin

et al. 2011

Journal of Toxicology and Environmental Health, Part A

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“…Long-term high-dose HBCDs exposure (30 mg/kg/day, 28 d) can result in increase of liver weight, [14] and 100 mg/kg/day continuous exposure for 90 d can cause liver nodules, fatty infiltration, liver necrosis and even liver carcinoma. [15] In addition, HBCDs exposure can also disrupt the thyroid function, [16] impact the immune system, [17,18] and lead to neurological disorders. [19,20] HBCDs have been included in the Priority Pollutants List of the OSPAR (No.793/93/EEC).…”

Section: Introductionmentioning

confidence: 99%

The cytological effects of HBCDs on human hepatocyte L02 and the potential molecular mechanism

An¹,

Zou²,

Chen³

et al. 2013

Journal of Environmental Science and Health, Part A

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The concentration of hexabromocyclododecanes (HBCDs) in the environment media and organism samples are gradually rising with the increase of HBCDs usage. This study is designed to investigate the cytological effects of HBCDs on human hepatocyte L02 and explore the potential molecular mechanism. The results of CCK-8 assay showed that high concentration of HBCDs (>20 μM) significantly suppressed cell survival, while comparatively lower dose of HBCDs (10(-13)-10(-7)M) slightly stimulated cell proliferation (P < 0.05). In the mean time, high concentration HBCDs markedly induced cell apoptosis and DNA damage, accompanying with increase of intracellular Ca(2+)level and decrease of mitochondrial membrane potential (P < 0.05). ROS level induced by low concentration of HBCDs was comparatively lower than that by high concentration of HBCDs. In addition, low concentration HBCDs exposure (10(-13)-10(-7)M) resulted in up-regulation of PCNA protein expression level in a time-dependent manner. However, high concentration HBCDs exposure led to increase of Apaf-1 expression level. In conclusion, loss of mitochondrial membrane potential and activation of Apaf-1 mediated pathway involve the L02 cell apoptosis induced by high concentration HBCDs exposure. However, low concentration HBCDs exposure could stimulate cell proliferation of L02 cells, which might be associated with enhancement of PCNA expression.

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“…In Taiwan, the conducted research on breast milk in Taiwanese mothers found PBDE concentrations to be 1.6-2.3 times higher than those of Japanese mothers (Chao et al, 2007;Horng et al, 2010). The bio-accumulating effect in human bodies is of concern due to the fact that several toxicological effects of PBDE congeners have been detected in experimental animals, such as neurotoxicity, behavioral changes, and endocrine disruption (McDonald, 2002;Darnerud, 2003;Kuiper et al, 2008;van der Ven et al, 2009). The major sources of human PBDE exposure are through diet, accounting for 73% of daily intake (Bocio, et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Monitoring and Dispersion Modeling of Polybrominated Diphenyl Ethers (PBDEs) in the Ambient Air of Two Municipal Solid Waste Incinerators and a Coal-fired Power Plant

Wang

et al. 2012

Aerosol Air Qual. Res.

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The concentration of polybrominated diphenyl ethers (PBDEs) in the ambient air of two municipal solid waste incinerators (MSWIs) and one coal-fired power plant (TPP) were determined. Along with the sites mentioned above, eight ambient air samples were collected. Cluster analysis was carried out to determine the relationship of PBDE characteristics between each site. Finally, PBDE dispersion modeling in the atmosphere was applied by using ISCST3 (Industrial Source Complex Short Term 3) to assess the impact of the above two municipal solid waste incinerators and one coal-fired power plant on the ambient air. The total-PBDE concentrations in the ambient air were between 24.9 and 139 pg/Nm 3 , averaging 59.8 pg/Nm 3 (n = 16). The BDE-209, BDE-47 and BDE-207 were the most predominant three among all 30 PBDE congeners, which contributed more than 58%, 9%, and 4% of total-PBDE mass to the ambient air, respectively. The results of cluster analysis indicated that no direct correlations existed among the emission sources (MSWI-A, MSWI-B, TPP) and the receptors (sampling sites). From the results of dispersion modeling, the annual total PBDE concentration in ambient air contributed by the MSWI-A, MSWI-B, TPP together were found to be 0.0259% ± 0.0208%. Hence, the results of both cluster analysis and dispersion modeling showed that MWSI-A, MSWI-B, and TPP were definitely not the major contributors of PBDEs to the ambient air environment. The ashes collected from the air pollution control devices of both the MSWIs and the TPP are probably a more important environmental issue and therefore should be paid more attention to.

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Endocrine effects of hexabromocyclododecane (HBCD) in a one-generation reproduction study in Wistar rats

Cited by 120 publications

References 53 publications

Perinatal Exposure to Environmental Contaminants Detected in Canadian Arctic Human Populations Changes Bone Geometry and Biomechanical Properties in Rat Offspring

Perinatal Exposure to Environmental Contaminants Detected in Canadian Arctic Human Populations Changes Bone Geometry and Biomechanical Properties in Rat Offspring

The cytological effects of HBCDs on human hepatocyte L02 and the potential molecular mechanism

Monitoring and Dispersion Modeling of Polybrominated Diphenyl Ethers (PBDEs) in the Ambient Air of Two Municipal Solid Waste Incinerators and a Coal-fired Power Plant

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