Staff Publications

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Level of Alkenylbenzenes in Parsley and Dill Based Teas and Associated Risk Assessment Using the Margin of Exposure Approach
Alajlouni, Abdul ; Al-Malahmeh, Amer J. ; Isnaeni, Farida Nur ; Wesseling, Sebas ; Vervoort, Jacques ; Rietjens, Ivonne M.C.M. - \ 2016
Journal of Agricultural and Food Chemistry 64 (2016)45. - ISSN 0021-8561 - p. 8640 - 8646.
alkenylbenzenes - estimated daily intake - margin of exposure - parsley and dill based teas - risk assessment - toxic equivalency factors

Risk assessment of parsley and dill based teas that contain alkenylbenzenes was performed. To this end the estimated daily intake (EDI) of alkenylbenzenes resulting from use of the teas was quantified. Since most teas appeared to contain more than one alkenylbenzene, a combined risk assessment was performed based on equal potency of all alkenylbenzenes or using a so-called toxic equivalency (TEQ) approach through defining toxic equivalency factors (TEFs) for the different alkenylbenzenes. The EDI values resulting from consuming one cup of tea a day were 0.2-10.1 μg/kg bw for the individual alkenylbenzenes, 0.6-13.1 μg/kg bw for the sum of the alkenylbenzenes, and 0.3-10.7 μg safrole equiv/kg bw for the sum of alkenylbenzenes when expressed in safrole equivalents. The margin of exposure (MOE) values obtained were generally

Concentrations of dioxins and dioxine-like PCBs in feed material in the Netherlands, 2001-11
Adamse, P. ; Fels-Klerx, H.J. van der; Schoss, S. ; Jong, J. de; Hoogenboom, L.A.P. - \ 2015
Food Additives & Contaminants. Pt. A, Chemistry, Analysis, Control, Exposure & Risk Assessment 32 (2015)8. - ISSN 1944-0049 - p. 1301 - 1311.
toxic equivalency factors - contaminated feed - milk - food - fat - residues - pcdfs - pcdds - eggs
This study aimed to obtain insights into contamination of feed materials used in the Netherlands with dioxins (polychlorinated dibenzo-p-dioxins and dibenzofurans) and dioxin-like polychlorinated biphenyls (PCBs). Monitoring results from the period 2001-11, covering in total 4938 samples, were statistically analysed and evaluated against the statutory limits set at the beginning or during this period. The percentage of samples exceeding maximum levels set within the European Union for either dioxins or the sum of dioxins and dioxin-like PCBs were below 1% for most feed categories, except for fish meal (4.1%), clay minerals (binders and anti-caking agents) (3.4%), and vegetable oils and byproducts (1.7%). For most feed categories, non-compliance with the action threshold (roughly 33% lower than maximum levels) for either dioxins or dioxin-like PCBs was up to three times higher than non-compliance with the respective maximum levels. Exceedance of action thresholds was just above 1% for animal fat, pre-mixtures and feed materials of plant origin excluding vegetable oils. For the categories fish meal, clay minerals, and vegetable oils and byproducts, the action thresholds were exceeded by 5.0%, 9.8% and 3.0% of the samples, respectively. In general, the percentages of samples that exceeded the action thresholds and maximum levels were lower than those reported for the European Union by the European Food Safety Authority (EFSA). In most of the feed materials, there seems to be a decreasing trend in concentrations of dioxins or dioxin-like PCBs over the years. However, a lowering of the limits of quantification during this period and the low concentrations in most samples precludes drawing strong conclusions.
Comparison of PCBs and PAHs levels in European coastal waters using mussels from the Mytilus edulis complex as biomonitors
Olenycz, M. ; Sokolowski, A. ; Niewinska, A. ; Wolowicz, M. ; Namiesnik, J. ; Hummel, H. ; Jansen, J.M. - \ 2015
Oceanologia = Oceanology 57 (2015). - ISSN 0078-3234 - p. 196 - 211.
polycyclic-aromatic-hydrocarbons - polychlorinated biphenyl congeners - chromatography mass-spectrometry - toxic equivalency factors - baltic sea - blue mussels - seasonal-variations - gas-chromatography - organic pollutants - marine-environment
Mussels from the Mytilus edulis complex were used as biomonitors for two groups of organic pollutants: polychlorinated biphenyls (PCBs, congeners: 28, 52, 101, 118, 138, 153 and 180) and polycyclic aromatic hydrocarbons (PAHs, naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benz(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene, indeno(1,2,3-cd)pyrene, dibenz(a,h)anthracene, benzo(g,h,i)perylene) at 17 sampling sites to assess their relative bioavailabilities in coastal waters around Europe. Because of the temporal differences in PCBs and PAHs concentrations, data were adjusted using Seasonal Variation Coefficients (SVC) before making large-scale spatial comparisons. The highest concentrations of PCBs were found near estuaries of large rivers flowing through urban areas and industrial regions. Elevated bioavailabilities of PAHs occurred in the vicinity of large harbors, urban areas, and regions affected by petroleum pollution as well as in some remote locations, which indicated long-range atmospheric deposition.
European developments following incidents with dioxins and PCBs in the food en feed chain
Hoogenboom, L.A.P. ; Traag, W.A. ; Fernandes, A. ; Rose, M. - \ 2015
Food Control 50 (2015). - ISSN 0956-7135 - p. 670 - 683.
toxic equivalency factors - dibenzo-para-dioxins - contamination incident - polychlorinated dibenzofurans - dr-calux(r) bioassay - pcdd/f-contamination - dietary-intake - chicken eggs - citrus pulp - p-dioxins
Incidents with dioxins and PCBs have resulted in a strategy within the EU to reduce the exposure of the population to these compounds. Maximum levels were set for food and feed products and criteria were developed for the analytical methods (both confirmatory and screening) used for official control measurements. Ideally, any analysis performed with the aim of comparing the result with the legal limits should be performed according to these criteria. It should also apply to monitoring, performed to estimate human exposure and trend analysis rather than compliance with limits, since risk assessments and EU-policies rely heavily on these data. In recent years, analytical capacity has largely increased to complement the additional testing. In line with the responsibility of producers for the safety of their products, self-control has strongly increased and has played an important role in the discovery of several of the incidents. However, the increased monitoring seems not to have resulted in a clear further decrease in the levels reported for food and feed in the last decade. This may in part be due to a lack of follow up when elevated levels (above action levels) are found, which would lead to a reduction of output from remaining sources. It may also be related to the sensitivity of applied methods and the data collected in databases. This paper reviews the incidents and developments that have taken place within the EU over the last 15 years in the area of dioxins and PCBs, including the role of applying screening and confirmatory methods for achieving the desired further reduction in the levels.
Internal effect concentrations of organic substances for early life development of egg-exposed fish
Foekema, E.M. ; Lopez Parron, M. ; Megia, M.T. ; Carolus, E.R.M. ; Berg, J.H.J. van den; Kwadijk, C.J.A.F. ; Dao, Q.T. ; Murk, A.J. - \ 2014
Ecotoxicology and Environmental Safety 101 (2014). - ISSN 0147-6513 - p. 14 - 22.
polybrominated diphenyl ethers - western scheldt estuary - zebrafish danio-rerio - flounder paralichthys-dentatus - trout salvelinus-fontinalis - toxic equivalency factors - medaka oryzias-latipes - southern north-sea - polychlorinated-biphenyls - hexabromocyclodo
The present study investigates the likelihood that early life development of marine fish from contaminated areas is affected by maternally transferred persistent organic substances (POPs). The common sole (Solea solea) was used as model species. Fertilized eggs were exposed via the water until hatching, 6 days post fertilization. The newly hatched larvae were allowed to develop further under unexposed conditions until the end of the metamorphosis. Effects on the larvae were determined for the dioxin-like polychlorinated biphenyl PCB 126, the technical PCB-mixture Arochlor 1254, polybrominated diphenylethers (PBDEs), and hexabromocyclododecane (HBCD), for an artificial mixture of PCBs and PBDEs, and for ‘field mixtures’ extracted from sole from the North Sea and the contaminated Western Scheldt estuary. Effect levels were expressed as tissue concentrations in the newly hatched larvae at the end of the exposure period. Exposure to PCBs, PBDEs, and the artificial and field mixtures caused mortality that started to occur shortly after the larvae became free-feeding (10 days post fertilization) and continued to increase until the onset of metamorphosis, 15 days later. The effects induced by the field mixtures correlated well with the SPCB concentrations in the tissue of the exposed larvae. No indications were found for synergistic effects or for substantial contribution of other (unknown) substances in the field mixtures. HBCD did not induce toxic effects. As lipid normalized POP levels in fish eggs are in general comparable to the levels in the tissue of the female fish, fish tissue concentrations are indicative of the internal exposure of the developing larvae as a result maternally transferred POPs will occur in the field. In sole from the Western Scheldt estuary POP levels are about twenty times lower than the larval tissue concentration that produced 50 percent early life stage mortality. Levels in North Sea sole are an order of a magnitude lower. At more heavily contaminated sites negative effect of PCBs, especially of those with dioxin-like toxicity can be expected
Dioxins (polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-furans) in traditional clay products used during pregnancy
Reeuwijk, N.M. ; Talidda, A. ; Malisch, R. ; Kotz, A. ; Tritsher, A. ; Fiedler, H. ; Zeilmaker, M.J. ; Kooijman, M. ; Wienk, K.J.H. ; Traag, W.A. ; Hoogenboom, L.A.P. - \ 2013
Chemosphere 90 (2013)5. - ISSN 0045-6535 - p. 1678 - 1685.
toxic equivalency factors - ball clay - united-states - geophagy - health - pcbs - contamination - humans - origin - soils
Geophagy, the practice of consuming clay or soil, is encountered among pregnant women in Africa, Eastern Asia and Latin America, but also in Western societies. However, certain types of clay are known to contain high concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). The aim of this study was to determine the PCDD/F contents of orally consumed clays purchased from Dutch and African markets. Congener patterns were compared with those of pooled human milk samples collected in eight African countries, to investigate a possible relationship with clay consumption. From the Dutch market thirteen clay products were examined, seven of African and six of Suriname origin. From seven African countries, twenty clay products were collected. All 33 clay products were screened with a cell-based bioassay and those showing a high response were analyzed by GC/HRMS. High PCDD/F concentrations were measured in three clay products from the Dutch market, ranging from 66 to 103 pg TEQ g(-1), whereas clay products from African countries were from 24 to 75 pg TEQ g(-1). Patterns and relatively high concentrations of PCDD/Fs in human milk samples from the Democratic Republic of the Congo and Côte d'Ivoire suggest a relationship with the consumption of contaminated clay. Frequent use of PCDD/F contaminated clay products during pregnancy may result in increased exposure of the mother and subsequently the developing fetus and new-born child. The use of these contaminated clays during pregnancy should be carefully considered or even discouraged.
Comparison of PCDD/F and dl-PCB levels in Turkish foodstuffs: industrial versus rural, local versus supermarket products, and assessment of dietary intake
Kilic, D. ; Cakirogullari, G.C. ; Ucar, Y. ; Theelen, R. ; Traag, W.A. - \ 2011
Food Additives & Contaminants. Pt. A, Chemistry, Analysis, Control, Exposure & Risk Assessment 28 (2011)7. - ISSN 1944-0049 - p. 913 - 924.
dioxin-like pcbs - toxic equivalency factors - porpoise phocoena-phocoena - polychlorinated-biphenyls - black-sea - human exposure - pcdfs - distributions - turkey
Polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs) and dioxin-like and non-dioxin-like (indicator) polychlorinated biphenyls (PCBs) were monitored in various foodstuffs of animal origin and edible oil samples obtained from two different cities in Turkey both rural and industrial. Total dioxin+dioxin-like PCBs and indicator PCB concentrations of pooled samples ranged 0.20-4.19 pg World Health Organization-Toxic Equivalency (WHO-TEQ)((1998))/g fat and 57.2-1710 pg/g fat, respectively. The dominant congeners were 2,3,4,7,8-PeCDF, 1,2,3,7,8-PeCDD, 2,3,7,8-TCDD and PCB126. Dietary intake of dioxin+dioxin-like PCBs and indicator PCBs from fish, dairy products, edible oil, egg and meat was 0.509 pg WHO-TEQ(1998)/kg bw (body weight)/day and 839 pg/kg bw/day in Afyon and 0.588 pg WHO-TEQ(1998)/kg bw/day and 1070 pg/kg bw/day in Kocaeli, respectively. The major contributors to total exposure were dairy products and fish. Despite the unexplained high contamination level in an individual egg sample from Kocaeli, average concentration levels in Turkey, even in industrialized regions, were low compared to reported concentrations in Western Europe. Exposure levels were well below the tolerable daily intake (TDI) of 2 pg WHO-TEQ(1998)/kg body weight.
The need and Potential of Biosensors to Detect Dioxins and Dioxin-Like Polychlorinated Biphenyls along the Milk, Eggs and Meat Food Chain
Chobtang, J. ; Boer, I.J.M. de; Hoogenboom, L.A.P. ; Haasnoot, W. ; Kijlstra, A. ; Meerburg, B.G. - \ 2011
Sensors 11 (2011)12. - ISSN 1424-8220 - p. 11692 - 11716.
aryl-hydrocarbon receptor - dibenzo-p-dioxins - toxic equivalency factors - solid-phase extraction - home-produced eggs - free-range eggs - calux-bioassay - dr-calux(r) bioassay - chemical contamination - microbial biosensors
Dioxins and dioxin-like polychlorinated biphenyls (DL-PCBs) are hazardous toxic, ubiquitous and persistent chemical compounds, which can enter the food chain and accumulate up to higher trophic levels. Their determination requires sophisticated methods, expensive facilities and instruments, well-trained personnel and expensive chemical reagents. Ideally, real-time monitoring using rapid detection methods should be applied to detect possible contamination along the food chain in order to prevent human exposure. Sensor technology may be promising in this respect. This review gives the state of the art for detecting possible contamination with dioxins and DL-PCBs along the food chain of animal-source foods. The main detection methods applied (i.e., high resolution gas-chromatography combined with high resolution mass-spectrometry (HRGC/HRMS) and the chemical activated luciferase gene expression method (CALUX bioassay)), each have their limitations. Biosensors for detecting dioxins and related compounds, although still under development, show potential to overcome these limitations. Immunosensors and biomimetic-based biosensors potentially offer increased selectivity and sensitivity for dioxin and DL-PCB detection, while whole cell-based biosensors present interpretable biological results. The main shortcoming of current biosensors, however, is their detection level: this may be insufficient as limits for dioxins and DL-PCBs for food and feedstuffs are in pg per gram level. In addition, these contaminants are normally present in fat, a difficult matrix for biosensor detection. Therefore, simple and efficient extraction and clean-up procedures are required which may enable biosensors to detect dioxins and DL-PCBs contamination along the food chain.
Correlates of Cytochrome P450 1A1 Expression in Bottlenose Dolphin (Tursiops truncatus) Integument Biopsies
Wilson, J.Y. ; Wells, R. ; Anguilar, A. ; Borrell, A. ; Tornero, V. ; Reijnders, P.J.H. ; Moore, M. - \ 2007
Toxicological sciences 97 (2007)1. - ISSN 1096-6080 - p. 111 - 119.
whales balaenoptera-physalus - porpoise phocoena-phocoena - toxic equivalency factors - dibenzo-p-dioxins - st-lawrence - skin biopsy - organochlorine contaminants - delphinapterus-leucas - hepatocyte cultures - sarasota bay
Integument biopsy is a nondestructive method for sampling free-ranging cetaceans, which allows for the determination of both contaminant concentrations and biomarker responses. Cytochrome P450 1A1 (CYP1A1) expression is induced by polycyclic aromatic hydrocarbons and planar halogenated aromatic hydrocarbons such as the non-ortho and mono-ortho polychlorinated biphenyls (PCBs). CYP1A induction has been used extensively as a biomarker of exposure to such compounds in vertebrates. We measured PCB concentrations and CYP1A1 expression in integument biopsies from bottlenose dolphins (Tursiops truncatus) resident in Sarasota Bay, FL. This population of dolphins has been the subject of long-term population and health assessment, affording the opportunity to evaluate the influence of age, sex, and reproductive status on CYP1A1 expression. CYP1A1 expression was seen in endothelial cells, vascular smooth muscle, and nerve cells in the dermis, similar to what has been observed in other cetacean species. Endothelial CYP1A1 expression varied along the length of the biopsy, which could be related to differences in the structure and functionality of the blubber in different parts of the integument. Neither age nor sex was related to CYP1A1 expression in these biopsies, and reproductive status did not relate to levels of CYP1A1 in females. Total PCB and toxic equivalent quotient concentrations in blubber were positively correlated with dermal endothelial CYP1A1 expression, although mono-ortho PCBs concentrations did not show this relationship. Contaminant concentrations appear to be stronger determinants of CYP1A1 expression in integument of these dolphins, than are age, sex, or reproductive status.
Polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls in fish from the Netherlands: concentrations, profiles and comparison with DR CALUX bioassay results
Leeuwen, S.P.J. van; Leonards, P.E.G. ; Traag, W.A. ; Hoogenboom, L.A.P. ; Boer, V.C.J. de - \ 2007
Analytical and Bioanalytical Chemistry 389 (2007)1. - ISSN 1618-2642 - p. 321 - 333.
polybrominated diphenyl ethers - toxic equivalency factors - eels anguilla-anguilla - calux-bioassay - international validation - organochlorine compounds - dietary-intake - great-lakes - pcbs - marine
Fish from Dutch markets were analysed for concentrations of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) and compared with the new European maximum residue levels (MRLs), set in 2006. In a first study on 11 different fish and shellfish from various locations, concentrations of PCDD/Fs were nearly all below the MRL for PCDD/Fs [4 pg toxic equivalents (TEQ) per gram wet weight (ww)] and nearly all below 8 pg total TEQ/g ww, the new MRL for the sum of PCDD/Fs and DL-PCBs. Some samples exceeded the total TEQ MRL, such as anchovy, tuna and sea bass. Furthermore, 20 (out of 39) wild eel samples exceeded the specific MRL for eel (12 pg total TEQ/g ww), as the study revealed PCDD/F TEQ levels of 0.2-7.9 pg TEQ/g ww and total TEQ values of 0.9 to 52 pg/g ww. TEQ levels in farmed and imported eel were lower and complied with the MRLs. Smoking eel, a popular tradition in the Netherlands, only had marginal effects on PCDD/F and DL-PCB concentrations. Owing to volatilization, concentrations of lower-chlorinated PCBs were reduced to below the limit of quantification after smoking. DL-PCBs contributed 61-97% to the total TEQ in all eel samples. This also holds for other fish and shellfish (except shrimps): DL-PCB contributed (on average) from 53 (herring) to 83% (tuna) to the total TEQ. Principal-component analysis revealed distinctive congener profiles for PCDD/Fs and non-ortho PCBs for mussels, pikeperch, herring and various Mediterranean fish. The application of new TCDD toxic equivalency factors (TEFs) set by the World Health Organization in 2006 (to replace the 1997 TEFs) resulted in lower TEQ values, mainly owing to a decreased mono-ortho PCB contribution. This decrease is most pronounced for eel, owing to the relative high mono-ortho PCB concentrations in eel. Consequently, a larger number of samples would comply with the MRLs when the new TEFs are applied. The DR CALUX (R) assay may be used for screening total TEQ levels in eel, in combination with gas chromatography-high resolution mass spectrometry confirmation of suspected samples. An almost 1:1 correlation was found when the 1997 TEFs were applied, but, surprisingly, a 1.4-fold overestimation occurred with application of the 2006 TEFs.
Determination of in vitro relative potency (REP) values for mono-ortho polychlorinated biphenyls after purification with active charcoal
Peters, A.K. ; Leonards, P.E.G. ; Zhao, B. ; Bergman, A. ; Denison, M.S. ; Berg, M. van den - \ 2006
Toxicology Letters 165 (2006)3. - ISSN 0378-4274 - p. 230 - 241.
dioxin-like compounds - aryl-hydrocarbon receptor - toxic equivalency factors - dibenzo-p-dioxins - monkeys macaca-fascicularis - o-deethylase induction - ah receptor - risk-assessment - h4iie cells - dependent induction
The TEF system for dioxin-like compounds has included assignment of TEF values for mono-ortho polychlorinated biphenyls (MO-PCBs). Small traces of aryl hydrocarbon receptor (AhR)-active impurities could result in artifactually higher relative potency (REP) values. MO-PCBs -105, -118, -156, and -167 were purified on an active charcoal column to remove AhR agonists that could be present as impurities. Activation or inhibition of AhR-dependent gene expression by purified MO-PCBs was studied in stably transfected cell lines (HlG1.1c3 mouse, H4G1.1c2 rat hepatoma), containing an AhR-responsive (AhR-EGFP) reporter gene. In addition, EROD activity was used as marker for CYP1A1 activity in these cell lines. MO-PCBs -105,-118,-156 induced AhR-EGFP expression in both rodent cell lines, with PCB-156 (10 mu M) being most effectively; inducing gene expression to similar to 27% of TCDD (mouse cells) and 62.5 +/- 3.4% (rat cells) of TCDD. This concurred with increased EROD activity in both cell lines to maxima of 20.5 +/- 1.5% and 68 +/- 3.2% of TCDD, respectively. No induction was observed for PCB-167. In the HIG1.1c3 mouse cells, PCB-105, -118 and -156 (10 mu M) significantly reduced TCDD-induced AbR-EGFP expression to 50.9 +/- 2.9%, 58.3 +/- 2.2% and 70.8 +/- 1.3% of TCDD. Reduced EROD activity was also observed, of 39.3 +/- 2.8%, 67 +/- 5% and 48.3 +/- 4% compared to TCDD. PCB-167 did not result in significant reduction. In rat cells, only PCB-156 resulted in significant decrease in TCDD-induced AhR-EGFP expression of 35%, suggesting species differences play a role. Our results suggest that purification of MO-PCBs is an essential step in determining accurate REP values, and could very likely lead to lower TEF values than those presently assigned by the WHO. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
Brominated flame retardants and endocrine disruption
Vos, J.G. ; Becher, G. ; Berg, M. van den; Boer, J. de; Leonards, P.E.G. - \ 2003
Pure and Applied Chemistry 75 (2003)ISSN 0033-. - ISSN 0033-4545 - p. 2039 - 2046.
polybrominated diphenyl ethers - toxic equivalency factors - polychlorinated-biphenyls pcbs - tetrabromobisphenol-a - factors tefs - in-vitro - exposure - wildlife - chemicals - rats
From an environmental point of view, an increasing important group of organohalogen compounds are the brominated flame retardants (BFRs), which are widely used in polymers and textiles and applied in construction materials, furniture, and electronic equipment. BFRs with the highest production volume are the polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBP-A), and hexabromocyclododecane (HBCD). Because of their persistence and low biodegradation profile, several of the PBDE congeners accumulate in biota and are widely found in the aquatic food chain. Their levels in the environment and in humans have increased during the last decades, in contrast to compounds such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT), for example. Humans may be exposed to PBDEs mainly through consumption of fatty food of animal origin (e.g., fish), but exposure through skin contact with textiles protected with flame retardants or through inhalation of BFRs volatilized from electronic and electric equipment may also occur. The levels of PBDEs in Swedish human milk showed a doubling in concentration every five years over the period 1972 to 1997 (2,2',4,4'-tetraBDE being the predominant congener). The levels of penta- and hexa-BDEs increased at the same rate in ringed seals collected in the Canadian Arctic from 1981 to 2000. PBDEs exhibit a great variety of biological effects, depending on the bromine substitution pattern. PBDEs are potential endocrine disrupters, based on shared toxicity with the structurally related PCBs, polychlorinated dibenzofurans (PCDFs), and polychlorinated dibenzo-p-dioxins (PCDDs) (partial aryl hydrocarbon- [Ah-] receptor agonist and antagonist activity in vitro, thyroid toxicity, and immune effects), including developmental toxicity. The potency of TBBP-A to interact with thyroid hormone homeostasis is indicated from in vitro studies in which the compound competes with thyroxin (T4) for binding to transthyretin (TTR). So far, the toxicological profile of many BFRs is too incomplete and insufficient to perform an adequate risk assessment, and further information is required regarding the potential for endocrine disruption of these compounds that are of increasing environmental concern
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