The HBM4EU Scoping document on flame retardants provides background information on these substances, identifies relevant policy questions on the group of substances and outlines research activities under HBM4EU.
The authors of the scoping document were Lisa Melymuk and Jana Klánová of Masaryk University. The document was produced in November 2017.
A short overview report was produced in 2019 to answer the main policy questions with the available data at the time.
This page was last updated in January 2020.
Uses of flame retardants
Flame retardant (FR) is the term given to any compound or mixture added to a consumer product or building material to reduce the flammability and thus improve product safety. Flame retardants can be either chemically-bound to the material of the consumer product, or chemical additives (not bound to the product material). A range of both inorganic and organic FRs are in use; however of concern with respect to HBM4EU are in particular the synthetic organic flame retardants. There are three primary types of synthetic organic FRs categorized based on their elemental composition, these being bromine (Br), chlorine (Cl) and phosphate (P).
Since the 1970s, the primary FR compounds used were the polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane1 (HBCDD). However, due to concerns regarding their persistence, toxicity and bioaccumulative potential, these compounds have been added to the Stockholm Convention on Persistent Organic Pollutants, including the most recent addition of deca-BDE (also called BDE-209, referring to the PBDE with 10 bromines) in 2017. Yet, although these compounds are regulated under the Stockholm Convention and through other regulatory mechanisms, the need for FRs has not decreased and this has led to a broadening of the market for FR compounds, with a wide range of replacement compounds used globally. These replacement compounds are typically brominated, chlorinated and organophosphate compounds, some of which are mentioned below. In the following document, OPE (organophosphate esters), refers to the organophosphate-based FRs, while NBFR (novel brominated flame retardant) refers to the brominated replacements for PBDEs and HBCDD.
1Six isomers of HBCDD exist. Therefore, sometimes the plural HBCDDs is used as synonymous for HBCDD.
For the extensive list of the 62 substances included in the substance group, listed according to availability of toxicology and human biomarker data, in category A, B, C, D, E please refer to Table 1 of the scoping document.
From the 62 FRs, there are 20 individual compounds that despite having evidence of toxicity, lack in HBM data:
- TPHP, TMPP, TCEP, TCIPP, TDCIPP, TNBP, TBBPA, and TBOEP are Cat. B compounds for which available HBM data suggests significant human exposure, and there is sufficient evidence of toxicity to warrant concern
- TEHP, EHDPP, DDC-DBF, ip-TPP, V6, 2,4,6-TBP and TDBPP are Cat. C and D compounds with very limited HBM data, and in some cases none at all within Europe, but suggestion of toxicological concern.
- DBNPG, TDBP-TAZTO, RBDPP, melamine polyphosphate and EBTEBPI are Cat. E compounds for which no HBM data exists but toxicological evidence suggests concern.
Additionally, there are 6 compounds which entirely lack toxicological and HBM data: diethylphosphinic acid, BDBP-TAZTO, 4’-PeBPO-BDE208, HBCYD, DBS and DBP-TAZTO. These compounds should receive attention in the form of suspect screening to determine if they are present in any human matrices and warrant further attention.
Hazardous properties of flame retardants
PBDEs and HBCDDs have been identified to have a range of adverse health effects, including potential neurotoxic, endocrine, and carcinogenic effects (Chevrier, 2010; Covaci, 2006; Herbstman, 2010). The toxicity of tetrabromobisphenol A (TBBPA) is also well-studied and it has been identified to have a range of potential hazardous properties (IHCP, 2006; Haneke, 2002; Lai, 2015; Birnbaum, 2003)
Early evidence suggests that a number of the replacement FRs may have similar health concerns (Dishaw, 2011; Patisaul, 2013; Springer, 2012). Moreover, insufficient evidence exists to evaluate toxicity for many of these new FRs. The toxicity and human exposure of selected FRs has been investigated in individual studies, and aquatic toxicity has received significant attention, but there remain large gaps in toxicity studies of directly applicability to human populations.
A number of OPEs have evidence of toxic effects in mammals, but generally toxicity data is insufficient, and is a crucial knowledge gap considering the high environmental levels of these compounds. Short-term and long-term toxicological data are needed, including additive or synergistic effects of FR mixtures. Many flame retardants exist in mixtures, e.g., the technical mixtures of the PBDEs, and Firemaster 550, which contains triphenyl phosphate (TPHP), isopropylated triphenyl phosphate isomers (ip-TPP), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)- 2,3,4,5-tetrabromophthalate (BEH-TEBP). In terms of toxicity, the PBDEs have received attention as mixtures and as individual compounds (Darnerud, 2001) and there is evidence of Firemaster 550 as an endocrine disrupting compound and obesogen (Patisaul, 2013). However, there is generally little attention given to the toxic effects of the typical mixtures of FRs occurring indoors and to which humans are exposed. Thus, the issue of mixture toxicity is highly relevant to FRs, and remains a large data gap within the toxicological knowledge on FRs.
Further knowledge gaps exist in the area of carcinogenicity, especially for hormonal cancers; there is limited information on long-term and chronic health effects; reproductive health and endocrine disrupting effects also require further investigation. Finally, epidemiological studies that include mixtures of FRs are critical to assess links between exposure and health outcomes.
Human exposure to flame retardants
FRs are widely used in consumer products and building materials, in particular in electronics, textiles and furnishings, automobiles and other vehicles, building insulation, flooring, appliances and ducting, and studies have identified a range of FRs in all of these product groups (Vojta, 2017; Kajiwara, 2011; ARCADIS, 2011; Stapleton, 2011; Ballesteros-Gómez, 2014; Stapleton, 2009). The amounts of and types of FRs vary widely even within product groupings, and can be found at up to percentage levels in consumer products, but typically are in the μg/g range.
There is extremely limited information on EU and/or global production of FRs. The provision of this information is challenging for the following reasons:
- FR producers maintain proprietary control of the chemical composition of some commercial FR mixtures, and information may not be publicly available;
- Regulations and/or information on commercial production of FRs provided for the EU region may not reflect the use in the EU or the potential for human exposure, since many FRs enter the EU already incorporated into consumer products manufactured in other regions, and chemicals already incorporated into consumer products may not be included in some chemical inventories;
- The FR market is rapidly changing in response to regulations and shifts in product requirements, and usage information becomes quickly out of date. Further complexity of information of FRs in consumer products arises from variability in FR mass in the same products due to manufacturing variability or use and complex products such as cars contain a range of FRs with components from global sources.
Human exposure to FRs can occur through a variety exposure pathways, via inhalation, ingestion (either through food or ingestion of indoor dusts, as FRs migrate from products and materials into the indoor and outdoor environment) and dermal exposure, including through direct contact with flame-retarded consumer products (Harrad, 2010). In addition to use as FRs, a number of these compounds (particularly the phosphorus-based FRs) also act as plasticizers,(van der Veen, 2012) and thus are also added to synthetic materials for this purpose. The exposure pathways differ based on the compound properties and FR use. For example, while adult exposure to some FRs is primarily through diet, for babies and toddlers, due to the hand-to-mouth behaviour and mouthing of toys, the primary exposure pathway is through ingestion of house dust (Jones-Otazo, 2005).
In general, human exposure to PBDEs is lower in Europe than in North America, (Hites, 2004) while evidence from indoor dust and chemical usage suggests higher human exposure to HBCDDs in Europe than in North America based on identified correlations between dust and serum concentrations (Harrad, 2008; Roosens, 2009). The strong interpretations of exposure trends from PBDEs suggest that sufficient biomarker data for other FRs, once obtained, will enable similar improvements in understanding of FR exposure and effects in the European population. Some evidence of regional differences in exposure pathways within Europe for the NBFRs and OPEs, (Dirtu, 2012) however there is no systematic overview of regional differences.
Technical challenges in biomonitoring flame retardants in humans
Highly lipophilic FRs, particularly those with higher persistence, such as the PBDEs, can be detected in parent compound form in human matrices, most commonly in human serum (Brasseur, 2014; Kalantzi, 2011; Darnerud, 2015) and breast milk (Siddique, 2012; Lignell, 2009).
However, many of the metabolites are uncertain, and metabolic pathways are only characterized for a limited number of FRs (Ballesteros-Gómez, 2015a; Su, 2015; Ballesteros-Gómez, 2015b; Van den Eede, 2013; Van den Eede, 2016a; Van den Eede, 2016b). Biomarkers for many FRs of emerging concern are unknown.
Many biomonitoring studies report high detection frequencies of FR biomarkers in human matrices, but there is little systematic assessment of temporal or spatial trends. PBDEs are one of the few compounds where generalization of trends and distributions has been made from biomarkers (Darnerud, 2015). Quantification of a rapidly increasing temporal trend of PBDEs in maternal milk in Sweden (Meironyte, 1999; Solomon, 2002) lead to initial concerns regarding human exposure to PBDEs and first regulatory actions.
Analytical methods for PBDEs and HBCDD in serum and milk are relatively well-established, and have been applied around the world (Darnerud, 2015; Sahlström, 2014; Tao, 2017; Zhu, 2009; Lignell, 2013; Müller, 2016; Thomsen, 2010; Eljarrat, 2009). Analysis for PBDEs is typically via GC-MS, and instrumental parameters vary in individual methods. Analysis of HBCDD can be via GC-MS or LC-MS, however the GC-MS method has limited accuracy (Melymuk, 2017) and does not allow quantification of individual isomers. LC-MS is strongly recommended for HBCDD. The widespread use of C13-labelled internal standards for both PBDEs and HBCDD allows reliable quantification of these compounds.
Within the replacement NBFRs and OPEs, analytical methods are less established, and recent interlaboratory comparisons have identified large inconsistencies in laboratory performance (Melymuk, 2017; Stubbings, 2017). As the group of flame retardants is defined by its use, not by its chemical identity, it includes many structurally different chemicals. Thus, analytical methods will differ for certain sub-groups of flame retardants. While the phosphorous flame retardants are a relatively homogenous group, the NBFRs vary greatly. Consequently, methods will have to be optimised for each individual compound. The availability of standards often limits method developments. However, new standards become available each year, and specific interests can be communicated to the producers of analytical standards. Certified reference materials are usually not available, or are not applicable. Older reference materials (e.g., <2000) are not often useful as they do not contain the current complex mixture of FRs that are the replacements for the PBDEs and HBCDD.
Legislative status in the European Union
A small number of FRs are restricted both within the EU as well as at the international level. PBDEs and HBCDD are restricted under the Stockholm Convention on Persistent Organic Pollutants, and now have limited use. Many replacement/alternative FRs are registered under REACH, however there are currently no regulations for a number of FR compounds. Given the existing regulations on flame retardants both at the international (e.g., Stockholm Convention) and European level (e.g., REACH), HBM4EU can contribute by providing information on the effect of legislative restrictions and bans on concentrations in the European human population, particularly with respect to establishing baseline exposure concentrations for current-use flame retardants. Evaluating and comparing temporal trends for banned/restricted vs. current-use FRs will also allow us to determine if current regulations are effective across the EU, and if the emerging FRs are showing signs of accumulation in the environment or within the European population. For the majority of FRs there are no established safety limits, health-based reference values or guidance values, and limited knowledge of usage volumes due to manufacturer confidentiality. Of the list of 62 FRs in HBM4EU, 1 is registered under REACH under the 10000-100000 t/y tonnage band, 7 FRs at 1000-10000 t/y and 9 at 100-1000 t/y; 3 FRs are not registered under REACH but listed under CoRAP based on (among others) high aggregated tonnage and wide dispersive use. 28 of the 62 FRs are not registered under REACH.
Of concern is the relative lack of information regarding the use, exposure pathways and toxicity of many of these compounds. The European Food Safety Authority (EFSA) identified 17 brominated FRs which are currently in use and with detectable levels in environmental and/or human matrices, and a further ten brominated FRs that have concentrations >0.1% in consumer products and materials, but lack any information on human and environmental levels or even occurrence at all (EFSA, 2012).
HBM4EU provides a platform to identify geographic patterns and time trends of exposure from existing data sets and to identify and rectify where major gaps exist through additional targeted investigation. This will allow regulatory agencies to identify any FRs that may be of concern and to make informed decisions.
Policy questions on flame retardants
Throughout the duration of this project, the following policy questions will be addressed:
- What are current HBM levels of legacy/regulated FRs (e.g., PBDEs and HBCDD)? How do these compare to any historical records? Is the current legislative framework and proposed actions leading to a significant decline in restricted compounds and is this uniform across the EU?
- What is the exposure of the European population to current use FRs? In particular, what is the exposure of sensitive sub-groups (e.g., infants and children)?
- How do the levels of legacy FRs compare to levels of new/emerging FRs? Is any temporal or spatial trend observed? Can we relate this to use patterns and/or production volume?
- How does exposure to FRs differ between adults and children, males and females?
- How does exposure differ by geographic area within Europe? Do countries/regions have different FR exposure levels?
- Are there one or more occupationally exposed sub-groups? What occupations are associated with high exposure to FRs?
- Is elevated exposure to FRs associated with particular consumption patterns or lifestyles?
- What are the relevant exposure pathways for FRs, e.g., diet, air, water, indoor environmental exposure?
- Do certain flame retardants co-occur in HBM matrices?
- What current information is available regarding toxicity of FRs, both as individual compounds and as the mixtures of FRs typically occurring in indoor environments and diet?
- Can exposure to FRs be linked with any adverse health effects?
- What are the population groups most at risk?
- As FR market shifts towards replacement/alternative FRs, does human exposure reflect that trend? E.g., DBDPE as replacement for BDE-209;
- What additional FRs should be prioritized for further information regarding exposure and/or toxicity? How can use and risk information be combined to identify and prioritize knowledge gaps for further assessment?
- Can reference values be established for any FRs?
Stakeholder comments on the scoping documents
In the interest of transparency and accountability, HBM4EU invites interested stakeholders to submit comments on the scoping document.
All submitted comments will be made available for download on this webpage and will be taken into consideration by the HBM4EU consortium, where possible.
ARCADIS. Identification and evaluation of data on flame retardants in consumer products; Brussels, 2011. https://www.europeanfiresafetyalliance.org/publications/identification-and-evaluation-of-data-on-flame-retardants-in-consumer-products/
Ballesteros-Gómez, A.; Brandsma, S. H.; de Boer, J.; Leonards, P. E. G. Analysis of two alternative organophosphorus flame retardants in electronic and plastic consumer products: Resorcinol bis-(diphenylphosphate) (PBDPP) and bisphenol A bis (diphenylphosphate) (BPA-BDPP). Chemosphere 2014, 116, 10–14. https://www.sciencedirect.com/science/article/pii/S0045653514000381
Ballesteros-Gómez, A.; Van den Eede, N.; Covaci, A. In Vitro Human Metabolism of the Flame Retardant Resorcinol Bis(diphenylphosphate) (RDP). Environ. Sci. Technol. 2015a, 49, 3897–3904. https://pubs.acs.org/doi/10.1021/es505857e
Ballesteros-Gomez, A.; Erratico, C. A.; Eede, N. Van den; Ionas, A. C.; Leonards, P. E. G.; Covaci, A. In vitro metabolism of 2-ethylhexyldiphenyl phosphate (EHDPHP) by human liver microsomes. Toxicol. Lett. 2015b, 232, 203–212. https://www.sciencedirect.com/science/article/pii/S0378427414014179Birnbaum, L. S.; Staskal, D. F. Brominated Flame Retardants: Cause for Concern? Environ. Health Perspect. 2003, 112, 9–17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241790/pdf/ehp0112-000009.pdf
Brasseur, C.; Pirard, C.; Scholl, G.; De Pauw, E.; Viel, J. F.; Shen, L.; Reiner, E. J.; Focant, J.-F. Levels of dechloranes and polybrominated diphenyl ethers (PBDEs) in human serum from France. Environ. Int. 2014, 65, 33–40. https://www.sciencedirect.com/science/article/pii/S0160412013003036
Cequier, E.; Sakhi, A. K.; Marcé, R. M.; Becher, G.; Thomsen, C. Human exposure pathways to organophosphate triesters — A biomonitoring study of mother–child pairs. Environ. Int. 2015, 75, 159–165. https://www.sciencedirect.com/science/article/pii/S0160412014003407
Chevrier, J.; Harley, K. G.; Bradman, A.; Gharbi, M.; Sjödin, A.; Eskenazi, B. Polybrominated diphenyl ether (PBDE) flame retardants and thyroid hormone during pregnancy. Environ. Health Perspect. 2010, 118, 1444–1449. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957927/pdf/ehp-118-1444.pdf
Covaci, A.; Gerecke, A. C.; Law, R. J.; Voorspoels, S.; Kohler, M.; Heeb, N. V.; Leslie, H.; Allchin, C. R.; de Boer, J. Hexabromocyclododecanes (HBCDs) in the Environment and Humans: A Review. Environ. Sci. Technol. 2006, 40, 3679–3688. https://pubs.acs.org/doi/pdf/10.1021/es0602492
Darnerud, P. O.; Eriksen, G. S.; Johannesson, T.; Larsen, P. B.; Viluksela, M. Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology. Environ. Health Perspect. 2001, 1019, 49–68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240542/
Darnerud, P. O.; Lignell, S.; Aune, M.; Isaksson, M.; Cantillana, T.; Redeby, J.; Glynn, A. Time trends of polybrominated diphenylether (PBDE) congeners in serum of Swedish mothers and comparisons to breast milk data. Environ. Res. 2015, 138, 352–360. https://www.sciencedirect.com/science/article/pii/S0013935115000663
Dirtu, A. C.; Ali, N.; Van den Eede, N.; Neels, H.; Covaci, A. Country specific comparison for profile of chlorinated, brominated and phosphate organic contaminants in indoor dust. Case study for Eastern Romania, 2010. Environ. Int. 2012, 49, 1–8. https://www.sciencedirect.com/science/article/pii/S0160412012001766
Dishaw, L. V.; Powers, C. M.; Ryde, I. T.; Roberts, S. C.; Seidler, F. J.; Slotkin, T. A.; Stapleton, H. M. Is the PentaBDE replacement, tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a developmental neurotoxicant? Studies in PC12 cells. Toxicol. Appl. Pharmacol. 2011, 256, 281–289. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089808/pdf/nihms266652.pdf
EFSA (European Food Safety Authority). EFSA Panel on Contaminants in the Food Chain (CONTAM); Scientific Opinion on Emerging and Novel Brominated Flame Retardants (BFRs) in Food. EFSA J. 2012, 10, 125. https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/j.efsa.2012.2908
Eljarrat, E.; Guerra, P.; Martínez, E.; Farré, M.; Alvarez, J. G.; López-Teijón, M.; Barceló, D. Hexabromocyclododecane in Human Breast Milk: Levels and Enantiomeric Patterns. Environ. Sci. Technol. 2009, 43, 1940–1946. https://pubs.acs.org/doi/abs/10.1021/es802919e?journalCode=esthag
Fromme, H.; Lahrz, T.; Kraft, M.; Fembacher, L.; Mach, C.; Dietrich, S.; Burkardt, R.; Völkel, W.; Göen, T. Organophosphate flame retardants and plasticizers in the air and dust in German daycare centers and human biomonitoring in visiting children (LUPE 3). Environ. Int. 2014, 71, 158–163. https://www.sciencedirect.com/science/article/pii/S0160412014002001
Haneke, K. E. Tetrabromobisphenol A [79-94-7] – Review of Toxicological Literature; Research Triangle Park, NC, USA, 2002. https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/tetrabromobisphenola_508.pdf
Harrad, S. J.; de Wit, C. A.; Abdallah, M. A.-E.; Bergh, C.; Björklund, J. A.; Covaci, A.; Darnerud, P. O.; de Boer, J.; Diamond, M. L.; Huber, S.; et al. Indoor contamination with hexabromocyclododecanes, polybrominated diphenyl ethers, and perfluoroalkyl compounds: an important exposure pathway for people? Environ. Sci. Technol. 2010, 44, 3221–3231. https://pubs.acs.org/doi/abs/10.1021/es903476t
Harrad, S. J.; Ibarra, C.; Abdallah, M. A.-E.; Boon, R.; Neels, H.; Covaci, A. Concentrations of brominated flame retardants in dust from United Kingdom cars, homes, and offices: Causes of variability and implications for human exposure. Environ. Int. 2008, 34, 1170–1175. https://www.sciencedirect.com/science/article/pii/S0160412008000822
Herbstman, J. B.; Sjödin, A.; Kurzon, M.; Lederman, S. a; Jones, R. S.; Rauh, V.; Needham, L. L.; Tang, D.; Niedzwiecki, M.; Wang, R. Y.; et al. Prenatal exposure to PBDEs and neurodevelopment. Environ. Health Perspect. 2010, 118, 712–719. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866690/pdf/ehp-118-712.pdf
Hites, R. A. Polybrominated diphenyl ethers in the environment and in people: a meta-analysis of concentrations. Environ. Sci. Technol. 2004, 38, 945–956.
IHCP, Institute for Health and Consumer Protection. 2,2’,6,6’-TETRABROMO-4,4’-ISOPROPYLIDENE DIPHENOL (TETRABROMOBISPHENOL-A or TBBP-A) Part II – Human Health – Summary Risk Assessment Report; Bootle, Merseyside, UK, 2006. https://echa.europa.eu/documents/10162/b1392373-31bd-4722-bf60-fc88225b5a76
Jones-Otazo, H. A.; Clarke, J. P.; Diamond, M. L.; Archbold, J. A.; Ferguson, G.; Harner, T.; Richardson, G. M.; Ryan, J. J.; Wilford, B. H. Is house dust the missing exposure pathway for PBDEs? An analysis of the urban fate and human exposure to PBDEs. Environ. Sci. Technol. 2005, 39, 5121–5130. https://pubs.acs.org/doi/abs/10.1021/es048267b?journalCode=esthag
Kajiwara, N.; Noma, Y.; Takigami, H. Brominated and organophosphate flame retardants in selected consumer products on the Japanese market in 2008. J. Hazard. Mater. 2011, 192, 1250–1259. https://www.sciencedirect.com/science/article/pii/S0304389411008053
Kalantzi, O. I.; Geens, T.; Covaci, A.; Siskos, P. A. Distribution of polybrominated diphenyl ethers (PBDEs) and other persistent organic pollutants in human serum from Greece. Environ. Int. 2011, 37, 349–353. https://www.sciencedirect.com/science/article/pii/S0160412010002047
Lai, D. Y.; Kacew, S.; Dekant, W. Tetrabromobisphenol A (TBBPA): Possible modes of action of toxicity and carcinogenicity in rodents. Food Chem. Toxicol. 2015, 80, 206–214. https://www.sciencedirect.com/science/article/pii/S0278691515001027
Lignell, S.; Aune, M.; Darnerud, P. O.; Cnattingius, S.; Glynn, A. Persistent organochlorine and organobromine compounds in mother’s milk from Sweden 1996–2006: Compound-specific temporal trends. Environ. Res. 2009, 109, 760–767. https://www.sciencedirect.com/science/article/pii/S0013935109000826
Lignell, S.; Aune, M.; Glynn, A.; Cantillana, T.; Isaksson, M.; Aune, M.; Glynn, A.; Cantillana, T. Polybrominated diphenylethers (PBDE) and hexabromocyclododecane (HBCD) in paired samples of blood serum and breast milk – a correlation study; Uppsala, 2013. http://www.imm.ki.se/Datavard/Rapporter/Sakrapport_korrelationPBDE_slutlig.pdf
Meironyte, D.; Noren, K.; Bergman, A. Analysis of polybrominated diphenyl ethers in Swedish human milk. A time-related trend study, 1972-1997. J. Toxicol. Environ. Heal. Part A 1999, 58, 329–341. https://www.ingentaconnect.com/content/tandf/uteh/1999/00000058/00000006/art00001
Melymuk, L.; Goosey, E.; Riddell, N.; Diamond, M. L. Interlaboratory study of novel halogenated flame retardants: INTERFLAB. Anal. Bioanal. Chem. 2015, 407, 6759–6769. https://link.springer.com/article/10.1007%2Fs00216-015-8843-7
Müller, M. H. B.; Polder, A.; Brynildsrud, O. B.; Lie, E.; Løken, K. B.; Manyilizu, W. B.; Mdegela, R. H.; Mokiti, F.; Murtadha, M.; Nonga, H. E.; et al. Brominated flame retardants (BFRs) in breast milk and associated health risks to nursing infants in Northern Tanzania. Environ. Int. 2016, 89–90, 38–47. https://www.sciencedirect.com/science/article/pii/S0160412015301355
Patisaul, H. B.; Roberts, S. C.; Mabrey, N.; Mccaffrey, K. A.; Gear, R. B.; Braun, J.; Belcher, S. M.; Stapleton, H. M. Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster® 550 in rats: an exploratory assessment. J. Biochem. Mol. Toxicol. 2013, 27, 124–136. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788594/
Roosens, L.; Abdallah, M. A.-E.; Harrad, S. J.; Neels, H.; Covaci, A. Exposure to hexabromocyclododecanes (HBCDs) via dust ingestion, but not diet, correlates with concentrations in human serum: Preliminary results. Environ. Health Perspect. 2009, 117, 1707–1712. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801203/
Sahlström, L. M. O.; Sellström, U.; de Wit, C. A.; Lignell, S.; Darnerud, P. O. Brominated Flame Retardants in Matched Serum Samples from Swedish First-Time Mothers and Their Toddlers. Environ. Sci. Technol. 2014, 48, 7584–7592. https://pubs.acs.org/doi/10.1021/es501139d
Siddique, S.; Xian, Q.; Abdelouahab, N.; Takser, L.; Phillips, S. P.; Feng, Y.-L.; Wang, B.; Zhu, J. Levels of dechlorane plus and polybrominated diphenylethers in human milk in two Canadian cities. Environ. Int. 2012, 39, 50–55. https://www.sciencedirect.com/science/article/pii/S0160412011002443
Solomon, G. M.; Weiss, P. M. Chemical contaminants in breast milk: Time trends and regional variability. Environ. Health Perspect. 2002, 110, 339–347. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240888/
Springer, C.; Dere, E.; Hall, S. J.; McDonnell, E. V.; Roberts, S. C.; Butt, C. M.; Stapleton, H. M.; Watkins, D. J.; McClean, M. D.; Webster, T. F.; et al. Rodent thyroid, liver, and fetal testis toxicity of the monoester metabolite of bis-(2-ethylhexyl) tetrabromophthalate (TBPH), a novel brominated flame retardant present in indoor dust. Environ. Health Perspect. 2012, 120, 1711–1719. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548273/
Stapleton, H. M.; Klosterhaus, S. L.; Eagle, S.; Fuh, J.; Meeker, J. D.; Blum, A.; Webster, T. F. Detection of organophosphate flame retardants in furniture foam and U.S. house dust. Environ. Sci. Technol. 2009, 43, 7490–7495. https://www.ncbi.nlm.nih.gov/pubmed/19848166
Stapleton, H. M.; Klosterhaus, S. L.; Keller, A.; Ferguson, P. L.; van Bergen, S.; Cooper, E. M.; Webster, T. F.; Blum, A. Identification of flame retardants in polyurethane foam collected from baby products. Environ. Sci. Technol. 2011, 45, 5323–5331. https://pubs.acs.org/doi/pdf/10.1021/es2007462
Stubbings, W. A.; Riddell, N.; Chittim, B.; Venier, M. Challenges in the Analyses of Organophosphate Esters. Environ. Sci. Technol. 2017, 4, 292–297. https://pubs.acs.org/doi/10.1021/acs.estlett.7b00195
Su, G.; Letcher, R. J.; Crump, D.; Gooden, D. M.; Stapleton, H. M. In Vitro Metabolism of the Flame Retardant Triphenyl Phosphate in Chicken Embryonic Hepatocytes and the Importance of the Hydroxylation Pathway. Environ. Sci. Technol. 2015, 2, 100–104. https://pubs.acs.org/doi/pdf/10.1021/acs.estlett.5b00041
Tao, F.; Abou-Elwafa Abdallah, M.; Ashworth, D. C.; Douglas, P.; Toledano, M. B.; Harrad, S. Emerging and legacy flame retardants in UK human milk and food suggest slow response to restrictions on use of PBDEs and HBCDD. Environ. Int. 2017, 105, 95–104. https://www.sciencedirect.com/science/article/pii/S0160412017303069
Thomsen, C.; Stigum, H.; Frøshaug, M.; Broadwell, S. L.; Becher, G.; Eggesbø, M. Determinants of brominated flame retardants in breast milk from a large scale Norwegian study. Environ. Int. 2010, 36, 68–74. https://www.sciencedirect.com/science/article/pii/S0160412009002086
Van den Eede, N.; de Meester, I.; Maho, W.; Neels, H.; Covaci, A. Biotransformation of three phosphate flame retardants and plasticizers in primary human hepatocytes: untargeted metabolite screening and quantitative assessment. J. Appl. Toxicol. 2016a, 36, 1401–1408. https://onlinelibrary.wiley.com/doi/full/10.1002/jat.3293
Van den Eede, N.; Ballesteros-Gómez, A.; Neels, H.; Covaci, A. Does Biotransformation of Aryl Phosphate Flame Retardants in Blood Cast a New Perspective on Their Debated Biomarkers? Environ. Sci. Technol. 2016b, 50, 12439–12445. https://pubs.acs.org/doi/abs/10.1021/acs.est.6b03214
Van den Eede, N.; Maho, W.; Erratico, C. A.; Neels, H.; Covaci, A. First insights in the metabolism of phosphate flame retardants and plasticizers using human liver fractions. Toxicol. Lett. 2013, 223, 9–15. https://www.sciencedirect.com/science/article/pii/S0378427413012848
van der Veen, I.; de Boer, J. Phosphorus flame retardants: properties, production, environmental occurrence, toxicity and analysis. Chemosphere 2012, 88, 1119–1153. https://www.sciencedirect.com/science/article/pii/S0045653512004353
Vojta, Š.; Bečanová, J.; Melymuk, L.; Komprdová, K.; Kohoutek, J.; Kukučka, P.; Klánová, J. Screening for halogenated flame retardants in European consumer products, building materials and wastes. Chemosphere 2017, 168, 457–466. https://www.sciencedirect.com/science/article/pii/S0045653516315685
Zhu L, Ma B, H. R. Brominated flame retardants in serum from the general population in northern China. Env. Sci Technol. 2009, 18, 6963–6968. https://pubs.acs.org/doi/abs/10.1021/es901296t