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.

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.

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:

1. FR producers maintain proprietary control of the chemical composition of some commercial FR mixtures, and information may not be publicly available;
2. 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;
3. 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.

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).

In contrast, some NBFRs and many OPEs are metabolized in the body, and more commonly used biomarkers of exposure are metabolites detected in urine (Cequier, 2015; Fromme, 2014)

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.

Following on the Advisory Board’s advice to strengthen the science-policy interface, HBM4EU developed a strategic and systematic approach to outreach and align science and policy. A legislative mapping exercise was done by RPA Consultants, providing relevant public policy processes that may benefit from the knowledge generated under HBM4EU. The documents are available for consultation here, with the tables presented here.

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.

Throughout the duration of this project, the following policy questions will be addressed:

1. 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?
2. 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)?
3. 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?
4. How does exposure to FRs differ between adults and children, males and females?
5. How does exposure differ by geographic area within Europe? Do countries/regions have different FR exposure levels?
6. Are there one or more occupationally exposed sub-groups? What occupations are associated with high exposure to FRs?
7. Is elevated exposure to FRs associated with particular consumption patterns or lifestyles?
8. What are the relevant exposure pathways for FRs, e.g., diet, air, water, indoor environmental exposure?
9. Do certain flame retardants co-occur in HBM matrices?
10. 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?
11. Can exposure to FRs be linked with any adverse health effects?
12. What are the population groups most at risk?
13. As FR market shifts towards replacement/alternative FRs, does human exposure reflect that trend? E.g., DBDPE as replacement for BDE-209;
14. 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?
15. Can reference values be established for any FRs?

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.

Please click here to submit your comments.

Please click here to access the Substance Report.

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