Brominated Flame Retardants: Toxicity and Ecotoxicity

Contents

Preface

English summary

Sammendrag

1. Method

2. Results

3. Conclusions

Literature

A. Annex 1
B. Annex 2
C. Annex 3

Foreword

The Danish EPA has prepared a list of substances that are undesirable in products due to their effects on man and/or the environment, in production, use and/or final disposal. Brominated flame retardants (BFR) are on this list of undesired substances. Increasing amounts of some of these substances have been detected in the marine environment (Norén, K. and Meironyté, D., 1998), and within the last few years they have been found in human breast milk and fat tissue in Sweden (Darnerud, P. O., Atuma, S., Aune, M., and Cnattingius, S., 1998, Lindström, G., Hardell, L., van Bavel, B., Wingfors, H., Sundelin, E., Liljegren, G., and Lindholm, P., 1998).

The BFR included in OECD's Risk Reduction Programme are the polybrominated biphenyls (PBB) and the polybrominated diphenyl ethers (PBDE). A voluntary agreement has been made in the OECD between the producers to reduce the risks of the substances PBDE and PBB. Tris(2,3-dibrompropyl)phosphate and PBB are prohibited in the European Union in textiles intended for skin contact ("Miljø- og Energiministeriets bekendtgørelse nr. 1042 af 17. december 1997 om begrænsning af salg og anvendelse af visse farlige stoffer og produkter til specielt angivne formål. §16"). Many of the BFR have not yet been classified or restricted. The commercial PBDE products, penta-, octa- and decabromodiphenyl ether, as well as hexabromocyclododecane are undergoing risk assessment in the EU.

In Denmark, a project was started for substance flow analysis of the most frequently used BFR, including those imported in manufactured goods. Consumption, use and possibilities of substitution have been investigated.

The objective of this project is to outline the existing knowledge about the environmental and health hazards of the BFR that are relevant for Denmark, based on the preliminary result of the substance flow analysis project. The method is a data screening, which naturally does not allow full identification and thorough evaluation of all existing relevant data.

English Summary

A toxicological and ecotoxicological data screening was made on BFR used in Denmark. The data screening in relevant sources was performed in ultimo 1998. Although a thorough data search was made this is not a garantie that all relevant information was identified and retrieved, e.g. relevant unpublished data may exist, and information may have been published since 1998.

Data on 12 out of 19 initially selected BFR were retrieved from generally well recognised handbooks and reviews as well as from documents/publications and data found via well known on-line and off-line databases. The amount and quality of retrieved data was variable.

With the exception of vinyl bromide and 2,2-Bis(bromomethyl)propan-1,3-diol (DBNPG), most of the BFR have a high n-octanol-water partition coefficient, which indicates potential accumulation in living organisms. The high molecular weight of some of these BFR may preclude their bioaccumulation in living organisms as indicated by the low bioconcentration factors (BCF) determined for decabromobiphenyl (DeBB) and octabromodiphenyl ether (OBDE). However, a very high BCF of 18,100 was measured for hexabromocyclododecane, which has a molecular weight of 642. This indicates that the bioconcentration of high-molecular-weight substances is not fully understood and, hence, the data on these chemicals should be carefully evaluated.

Both vinyl bromide and DBNPG are suspected to be carcinogenic. Other data indicate that commercial products of decabromobiphenyl (DeBB) and brominated styrene homopolymer may also have a carcinogenic potential. Two of the compounds, 2,4,6-tribromophenol and octabromodiphenylether (OBDE), represent a possible risk of harm to the human foetus. OBDE has an effect on the liver, which is considered the primary target organ. Hexabromocyclododecane (HBCD) and pentabromodiphenylether (PeBDE) have an effect on the liver and thyroid gland. It is not known if it is a specific endocrine effect on the thyroid gland, and if the effect observed in rodents is relevant for human beings. Future research may come closer to the answer. Of all the BFR screened, only the PBDE has been found in humans. Congeners of the commercial PeBDE product were detected in adipose tissue, blood and breast milk. An OBDE congener has been identified in human adipose tissue and blood serum. DeBDE was detected and quantified in blood serum from 3 categories of workers. The general lack of data of the occurrence of BFR in human tissues and liquids may be because of missing investigations and/or inadequate analyses.

The substances HBCD, 2,4,6-tribromophenol, and tetrabromobisphenol A (TBBPA) are toxic to aquatic organisms and may cause long-term adverse effects in the aquatic environment. Pentabromotoluene, OBDE, PeBDE, and DeBDE are considered not readily biodegradable. Brominated styrene, vinyl bromide, DBNPG and DeBB were not assessed due to scarcity of data.

Some of the frequently used brominated flame retardants, TBBPA, HBCD and PBDEs, are present in sediment, mussels and fish. PBDEs have been found in whales and seals. Some of the PBB and the PBDE are highly hydrophobic and resistant to degradation processes. It is therefore possible that these chemicals may accumulate in aquatic sediments or bioconcentrate in living organisms. Signs of toxicity of individual PBB and PBDE to early life stages in rainbow trout were reported. The presence of some of the PBBs and PBDEs in mussels, fish, seals and dolphins as well as in sperm whales, which normally stay and feed in deep ocean water, combined with the ongoing industrial production of these compounds indicate that an environmental problem is rising.

Because of their environmental properties the continued release of HBCD, TBBPA, 2,4,6-tribromophenol, 5BT, OBDE, PeBDE and DeBDE may represent an increasing risk to aquatic organisms.

Sammendrag

En toksikologisk og økotoksikologisk datasøgning blev foretaget på nogle udvalgte bromerede flammehæmmere (BFR), som forekommer i Danmark. Der blev fundet data på 12 ud af de 19 først udvalgte BFR i anerkendte håndbøger og oversigtsværker samt i en række publikationer fundet via søgning i en række velkendte on-line og off-line databaser. Mængden og kvaliteten af de fundne data er meget svingende for de udvalgte bromerede flammehæmmere.

Det er svært at konkludere noget generelt om de bromerede flammehæmmeres skadelighed for sundheden. Med undtagelse af vinylbromid og 2,2-Bis(brommethyl)propan-1,3-diol (DBNPG)), så har de fleste bromerede flammehæmmere en høj n-octanol-vand fordelingskoefficient, som indikerer en potentiel akkumulering i levende organismer. Den høje molekylevægt af nogle af disse BFR kan forhindre bioakkumulering i levende organismer, som det antydes af de lave biokoncentreringsfaktorer (BCF), der er blevet bestemt for decabrombiphenyl (DeBB) and octabromdiphenyl ether (OBDE). Der er dog målt en meget høj BCF på 18.100 for hexabromcyclododecan, der har en molekylevægt på 642. Dette indikerer, at biokoncentrering af stoffer med høj molekylevægt ikke er fuldstændigt belyst, og derfor bør data om disse stoffer vurderes omhyggeligt. Både vinylbromid og DBNPG er mistænkt for at være kræftfremkaldende, og der er også data, som tyder på, at handelsprodukter af decabrombiphenyl (DeBB) og bromeret styren homopolymer kan have et kræftfremkaldende potentiale. To af stofferne, 2,4,6-tribromphenol og octabromdiphenylether (OBDE), er mistænkt for at være fosterskadende. OBDE har en effekt på leveren, som anses for at være målorganet. Hexabromcyclododecan (HBCD) og pentabromdiphenylether (PeBDE) har en effekt på lever og skjoldbruskkirtlen. Hvorvidt det drejer sig om en specifik endokrin effekt på skjoldbruskkirtlen, og om effekten, som er set hos gnavere, også har relevans for mennesker, må fremtidige undersøgelser vise. Af de undersøgte stoffer er det kun PBDE, som er fundet i mennesker. PeBDE er fundet i fedtvæv, blod og mælk, OBDE er fundet I fedtvæv og blod og DeBDE er fundet hos arbejdere på tre forskellige arbejdspladser. De sparsomme/manglende humane data kan skyldes manglende undersøgelser og/eller utilstrækkelige analyser.

Stofferne HBCD, 2,4,6-tribromphenolog tetrabrombisphenol A er giftige over for akvatiske organismer og kan forårsage uønskede langtidsvirkninger i vandmiljøet. Pentabromtoluen (5BT), OBDE, PeBDE og DeBDE betragtes som ikke let bionedbrydelige. Bromeret styren, vinylbromid, DBNPG og DeBB kunne ikke klassificeres på det foreliggende datamateriale.

De mest udbredte bromerede flammehæmmere (TBBPA, HBCD, PBB og PBDE) forekommer i sediment, muslinger og fisk. PBB og PBDE er desuden genfundet i delfiner, kaskelothvaler og sæler. Nogle PBB og PBDE er hydrofobe samt svært nedbrydelige. Det er derfor muligt, at disse stoffer kan akkumuleres i akvatiske sedimenter eller biokontreres i levende organismer. Tegn på toksisk virkning overfor tidlige livsstadier i regnbueørreder blev observeret fra enkelte PBB og PBDE. Tilstedeværelsen af PBB og PBDE i muslinger, fisk, sæler og delfiner så vel som i kaskelothvaler, der normalt fouragerer og opholder sig i oceanernes dybhav , kombineret med den igangværende industrielle produktion af disse stoffer indikerer at et muligt miljøproblem kan være stigende.

HBCD, TBBPA, 2,4,6-tribromophenol, 5BT, OBDE, PeBDE og DeBDE vil på baggrund af deres miljømæssige egenskaber kunne udgøre en stigende risiko for akvatiske organismer.

1. Method

The preliminary result of the substance flow analysis project indicates that the substances in table 1 are used in Denmark, as pure substances or in manufactured goods. A health and environmental assessment was made, if possible, on these substances after the method outlined below.

Table 1. Chemical substances selected

Data were retrieved primarily from well recognised handbooks and reviews of toxicological and ecotoxicological relevance. Furthermore, a data search was made in the draft EU risk assessments and in relevant bibliographic databases. In appendix 3 of this re-port is a list of used standard sources. This list is part of CETOX's standard operating procedure for data screening of chemical sub-stances and is a further development of the strategy described by the Danish EPA in 1993 "Retningslinier for datasøgning og udarbejdelse af klassifikationsskemaer undtagen miljøfarlige egen-skaber" (Miljøstyrelsen 1993).

Based on the data screening the substances were divided into three groups: 

1. Substances with some data
2. Substances with few data
3. Substances with (nearly) no data

It is known from experience that it is often difficult to find relevant data on chemical substances, when there is almost no information in the standard sources. Therefore and because of limited resources, it was decided not go further with those substances in this project.

A more thorough data search was made on each of the substances in groups 1 and 2 in the following databases: Toxline, HSDB, RTECS, IRIS and CCRIS. A more focused data search was per-formed in the databases Medline (from 1990), Embase (from 1990), Biosis (from 1993) and Toxline with respect to endocrinological and immunotoxic effects, effects on human beings and contents of the substances in body fluids. Further a focused data search was performed in the database Current Contents (from 1994-1998) for data with ecotoxicological relevance.

On few occasions, and when no data were available, structure ac-tivity relation analyses was used in the environmental assessment. In these cases, the similar chlorinated compound was used on a "worst case" basis. Especially the potential bioaccumulation of BFR is difficult to assess as the broadly accepted use of the octanol-water partition coefficient may lead to an overestimation of the bioaccumulation because the potential of a substance to bio-concentrate decreases above certain molecular dimensions. It has been proposed that chemicals with a molecular weight above 700 should not be considered potentially bioaccumulative (European Commission, 1996). However, this cut-off value has been subject to criticism and an alternative cut off value of 1000 has been proposed (SCTEE, 1999).

Based on the data retrieved, a short toxicological and ecotoxicological profile was made on each substance. Each profile was closed by a conclusion on the amount and quality of data retrieved and on the possible hazards of the substance.

2. Results

Twelve substances (two were isomers) were selected for further evaluation (table 2). The health and environmental assessment is presented in appendix 2. The substances not assessed in this project because of missing data in the preliminary data screening are listed in table 3. The main conclusions on all evaluated compounds are presented in table 4.

Many of the data and conclusions of some of the BFR were found in well recognised international evaluations/reviews, e.g. WHO's International Programme on Chemical Safety and International Agency for Research on Cancer. It was not possible to locate good national or international assessments on all selected BFR, and many data were found in old and not easily accessible documents. The validity of these tests varies and is often not possible to evaluate. A thorough evaluation of each study was not possible within the limits of this project.

The chemical composition of commercial PBDE products varies with respect to purity and composition of isomers and impurities (see Appendix 2 and Table 5). The documentation of the selected PBDE (PeBDE, OBDE and DeBDE) is seldom based on "pure" substances, and the purity of the individual PBDE is often lower in old products compared to new commercial products. Based on the typical composition of commercial PeBDE, OBDE and DeBDE products, it appears difficult to extrapolate toxic effects from one PBDE to another.

Table 2. Chemical substances subjected to health and environmental assessment

Table 3. Chemical substances with no or only very few data in the preliminary data screening

Table 4. The main conclusions from the health and environmental assessment

Table 5. Typical chemical composition of selected PBDE (%)

Abbreviations see Appendix 1.

3. Conclusion

The amount and quality of data on the selected BFR varied considerably.

It is difficult to make a general conclusion on the health effects of BFR. With the exception of vinyl bromide and 2,2-Bis(bromomethyl)propane-1,3-diol (DBNPG), most of the BFR have a high n-octanol-water partition coefficient, which indicates potential accumulation in living organisms.

Both vinyl bromide and DBNPG are suspected to be carcinogenic and other data indicate that commercial products of decabromobiphenyl (DeBB) and brominated styrene homopolymer may also have a carcinogenic potential.

Two of the compounds, 2,4,6-tribromophenol and octabromodiphenylether (OBDE), represent a possible risk of harm to the human foetus. Hexabromocyclododecane (HBCD) and pentabromodiphenylether (PeBDE) have an effect on the liver and thyroid gland. It is not known if it is a specific endocrine effect on the thyroid gland, and if the effect observed in rodents is relevant for human beings. Future research may come closer to the answer.

Of all the BFR screened, only the PBDE has been found in humans. PeBDE was detected in adipose tissue, blood and breast milk of human beings. OBDE has been identified in human adipose tissue (up to 8 mg/kg fat) and blood serum (not quantified). DeBDE was detected and quantified in blood serum from all of 3 categories of workers: Hospital cleaners, clerks working full-time at computer screens and personnel at an electronics dismantling plant. The highest blood serum concentrations were in workers at the electronics dismantling plant (median 4.8 mg/kg fat). The serum conc. decreased during summer vacation in the electronics dismantling workers, and results indicated a shorter half-life with increasing degree of bromination. The exposure to PBDE may occur via contaminated food as well as via inhalation of airborne particulate matter.

The substances 2,4,6-tribromophenol, HBCD and tetrabromobisphenol A (TBBPA) were considered to be toxic to aquatic organisms and they may cause long-term adverse effects in the aquatic environment. The substances pentabromotoluene (5BT), OBDE, PeBDE and DeBDE are not readily biodegradable in screening tests. Brominated styrene, vinyl bromide, DBNPG and DeBB were not assessed due to scarcity of data.

Some of the brominated flame retardants included in this investigation are potentially toxic to aquatic organisms and may cause long-term adverse effects in the aquatic environment. The brominated flame retardants, most frequently used (TBBPA, HBCD, PBB and PBDE) are present in sediment, mussels and fish. PBB and PBDE are further present in dolphins, sperm whales and seals. Similar to the polychlorinated biphenyls (PCB) and polychlorinated diphenyl ethers (PCDE) some of the PBB and the PBDE are highly hydrophobic and resistant to degradation processes (de Boer, J., Wester, P. G., Klamer, H. J., Lewis, W. E., and Boon, J. P., 1998). It is therefore possible that these chemicals may accumulate in aquatic sediments or bioconcentrate in living organisms. Signs of toxicity of individual PBB and PBDE to early life stages in rainbow trout were reported (Hornung, M. W., Zabel, E. W., and Peterson, R. E., 1996). Both PBB and PBDEs are slowly degraded in the environment (Pijnenburg, A. M., Everts, J. W., de Boer, J., and Boon, J. P., 1995). The presence of PBBs and PBDEs in mussels, fish, seals and dolphins as well as in sperm whales, which normally stay and feed in deep ocean water, combined with the ongoing industrial production of these compounds indicate that an environmental problem is rising (de Boer, J., Wester, P. G., Klamer, H. J., Lewis, W. E., and Boon, J. P., 1998).

The scientific basis for a risk evaluation of the BFR, included in this investigation, in the aquatic environment is very small and more knowledge is required to improve this. Because of their environmental properties the continued release of HBCD, TBBPA, 2,4,6-tribromophenol, 5BT, OBDE, PeBDE and DeBDE may represent an increasing risk to aquatic organisms.

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Appendix 1 - Abbreviations

Chemical substances:

Other abbreviations:

Appendix 2 - Data sheets

Appendix 3 - Standard References

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