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Directorate-General for Health and Food Safety
Opinion on the results of the Human Risk Assessment of: Pentabromodiphenyl ether [CAS N° 32534-81-9] carried out in the framework of Council Regulation (EEC) 793/93 on the evaluation and control of the risks of existing substances - Opinion expressed at the 16th CSTEE plenary meeting, Brussels, 19th of June 2000.
Terms of reference
The CSTEE has been invited to examine the Risk Assessment Report for Pentabromodiphenyl ether and address the following issues:
1. Does the CSTEE agree with the conclusions of the Risk Assessment Report?
2. If the CSTEE disagrees with such conclusions, the CSTEE is invited to elaborate the reasons for this divergence of opinion.
The CSTEE has given an opinion (4 February 2000) on the environmental risk assessment and the present opinion is on the human risk assessment, which was obtained later.
Introduction
Polybrominated diphenyl ethers are used as an additive flame retardant mainly in polymers and textiles. There are three groups of products with an average of five, eight or ten bromine atoms in the molecules. The products containing compounds with an average of five bromine atoms are called pentabromodiphenyl ethers, even if there also are considerable amounts of tetrabromo- and hexabromodiphenyl ethers in these products. These substances have been widely found in environmental samples and a risk assessment was performed under Regulation 793/93. The human health part of that is ready [CSTEE/2000/11 – Add.1, Diphenyl ether, pentabromo derivative, Draft for written consultation, February 2000] and has been examined by the CSTEE which has the following main comments to make on the chapters indicted.
1. General substance information
The problem with the complexity of the product is well handled and efforts have been made to compare results for the product with the total results of the components. In most cases these results are in good agreement. The acronym used in the document, PeBDPE, is long and the more common PeBDE is easier to use. There is no reference to the numbering system for the congeners (the same as for the PCBs), which is often used. This would make the text easier to read.
2. General information on exposure
PeBDE is not produced within the EU (although in section 3.1.4.4 samples from downstream an PeBDE production plant in the UK are mentioned) and the import data supplied by industry indicate that <300 tonnes/year of the product is imported. The major problem is to estimate the amount imported in finished articles. The total amount of PeBDE present in articles is estimated to 1100 tonnes/year, which seems to be rather low.
The major use of PeBDE is in polyurethane foam and the assessment assumes this to be the only use. Some of the data on environmental concentrations indicate that there may also be, or at least have been, other uses, such as in the textile industry. Emissions from diffuse sources, including imported finished articles, may also be of greater importance than is obvious from the present report, although there are presently very few data on these emissions.
The possible formation of polybrominated dibenzo-p-dioxins and dibenzofurans is discussed thoroughly in Appendix 1 of the assessment. It is focussed on thermal reactions and the conclusion is that the major problems may occur in production and recycling of polymers containing PeBDE. In waste incineration it is expected that problems with polychlorinated dibenzo-p-dioxins and dibenzofurans are much more severe and that measures taken to decrease those compounds will also reduce the brominated counterparts. It is surprising that there is no reference to the WHO/IPCS Environmental Health Criteria 205 (Polybrominated Dibenzo-p-dioxins and Dibenzofurans) in the report. That document contains most of the information in Appendix 1 plus a lot more (including effects assessments).
4.1.1.1 Occupational exposure
No measured data are presented describing the occupational exposure. The inhalation exposure during manufacture and use of PeBDE is expected to be low due to the low vapour pressure of the product. In the manufacture of articles from polyurethane foam containing PeBDE, hot wires can be used to cut the material. The argument for low exposure in this process is that "polyurethane foam will only be effective as long as the fire retardant agent is present and thus migration during the handling of polyurethane foam is considered to be unlikely". This is probably not true as even if a substantial fraction of the flame retardant is lost there will be enough left in the material to act as flame retardant. It is thus essential that local exhaust ventilation is used to take care of the fumes from this process.
Dermal exposure has been estimated with the EASE model as a non-dispersive use with intermittent contact, and operators handling formulations are expected to be exposed to 0.1 to 1 mg/cm2/day. The corresponding prediction for operators handling polyurethane foam is 1 to 5 mg/cm2/day, but this is said to be an overestimation as "there will only be very low levels of PeBDE at the surface of the polyurethane foam". In the use section of the report it is claimed that concentrations of the flame retardant in the polymer is between 5 and 30%, and this can not correspond to very low levels at the surface.
4.1.1.3 Indirect exposure via the environment
As was mentioned in the CSTEE opinion on the environmental part of this risk assessment, the EUSES predictions of concentrations in root crops is probably to high. This is the major term in the indirect exposure and thus the real exposure may be much lower than the data given in the report. The final calculation of levels in man gives a reasonable agreement with measured data, but this is probably a result of too high intake and too short half-lives being used in the calculation.
4.1.2 Effects assessment
It is mentioned that all available toxicity studies have been conducted with the commercial mixture, but at least one CALUX assay, described in section 4.1.2.2.2, was using pure congeners. There are also today several other studies performed with pure substances.
4.1.2.1.1 Studies in animals
At least one study of absorption rates in fish have been published (Burreau et al, Environ. Toxicol. Chem. 1998, 17, 1065-72). There the absorption of BDE47 (92%), BDE99 (62%) and BDE153 (40%) in pike was investigated. These results are in agreement with the data used in the report based on data for similar haloaromatics.
Tissue disposition, metabolism and excretion of 14C-BDE99 have also been reported recently (Hakk et al, 1999, Organohalogen Compounds, 40, 337-40; Larsen et al, 1999, Organohalogen Compounds, 40, 371-4). Feces was the major route of elimination and a number of metabolites containing hydroxy or methoxy groups were found. Covalently bound 14C also indicated the formation of reactive metabolites.
4.1.2.6 Effects of repeated exposure
4.1.2.6.1. Studies in animals
There are well-known differences in thyroid physiology between rats and humans, so that perturbation of thyroid hormone homeostasis by chemical exposures in rats is not necessarily predictive for humans. However, recent studies on hydroxylated organohalogens indicate changes in thyroid hormone levels and neurobehavioral changes in both animals and humans (for a review, see Brouwer et al, Toxicology and Industrial Health, 1998, 14, 59-84).
4.1.2.6.2 Human data
The report refers to a case study of one individual who developed acneforms, which he claimed to be a consequence of watching TV and playing computer games. The levels given in the report are three orders of magnitude higher than in the original report.
4.1.3 Risk characterisation
4.1.3.2. Consumers
It is claimed in the report that there is no information from animals regarding the metabolism of PeBDE. Recently there have been several reports on this (e.g. Meerts et al, 1998, Organohalogen Compounds, 37, 309-12) and hydroxylated PeBDEs have also been found in wildlife (Asplund et al, 1997, Organohalogen Compounds, 33, 355-59) - see also above under 4.1.2.1.1 Studies in animals.
The report concludes that exposure to consumers from PeBDE-containing foams is negligible. The analyses of human breast milk, however, indicate a continuous increase of PeBDE over the period 1972 to 1997. This is in contrast to the environmental concentrations, which have levelled out or are decreasing over the last decade. This indicates another exposure pathway for humans, which may be exposure from consumer goods.
4.1.3.4 Combined exposure
The calculated combined exposure indicates that occupational exposure is much higher than the indirect exposure. It is not clear to CSTEE what the authors mean with the sentence "These estimates do not take account of bioaccumulation", or how the very exact figure for worker exposure was derived.
CSTEE Conclusions
The CSTEE generally agrees with the conclusions drawn in the report, but have the following comments:
- The research on brominated flame retardants is accelerating rapidly and lot of new information has been produced over the last few years. This information may not have changed the conclusions a lot, but could possibly have strengthened several of them.
- The indications of decreasing levels in the environment and increasing levels in the general population may be explained by a consumer exposure. Further information is therefore needed in this field. This information may also be important for other additives, including possible substitutes for PeBDE.
- If the consumer exposure is important, levels in man can continue to increase for a long time, even after a total ban of the product. Any measures taken therefore have to be monitored carefully.
- The potential problems with PeBDE exposure of breast-fed children should have been addressed, especially in the light of the developmental effects seen in rats.
- Further information is required regarding the potential of PeBDE for endocrine disruption and/or dioxin-like effects, as PeBDE shares some toxicity with the structural related compounds PCBs and dioxins (partial Ah-receptor agonist and antagonist activities in vitro, thyroid toxicity, immune effects). These studies should include receptor activity tests. Also, further studies are indicated regarding the potential effects on the immune system following neonatal dosing. Finally, further studies are indicated regarding the potential to interact with the thyroid hormone system.
----------------------------------------
1 Regulation 793/93 provides a systematic framework for the evaluation of the risks to human health and the environment of those substances if they are produced or imported into the Community in volumes above 10 tonnes per year. The methods for carrying out an in-depth Risk Assessment at Community level are laid down in Commission Regulation (EC) 1488/94 which is supported by a technical guidance document.
Terms of reference
The CSTEE has been invited to examine the Risk Assessment Report for Pentabromodiphenyl ether and address the following issues:
1. Does the CSTEE agree with the conclusions of the Risk Assessment Report?
2. If the CSTEE disagrees with such conclusions, the CSTEE is invited to elaborate the reasons for this divergence of opinion.
The CSTEE has given an opinion (4 February 2000) on the environmental risk assessment and the present opinion is on the human risk assessment, which was obtained later.
Introduction
Polybrominated diphenyl ethers are used as an additive flame retardant mainly in polymers and textiles. There are three groups of products with an average of five, eight or ten bromine atoms in the molecules. The products containing compounds with an average of five bromine atoms are called pentabromodiphenyl ethers, even if there also are considerable amounts of tetrabromo- and hexabromodiphenyl ethers in these products. These substances have been widely found in environmental samples and a risk assessment was performed under Regulation 793/93. The human health part of that is ready [CSTEE/2000/11 – Add.1, Diphenyl ether, pentabromo derivative, Draft for written consultation, February 2000] and has been examined by the CSTEE which has the following main comments to make on the chapters indicted.
1. General substance information
The problem with the complexity of the product is well handled and efforts have been made to compare results for the product with the total results of the components. In most cases these results are in good agreement. The acronym used in the document, PeBDPE, is long and the more common PeBDE is easier to use. There is no reference to the numbering system for the congeners (the same as for the PCBs), which is often used. This would make the text easier to read.
2. General information on exposure
PeBDE is not produced within the EU (although in section 3.1.4.4 samples from downstream an PeBDE production plant in the UK are mentioned) and the import data supplied by industry indicate that <300 tonnes/year of the product is imported. The major problem is to estimate the amount imported in finished articles. The total amount of PeBDE present in articles is estimated to 1100 tonnes/year, which seems to be rather low.
The major use of PeBDE is in polyurethane foam and the assessment assumes this to be the only use. Some of the data on environmental concentrations indicate that there may also be, or at least have been, other uses, such as in the textile industry. Emissions from diffuse sources, including imported finished articles, may also be of greater importance than is obvious from the present report, although there are presently very few data on these emissions.
The possible formation of polybrominated dibenzo-p-dioxins and dibenzofurans is discussed thoroughly in Appendix 1 of the assessment. It is focussed on thermal reactions and the conclusion is that the major problems may occur in production and recycling of polymers containing PeBDE. In waste incineration it is expected that problems with polychlorinated dibenzo-p-dioxins and dibenzofurans are much more severe and that measures taken to decrease those compounds will also reduce the brominated counterparts. It is surprising that there is no reference to the WHO/IPCS Environmental Health Criteria 205 (Polybrominated Dibenzo-p-dioxins and Dibenzofurans) in the report. That document contains most of the information in Appendix 1 plus a lot more (including effects assessments).
4.1.1.1 Occupational exposure
No measured data are presented describing the occupational exposure. The inhalation exposure during manufacture and use of PeBDE is expected to be low due to the low vapour pressure of the product. In the manufacture of articles from polyurethane foam containing PeBDE, hot wires can be used to cut the material. The argument for low exposure in this process is that "polyurethane foam will only be effective as long as the fire retardant agent is present and thus migration during the handling of polyurethane foam is considered to be unlikely". This is probably not true as even if a substantial fraction of the flame retardant is lost there will be enough left in the material to act as flame retardant. It is thus essential that local exhaust ventilation is used to take care of the fumes from this process.
Dermal exposure has been estimated with the EASE model as a non-dispersive use with intermittent contact, and operators handling formulations are expected to be exposed to 0.1 to 1 mg/cm2/day. The corresponding prediction for operators handling polyurethane foam is 1 to 5 mg/cm2/day, but this is said to be an overestimation as "there will only be very low levels of PeBDE at the surface of the polyurethane foam". In the use section of the report it is claimed that concentrations of the flame retardant in the polymer is between 5 and 30%, and this can not correspond to very low levels at the surface.
4.1.1.3 Indirect exposure via the environment
As was mentioned in the CSTEE opinion on the environmental part of this risk assessment, the EUSES predictions of concentrations in root crops is probably to high. This is the major term in the indirect exposure and thus the real exposure may be much lower than the data given in the report. The final calculation of levels in man gives a reasonable agreement with measured data, but this is probably a result of too high intake and too short half-lives being used in the calculation.
4.1.2 Effects assessment
It is mentioned that all available toxicity studies have been conducted with the commercial mixture, but at least one CALUX assay, described in section 4.1.2.2.2, was using pure congeners. There are also today several other studies performed with pure substances.
4.1.2.1.1 Studies in animals
At least one study of absorption rates in fish have been published (Burreau et al, Environ. Toxicol. Chem. 1998, 17, 1065-72). There the absorption of BDE47 (92%), BDE99 (62%) and BDE153 (40%) in pike was investigated. These results are in agreement with the data used in the report based on data for similar haloaromatics.
Tissue disposition, metabolism and excretion of 14C-BDE99 have also been reported recently (Hakk et al, 1999, Organohalogen Compounds, 40, 337-40; Larsen et al, 1999, Organohalogen Compounds, 40, 371-4). Feces was the major route of elimination and a number of metabolites containing hydroxy or methoxy groups were found. Covalently bound 14C also indicated the formation of reactive metabolites.
4.1.2.6 Effects of repeated exposure
4.1.2.6.1. Studies in animals
There are well-known differences in thyroid physiology between rats and humans, so that perturbation of thyroid hormone homeostasis by chemical exposures in rats is not necessarily predictive for humans. However, recent studies on hydroxylated organohalogens indicate changes in thyroid hormone levels and neurobehavioral changes in both animals and humans (for a review, see Brouwer et al, Toxicology and Industrial Health, 1998, 14, 59-84).
4.1.2.6.2 Human data
The report refers to a case study of one individual who developed acneforms, which he claimed to be a consequence of watching TV and playing computer games. The levels given in the report are three orders of magnitude higher than in the original report.
4.1.3 Risk characterisation
4.1.3.2. Consumers
It is claimed in the report that there is no information from animals regarding the metabolism of PeBDE. Recently there have been several reports on this (e.g. Meerts et al, 1998, Organohalogen Compounds, 37, 309-12) and hydroxylated PeBDEs have also been found in wildlife (Asplund et al, 1997, Organohalogen Compounds, 33, 355-59) - see also above under 4.1.2.1.1 Studies in animals.
The report concludes that exposure to consumers from PeBDE-containing foams is negligible. The analyses of human breast milk, however, indicate a continuous increase of PeBDE over the period 1972 to 1997. This is in contrast to the environmental concentrations, which have levelled out or are decreasing over the last decade. This indicates another exposure pathway for humans, which may be exposure from consumer goods.
4.1.3.4 Combined exposure
The calculated combined exposure indicates that occupational exposure is much higher than the indirect exposure. It is not clear to CSTEE what the authors mean with the sentence "These estimates do not take account of bioaccumulation", or how the very exact figure for worker exposure was derived.
CSTEE Conclusions
The CSTEE generally agrees with the conclusions drawn in the report, but have the following comments:
- The research on brominated flame retardants is accelerating rapidly and lot of new information has been produced over the last few years. This information may not have changed the conclusions a lot, but could possibly have strengthened several of them.
- The indications of decreasing levels in the environment and increasing levels in the general population may be explained by a consumer exposure. Further information is therefore needed in this field. This information may also be important for other additives, including possible substitutes for PeBDE.
- If the consumer exposure is important, levels in man can continue to increase for a long time, even after a total ban of the product. Any measures taken therefore have to be monitored carefully.
- The potential problems with PeBDE exposure of breast-fed children should have been addressed, especially in the light of the developmental effects seen in rats.
- Further information is required regarding the potential of PeBDE for endocrine disruption and/or dioxin-like effects, as PeBDE shares some toxicity with the structural related compounds PCBs and dioxins (partial Ah-receptor agonist and antagonist activities in vitro, thyroid toxicity, immune effects). These studies should include receptor activity tests. Also, further studies are indicated regarding the potential effects on the immune system following neonatal dosing. Finally, further studies are indicated regarding the potential to interact with the thyroid hormone system.
----------------------------------------
1 Regulation 793/93 provides a systematic framework for the evaluation of the risks to human health and the environment of those substances if they are produced or imported into the Community in volumes above 10 tonnes per year. The methods for carrying out an in-depth Risk Assessment at Community level are laid down in Commission Regulation (EC) 1488/94 which is supported by a technical guidance document.
