DRAFT
R013_0502_hh
UPDATE OF THE RISK ASSESSMENT ADDENDUM
OF
BIS(PENTABROMOPHENYL) ETHER
(DECABROMODIPHENYL ETHER)
CAS Number: 1163-19-5
EINECS Number: 214-604-9
Human Health Draft
23rd of February 2005
CONTENTS
CONTENTS
0 OVERALL RESULTS OF THE RISK ASSESSMENT......
4.HUMAN HEALTH
4.1.1.2 Occupational exposure
4.1.1.3 Consumer exposure
4.1.1.4 Humans exposed via the environment
4.1.1.4.1Discussions on the model
4.1.1.4.2Exposure routes to DBDPE
4.1.1.5Exposure to infants via milk
4.1.1.5.1Exposure to infants via human breast milk
4.1.1.5.2 Exposure to infants via cows’ milk
4.1.1.6Combined exposure
4.1.2 Effects assessment: Hazard identification and dose (concentration)-response (effect) assessment:
4.1.2.1 Toxicokinetics, metabolism and distribution:
4.1.2.1.1Summary and discussion
4.1.2.9 Toxicity for reproduction
4.1.2.9.1 Developmental Neurotoxicity:
4.1.3Risk characterisation
4.1.3.2 Workers
4.1.3.2.1 and 4.1.3.2.2. Repeated dose toxicity and carcinogenesis
4.1.3.2.3 Developmental neurotoxicity
4.1.3.3 Consumers
4.1.3.4 Humans exposed via the environment
4.1.3.4.1Repeated dose toxicity / carcinogenicity
4.1.3.4.2Developmental neurotoxicity
4.1.3.4.3Infants exposed via milk
5. RESULTS
6. REFERENCES
7. OTHER PAPERS REVIEWED THAT DID NOT CONTAIN SIGNIFICANT NEW INFORMATION RELEVANT TO THE RISK ASSESSMENT
8.OTHER PAPERS NOT YET REVIEWED:
TABLES
Table 4.1.1.4A: Estimated total daily human intake for exposure of man via environmental routes for each scenario
Table 4.1.1.4B: Estimated daily human intake for exposure of man via environmental routes
Table4.1.1.4.2A: Estimated daily human intake for exposure of man via environmental routes for the generic production scenario (considering a maximum soil pore water concentration of 0.1 µg/L)
Fig4.1.2.1.1A: Fecal and biliary metabolites formed and identified by mass spectrometry
following dose of decabromodiphenyl ether in the rat (quoted in Hakk and Letcher, 2003).
Table 4.1.2.1.1.A: Summary of levels of decabromodiphenyl ether in human blood serum collected in a general population (WWF 2003 and 2004 and Sjödin et al., 2001b) and in Swedish workers (Jakobsson et al., 2003).
Table 4.1.2.1.1B Summary of levels of decabromodiphenyl ether in blood serum Swedish workers (Jakobsson et al., 2003)
Table 4.1.2.9A: Summary of effects seen on spontaneous behaviour in mice (Viberg et al., 2003)
Table 4.1.2.9B: Distribution of 14C-label in mice tissues (Viberg et al. 2003)
1
23/02/2005
DRAFT
R013_0502_hh
0 OVERALL RESULTS OF THE RISK ASSESSMENT
Cas N° :1163-19-5
EINECSN° :214-604-9
IUPAC name :Bis(pentabromodiphenyl)ether
Decabromodiphenyl ether
Human Health
Workers
Conclusion (i) :
There is a need for further information and /or testing.
A conclusion (i) applies to the human health part (section 4.1.2.10.5) because an appropriate NOAEL cannot be derived from the available neurotoxicity study. New data is consequently expected namely a developmental neurotoxicity study before this part of the risk characterisation can be filled.
Consumers
Conclusion (ii):
There is at present no need for further information and/or testing and for risk reduction measures beyond those which are being applied already.
This conclusion was reached in the risk assessment report because consumer exposure was considered negligible. However, consumers may be exposed to DBDPE released from consumer products (electronic equipment and fabrics). Exposure is not yet quantified in this report but will be considered when further information about the neurotoxic developmental effects become available.
Humans exposed via the environment
Conclusion (i) applies to the risk characterisation for human exposed via the environment.
-Although no risk has currently been identified, additional information are needed on current concentrations of decabromodiphenyl ether in humans due to the remaining uncertainties on DecaBDPE exposure. Consequently, a suitable bio-monitoring programme, including breast milk, and a trend analysis over a certain time period, are required.
-In order to complete the risk assessment for developmental neurotoxicity an appropriate NOAEL should be derived for this endpoint. A developmental neurotoxicity study is consequently expected.
4.HUMAN HEALTH
4.1.1.2Occupational exposure
Updated information
Sjödin et al. (2001a) analysed BDE-209 in personal air samples from a plant recycling electronic goods. The sampling train was comprised of a 25-mm, binder-free borosilicate glass fiber filter followed by two 15-mm polyurethane foam plugs to trap the particulate and the semivolatile fractions, respectively. The sampling rate was 3.0l/min, for a total volume of 1.5cubic metre. Filters and plugs were analysed separately, after two successive extractions with methylene chloride in an ultrasonic bath and other sample preparation steps. The analytical conditions by gas chromatography were splitless injections with oven temperature programming from 80°C (2minutes) to 300°C (at 10°C/min, then holding 6minutes at this temperature) on a DB-5 capillary column (30m x 0.25mm. i.d., 0,25µm film thickness). DBDPE was identified through its retention time compared with that of an authentic sample, together with in-line mass spectrometry. On 12 samples, the mean and range of BDE-209 were 36 and 12-70 ng/m3, respectively; in two samples taken near the shredder, the concentrations were 150 and 200 ng/m3. The concentrations measured in other working environments (corrected for the background in blank samples) were much lower, namely 0.22 (mean; n = 6) and <0.04-0.32 (range) ng/m3 for the highest ones (assembly of circuit boards; maximum value of around 0.09 ng/m3 in other locations, <0.04 ng/m3 outdoors).
In recent studies (Jakobsson et al., 2002 and 2003) conducted in Swedish workers, decabromodiphenyl ether was found in blood / blood serum concentration in the range of <0.7g/kg lipid up to 278g/kg lipid in rubber wire producers (see section 4.1.2.1.1).
4.1.1.3Consumer exposure
Updated information
Recent studies report decabromodiphenyl ether measurements in house dust:
- Santillo D et al., 2003 conducted a study about chemical contaminant in house dust, using samples of dust collected in 2002 from vacuum cleaners by 100 volunteer households in 10 regions across UK. In addition two dust samples from other countries were included for comparative purposes, namely 1 from Denmark and 1 from Finland. Quantitative analysis of brominated flame retardants was performed by GC-MS using ECNI by the Netherlands Institute for Fisheries Research. Limit of detection (dry weight basis) was 0.12-0.62 ppb (ng/g). Analysis of blank samples (background level of the laboratory) are not reported. Decabromodiphenyl ether was by far the most abundant PBDPE present in the UK samples. It was found in all samples at levels between 3,800 and 19,900 ppb with a mean of 9,820 ppb and a median of 7,100 ppb. Levels of decabromodiphenyl ether were much lower in non-UK samples (100 ppb in Finland and 260 ppb in Denmark). This difference deserves further investigation as they may well reflect existing regional differences within Europe regarding the extent of use of decabromodiphenyl ether.
- As a follow-up of its breast milk study, the Environmental Working Group (EWG) asked ten women in the U.S. to collect samples of dust from their vacuum cleaners. PBDPEs levels in the samples averaged 4,629 ppb, ranging from 614 to 16,366 ppb. DBDPO was the dominant congener found, with average level of 2,394 ppb and a concentration range from < 400 to 7,510 ppb. Analytical details are not available (Sharp R and Lunder S, 2004).
- To evaluate the potential for electronic equipment to be a source of exposure to brominated flame retardants, the Computer Take Back Campaign and Clean Production Action gathered 16 wipe samples of dust from surface of computer monitors in public facilities across the U.S, including University, State House, school, children museum. Deca-, Octa-, Nona-BDPE and tetrabromobisphenol A (TBBPA) were found in every sample. The highest levels were found for decabromodiphenyl ether with concentrations ranging 2.09 to213.00 pg/cm2 (McPherson A. et al, 2004).
Whether decabromodiphenyl ether migrates out of products and finds its way in dust or comes from the breakdown of the product matrix itself is not clear. However these studies show that inhalation of dust particles containing DBDPE should be considered as a potential pathway of consumer exposure. Particles that lay on the ground or on furniture may also be a source of dermal and oral exposure for children. The results could be used for exposure assessment by taking commonly accepted dust uptake data. This could be considered in a further update.
Hays et al., 2003 have specifically dealt with the exposure of infants and children to decabromodiphenyl ether, which was included in the U.S. EPA voluntary children's chemical evaluation program (VCCEP). A child-specific assessment of decabromodiphenyl ether was performed following the VCCEP guidance for a tier 1 exposure assessment (e.g., screening-level assessment using currently available data and conservative assumptions). Exposure pathways that were considered included general environmental exposures, breast milk exposures, inhalation of decabromodiphenyl ether particulates in air, and mouthing decabromodiphenyl ether -containing consumer products. For each exposure scenario, a mid-range estimate and an upper estimate of intake were calculated. The highest exposure was for the infant (manufacturer scenario) with 0.76 mg/kg/day and the lowest exposure estimated for the child’s exposure with 0.0012 mg/kg/day. Despite the uncertainties, results indicate that the aggregate exposures for children to decabromodiphenyl ether for each scenario evaluated were at least an order of magnitude (most being several orders of magnitude) below the National Academy of Sciences reference dose for decabromodiphenyl ether (4 mg/kg-day), whose evaluation relies on more recent and more appropriate data than that of the USEPA's Integrated Risk Information System (IRIS). The authors conclude that, using the available data, current levels of decabromodiphenyl ether in the U.S. are not likely to represent an adverse health risk for children[1].
In recent studies (see section 4.1.2.1.1), decabromodiphenyl ether was found in blood serum samples in human population in a biomonitoring study by WWF, 2003 at a median concentration of 83 g/kg. lipid and maximum concentration of 241 g/kg. Lipid. In a second survey (WWF, 2004), decabromodiphenyl ether was found at a median concentration of 53 g/kg. lipid and maximum concentration of 2,400 g/kg. lipidWhereas in blood serum samples collected from blood donors in the United States, decabromodiphenyl ether was found at a median concentration <0.96 g/kg lipid and in a range <0.96 – 33.6 g/kg lipid. However, the representativeness of the population studies compared with the general population is not assured and potential occupational exposure of the population studied is difficult to appreciate. Moreover, rather limited information is available on the sources of exposure.
4.1.1.4 Humans exposed via the environment
The exposure to man via environmental routes has been estimated using EUSES (see Appendix B). The results are reported in Table 4.1.1.4A and Table 4.1.1.4B. Calculations of the daily doses have been performed using the following values for absorption: 2% for dermal route, 26% for the oral route (except for the scenario exposure to infants via human breast milk where a value of 100% has been used considering that all decaBDPE in breast milk is in a bioavailable form) and 100% for the inhalation route.
Table 4.1.1.4A: Estimated total daily human intake for exposure of man via environmental routes for each scenario
Scenario / Estimated total daily dose (mg/kg bw/day)Local Production(generic)a / 2.2x10-1
Local – Production (site specific)a b / 2.0x10-3
Local – Polymer and rubber processing / 2.6104
Local – Textiles (formulation of back coatings) / 1.0x10-3
Local – Textiles (application of back coatings) / 1.0x10-3
Local – Textiles (combined compounding and application site) / 2.0x10-3
Local – Polymers recycling of electronic equipment – particulate loss / 4.5105
Regional / 5.2105
Note:a) Production no longer occurs in the EU.
b) At the production site, no application of sewage sludge to agricultural soil occurred.
Table 4.1.1.4B: Estimated daily human intake for exposure of man via environmental routes
Scenario / Route / Predicted concentration / Estimated daily dose (mg/kg bw/day)Local Production(generic)a / Wet fish / 6.8103 mg/kg / 1.1105
Root tissue of plants / 3.9x101 mg/kg / 2.1x10-1
Leaves of plants / 1.2103 mg/kg / 2.1105
Drinking water / 3.0103 mg/L / 8.6105
Meat / 7.5x10-1 mg/kg / 3.2103
Milk / 2.4x10-1 mg/kg / 1.9103
Air / 1.710-6 mg/m3 / 1.9106
Total local daily dose / 0.22
Local / Wet fish / 3.8x10-5 mg/kg / 6.2x10-8
Polymer and rubber processing / Root tissue of plants / 2.0x10-2 mg/kg / 1.1x10-4
Leaves of plants / 3.7x10-3 mg/kg / 6.3x10-5
Drinking water / 2.4x10-6 mg/L / 6.8x10-8
Meat / 1.2x10-2 mg/kg / 5.2x10-5
Milk / 3.8x10-3 mg/kg / 3.1x10-5
Air / 5.9x10-6 mg/m3 / 6.4x10-6
Total local daily dose / 2.6x10-4
Local – Textiles / Wet fish / 2.17104 mg/kg / 3.6107
(combined compounding and / Root tissue of plants / 3.6x10-1mg/kg / 2.0x10-3
application site) / Leaves of plants / 6. 6104 mg/kg / 1.1105
Drinking water / 2.8105 mg/L / 8.1107
Meat / 9.2x10-3 mg/kg / 3.9105
Milk / 2.9x10-3 mg/kg / 2.3105
Air / 1.110-6 mg/m3 / 2.2107
Total local daily dose / 2.0x10-3
Local / Wet fish / 3.1x10-5 mg/kg / 5.1x10-8
Polymers recycling of electronic / Root tissue of plants / 5.0x10-3 mg/kg / 2.7x10-5
equipment – particulate loss / Leaves of plants / 3.9x10-4 mg/kg / 6.7x10-6
Drinking water / 1.9x10-6 mg/L / 5.6x10-8
Meat / 1.5x10-3 mg/kg / 6.3x10-6
Milk / 4.7x10-4 mg/kg / 3.7x10-6
Air / 6.2x10-7 mg/m3 / 6.8x10-7
Total local daily dose / 4.5x10-5
Regional / Wet fish / 3.1x10-5 mg/kg / 5.1x10-8
Root tissue of plants / 6.5x10-3 mg/kg / 3.6x10-5
Leaves of plants / 3.4x10-4 mg/kg / 5.8x10-6
Drinking water / 1.9x10-6 mg/L / 5.6x10-8
Meat / 1.4x10-3 mg/kg / 6.0x10-6
Milk / 4.4x10-4 mg/kg / 3.5x10-6
Air / 5.5x10-7 mg/m3 / 6.0x10-7
Total local daily dose / 5.2x10-5
Note:a) Production no longer occurs in the EU.
4.1.1.4.1Discussions on the model
There is considerable uncertainty inherent in the approach taken by EUSES (and the Technical Guidance Document) - E.C., 1996 and E.C., 2003.
First, in the indirect exposure assessed at the local scale, all food products are derived from the vicinity of one point source. In reality, people do not consume 100% of their food products from the immediate vicinity of a point source. Therefore, the local assessment represents a situation which does not exist in reality. Besides, for each food product, the highest country-averaged consumption rate from the Member States is used. Therefore, the total food basket is unrealistic.
Secondly, there is also a high uncertainty in estimating the concentrations of substances with high logKow values in various parts of the food chain. For instance, the concentrations in drinking water are high, frequently close to or above the water solubility of the substance, and are sometimes higher than the concentrations predicted/found in surface waters. The reason for this is that within EUSES the drinking water concentrations are related to the soil pore water concentrations. For poorly soluble substances like decabromodiphenyl ether, very high concentrations in soil are predicted due to application of sewage sludge containing the substance. This then leads to high values for the estimated soil pore water concentrations (and hence drinking water concentrations), which in turn leads to very high concentrations in plant roots, and hence other parts of the food chain e.g. leaves, meat and milk.
The partition coefficients for the various parts of the food chain depend crucially on the log Kow value of the substance (for decabromodiphenyl ether only a measured fish bioconcentration value was available, all other partition coefficients were estimated from log Kow), but it is not known if the assumptions/methods used in EUSES are valid for substances with very high log Kow values. This may be a particular problem for decabromodiphenyl ether since the available bioconcentration and uptake data indicate that the actual uptake by freshwater aquatic organisms is very much less than would be predicted from the log Kow value.
The predicted daily human intake figures for decabromodiphenyl ether are 220µg/kg bw/day for production, 0.26µg/kg bw/day for polymer and rubber processing, 2µg/kg for textiles (combined formulation/application), 0.04 µg/kg for polymers recycling of electronic equipment and 0.05µg/kg at the regional level. It should be reminded that production of DBDPE in the EU has now ceased. Therefore, calculations for the production site is only for information. The second highest intake (combined formulation and application in textiles), is still 100 fold lower than intake through exposure to the generic production site.
In all cases, uptake from root crops is predicted to account for the vast majority (≥90%) of the daily dose.
4.1.1.4.2Exposure routes to DBDPE
There could be a high uncertainty on the fate and behaviour of decabromodiphenyl ether through trophic chains. For example, the actual uptake by terrestrial and marine mammals could be significant but seems to occur if the organisms are exposed to decabromodiphenyl ether in a form that optimises uptake. Then, a possible metabolisation of decabromodiphenyl ether to form lower brominated diphenyl ether congeners is still not certain.
Exposure due to uptake of contaminated water
As mentioned above, there are considerable uncertainties in the predictions of the water concentrations, particularly regarding the soil pore water concentrations and whether decabromodiphenyl ether in soil pore water is actually taken up by plant roots.
If it is assumed that the maximum soil pore water concentration is 0.1 µg/L (i.e. the upper limit for the water solubility of decabromodiphenyl ether), then the resulting maximum concentration in plant roots can be estimated using the following equation:
whereCrootplant = concentration in root tissue
Kplantwater = partition coefficient between plant tissue and water = 9,050m3/m3 for a log Kow value of 6.27.
RHOplant = bulk density of plant tissue =700kg/m3
Cporewater = concentration in soil pore water
Using a soil pore water concentration of 0.1mg/m3 (i.e. 0.1µg/L), the resulting concentration in plant roots is 1.29mg/kg. This results in a daily human intake of 7µg/kg bw/day, assuming an adult body weight of 70kg and a daily consumption of 0.384kg of root crops. This figure is the maximum possible intake from this source as it is based on the soil pore water being saturated with decabromodiphenyl ether, and assuming that the uptake from water can be estimated based on the log Kow value.
Calculations using EUSES with the same release estimates as used for Table 4.1.1.4A, but where the soil pore water and drinking water concentrations are set to a maximum value of 0.1µg/L, indicate that the maximum total daily human dose from all sources is around 12µg/kg bw/day for production, 0.26µg/kg bw/day for polymer processing, 1.06µg/kg bw/day for textile (compounding), 1.06µg/kg bw/day for textile (application), 0.044µg/kg bw/day for recycling of electronic equipment, and 0.05µg/kg bw/day at a regional level. Again, the majority of the dose is predicted to come from root crops. Details of predicted concentrations and estimated daily doses for the generic production site are exposed in Table 4.1.1.4.2A (only the generic local production scenario has been recalculated as the calculations for the other scenarios remain the same):
Table4.1.1.4.2A: Estimated daily human intake for exposure of man via environmental routes for the generic production scenario (considering a maximum soil pore water concentration of 0.1 µg/L)
Scenario / Route / Predicted concentration / Estimated daily dose (mg/kg bw/day)Local Production(generic)a / Wet fish / 6.8103 mg/kg / 1.1105
Considering maximum soil pore / Root tissue of plants / 1.29 mg/kg / 7.1103
water concentration of 0.1 µg/l / Leaves of plants / 1.06103 mg/kg / 1.8105
Drinking water / 1.0103 mg/L / 2.9106
Meat / 0.74 mg/kg / 3.2103
Milk / 0.23 mg/kg / 1.9103
Air / 1.710-6 mg/m3 / 1.9106
Total local daily dose / 0.012
Some of the other estimated concentrations in food are also sensitive (indirectly) to the soil pore water concentration (i.e. the concentration in plant roots affects the estimated concentration in plant leaves and hence the concentration in meat and so the concentration in milk) but the interrelation between the various media is complex.