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Total Consumer Exposure to Polybrominated Diphenyl Ethers in North America and Europe David Trudel, Martin Scheringer,* Natalie von Goetz, and Konrad Hungerb€uhler Institute for Chemical and Bioengineering, ETH Zurich, Zurich, Switzerland
bS Supporting Information ABSTRACT: Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants in textiles, polyurethane foams, and plastics. PBDEs exert toxic effects in various organisms, including humans, and are ubiquitous in the outdoor and indoor environment. Here we estimate total daily PBDE doses received by consumers in North America and Europe, along with the most important pathways and congeners, and derive PBDE elimination half-lives for chronic exposure. We estimate distributions for all parameters (PBDE concentrations in exposure media, food consumption rates, etc.) and conduct a probabilistic exposure assessment. We find that Americans are exposed the most, likely due to stricter fire regulations, followed by consumers from the UK and Continental Europe. In the central quantiles of the exposure distributions derived, food is the dominant pathway; in the upper quantiles either food or oral and dermal exposure to dust. This reflects the lipophilic and persistent nature of PBDEs and their use in products for indoor-use. Median elimination half-lives are in a range of 1-3 years except for BDE-153 with about seven years and BDE-209 with 4-7 days.
’ INTRODUCTION Polybrominated diphenyl ethers (PBDEs) are flame retardants used to prevent inflammation of textiles, foams, and plastics used in airplanes, automobiles, computer screens, mattresses, and numerous other products.1 Three technical mixtures (pentaBDE, octaBDE, and decaBDE) have been used in large amounts (more than 50kt in 20012) in the last decades. Because of neurobehavioral toxicity and endocrine disrupting effects of pentaBDE, and fetal toxicity and teratogenicity of octaBDE,3 these mixtures have been banned throughout Europe and voluntarily phased out in North America.4 In 2009 penta- and octaBDE were included in the Stockholm Convention on Persistent Organic Pollutants.5 DecaBDE is still in use without restrictions in most states of the US and in Canada6 but will be phased out until the end of 2013.7 DecaBDE is no longer used in Europe for electronics and electrical applications and Norway has completely banned the production and use of decaBDE.6 It has been argued that decaBDE is less toxic than the penta- and octaBDE mixtures;3 however, the scientific discussion about toxic effects of decaBDE is still ongoing.8 Moreover, recent studies have shown that decaBDE might degrade to lowerbrominated congeners in the environment,9 in rats,10 and in humans,11 which implies a higher risk potential for decaBDE than previously assumed. Due to the toxic effects of PBDEs and their widespread use in consumer products, a detailed assessment of the exposure of the r 2011 American Chemical Society
general population to PBDEs is essential for risk assessment. Consumer exposure to PBDEs depends on the legal framework regarding fire prevention, on food consumption patterns, and on consumer behavior in general. Because of stricter fire prevention measures in the US, more consumer products contain PBDEs, which might result in higher exposure to PBDEs in the US than in other countries.12 Although several studies have been published on consumer exposure to PBDEs in the US13,14 and Europe,15 to our knowledge none of them have performed an exposure assessment of PBDE uptake in North America and Europe by applying a consistent methodology to both regions, which is essential for comparison. Here we present a probabilistic total human exposure assessment of PBDEs for seven consumer groups in North America and four regions in Europe. The consistent methodology used makes it possible to identify the boundary conditions (legal framework, consumption patterns, etc.) as well as pathways and congeners that are most important for exposure to PBDEs for each of the consumer groups in each region. In the present work, we have defined two main objectives. First, for all major pathways and congeners we estimate the uptake of PBDEs in the human Received: October 18, 2010 Accepted: January 21, 2011 Revised: January 20, 2011 Published: February 24, 2011 2391
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Environmental Science & Technology body based on measured concentrations in the relevant exposure media combined with substance properties, anthropometric and behavioral parameters and other relevant exposure factors such as dust loading on skin or uptake fractions in the gut. Second, using our calculated doses in combination with PBDE biomonitoring data from the literature and a one-compartment pharmacokinetic model, we propose a new set of human elimination halflives for all investigated PBDE congeners.
’ MATERIALS AND METHODS Exposure Model. We included eight different exposure pathways in our assessment (oral uptake of food, dust, soil, and organic films; inhalation of air; and dermal uptake of dust, soil, and organic films). On the basis of these pathways, total doses were calculated separately for five regions, seven consumer groups, and eight congeners. The model equations used for the different pathways are given in the Supporting Information (SI) in Section 1, and all input parameters with their distributions and references are listed in Table S4. Regions. To consider different legal frameworks and behavior patterns, the US and Canada and four regions of Europe were investigated. The US and Canada were treated as one region (North America, NA), because not enough data were available to treat them separately. Europe was divided into four different regions: the United Kingdom and Ireland (UK), Northern Europe (NE), Central Europe (CE), and Southern Europe (SE). NE consists of the Scandinavian and Baltic countries, CE of countries and regions such as The Netherlands, Belgium, Germany, Switzerland, Northern France, and Austria, and SE of countries and regions such as Portugal, Spain, Italy, Southern France, and Greece. Consumer Groups and PBDE Congeners. To reflect different behavior patterns and anthropometric characteristics (such as body weight), seven different consumer groups were defined. These are infants (below 1 year), toddlers (1-5 years), children (5-12 years), female and male teenagers (12-20 years), and female and male adults (20-65 years). All doses presented here are given on a congener basis. We focus on the most abundant eight congeners, which are BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, and BDE-209. Pathways. We calculated the total consumer exposure to PBDEs by modeling all pathways that have been reported to be of potential relevance for consumer exposure to PBDEs and by summing up their individual contributions. In total, there are eight exposure pathways via three routes of exposure (oral, inhalation, and dermal) to be considered for PBDEs. The oral pathways are food intake, inadvertent ingestion of dust and soil, and hand-to-mouth contact with organic films on surfaces of indoor environments. The inhalation pathway is breathing of air, and the dermal pathways are contact with dust, soil, and organic films. For all pathways, PBDE concentrations in the exposure media (food, dust, air, etc.), rates of the consumers’ contact with the exposure media, and the corresponding uptake fractions and body weights were collected from a large variety of sources; these factors were then combined to yield an estimate of PBDE uptake for each pathway, PBDE congener, and consumer group. All equations for these calculations are given in Section 1 of the SI. All exposure calculations were carried out probabilistically. We defined distributions for all input parameters and propagated them through the exposure model by Monte Carlo simulation
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(MCS). To quantify food intake without creating unrealistic intake scenarios, we used a method developed by Trudel et al.16 This method (“energy-based method” or EBM) ensures that only physiologically possible intake scenarios are created in the MCS. For every food group, its specific energy contribution is calculated by multiplying the amount of food consumed by the according energy density of the food item. Then, all energy contributions are summed up, and the total energy intake is compared to the distribution of total energy intakes of the consumer group considered (for values and references see SI, Table S4). If the sum of all energy contributions is smaller or larger than the first or the 99th quantile of the total energy intake distribution for the modeled consumer group, the MCS run is discarded. Pharmacokinetic Model. We used our estimated PBDE uptakes in combination with PBDE biomonitoring data from the literature as input to a one-box pharmacokinetic (PK) model to derive PBDE elimination half-lives (both PBDE concentrations in exposure media underlying our uptake estimates and biomonitoring data are from the years 2001-2010). Because we assume steady-state conditions, we derive half-lives for female and male adults only (steady-state conditions may not have been reached for younger consumers). The elimination half-life of congener k is obtained from the PK model as k ¼ t1=2
LT lnð2ÞCLT k fi Dik
ð1Þ
with CLT k (ng/glipid) as concentration of congener k measured in (glipid/kgbw) as a fraction of lipid lipid tissue of humans; f LT i tissue of individuals in consumer group i; and Dik (ng/kgbw/d) as a dose of congener k taken up by an individual in consumer group i. Values of all parameters and their distributions are given in Table S4 of the SI. Because BDE-209 is not equally distributed in the body fat17 and thus eq 1 is not valid, the half-life of BDE-209 was estimated with a one-compartment steady-state PK model based on the volume-of-distribution concept 209 ¼ t1=2
LB lnð2ÞVD f AS CLB 209 f F Di, 209
ð2Þ
with VD (mL/kgbw) as the volume of distribution from rats normalized to body weight, f AS (-) as allometric scaling factor to extrapolate the volume of distribution from rats to humans, CLB 209 (ng/glipid) as concentration of BDE-209 in lipids of blood serum, f LB (glipid/gserum) as fraction of lipids in blood serum, F (gserum/ mL) as density of blood serum, and Di,209 (ng/kgbw/d) as dose of BDE-209 for individuals in consumer group i. Because the pharmacokinetic behavior of BDE-209 is uncertain, we derived an additional set of BDE-209 human half-lives rat 17,18 To this end, we (thuman 1/2 ) from two half-lives in rats (t1/2). 18,19 used two allometric scaling equations human rat rat t1=2 ¼ 8 3 t1=2 ; t1=2 < 10 d ð3Þ and human rat t1=2 ¼ 4:33 3 t1=2
ð4Þ
The first is limited to half-lives in rats below 10 d; the second has no restriction regarding the half-life in rats. Input Parameters. We assumed that concentrations and most other parameters used in our models are lognormally 2392
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P Figure 1. Box plots for total dose distributions of BDEs in the five modeled regions. Gray dots: arithmetic means. Lower horizontal line of the box: 25th quantile, middle line: median; upper line: 75th quantile. Lower vertical line: range of data between the 25th quantile and the 25th quantile minus 1.5 times the interquartile range. Upper vertical line: range of data between the 75th quantile and the 75th quantile plus 1.5 times the interquartile range. Single dots: data points exceeding the range indicated by vertical lines.
distributed20 (body weight data sets were fitted with either gamma, beta, student, normal or Weibull distributions). For some input parameters, distributions had to be summed up (e.g., consumption of various sorts of fish to one food category “fish”) or averaged (e.g., several studies that measured concentrations of PBDEs in fish). Details of these data processing steps are given in the SI, Section 2. In some European regions not all congeners were measured in all matrices (e.g., BDE-183 was not measured in breast milk of UK consumers). Therefore, such missing input parameter values were substituted in every MCS run by the median of the other regions where data were available. The same averaging approach was used for about a third of the European food intake distributions that were missing and had to be substituted (for European toddlers, for example, only food consumption data from UK, CE, and SE were available). The aim of this procedure is to avoid arbitrary differences in dose estimates that would just be due to incomplete data sets. However, the most influential parameters such as concentration of PBDEs in fish are available for all regions and, thus, differences between the regions are not blurred by the averaging procedure. A detailed list of all parameters that were used in the exposure and PK models with their distribution, number of data points and estimates of their fifth, 50th, and 95th quantile, as well as references is given in Table S4 (for exposure models) and S5 (for PK model) of the SI. Sensitivity Analysis. To identify the most influential input parameters, the contribution to variance (CtV) was calculated.21 To this end, first the Spearman rank order correlations between a given model result and each model input were calculated; then the rank order correlations of all input parameters were squared and finally normalized by the sum of all squared correlations.
A CtV above zero indicates a positive correlation between input and output parameter, a CtV below zero a negative correlation.
’ RESULTS Regions. Figure 1 shows that the median doses vary by about a factor of 2-3 between the five regions with NA and UK having slightly higher doses for infants and CE for teens and adults than the other regions (see also Table S6). However, the 95th quantiles of the doses are higher in NA by a factor of 3-11 compared to the three Continental European regions, which are all in a similar range. Doses for UK consumers are higher by a factor of 2-5 compared to Continental Europe. These differences are even more pronounced for the 99th quantile, where doses for NA exceed the lowest ones (CE) by a factor of 5-14; doses for the UK still exceed those for CE by a factor of 3-9. The spread of dose estimates in NA with 2.5-4 orders of magnitude is larger than in the European regions with a spread of 1.5-2.5 orders of magnitude. Consumer Groups. Figure 1 displays the hockey-stick-like dose pattern typical for consumers grouped according to age. Especially the consumer groups in NA, UK, and NE follow this pattern with infants taking up the highest dose, followed by toddlers, children, and then teenagers and adults. The doses of infants are on average higher than the doses of adults by a factor of 5 and doses of toddlers and children are higher by a factor of 3 compared to adults. For CE and SE, the pattern is less obvious. Exposure Pathways. Figure 2 shows the relationship between total dose levels and contributions of the different pathways for NA (NA consumers are shown, because their doses are 2393
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Figure 2. Relationship between contribution of single pathways to total dose for NA consumers (y-axis) and quantiles of the dose distribution (x-axis). 0 and 100 on x-axis correspond to minimum and maximum total dose, respectively.
highest). For infants the ingestion of food is the dominant pathway in the higher and lower dose range; between the 30th and 70th quantile of the total dose, oral uptake of dust dominates. For the other consumer groups, ingestion of food is dominant up to about the 60th quantile; above the 60th quantile, oral and dermal exposure to PBDEs in dust are the dominant pathways. In the lower and middle quantiles, inhalation of air also contributes to PBDE exposure. The influence of the other pathways is generally marginal. Results for European regions are given in Section 6.1 of the SI. This pattern is roughly similar for the UK, except that for infants the influence of the food pathway steadily decreases from lower to higher quantiles. For the other European regions the food pathway is dominant for all consumers over a large range of the dose distributions. Generally, oral exposure to PBDEs in dust gains importance toward higher doses and in about half of the 35 investigated dose distributions contributes more to the highest total doses than any of the other pathways. The contribution of dermal uptake via dust and inhalation of contaminated air is generally marginal. Congeners. The relative contribution of single congeners to total doses in relation to the quantiles of the total dose distributions is shown in Figure S5 in the SI (again for NA consumers). Up to the 70th quantile, the congener composition of the doses is approximately constant, with BDE-47, 99, and 209 as the most dominant congeners. From the 70th quantile on, BDE-209 gains importance at the expense of the other congeners (except for infants). This pattern is roughly similar for all consumer groups and regions except for CE, where the influence of BDE-209 is less dominant compared to other European regions. BDE-100 and BDE-153 also contribute to total doses (together about 20%), whereas the influence of BDE-154, BDE-183, and BDE-28 on total doses is generally marginal (see SI, section 6.2).
Other Studies. We compared our dose estimates with total dose estimates from a US study14 and a Belgian study22 (Table 1). The estimates from these studies also show the hockey-stick-like dose pattern with doses decreasing with increasing age. The dose estimates by Lorber14 are about four times higher than our median dose estimates. The estimates of Roosens et al.22 are higher for infants (about four times) but lower for older consumers (about three times) when compared to our estimates for CE (the region including Belgium). Half-Lives. Most of our half-life estimates (Table 2) are about 1-3 years (median values) except for BDE-153, which has a median half-life of about 7 years, and BDE-209 with a half-life of 4-7 days. Our half-life estimates for BDE-47 to BDE-154 and BDE-209 are shorter by a factor of about 2-7 than estimates derived from rat studies.18,19 The half-life estimates for BDE-209 are also shorter by a factor of about 2 than estimates from a study conducted with occupationally exposed workers.23 Our median half-life estimate for BDE-183, however, exceeds the half-life obtained from workers 23 by a factor of about ten.
’ DISCUSSION Regions. According to our analysis, NA consumers take up the highest doses of PBDEs, followed by the UK consumers and the other European regions (see Figure 1 and Table S6). This trend is most visible in the higher quantiles of the dose distributions. The higher doses in NA are likely due to the strict fire regulations in North America.12,24 North America was the largest consumer of PBDEs in 2001 with 49% of the global demand (Europe 12%).2 Use of pentaBDE and octaBDE ceased by the end of 2004, but decaBDE is still in use in many NA consumer 2394
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Table 1. Comparison of Total Dose Estimates Derived in This Study with Estimates from Two Other Total Exposure Studies region
pathways
520
this study
28, 47, 99, 100,
oral (food, dust, soil, film),
toddlers (1 to 5y)
7.4
240
this study
153, 154, 183, 209
inhalation (air),
children (5 to 12y)
3.8
130
this study
dermal (dust, soil, film)
teens (12 to 20y)a
2.1
86
this study
adults (20 to 65y)a
1.7
52
NA
consumer groups infants (0 to 1y)
NA
12
Q95
reference
this study
toddlers (1 to 6y)
49
Lorber 2008 14
14
Lorber 2008 14
28, 47, 99, 100,
oral (food, dust, soil),
children (6 to 12y)
138, 153, 154, 183, 209
inhalation (air), dermal (dust, soil)
teens (12 to 20y) adults
9.1 7.7
infants (0 to 1y)
7.4
39
this study
28, 47, 99, 100,
oral (food, dust, soil, film),
toddlers (1 to 5y)
6.1
26
this study
153, 154, 183, 209
inhalation (air),dermal (dust,
children (5 to 12y)
6.0
23
this study
soil, film)
teens (12 to 20y)a
3.7
14
this study
13
this study
CE
adults (20 to 65y)a CE (Belgium)b
Q50 or mean
congeners
infants (0 to 0.5y) 28, 47, 99, 100, 153, 154, 209
oral (food, dust, soil), inhalation (air)
3.4 38
Lorber 2008 14 Lorber 2008 14
140
Roosens et al. 2010 22
toddlers (3 to 6y) children (6 to 10y)
5.7 4.6
12 8.1
Roosens et al. 2010 22 Roosens et al. 2010 22
teens (10 to 21y)c
3.0
4.8
Roosens et al. 2010 22
adults (21 to 61y)d
2.2
3.7
Roosens et al. 2010 22
a
Average of female and male teens and adults, respectively. b Average of working and nonworking. c Average of 10 to 15y and 15 to 21y old teens. d Average of 21 to 31y, 31 to 41y, 41 to 51y, and 51 to 61y old adults.
Table 2. Half-Life Estimates (Days) Derived from Consumers (This Study), Rats, and Workers derived from consumers (this study)a Q5
Q50
Q95
derived from rats
derived from workers
BDE-28
56
1100
39000
-
-
BDE-47 BDE-99
28 17
510 280
29000 7900
1100b 2000b
-
BDE-100
43
670
30000
1100b
-
BDE-153
200
2700
80000
5700b
-
BDE-154
12
480
14000
2100b
-
BDE-183
43
1000
22000
-
94c
BDE-209
0.3-1.3d
4-7d
22-40d
11-31e
15c
a
Derived from doses and biomonitoring data by means of eqs 1 and 2. b Extrapolated from rats by Geyer et al.19 c Derived from biomonitoring data in workers by Thuresson et al.23 d Range due to inclusion (lower bound) or exclusion (upper bound) of two studies with samples taken from breastmilk.13,25 e Extrapolated from two rat studies10,17 (half-lives = 2.5 days and 3.9 days) by allometric scaling equations from refs 18 and 19.
products.24 The finding that doses of Americans tend to be higher than doses of Europeans is supported by human biomontoring data that indicate, except for BDE-209, higher PBDE levels in tissues of Americans compared to Europeans.12,25 The secondhighest doses (again most pronounced in the higher quantiles) are for UK consumers, which is again likely due to stricter fire regulations in the UK compared to other European regions.26 In contrast to the higher quantiles of the dose distributions, the median dose estimates vary only slightly between the regions, see Figure 1 and Table S6. The medians of the dose distributions are mostly dominated by the food pathway, which is probably less influenced by local fire regulations. The upper quantiles of the dose distributions, in contrast, are different between regions mainly due to higher PBDE concentrations in dust of NA homes, offices, and cars than in Europe. The large spreads of the dose distributions are mainly caused by the considerable uncertainty
and variability of dust intake rates and variability of PBDE concentrations in dust. Consumer Groups. The hockey-stick-like dose pattern, which is best visible in NA, UK, and NE, is due to different behavior and consumption patterns as well as different anthropometric characteristics of the seven consumer groups. Such a hockey stick-like dose pattern was also found in other exposure and biomonitoring studies.22,27 The main reasons for the higher doses of infants are their consumption of contaminated breast milk, their high dust intakes relative to their body weight, their high dust loadings on skin, and their low body weight (see also CtV in Section 8 of the SI). In CE and SE, the hockey stick-like dose pattern is less pronounced. This is because of the high BDE-47 and BDE-100 concentrations in fish consumed in CE and the high consumption rates of fish in SE (see also CtV in the SI, Figure S13 and 2395
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Environmental Science & Technology S14). Fish consumption is relevant for toddlers, children, teens, and adults and makes the doses received by these groups more similar than in the other regions. Exposure Pathways. Our results indicate that exposure to food and dust, and to some extent to air, are main sources of PBDEs taken up by consumers. Food intake is an important pathway, because PBDEs can be found in considerable amounts in foods such as fish, meat, or dairy products that are consumed on a regular basis and in considerable amounts (see CtV for foodrelated input parameters). The uptake of PBDEs via food in the lower quantiles of NA infants is due to the consumption of infant formula with low concentrations, in the upper quantiles due to breast milk with high concentrations of PBDEs. In the upper quantiles of the dose distributions, another potentially important pathway is ingestion of dust, because measured PBDE concentrations in dust are high and the amounts of dust ingested can also be high; the latter show large variability and uncertainty (see CtV for dust ingestion and concentrations in dust in Figures S10 and S11). More research is needed to reduce uncertainty in these factors. Additionally, bioavailability of PBDEs in dust should be further investigated. Besides the oral intake of dust, also the dermal pathway may contribute to total doses (up to 40% in the 99th quantile). This is due to the high concentrations of PBDEs in dust and the nonnegligible part of PBDEs that is assumed to cross the skin barrier. Also Lorber14 found that the dermal uptake of soil and dust might considerably contribute (about 16%) to total PBDE exposure. However, the uptake rates used here are based on a single study for BDE-99 only.28 Therefore, they are subject to large uncertainties that may be reduced by measurements of congener-specific uptake rates. The inhalation of contaminated air can be of some importance due to high concentrations of BDE-47 in indoor air (NA) (see CtV in the SI, Figure S10). PBDE uptake from exposure to organic films is marginal. Congeners. We found that BDE-47 and BDE-99 dominate consumer exposure to PBDEs, which is reasonable, because they were the major components (together around 90%) of technical pentaBDE.4 Due to the phase-out of pentaBDE use in consumer products and, subsequently, reduced emissions of BDE-47 and BDE-99 into indoor environments, the contribution of these congeners to exposure nowadays is mainly via the food and not via the dust pathways. Thus, PBDE contamination of foods likely results from past emissions but probably also from ongoing emissions from dumpsites and older products that still contain pentaBDE. Also BDE-209 contributes significantly to the doses. BDE-209 is the main component (>90%) of the technical decaBDE mixture,4 which has been used in the largest quantities in the recent years.2 Hence, BDE-209 is present in many consumer products and likely leads to contaminated indoor environments and, thereby, to high body burdens via intake of contaminated dust and air but not so much via food. Finally, BDE-183 is not an important congener, because the technical octaBDE mixture was used less extensively than penta- or decaBDE in the US2 and octaBDE consisted of up to 50% of BDE-209.4 Half-Lives. The wide spread of our half-life estimates (Table 2) directly corresponds to the large variability of our dose estimates, which is propagated through eqs 1 and 2. The median half-lives for BDE-28 to BDE-154 and BDE-209 are still on the same order of magnitude as half-lives derived from rats18,19 but are all slightly lower (factors 2-7). This bias might
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be caused by the steady-state assumption that we used. For the lighter congeners with long half-lives, steady-state may not have been reached completely. Assuming steady-state in the model (see eq 1) while in reality uptake is still higher than elimination leads to an underestimation of elimination half-lives. Another possible explanation of the bias is that there is a mechanistic difference between PBDE elimination in humans and rats. For BDE-209, we derived two half-life distributions, one with a median of 4 d and one with a median of 7 d. The lower value is based on all biomonitoring data selected for BDE209.13,25,27,29-32 However, all European studies used29-32 and one study from the US27 report BDE-209 levels in blood, whereas the two other studies from the US report levels in breast milk. Lipid-normalized BDE-209 levels from these two latter studies are lower by a factor of 10-100 than the levels derived from blood samples. A possible explanation of this observation is that transfer of BDE-209 from blood to breast milk may be slow compared to metabolism of BDE-209. This interpretation is consistent with the finding that BDE-209 is not uniformly distributed in body lipids in rats.17 We therefore recalculated the elimination half-life of BDE-209 using only the levels measured in blood and obtained a median half-life of 7 days. The finding that BDE-209 has a much shorter half-life than the other congeners indicates that BDE-209 has a different pharmacokinetic behavior. Our BDE-209 half-life estimates also support the estimate of 15 days reported by Thuresson et al.23 and show that the half-life of BDE-209 is short not only in occupational settings but likely also in chronic non-occupational exposure situations. Finally, the half-life found for BDE-183 is distinctly longer than the one reported by Thuresson et al.23 This might be due to a behavior of BDE-183 in human bodies that resembles that of BDE-209 and should therefore be modeled with a PK model based on the volume of distribution (VD). However, we were not able to identify a value of VD for BDE-183 and consequently could not apply eq 2 to derive another set of half-lives for BDE183. Further research is needed to better understand the pharmacokinetics of BDE-183 in animals and humans.
’ ASSOCIATED CONTENT
bS
Supporting Information. Information about data treatment, all model parameters and distributions used, and results for all geographical regions. This material is available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION Corresponding Author
*Phone: þ41-44-632 3062. Fax: þ41-44-632 1189. E-mail:
[email protected]. Corresponding author address: Safety and Environmental Technology Group, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
’ ACKNOWLEDGMENT For providing raw data we thank Helle Knutsen, Kevin Jones, Per Ola Darnerud, Christina Tlustos, Manolis Mandalakis, Stuart Harrad, Adrian Covaci, Arnold Schecter, Dave Stone, Wilhelm Knoth, Aida Turrini, Stefan Voorspoels, and Arantxa Bartolome. We thank Ake Bergman for support in the interpretation of BDE209 half-lives, and Christian Bogdal and Roland Ritter for helpful comments. Funding of this study by the Swiss Federal Office of Public Health is gratefully acknowledged. 2396
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Environmental Science & Technology
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