Persistent organochlorine and organobromine compounds in mother's milk from Sweden 1996–2006: Compound-specific temporal trends

ARTICLE IN PRESS Environmental Research 109 (2009) 760–767

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Persistent organochlorine and organobromine compounds in mother’s milk from Sweden 1996–2006: Compound-specific temporal trends$ Sanna Lignell a, Marie Aune a, Per Ola Darnerud a, Sven Cnattingius b, Anders Glynn a, a b

National Food Administration, P.O. Box 622, SE-751 26 Uppsala, Sweden Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, P.O. Box 281, SE-171 77 Stockholm, Sweden

a r t i c l e in f o

a b s t r a c t

Article history: Received 7 November 2008 Received in revised form 24 April 2009 Accepted 27 April 2009 Available online 27 May 2009

High body burdens of persistent halogenated organic pollutants (POPs) among pregnant and nursing women are of concern because of exposure of the growing foetus and breast-feeding infant. We examined the temporal trends of polychlorinated biphenyls (PCBs), dibenzo-p-dioxin (PCDDs) and dibenzofurans (PCDFs), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) in milk samples from Swedish women. POPs were analysed in individual mother’s milk samples from randomly recruited primiparas (N ¼ 335) who lived in Uppsala County and delivered between 1996 and 2006. Results were adjusted for life-style factors that are associated with POP body burdens. PCB levels declined 3.9–8.6% per year. The levels of PCDDs decreased faster (6–9% per year) than the levels of PCDFs (3–6% per year). Temporal trends of PBDEs did not follow any consistent pattern. Concentrations of BDE-47 and BDE-99 decreased, while the concentrations of BDE-153 increased. No change in BDE-100 concentrations was observed. In most samples, concentrations of HBCD were below the quantification limit (o0.20 ng/g lipid). Generally, adjustment of the temporal trends of PCBs and PCDD/Fs for personal characteristics of the mothers (age, body mass index (BMI), weight changes during and after pregnancy) resulted in faster declining rates, with age having the greatest influence. The age of the participating mothers increased during the study period, and since the POP levels increased with increasing age, this counteracted the decreasing temporal trends in the unadjusted model. It is consequently important to include personal characteristics in the analysis of temporal trends of POPs. Compound-specific temporal trends are probably caused by differences in sources of exposure, as well as by differences in persistence between compounds. & 2009 Elsevier Inc. All rights reserved.

Keywords: Mother’s milk Breast milk Trend Polychlorinated biphenyls Dioxins Polybrominated diphenyl ethers

1. Introduction The use and emissions of many persistent halogenated organic pollutants (POPs), e.g. the industrial chemicals polychlorinated biphenyls (PCBs) and the contaminants polychlorinated dibenzop-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs),

Abbreviations: BFR, brominated flame retardant; BMI, body mass index; HBCD, hexabromocyclododecane; LOQ, limit of quantification; NFA, Swedish National Food Administration; PBDE, polybrominated diphenyl ether; PCB, polychlorinated biphenyl; PCDD, polychlorinated dibenzo-p-dioxin; PCDF, polychlorinated dibenzofuran; POP, persistent halogenated organic pollutant; RIVM, National Institute of Public Health and the Environment (the Netherlands); SE, standard error; sumPBDE, sum of BDE-47, BDE-99, BDE-100, BDE-153 and BDE-154; TEF, toxic equivalence factor; TEQ, toxic equivalent; total TEQ, sum of mono-ortho PCB TEQ, non-ortho PCB TEQ and PCDD/F TEQ; TWI, tolerable weekly intake $ The work described in this paper was funded in part by the Swedish Environmental Protection Agency. The Ethics Committee of the Medical Faculty at Uppsala University approved the design of the study, and informed consent was obtained from the study participants.  Corresponding author. Fax: +46 18 105848. E-mail address: [email protected] (A. Glynn). 0013-9351/$ - see front matter & 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.envres.2009.04.011

have been banned or restricted since the 1970s. Consequently, the levels of these substances have declined in the environment and in foods. Humans are exposed to POPs mainly from food (Ahlborg et al., 1995), and decreasing levels of PCBs and PCDD/Fs in human milk samples have been reported from industrialized countries (Fu¨rst, 2006; Nore´n and Meironyte´, 2000). In contrast, the levels of polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD) and other brominated flame retardants (BFRs) in humans have increased from the 1970s to the 1990s (Fa¨ngstro¨m et al., 2005, 2008; Hites, 2004; Schecter et al., 2005; Thomsen et al., 2002) due to extensive use by the industry. In Sweden, there are indications that the levels of some PBDE-congeners and HBCD have stabilised since the later half of the 1990s (Fa¨ngstro¨m et al., 2008), although no firm conclusions about changes in temporal trends could be reached due to the use of pooled samples in the study. For BFRs, the exposure pathways are not fully elucidated, but it is suggested that indoor dust and food are important sources of human exposure (Darnerud et al., 2001; Jones-Otazo et al., 2005; Lorber, 2008; Sjo¨din et al., 2003). In Sweden, fish consumption is a major source of POP exposure (Darnerud et al., 2006). Fatty fish from the Baltic Sea is highly

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contaminated with POPs, and while the levels of PCBs have steadily declined in this type of fish (i.e. herring) since the 1980s, the levels of PCDD/Fs have not changed (Bignert et al., 2007). Data on BFRs in biota from the Baltic Sea (guillemot eggs) show that the levels of HBCD have steadily increased since 1968, whereas the levels of PBDEs increased to a peak around 1985–90 and declined thereafter (Bignert et al., 2007). Due to the relatively high lipid content, mother’s milk is a good matrix for determination of the body burden of lipophilic POPs among pregnant and nursing women, and mother’s milk levels of POPs also give a good estimate of the exposure of the growing foetus and the breast-feeding infant. In earlier studies of temporal trends of POPs in milk among mothers from Sweden, pooled milk samples have been used (Fa¨ngstro¨m et al., 2008; Nore´n and Meironyte´, 2000). In this type of study, it is not possible to adjust trends for changes in life-style/medical factors that may be determinants of POP body burdens among study participants during the study period (Albers et al., 1996; Dewailly et al., 1996; Glynn et al., 2007; Schade and Heinzow, 1998). Consequently, there is a risk that the rates of the temporal trends are over- or under-estimated in studies using pooled samples. In the present study we sampled individual milk samples from first-time mothers (i.e., primiparas) in Uppsala, Sweden, who gave birth between 1996 and 2006. The aim of our study was to examine the concentrations of PCBs, non-ortho PCBs, PCDD/Fs, PBDEs and HBCD in individual milk samples, and to investigate how the levels of these contaminants have changed among primiparous women during the last 10 years. The temporal trends in mother’s milk were compared with trends observed in biota from the Baltic Sea environment. We sampled mother’s milk from individual women and could therefore adjust the temporal trends for important personal determinants of POP body burdens. We also wanted to determine how the introduction of new toxic equivalence factors (TEFs) for some of the PCDD/F- and PCB-congeners (Van den Berg et al., 1998, 2006) affected the results of the calculated temporal trends. Data from the earlier period of the study of primiparas in Uppsala have been published earlier (Glynn et al., 2001; Lind et al., 2003).

2. Materials and methods 2.1. Study population and sampling From fall 1996 to spring 1999, pregnant, primiparous women living in Uppsala County, who were in late pregnancy (week 32–34), were asked to participate in the study (N ¼ 405) (Glynn et al., 2007). Of these women, 211 (52%) agreed to donate mother’s milk for chemical analysis. From April 2000 to March 2001, from March 2002 to February 2003 and from January to December 2004 and 2006 primiparous mothers were randomly recruited among women who delivered at Uppsala University Hospital. At each sampling period, 30–32 women (46–63% of all women who were asked) participated in the study. A total of 335 women were recruited from 1996 to 2006. Data on maternal characteristics were obtained via personal interviews and questionnaires, and included age, height, weight before pregnancy, birth weight of the child, weight change during and after pregnancy, education, country of birth, smoking and dietary habits. The mothers sampled milk at home during the third week after delivery (day 14–21 post partum) (Glynn et al., 2001).

2.2. Chemical analysis The milk samples were analysed for tri- to hepta-chlorinated PCB-congeners (mono-ortho substituted congeners PCB 28, PCB 105, PCB 118, PCB 156 and PCB 167, di-ortho substituted congeners PCB 52, PCB 101, PCB 138, PCB 153 and PCB 180, and non-ortho congeners PCB 77, PCB 126 and PCB 169). The analysis also included seventeen 2,3,7,8-substituted PCDDs and PCDFs, five PBDE-congeners (BDE-47, BDE-99, BDE-100, BDE-153, and BDE-154) and HBCD. PCBs, PBDEs and HBCD were analysed at the Swedish National Food Administration (NFA) according to a previously described method (Atuma et al.,

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2000; Atuma and Aune, 1999; Aune et al., 1999; Lind et al., 2003), with the exception of non-ortho PCBs in samples from 1996 to 1999 and 2006. After extraction and separation the final analyses of mono- and di-ortho PCB-congeners were performed on a gas chromatograph with dual electron-capture detectors. The non-ortho PCBs, PBDEs and HBCD were analysed by gas chromatography/mass spectroscopy/electron-capture negative ionization (GC/MS/ECNI) and detected by the single ion monitoring technique. All samples were fortified with internal standards (PCB 53, PCB 189, BDE-85 and 13C-labelled congeners for non-ortho PCBs) prior to extraction to correct for analytical losses and to ensure quality control. The limit of quantification (LOQ) was determined as the mean plus six times the standard deviation of a blank sample. In cases when this LOQ was lower than the lowest calibrated level, the lowest calibrated level was used as LOQ. Values below the LOQ were reported as oLOQ. A number of control samples were analysed together with the samples to verify the accuracy and precision of the measurements. The laboratory is accredited for analysis of PCBs and BFRs in human milk. PCDDs and PCDFs (samples from 1996 to 2004) and non-ortho PCBs (samples from 1996 to 1999) were analysed at the National Institute of Public Health and the Environment, the Netherlands (RIVM), using an earlier described method (van der Velde et al., 1994). Briefly, samples were analysed according to a validated procedure consisting of a milk extraction procedure, a clean-up using active carbon and alumina chromatography, and identification and quantification of the analytes using gas chromatography with high-resolution mass spectrometry with the isotope dilution technique. The LOQ was set at the signal-to-noise ratio of 3:1 for each compound analysed in the sample extracts. A number of control samples of human milk were inserted in each batch of samples to verify the accuracy and precision of the measurements (Glynn et al., 2001). In milk samples from 2006, the analyses of PCDD/Fs and non-ortho PCBs were performed by the Department of Chemistry at Umea˚ University using a similar method for sample extraction, cleanup (Danielsson et al., 2005) and quantification. A comparison study was performed in which PCB 126 was analysed in 26 samples at both NFA and RIVM. The two laboratories showed no systematic differences in results (Wilcoxon signed rank test, p ¼ 0.798). A similar study was performed comparing the PCDD/F, PCB 126 and PCB 169 results in 10 samples analysed both at RIVM and at Umea˚ University. Results of non-ortho PCB analyses performed at the NFA and Umea˚ University were also compared. The results of the comparisons showed that, in most cases, the median quotients of levels reported by the two laboratories were close to 1. In a few cases, the median quotients were slightly above or below 1 (po0.05 in a Wilcoxon signed rank test).

2.3. Calculations and statistics Women who were born outside the Nordic countries (N ¼ 10) were excluded before the statistical analysis due to the fact that these women differed significantly in their body burdens of PCBs compared with women born in Nordic countries (Glynn et al., 2007). Mother’s milk concentrations of POPs were lipid adjusted and statistical analyses were performed on logarithmically transformed data, since the distribution of data closely followed a log-normal distribution. Toxic equivalents (TEQs) were calculated using both 1998 and 2005 TEFs (Van den Berg et al., 1998, 2006). Total TEQ was calculated as the sum of mono-ortho PCB TEQ, non-ortho PCB TEQ and PCDD/F TEQ. When the concentrations were below the LOQ, half of LOQ was taken as an estimated value. This substitution method did not significantly affect the TEQ concentrations. For example, the total TEQ concentrations calculated with oLOQ results set to 1/2 LOQ were found to be only on average 2% higher than when oLOQ results were set to zero. Level of significance was set to 0.05 in all statistical tests. Simple and multiple linear regressions (MINITAB 15s Statistical Software for Windows) were used to analyse associations between POP concentrations in mother’s milk and sampling year. Independent variables (life-style/medical factors) that have been shown to be associated with serum and mother’s milk concentrations of organochlorine compounds (Glynn et al., 2007; Schade and Heinzow, 1998) were included as explanatory variables in the multiple model. The variables considered were age of the mother (years), pre-pregnancy body mass index (BMI) (kg/m2), body weight change during pregnancy (% per week), and weight change during the period from delivery to milk sampling (%). In order to obtain a normal distribution of the residuals obtained in the regression analyses, some outliers (with standardized residuals Z3) were omitted from the analysis. As a consequence of the logarithmic transformation of the dependent variable ‘‘POP concentration’’, the associations between sampling year and POP concentrations are presented as percent change of concentrations per year, and not as change in absolute levels: %change ¼ ð1  expðbÞÞ  100 where b is the regression coefficient for the independent variable ‘‘sampling year’’ in the simple regression and the partial regression coefficient for the same variable in the multiple regression analysis.

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3. Results 3.1. Study participants The median age of the primiparas participating in the study was 29 years (range 19–41) and the median pre-pregnancy BMI was 22 kg/m2 (range 16–38). The median weight increase during pregnancy was 0.61% of the initial weight per week (range 0.03–1.5), and the median weight reduction from delivery to sampling was 9.4% (range 2 to 21). Among the mothers, 38% had more than 3 years of higher education while 41% had no higher education than 3–4 years of high school. Fifteen percent of the women smoked during pregnancy. 3.2. Residue concentrations Concentrations of PCB 52, PCB 101, PCB 77, 1,2,3,7,8,9-HxCDF, 1,2,3,4,7,8,9-HpCDF, BDE-154 and HBCD were, in most milk samples (460%), below the LOQ (results not shown). PCB 153 showed the highest mean concentration in mother’s milk lipids of all compounds studied (Table 1). Among the PCDD/Fs, 1,2,3,4,6,7,8-HpCDD and octaCDD showed the highest mean concentrations (16 and 79 pg/g lipid, respectively). However, the congeners that contributed most to the PCDD/F TEQ concentrations were 2,3,7,8-TCDD; 1,2,3,7,8-PeCDD; 1,2,3,6,7,8-HxCDD and 2,3,4,7,8-PeCDF, in total 87% (range 75–93%) (Table 1). The mean concentrations of the remaining PCDD/Fs (1,2,3,4,7,8HxCDD; 1,2,3,7,8,9-HxCDD; 2,3,7,8-TCDF; 1,2,3,7,8-PeCDF; 1,2,3,4, 7,8-HxCDF; 1,2,3,6,7,8-HxCDF; 2,3,4,6,7,8-HxCDF; 1,2,3,4,6,7,8HpCDF and octaCDF) varied between 0.21 and 2.1 pg/g lipids (results not shown). Among the PBDEs, BDE-47 showed the highest mean concentration (Table 1). The mean levels of the PBDE-congeners were lower than most mono- and di-ortho PCBs. 3.3. Temporal trends The levels of all PCBs decreased significantly during the study period (Table 2 and Fig. 1). The fastest decline was shown for PCB 118, PCB 153 and PCB 180, while the slowest decline was observed for PCB 169, PCB 28 and PCB 105. The estimated decrease in mono-ortho PCB TEQ levels was 10% faster when the TEF system from 2005 was used than when using the 1998 TEF system (results for 1998 TEFs not shown). There were small differences (o4%) in the temporal trends of non-ortho PCB TEQs when the two different TEF systems were compared. In most cases, adjustment of the temporal trends for life-style factors resulted in faster declining rates and considerably higher R2-values of the regression model (Table 2). Generally, age of the mother (positive associations) and sampling year (negative associations) had the greatest influence on the levels of PCBs in mother’s milk. For most PCB-congeners, age of the mothers explained 20–39% of the variation in levels, and sampling year explained 15–30%. The levels of many PCBs were also significantly associated with pre-pregnancy BMI and weight gain during pregnancy (negative associations) and with weight loss after delivery (positive associations) although these associations were weak (R2 ¼ 0.6–7%). The levels of all analysed PCDD/F-congeners, except for 2,3,7,8TCDF; 1,2,3,7,8-PeCDF and 2,3,4,6,7,8-HxCDF, decreased significantly during the study period (Table 2 and Fig. 1). The decline was generally faster for the PCDD-congeners than for the PCDFcongeners. Among the four congeners that contributed most to the PCDD/F TEQ concentrations, the fastest decline was shown for 1,2,3,6,7,8-HxCDD, followed by 2,3,7,8-TCDD; 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF. Only minor differences in annual changes (o5%)

were observed when the two different TEF systems were used (results for 1998 TEQs not shown). The simple regression model explained a smaller fraction of the variation in PCDD/F and TEQ levels than the multiple model (Table 2). Similar as in the case of PCBs, age of the mother and sampling year were the most influential determining factors in the multiple regression model, and these factors explained 23% (age) and 30% (sampling year) of the variation in levels of total TEQ. BMI and weight changes during and after pregnancy were also significantly associated with the TEQ levels in mother’s milk, although the associations were weak (R2 ¼ 1–3%). Dissimilar trends were observed for the different PBDEcongeners during the study period (Table 2 and Fig. 1). Regression analysis showed that the concentrations of BDE-47 and BDE-99 decreased while the levels of BDE-153 increased. No significant trend was observed for BDE-100. All in all, this resulted in a small but significant decrease in the concentrations of sum of BDE-47, BDE-99, BDE-100, BDE-153 and BDE-154 (sumPBDE) between 1996 and 2006 (2% per year). In contrast to PCBs and PCDD/Fs, the R2-values were low both in the simple and in multiple regression models. The multiple model only explained 3–13% of the variation in levels of BDE-47, BDE-99 and sumPBDE, and the only significant associations between the concentrations of these congeners and the explanatory variables were negative associations between weight gain during pregnancy and the levels of BDE-99 and sumPBDE. However, BDE-153 deviated from the other congeners in this aspect, and the levels were significantly associated with age and weight loss after delivery (positive associations), as well as with BMI and weight gain during pregnancy (negative associations). However, the inclusion of these factors in the regression model did not affect the temporal trend (Table 2).

4. Discussion Our results show that the levels of most PCBs and PCDD/Fs in mother’s milk from primiparous women in Uppsala have decreased from 1996 to 2006. Earlier studies of PCBs and PCDD/ Fs in pooled mother’s milk samples from Stockholm, Sweden, have shown that the body burdens of nursing women have decreased from the beginning of the 1970s–1997 (Nore´n and Meironyte´, 2000; Vaz et al., 1993). Our data show that these downward trends have continued during the time period 1996–2006. The continuous decline in PCDD/F TEQ levels in Swedish mother’s milk during the last decade deviate from the lack of temporal trend of PCDD/F TEQ levels in biota (herring) from the Baltic Sea area, on the Swedish east and south coasts, during the last 15 years (Bignert et al., 2007). Swedish market basket studies in 1999 and 2005 suggest that there have been a decline in PCDD/ F levels in foods on the Swedish market (Ankarberg et al., 2006; Darnerud et al., 2006). Taken together, the results indicate that the PCDD/F contamination of foods on the Swedish market has followed a different trend than the contamination of the Baltic Sea environment. This could be due to the efforts to decrease the PCDD/F contamination of animal feed in European food production, and contamination of food on the European market (Gallani et al., 2004). There were large differences in the rate of decline of individual PCB and PCDD/F-congeners in mother’s milk during the 10-year study period. Among the PCDD/Fs, PCDDs decreased faster than the PCDFs in mother’s milk. This suggests that the sources of PCDF contamination have not been eliminated to the same extent as the sources of PCDDs, and/or that PCDFs are more persistent than PCDDs. Half-times for PCB 28, PCB 105, PCB 167 and PCB 169, i.e. the estimated number of years required for the levels to decline by 50% in the population, were almost twice as long as the half-times

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Table 1 Concentrations of POPs in mother’s milk from primiparas in Uppsala, Sweden, 1996–2006. Substance

Mean7SD

Median

Range

%oLOQa

PCBs (ng/g lipid) (N ¼ 325) PCB 28 PCB 105 PCB 118 PCB 138 PCB 153 PCB 156 PCB 167 PCB 180 Mono-ortho TEQ98 (pg/g lipid)b,c Mono-ortho TEQ05 (pg/g lipid)b,d

2.873.9 1.371.3 1176.6 29713 58728 4.572.5 1.370.79 28713 3.571.9 0.5570.31

1.8 1.0 9.5 26 52 3.9 1.2 25 3.1 0.48

o0.50–31 o0.30–15 2.9–64 7.8–94 12–186 o0.90–24 o0.36–5.7 5.0–84 0.56–18 0.13–2.7

10 29 0 0 0 1 19 0 – –

o15–125 o12–65 0.97–13 1.3–14

6 25 – –

Non-ortho PCBs (pg/g lipid) (N ¼ 220) PCB 126 PCB 169 Non-ortho TEQ98e,c Non-ortho TEQ05e,d PCDD/F (pg/g lipid) (N ¼ 184) 2,3,7,8-TCDD 1,2,3,7,8-PeCDD 1,2,3,6,7,8-HxCDD 2,3,4,7,8-PeCDF PCDD TEQ98c PCDD TEQ05d PCDF TEQ98c PCDF TEQ05d PCDD/F TEQ98c PCDD/F TEQ05d Total TEQ98c,f (pg/g lipid) (N ¼ 183) Total TEQ05d,f (pg/g lipid) (N ¼ 183)

44722 22712 4.672.3 5.172.4

0.9470.45 2.570.97 8.373.6 6.273.0 4.771.8 4.771.8 3.571.6 2.371.0 8.273.3 7.072.7 1676.7 1375.1

Polybrominated diphenyl ethers (PBDE) (ng/g lipid) (N ¼ 276) BDE-47 1.971.7 BDE-99 0.4570.51 BDE-100 0.3670.40 BDE-153 0.6470.45 g 3.572.7 SumPBDE

39 20 4.2 4.6

0.86 2.3 7.5 5.5 4.3 4.3 3.1 2.0 7.4 6.4

o0.10–2.8 0.66–6.5 2.1–21 2.0–21 1.4–12 1.4–12 1.2–11 0.81–7.0 2.8–23 2.3–19

– – – – – –

5.5–39 4.1–31

– –

15 12

1.5 0.32 0.29 0.57 2.9

o0.40–16 o0.12–5.2 o0.10–5.1 0.20–4.6 0.91–28

3 0 0 0

1 16 9 2 –

a

Percent of the samples with concentrations below LOQ. In calculations of mean and SD, results LOQ were set to 1/2 LOQ. Sum of PCB 105, PCB 118, PCB 156 and PCB 167 TEQs. c TEQs calculated with TEFs from 1998 (Van den Berg et al., 1998). d TEQs calculated with TEFs from 2005 (Van den Berg et al., 2006). e Sum of PCB 77, PCB 126 and PCB 169 TEQs. f Sum of mono-ortho PCB TEQ, non-ortho PCB TEQ and PCDD/F TEQ. g Sum of BDE-47, BDE-99, BDE-100, BDE-153 and BDE-154. b

for the other studied PCBs. The longer half-times of some congeners could partly be due to a higher number of samples with levels below LOQ than for other congeners. The comparatively small difference in half-times for the other studied PCBs suggests uniform decline rates of different PCB-congeners in food. Studies of PCBs in food-producing animals (bovines and swine) in Sweden between 1991 and 1997 (Glynn et al., 2000) showed similar rates of decline as among the Uppsala women, and the PCB levels in biota (e.g. guillemot eggs) from the Swedish coasts decreased with 5–10% per year between 1978 and 2005 (Bignert et al., 2007). Furthermore, the mean levels of PCBs in fish, meat, dairy products and eggs were 38–89% lower in a Swedish market basket study performed in 2005 compared with a study from 1999 (Ankarberg et al., 2006; Darnerud et al., 2006). Similar to our studies, results from monitoring programs in Germany have also shown that the levels of PCBs and PCDD/Fs in mother’s milk have decreased since the middle of the 1980s up to 2005 (Fu¨rst, 2006; Raab et al., 2007). Furthermore, studies comparing data from more or less equivalent studies conducted at different time points have shown decreasing body burdens of PCDD/Fs and PCBs since the beginning of the 1980s up to the mid-

2000s in, e.g. Finland, Norway, the United States and Canada (Becher et al., 1995; Craan and Haines, 1998; Johansen et al., 1994; Kiviranta et al., 1999; Lorber et al., 2008). Our study design made it possible to adjust the temporal trends for alterations in personal characteristics among the participants during the study period. Besides sampling year, age of the mother had the greatest influence on the levels of PCBs and PCDD/Fs in mother’s milk. Most POPs accumulate in the body, and a higher cumulative exposure among older women probably contributes to the positive association between age and POP levels. There is probably also a birth cohort effect, since environmental and food levels of many POPs decreased in Sweden during the 1960s–1990s (Bignert et al., 2007). Women born in the 1960s and the 1970s thus experienced higher levels of exposure during childhood and adolescence than women born in the late 1970s and 1980s. The adjustment of the temporal trends for personal characteristics resulted in faster declining rates. One explanation to this is that the age of the primiparas increased during the study period (0.14 years of age/year, p ¼ 0.05). Since the POP levels increased with increasing age, the increasing age counteracted the decreasing temporal trends in the unadjusted regression model.

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Table 2 Annual change (% per year) in concentrations of POPs in mother’s milk, 1996–2006. Substance

PCB 28 PCB 105 PCB 118 PCB 138 PCB 153 PCB 156 PCB 167 PCB 180 Mono-ortho TEQ05e,g PCB 126 PCB 169 Non-ortho TEQ05f,g 2,3,7,8-TCDD 1,2,3,7,8-PeCDD 1,2,3,4,7,8-HxCDD 1,2,3,6,7,8-HxCDD 1,2,3,7,8,9-HxCDD 1,2,3,4,6,7,8-HpCDD OctaCDD 2,3,7,8-TCDF 1,2,3,7,8-PeCDF 2,3,4,7,8-PeCDF 1,2,3,4,7,8-HxCDF 1,2,3,6,7,8-HxCDF 2,3,4,6,7,8-HxCDF 1,2,3,4,6,7,8-HpCDF OctaCDF PCDD TEQ05g PCDF TEQ05g PCDD/F TEQ05g Total TEQ05g,h BDE-47 BDE-99 BDE-100 BDE-153 SumPBDEi

Simple regressiona

Multiple regressionb

Mean

SE

R2 (%)d

Mean

SE

R2 (%)d

Half-timec (years)

4.3* 3.8* 8.2* 6.2* 7.3* 5.0* 4.4* 6.1* 6.9* 6.7* 1.6 6.1* 5.8* 5.1* 6.2* 7.2* 7.7* 9.0* 7.6* 0.2 0.6 4.3* 3.5* 2.5* 0.1 3.3* 6.1* 6.0* 3.7* 5.2* 5.5* 4.2* 7.6* 0.91 +4.9* 1.7

1.4 1.4 0.7 0.7 0.7 0.8 1.1 0.7 0.7 0.9 1.1 0.9 0.8 0.7 0.8 0.7 0.7 1.0 0.8 1.2 1.2 0.9 0.6 0.7 1.0 0.9 1.4 0.7 0.8 0.7 0.7 1.1 1.2 1.3 0.8 1.0

3 2 28 20 24 10 4 18 20 19 0.6 18 22 20 25 35 35 28 29 0 0 10 13 5 0 6 8 28 9 23 23 5 12 0 12 0.8

3.9* 4.2* 8.6* 6.8* 8.0* 5.7* 5.4* 7.3* 7.4* 7.0* 3.3* 6.5* 6.9* 5.8* 7.1* 7.6* 7.9* 9.3* 8.3* 0.9 0.2 5.3* 4.0* 3.1* 0.9 3.4* 5.6* 6.7* 4.6* 5.9* 6.3* 4.3* 7.5* 1.2 +4.9* 2.0*

1.4 1.2 0.5 0.5 0.5 0.5 0.9 0.4 0.5 0.7 0.7 0.7 0.6 0.5 0.6 0.5 0.7 1.0 0.8 1.1 1.2 0.7 0.6 0.6 0.9 0.9 1.5 0.5 0.6 0.5 0.5 1.1 1.2 1.2 0.7 0.9

7 25 56 54 67 61 41 75 59 45 53 48 54 58 56 65 45 38 40 14 4 48 38 32 16 10 9 64 47 62 61 7 13 2 31 3

17 16 8 10 8 12 13 9 9 10 21 10 10 12 9 9 8 7 8 – – 13 17 22 – 20 12 10 15 11 11 16 9 – – 34

SE, standard error. *po0.05. a Results of simple linear regression of the association between ln-transformed POP levels and the year of sampling. b Results of multiple linear regression of the association between ln-transformed POP levels and year of sampling. Variables adjusted for age, pre-pregnancy BMI and body weight change during pregnancy and after delivery. c Estimated time for the concentrations to be halved in the population. d Coefficient of determination for the whole regression model. e Sum of PCB 105, PCB 118, PCB 156 and PCB 167 TEQs. f Sum of PCB 77, PCB 126 and PCB 169 TEQs. g TEQs calculated with TEFs from 2005 (Van den Berg et al., 2006). h Sum mono-ortho PCB TEQ, non-ortho PCB TEQ and PCDD/F TEQ. i Sum of BDE-47, BDE-99, BDE-100, BDE-153 and BDE-154.

The importance of age-adjustment of temporal trend data is further emphasized when the results from our study are compared with those of the Stockholm study (Nore´n and Meironyte´, 2000). The half-times were shorter in our study compared with those reported in the Stockholm study. For instance, the half-times of PCB 118, PCB 138 and PCB 153 in our study were 8–10 years, whereas half-times in the Stockholm study were estimated to 11–17 years. In the Stockholm study, no statistical adjustment could be made for the increased average age of the mothers donating milk during the study period, causing under-estimated rates of decline. Moreover, the pooled samples from Stockholm contained milk from both primiparous and multiparous women. It is well known that the mother’s milk PCB and PCDD/F levels decrease both with time spent breastfeeding and with increasing parity (Dewailly et al., 1996; Schade and Heinzow, 1998; Tajimi et al., 2004; Vaz et al., 1993). We only recruited primiparas in our study, and sampled their milk between 14 and 21 days after birth, thus avoiding variation in PCB and PCDD/F levels due both to differences in the number of

nursed children and to the time of sampling during breast-feeding of the first child. In the multiple regression model, there were also significant associations between mother’s milk levels of most PCBs and PCDD/Fs and pre-pregnancy BMI, weight gain during pregnancy (negative associations), and weight loss after delivery (positive association). Consequently, changes in body constitution may influence mother’s milk levels of POPs. The negative associations could be caused by a ‘‘dilution’’ effect of an increased body weight, and the positive associations by a mobilization of POPs from body fat during weight loss. The introduction of new TEFs for PCDD/Fs and PCBs in year 2005 (Van den Berg et al., 2006) makes it difficult to compare results between studies before and after 2005. In our study, the new TEFs resulted in lower median concentrations of mono-ortho PCB TEQ, PCDF TEQ, PCDD/F TEQ and total TEQ and in somewhat higher median concentration of non-ortho TEQ (Table 1). The main reasons for these changes are the reduction of the TEFs for PCB 156, PCB 118 and 2,3,4,7,8-PeCDF, as well as the increase of the TEF

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0.043∗c-0.592∗d+0.020∗d

150

100

50

0 1995

1997

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2005

15

10

5

1997

1999

5 ln(BDE-153)=-0.061+0.023∗a+0.048∗b-

4

BDE-99 in milk (ng/g lipid)

BDE-153 in milk (ng/g lipid)

ln(PCDD/F TEQ)=1.12+0.054∗a0.061∗b-0.017∗c-0.429∗d+0.015∗e

0 1995

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0.053∗c-0.588∗d+0.018∗e

3 2 1 0 1995

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ln(PCB 153)=3.49+0.068∗a-0,083*b-

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1997

1999

2001 year

2003

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2007

2001 year

2003

2005

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ln(BDE-99)=0.062-0.013∗a-0.077∗b0.010∗c-0.479∗d+0.007∗e

4 3 2 1 0 1995

1997

1999

2001 year

2003

2005

2007

Fig. 1. Temporal trends (1996–2006) of PCB 153 (N ¼ 325), PCDD/F TEQ05 (N ¼ 184), BDE-153 (N ¼ 276) and BDE-99 (N ¼ 276) in mother’s milk from primiparas in Uppsala, Sweden. Each point corresponds to the contaminant level in a milk sample from an individual woman. The equations were obtained from multiple regression analyses where a ¼ age of the mother (years), b ¼ sampling year (0 ¼ 1996, 1 ¼ 1997 etc.), c ¼ pre-pregnancy BMI (kg/m2), d ¼ body weight change during pregnancy (% per week) and e ¼ weight change from delivery to milk sampling (%). The lines represent the regression equations where a, c, d and e were set to the median in the population.

for PCB 169. Mono-ortho PCB TEQs were affected to the greatest extent by the new TEFs, and the reduction in mono-ortho PCB TEQ levels contributed most to the reduction of the total TEQ levels. However, there were no major influences of the new TEFs on the estimated temporal trends of levels of TEQs in mother’s milk. The non-ortho PCBs and the PCDD/Fs were not analysed by the same laboratory throughout the whole study period. A few slight, but statistically significant, differences between the laboratories could be discovered in the results of control sample analysis. However, when the analytical results were corrected for these interlaboratory differences, there were only small differences in the estimated median TEQ concentrations (o1%) and in the temporal trends (annual changes) of TEQs (3–12%). We used uncorrected results in the statistical analysis. The temporal trends of PBDEs deviated from the consistent pattern of decreasing trends of PCBs and PCDD/Fs. The concentrations of BDE-47 and BDE-99 decreased, and concentrations of BDE-153 increased during the study period, while concentrations of BDE-100 did not change at all. The resulting slow decline of sumPBDE is uncertain since the estimated half-time (34 years) was much longer than the duration of the study period. Compared to our results, the Stockholm study suggests similar temporal trends for BDE-47, BDE-99 and BDE-153, although no statistical evaluation of the temporal trends could be done (Fa¨ngstro¨m et al., 2008). The decline in levels of BDE-47 and BDE-99 could be explained by a voluntarily reduced use of lower brominated PBDEs

(pentaBDE) in Sweden since the 1990s, as indicated by the rapid decline in environmental levels (Bignert et al., 2007). Different technical mixtures as sources of PBDEs and differences in persistence may explain the observed differences in temporal trends between congeners. BDE-47 and BDE-99 dominate in some pentaBDE products, whereas BDE-153 is a more significant component of some octaBDE products (La Guardia et al., 2006). Moreover, estimations of elimination half-lives of PBDEs in humans have shown that the half-lives increase with increasing bromination (Geyer et al., 2004). A slower elimination of higher brominated PBDEs has also been demonstrated in a kinetic study in rats (von Meyerinck et al., 1990). Our results and the findings of the Stockholm study show that the decline in levels of lower brominated PBDE-congeners in humans is delayed with approximately 10 years compared with the decline observed in guillemot eggs from the Baltic Sea area (Bignert et al., 2007). The presence of the PBDEs in older consumer products in the home and work environment, and persistence of PBDE-contaminated dust in these environments may contribute to this delay (Stapleton et al., 2005). Worldwide, most other studies of temporal trends of PBDEs in human samples cover earlier time periods than our study and show increasing levels. For example, studies of mother’s milk from the Faroe Islands and serum samples from Norway and the United States showed increasing levels of PBDEs from the later part of the 1970s to the beginning of the 2000s (Fa¨ngstro¨m et al., 2005; Sjo¨din et al., 2004;

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Thomsen et al., 2002). A Japanese study also reported increasing levels of PBDEs in mother’s milk from the 1970s up to 1998, but similar to our results the concentrations seemed to level off from 1998 to 2000 (Akutsu et al., 2003). Among the PBDEs, BDE-153 was the only congener that showed significant associations with age. The lack of associations between maternal age and the levels of BDE-47, BDE-99 and BDE100 support the hypothesis that these congeners might be less persistent than BDE-153 (Geyer et al., 2004) and, consequently, does not accumulate in the body during life-time to the same extent as BDE-153. Similar to our findings, studies in Germany and the United States did not find any significant associations between levels of sumPBDE in milk and maternal age (Raab et al., 2008; Schecter et al., 2003). However, these studies did not present correlations between age and the individual PBDE-congeners. In order to get normal distributed residuals in our regression analyses, observations with standardized residuals Z3 were omitted. Depending on substance, the number of observations that were removed varied between 0 and 7, and this did not affect the estimated temporal trends to any significant extent. When all observations were included in the regression analyses, the mean annual changes increased or decrease with on average 5%. The largest change was seen for PCB 169 where the rate of decline decreased with 30% from 3.3% to 2.3% per year. Based on developmental effects in male rat offspring, the European Scientific Committee on Foods established a tolerable weekly intake (TWI) of 14 pg total TEQ/kg body weight for PCDD/Fs and dioxin-like PCBs (EC-SCF, 2001). The TWI represents a safe intake of dioxin-like compounds during the life-time before and during pregnancy, protecting the foetus from toxic exposure. We used the same 1-compartment, first-order pharmacokinetic model as the EC-SCF, a half-life of elimination of dioxins of 7.5 years, and a 50% absorption of dioxins from food for humans (EC-SCF, 2000) to estimate the steady-state body burden at the TWI level. This resulted in an estimated body burden of 3.9 ng total TEQ/kg body weight or, assuming 30% body fat in women in the age of about 30 years (ICRP 2002), 13 ng/kg body fat. In our study, the median total TEQ concentration in mother’s milk (12 ng/kg lipid) was only 10% lower, and 38% of the women exceeded the TWI-body burden. However, the levels of total TEQ in mother’s milk have decreased during the study period, and the median total TEQ concentration in mother’s milk sampled in 2006 (8.2 ng/kg lipid) was 38% lower than the TWI-body burden. The highest observed total TEQ level in the 2006 samples was 15 ng/kg lipid, and 13% of the women (N ¼ 4) exceeded the TWI-body burden. We only sampled a small part of the Swedish population of young women in one region, and it is likely that there are parts of the population that have higher body burdens than those observed by us. It is thus important to continue the efforts to reduce the levels of these substances in the environment and in foods in order to further reduce the exposure of foetuses and breast-feeding infants. In conclusion, our results show that the levels of PCBs and PCDD/Fs in mother’s milk in Uppsala County in Sweden have decreased during the last 10 years, while the levels of PBDEs do not show any consistent trend. The different trends among the PBDEs point to the importance of analysing trends of individual congeners. It is also important to consider age of the mothers when temporal trends of POPs are examined, since there is a trend among Swedish women of having the first child at older ages (Persson et al., 2006).

Acknowledgements We are grateful to the participating women who showed dedication to the project. Appreciation is expressed to the

midwives who assisted in recruitment and sample collection and to the laboratory personnel for technical assistance. The financial support from the Swedish Environmental Protection Agency is acknowledged.

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