Are temporal trends of some persistent organochlorine and organobromine compounds in Swedish breast milk slowing down?

We investigated body burdens of persistent organic pollutants (POPs) in Swedish first-time mothers by measurements in breast milk, and followed up the temporal trends between 1996 and 2017. POPs were analysed in individual samples (n = 539) from participants from Uppsala county, Sweden. This made it possible to adjust temporal trends for age of the mother, pre-pregnancy BMI, weight gain during pregnancy, weight loss after delivery, and education, the main determinants for POP body burdens, apart from sampling year. We also compared observed body burdens with the body burdens determined to be safe from a health perspective in the risk assessment of dioxin-like polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), published by the European Food Safety Authority (EFSA). Declining temporal trends in breast milk of on average -4 to 14% per year were observed 1996-2017 for PCBs, PCDD/Fs, chlorinated pesticides, and brominated flame retardants, except for the polybrominated diphenyl ethers (PBDEs) BDE-153 and BDE-209. The toxic equivalents (TEQs) for PCDD declined faster than PCDF TEQs, -6.6% compared to -3.5% per year. For CB-169, CB-180, PCDDs, PCDFs, Total TEQ, and hexachlorobenzene (HCB), a change point year (CP) was observed around 2008-2009 and after that, the decline in levels has slowed down. If breast milk levels follows the exponential declining trend of total TEQ estimated for the entire period (-5.7% per year), 97.5% of first time mothers from the Uppsala area will have body burdens below the estimated safe level in year 2022. If instead it follows the estimated % decline after the CP in 2008 (-1.6% per year), it will take until 2045 before 97.5% is below the estimated safe level. It is important to proceed with the monitoring of POPs in breast milk from Swedish mothers in order to further observe if the levels are stabilizing or continue to decline.

Cholesterol Crystals and NLRP3 Mediated Inflammation in the Uterine Wall Decidua in Normal and Preeclamptic Pregnancies.

Preeclampsia is a hypertensive and inflammatory pregnancy disorder associated with cholesterol accumulation and inflammation at the maternal-fetal interface. Preeclampsia can be complicated with fetal growth restriction (FGR) and shares risk factors and pathophysiological mechanisms with cardiovascular disease. Cholesterol crystal mediated NLRP3 inflammasome activation is central to cardiovascular disease and the pathway has been implicated in placental inflammation in preeclampsia. Direct maternal-fetal interaction occurs both in the uterine wall decidua and at the placental surface and these aligned sites constitute the maternal-fetal interface. This study aimed to investigate cholesterol crystal accumulation and NLRP3 inflammasome expression by maternal and fetal cells in the uterine wall decidua of normal and preeclamptic pregnancies. Pregnant women with normal (n = 43) and preeclamptic pregnancies with (n = 28) and without (n = 19) FGR were included at delivery. Cholesterol crystals were imaged in decidual tissue by both second harmonic generation microscopy and polarization filter reflected light microscopy. Quantitative expression analysis of NLRP3, IL-1ß and cell markers was performed by immunohistochemistry and automated image processing. Functional NLRP3 activation was assessed in cultured decidual explants. Cholesterol crystals were identified in decidual tissue, both in the tissue stroma and near uterine vessels. The cholesterol crystals in decidua varied between pregnancies in distribution and cluster size. Decidual expression of the inflammasome components NLRP3 and IL-1ß was located to fetal trophoblasts and maternal leukocytes and was strongest in areas of proximity between these cell types. Pathway functionality was confirmed by cholesterol crystal activation of IL-1ß in cultured decidual explants. Preeclampsia without FGR was associated with increased trophoblast dependent NLRP3 and IL-1ß expression, particularly in the decidual areas of trophoblast and leukocyte proximity. Our findings suggest that decidual accumulation of cholesterol crystals may activate the NLRP3 inflammasome and contribute to decidual inflammation and that this pathway is strengthened in areas with close maternal-fetal interaction in preeclampsia without FGR.

Cyclodextrin Reduces Cholesterol Crystal-Induced Inflammation by Modulating Complement Activation.

Cholesterol crystals (CC) are abundant in atherosclerotic plaques and promote inflammatory responses via the complement system and inflammasome activation. Cyclic oligosaccharide 2-hydroxypropyl-ß-cyclodextrin (BCD) is a compound that solubilizes lipophilic substances. Recently we have shown that BCD has an anti-inflammatory effect on CC via suppression of the inflammasome and liver X receptor activation. The putative effects of BCD on CC-induced complement activation remain unknown. In this study, we found that BCD bound to CC and reduced deposition of Igs, pattern recognition molecules, and complement factors on CC in human plasma. Furthermore, BCD decreased complement activation as measured by terminal complement complex and lowered the expression of complement receptors on monocytes in whole blood in response to CC exposure. In line with this, BCD also reduced reactive oxygen species formation caused by CC in whole blood. Furthermore, BCD attenuated the CC-induced proinflammatory cytokine responses (e.g., IL-1α, MIP-1α, TNF, IL-6, and IL-8) as well as regulated a range of CC-induced genes in human PBMC. BCD also regulated complement-related genes in human carotid plaques treated ex vivo. Formation of terminal complement complex on other complement-activating structures such as monosodium urate crystals and zymosan was not affected by BCD. These data demonstrate that BCD inhibits CC-induced inflammatory responses, which may be explained by BCD-mediated attenuation of complement activation. Thus, these findings support the potential for using BCD in treatment of atherosclerosis.

Serum levels of brominated flame retardants (BFRs: PBDE, HBCD) and influence of dietary factors in a population-based study on Swedish adults.

The aim of this study was to investigate associations between serum concentrations of brominated flame retardants and personal characteristics, including diet, in adults participating in a population-based study in Sweden 2010-11. Moreover, observed concentrations were used in a health risk assessment, using published health-based reference values. Serum samples of 170 adult individuals of both sexes were analyzed for 10 PBDE congeners and HBCD by GC-MS. When including concentrations between LOD and LOQ, highest median serum concentration was observed for BDE-153 (1.2 ng/g serum lipid), followed by BDE-209 (0.95 ng/g lipid), BDE-47 (0.49 ng/g lipid) and BDE-100 (0.21 ng/g lipid). Median concentration of HBCD was 0.10 ng/g lipid. A few markedly elevated concentrations of BDE-209, HBCD (77-78 ng/g lipid) and BDE-47 (44 ng/g lipid) were observed. The only statistical significant findings were higher BDE-153 concentrations in men than in women, and positive associations between serum BDE-153 concentrations and consumption of fish (total), beef, mutton and poultry. PBDE concentrations were in accordance with concentrations reported in other European countries but generally lower than those found in North America. Median PBDE serum concentrations observed in adults from Sweden suggest sufficient health protection, when compared with published health-based reference values, although some outliers with high serum concentrations had lower safety margins.

Environmental organic pollutants in human milk before and after weight loss.

Many persistent organic pollutants (POPs) are banned because they accumulate in organisms and are toxic. Lipophilic POPs are stored in maternal adipose tissue and concentrations in human milk (HM) may increase during weight loss. Our aim was to examine associations between weight loss and concentrations of chlorinated POPs in HM in lactating women participating in a weight loss study. We analysed POPs (PCB 28, PCB 153, HCB, DDE) in HM at 12 and 24 weeks postpartum from 32 women who participated in a randomized, 2 × 2 factorial trial of diet and exercise for postpartum weight loss. Participants donated milk before and after the intervention period. We examined associations between weight loss and change in POP concentrations and estimated the intake of POPs by their breastfed infants. Most (n = 27) women lost weight during intervention, 0.45 ± 0.30 kg/week (mean ± SD). Among these women, the concentration of PCB 153 in HM was significantly (p = 0.04) higher at follow-up than at baseline. Weight loss was significantly positively associated with changes in concentrations of all studied POPs (2.0-2.4% increase per percent weight loss). Estimated mean intakes of POPs (ng/day) remained stable because infant milk consumption decreased during the study period. As infants gained weight, estimated mean intakes per kg body weight decreased 17-22%. Changes in concentrations of POPs in HM correlated positively with maternal weight loss, but it is unlikely that the balance between the benefits and risks of breastfeeding will change if the weight loss is restricted to 0.5 kg per week.

Maternal body burdens of PCDD/Fs and PBDEs are associated with maternal serum levels of thyroid hormones in early pregnancy: a cross-sectional study.

BACKGROUND: Thyroid hormones (THs) regulate many biological functions in the human body and are essential for normal brain development. Epidemiological studies have observed diverging associations between halogenated persistent organic pollutant (POP) exposure and concentrations of THs in pregnant women and their infants. We investigated whether background exposure to polybrominated diphenyl ethers (PBDEs) is related to TH status in a Swedish population of pregnant women and their infants. Furthermore, we examined associations between polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) and TH status in early pregnancy as an extension of an earlier study focusing on late pregnancy TH status. METHODS: Free thyroxine (T4), total triiodo-thyronine (T3) and thyroid stimulating hormone (TSH) were analysed in serum from first-time mothers (N = 220-281) in the first and third trimester, and in infants (N = 115-150) 3 weeks and 3 months after delivery. Antibodies to thyroid peroxidase (anti-TPO) (N = 260) were measured in maternal third trimester serum. Maternal body burdens of PCBs (N = 281) were estimated from serum lipid PCB concentrations in late pregnancy, and PCDD/F (N = 97) and PBDE (N = 186) body burdens were estimated from concentrations in mother's milk lipids 3 weeks after delivery. Linear regression models allowed for covariate adjustment of the associations between ln-transformed POP body burdens and concentrations of TH and anti-TPO. RESULTS: Maternal body burden of BDE-153 was inversely associated with first trimester total T3, otherwise no associations between PBDEs and first and second trimester THs were observed. No associations were found between maternal PBDE body burdens and infant THs. Maternal body burden of PCDD/Fs were inversely associated with first trimester total T3. No associations were observed between PCBs and first trimester THs. Third trimester anti-TPO was not associated with maternal PCBs, PCDD/Fs and PBDEs. CONCLUSIONS: Our results suggest that maternal PCDD/F and BDE-153 body burdens influence maternal TH status in early pregnancy, which is a critical period when maternal TH status influences fetal development.

Influence of contaminated drinking water on perfluoroalkyl acid levels in human serum--A case study from Uppsala, Sweden.

In 2012 a contamination of drinking water with perfluoroalkyl acids (PFAAs) was uncovered in the City of Uppsala, Sweden. The aim of the present study was to determine how these substances have been distributed from the contamination source through the groundwater to the drinking water and how the drinking water exposure has influenced the levels of PFAAs in humans over time. The results show that PFAA levels in groundwater measured 2012-2014 decreased downstream from the point source, although high ΣPFAA levels (>100ng/L) were still found several kilometers from the point source in the Uppsala aquifer. The usage of aqueous film forming fire-fighting foams (AFFF) at a military airport in the north of the city is probably an important contamination source. Computer simulation of the distribution of PFAA-contaminated drinking water throughout the City using a hydraulic model of the pipeline network suggested that consumers in the western and southern parts of Uppsala have received most of the contaminated drinking water. PFAA levels in blood serum from 297 young women from Uppsala County, Sweden, sampled during 1996-1999 and 2008-2011 were analyzed. Significantly higher concentrations of perfluorobutane sulfonic acid (PFBS) and perfluorohexane sulfonic acid (PFHxS) were found among women who lived in districts modeled to have received contaminated drinking water compared to unaffected districts both in 1996-1999 and 2008-2011, indicating that the contamination was already present in the late 1990s. Isomer-specific analysis of PFHxS in serum showed that women in districts with contaminated drinking water also had an increased percentage of branched isomers. Our results further indicate that exposure via contaminated drinking water was the driving factor behind the earlier reported increasing temporal trends of PFBS and PFHxS in blood serum from young women in Uppsala.

TLR8 Senses Staphylococcus aureus RNA in Human Primary Monocytes and Macrophages and Induces IFN-ß Production via a TAK1-IKKß-IRF5 Signaling Pathway.

Staphylococcus aureus may cause serious infections and is one of the most lethal and common causes of sepsis. TLR2 has been described as the main pattern recognition receptor that senses S. aureus and elicits production of proinflammatory cytokines via MyD88 -: NF-κB signaling. S. aureus can also induce the production of IFN-ß, a cytokine that requires IFN regulatory factors (IRFs) for its transcription, but the signaling mechanism for IFN-ß induction by S. aureus are unclear. Surprisingly, we demonstrate that activation of TLR2 by lipoproteins does not contribute to IFN-ß production but instead can suppress the induction of IFN-ß in human primary monocytes and monocyte-derived macrophages. The production of IFN-ß was induced by TLR8-mediated sensing of S. aureus RNA, which triggered IRF5 nuclear accumulation, and this could be antagonized by concomitant TLR2 signaling. The TLR8-mediated activation of IRF5 was dependent on TAK1 and IκB kinase (IKK)ß, which thus reveals a physiological role of the recently described IRF5-activating function of IKKß. TLR8 -: IRF5 signaling was necessary for induction of IFN-ß and IL-12 by S. aureus, and it also contributed to the induction of TNF. In conclusion, our study demonstrates a physiological role of TLR8 in the sensing of entire S. aureus in human primary phagocytes, including the induction of IFN-ß and IL-12 production via a TAK1 -: IKKß -: IRF5 pathway that can be inhibited by TLR2 signaling.

Reconstituted High-Density Lipoprotein Attenuates Cholesterol Crystal-Induced Inflammatory Responses by Reducing Complement Activation.

Chronic inflammation of the arterial wall is a key element in the development of atherosclerosis, and cholesterol crystals (CC) that accumulate in plaques are associated with initiation and progression of the disease. We recently revealed a link between the complement system and CC-induced inflammasome caspase-1 activation, showing that the complement system is a key trigger in CC-induced inflammation. HDL exhibits cardioprotective and anti-inflammatory properties thought to explain its inverse correlation to cardiovascular risk. In this study, we sought to determine the effect of reconstituted HDL (rHDL) on CC-induced inflammation in a human whole blood model. rHDL bound to CC and inhibited the CC-induced complement activation as measured by soluble terminal C5b-9 formation and C3c deposition on the CC surface. rHDL attenuated the amount of CC-induced complement receptor 3 (CD11b/CD18) expression on monocytes and granulocytes, as well as reactive oxygen species generation. Moreover, addition of CC to whole blood resulted in release of proinflammatory cytokines that were inhibited by rHDL. Our results support and extend the notion that CC are potent triggers of inflammation, and that rHDL may have a beneficial role in controlling the CC-induced inflammatory responses by inhibiting complement deposition on the crystals.

Time trends of polybrominated diphenylether (PBDE) congeners in serum of Swedish mothers and comparisons to breast milk data.

In the present study our main focus was blood serum levels and time trends of the fully brominated diphenyl ether (PBDE) BDE-209 in Swedish first-time mothers, as relatively a few human data on this congener are currently available. Also, levels and temporal trends in serum of other more commonly reported PBDE congeners and HBCD were studied. In an ongoing study on POPs in Uppsala Primiparas (POPUP), serum samples (N=413) from first-time mothers from 1996 to 2010 were used. Pooling of individual samples (5-25 individuals/pool, approx. 3 pools/year) resulted in 36 pooled samples used for PBDE/HBCD analysis on GC-LRMS. In addition, serum/breast milk correlations for PBDE and HBCD levels in 30 paired samples from individual mothers sampled 2010 were studied. The mean serum level of BDE-209 (1.3ng/g lipid wt.) was highest of all studied PBDE congeners, followed by BDE-47 and BDE-153. There was no significant temporal trend for BDE-209 during the study period, whereas the levels of BDE-47, BDE-99, BDE-100 and of HBCD decreased significantly in pooled serum 1996-2010. After omission of one outlier, a significant increasing trend was observed for BDE-153. The serum/milk PBDE quotients in paired individual samples from 2010 ranged from 0.83 to 17, with the highest quotient for BDE-209. Differences in PBDE transfer from blood to milk are probably related to molecular weight or size. The correlations between serum and milk levels of tetra- to hexa-brominated congeners were generally strong (r=0.83-0.97), but weaker for BDE-183 (r=0.57) and BDE-209 (r=0.38). Regarding HBCD, serum levels in 2010 were mostly beneath LOQ which made serum/milk quotients impossible. The decreasing levels of some BFR compounds in serum over time show that exposures have decreased after the production and use of some of these substances have been restricted. The lack of temporal trend of BDE-209 suggests that the human exposure to this congener in Sweden has been stable for more than a decade.

Cholesterol crystals induce complement-dependent inflammasome activation and cytokine release.

Inflammation is associated with development of atherosclerosis, and cholesterol crystals (CC) have long been recognized as a hallmark of atherosclerotic lesions. CC appear early in the atheroma development and trigger inflammation by NLRP3 inflammasome activation. In this study we hypothesized whether CC employ the complement system to activate inflammasome/caspase-1, leading to release of mature IL-1ß, and whether complement activation regulates CC-induced cytokine production. In this study we describe that CC activated both the classical and alternative complement pathways, and C1q was found to be crucial for the activation. CC employed C5a in the release of a number of cytokines in whole blood, including IL-1ß and TNF. CC induced minimal amounts of cytokines in C5-deficient whole blood, until reconstituted with C5. Furthermore, C5a and TNF in combination acted as a potent primer for CC-induced IL-1ß release by increasing IL-1ß transcripts. CC-induced complement activation resulted in upregulation of complement receptor 3 (CD11b/CD18), leading to phagocytosis of CC. Also, CC mounted a complement-dependent production of reactive oxygen species and active caspase-1. We conclude that CC employ the complement system to induce cytokines and activate the inflammasome/caspase-1 by regulating several cellular responses in human monocytes. In light of this, complement inhibition might be an interesting therapeutic approach for treatment of atherosclerosis.

Prenatal exposure to polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) may influence birth weight among infants in a Swedish cohort with background exposure: a cross-sectional study.

BACKGROUND: Prenatal exposure to persistent organic pollutants, e.g. polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) has been suggested to negatively affect birth weight although epidemiological evidence is still inconclusive. We investigated if prenatal exposure to PCBs and PBDEs is related to birth weight in a Swedish population with background exposure. METHODS: Breast milk was sampled during the third week after delivery from first-time mothers in Uppsala county, Sweden 1996-2010 (POPUP cohort) (N = 413). Samples were analysed for di-ortho PCBs (CB-138, 153, 180) and tetra- to hexa- brominated PBDEs (BDE-47, 99, 100, 153). Simple and multiple linear regression models were used to investigate associations between lipid-adjusted, ln-transformed PCB and PBDE concentrations, and birth weight. Covariates included in the multivariate regression model were PCB and PBDE exposure, maternal age, pre-pregnancy BMI, weight gain during pregnancy, education, smoking, gender of the infant and gestational length. The effect of including fish consumption was also investigated. RESULTS: In the multivariate model, prenatal exposure to di-ortho PCBs was significantly associated with increased birth weight (ß = 137; p = 0.02). The result did not change when gestational length was added to the model. An inverse association between PBDE(4) (sum of BDE-47, -99, -100 and -153) and birth weight was observed in the multivariate model including gestational length (ß = -106; p = 0.04). Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders of the association between di-ortho PCBs and birth weight. The associations were not alleviated after adjustment for fish consumption, a major source of PCB and PBDE exposure. The observed associations were stronger for boys than for girls. CONCLUSIONS: Our results indicate that prenatal exposure to di-ortho PCBs and PBDE(4) may influence birth weight in different directions, i.e. PCB exposure was associated with higher birth weight and PBDE exposure with lower birth weight. Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders that may hide positive association between di-ortho PCB exposure and birth weight if they are not included in the statistical model. We speculate that even small PCB- and PBDE-induced shifts in the distribution of birth weight may influence future public health in populations with background exposure.

The NLRP12 inflammasome recognizes Yersinia pestis.

Yersinia pestis, the causative agent of plague, is able to suppress production of inflammatory cytokines IL-18 and IL-1ß, which are generated through caspase-1-activating nucleotide-binding domain and leucine-rich repeat (NLR)-containing inflammasomes. Here, we sought to elucidate the role of NLRs and IL-18 during plague. Lack of IL-18 signaling led to increased susceptibility to Y. pestis, producing tetra-acylated lipid A, and an attenuated strain producing a Y. pseudotuberculosis-like hexa-acylated lipid A. We found that the NLRP12 inflammasome was an important regulator controlling IL-18 and IL-1ß production after Y. pestis infection, and NLRP12-deficient mice were more susceptible to bacterial challenge. NLRP12 also directed interferon-γ production via induction of IL-18, but had minimal effect on signaling to the transcription factor NF-κB. These studies reveal a role for NLRP12 in host resistance against pathogens. Minimizing NLRP12 inflammasome activation may have been a central factor in evolution of the high virulence of Y. pestis.

Perfluorinated alkyl acids in blood serum from primiparous women in Sweden: serial sampling during pregnancy and nursing, and temporal trends 1996-2010.

We investigated temporal trends of blood serum levels of 13 perfluorinated alkyl acids (PFAAs) and perfluorooctane sulfonamide (FOSA) in primiparous women (N = 413) from Uppsala County, Sweden, sampled 3 weeks after delivery 1996-2010. Levels of the short-chain perfluorobutane sulfonate (PFBS) and perfluorohexane sulfonate (PFHxS) increased 11%/y and 8.3%/y, respectively, and levels of the long-chain perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) increased 4.3%/y and 3.8%/y, respectively. Concomitantly, levels of FOSA (22%/y), perfluorooctane sulfonate (PFOS, 8.4%/y), perfluorodecane sulfonate (PFDS, 10%/y), and perfluorooctanoate (PFOA, 3.1%/y) decreased. Thus, one or several sources of exposure to the latter compounds have been reduced or eliminated, whereas exposure to the former compounds has recently increased. We explored if maternal levels of PFOS, PFOA, and PFNA during the early nursing period are representative for the fetal development period, using serial maternal serum samples, including cord blood (N = 19). PFAA levels in maternal serum sampled during pregnancy and the nursing period as well as in cord blood were strongly correlated. Strongest correlations between cord blood levels and maternal levels were observed for maternal serum sampled shortly before or after the delivery (r = 0.70-0.89 for PFOS and PFOA). A similar pattern was observed for PFNA, although the correlations were less strong due to levels close to the method detection limit in cord blood.

Occurrence and levels of organochlorine compounds in human breast milk in Bangladesh.

In low-income countries, the use of some organochlorine pesticides is still common in order to increase food production. Monitoring the chemical exposure is an important step in risk-reducing strategies. This is the first study to report concentrations of organochlorines in breast milk of women from Bangladesh where farming is the main income source. Organochlorines such as p,p'-DDT, o,p'-DDT, p,p'-DDE, p,p'-DDD (i.e., ∑DDT), HCB, α-, ß- and γ-HCH, trans-chlordane, cis-chlordane, oxy-chlordane, trans-nonachlor, cis-nonachlor, mirex and polychlorinated biphenyls (CB 28, 52, 99, 101, 105, 114, 118, 123, 128, 138, 141, 149, 153, 156, 157, 163, 167, 170, 180, 183, 187, 189, 194) were analyzed in breast milk collected in 2002 from 72 first-time mothers (median age 20years) living in the rural area Matlab, Bangladesh. While the concentrations of PCBs and many of the pesticides were low, the concentrations of p,p'-DDT and its metabolite p,p'-DDE were high (median 349 and 1645ngg(-1)lipid, respectively) in comparison to other countries. The median value of ∑DDT was 2123ngg(-1)lipid. The estimated daily exposure to p,p'-DDT, p,p'-DDE and ∑DDTs was 10, 30 and 42µgkg(-1) body weight, respectively, in 3months old infants. The p,p'-DDE/p,p'-DDT ratio ranged from 1 to 23, where 58% of the mothers had a ratio below 5 indicating recent or ongoing DDT exposure. This study reports infant exposure and maternal body burden of organochlorines through breast milk. Although the findings give no reason to limit breast-feeding, it is essential to identify the main exposure sources and find means to decrease the exposure.

4-Nonylphenol and bisphenol A in Swedish food and exposure in Swedish nursing women.

4-Nonylphenol (NP) and bisphenol A (BPA) are phenolic substances used in high volumes by the industry. Studies on cells and in experimental animals have shown that both these compounds can be classified as estrogenic hormone disrupters. Information about the exposure of humans to NP and BPA is still scarce, especially regarding levels in human blood. The first aim of this study was to investigate possible sources of NP and BPA exposure from food, by analyzing the levels of NP and BPA from a Swedish food market basket, based on the Swedish per capita food consumption. A second aim was to investigate blood serum levels of NP and BPA, as well as NP-ethoxylates, among young women in Sweden (n=100). Moreover, associations between food consumption and blood NP and BPA levels were studied. In food, NP was to some extent found at levels above limit of quantification (LOQ 20 ng/g fresh weight) in fruits, cereal products, vegetables, and potatoes. BPA levels above LOQ (2 ng/g fresh weight) were found in fish, meats, potatoes, and dairy products. The estimated mean intakes per capita were (medium bound) 27 µg NP/day and 3.9 µg BPA/day, showing that food is a source of BPA and NP in the general Swedish population. In blood serum, free NP above limit of detection (LOD 0.5 ng/g) was detected in 46% of the study participants while detectable levels of total NP (LOD 0.8 ng/g) were observed in 43%. The corresponding percentages for BPA were 25% and 22%, respectively. The results indicate that there is a continuous source of exposure to NP and BPA that is high enough for free NP and BPA to be detected in some consumers. Among the participants with quantifiable levels of free and total NP (n=38), 85% (median, range: 38-112%) of the NP was present as free NP. For BPA 76% (49-109%) was detected as free BPA (n=15). All women had levels of ethoxylates of NP below LOD (0.1-0.7 ng/g). A significantly higher total consumption of fruits and vegetables was reported in questionnaires by participants with NP levels at or above LOD than among women with levels below LOD. This result is supporting the market basket results of relatively high NP levels in these types of food.

Levels of brominated flame retardants and other pesistent organic pollutants in breast milk samples from Limpopo Province, South Africa.

The non-occupational exposure to brominated flame retardants, and other persistent organic pollutants (POPs) was studied by collecting human breast milk samples from mothers residing in Thohoyandou area, a rural district in the Limpopo Province, northern part of South Africa (SA). Of all collected samples to be analysed (n=28), those with large enough milk volumes, (n=14) were quantified for polybrominated diphenyl ethers (PBDEs) (9 congeners: BDE-28, 47, 66, 99, 100, 138, 153, 154, and 183) and hexabromocyclododecane (HBCD) on a GC equipped with dual capillary columns and dual electron-capture detectors (ECD). The levels of PBDE congeners (median sumBDE 1.3 ng/g of lipids) and of HBCD were not far from levels generally found in European studies, and this study may be the first report on the presence of PBDEs and HBCD in SA breast milk. On a congener basis, the finding of comparably high BDE-183 levels suggests a specific PBDE usage, or contamination situation in SA. Apart from BFRs, the high DDT levels found in the breast milk from this area (median and maximum sumDDT levels of about 4600 and over 20,000 ng/g of lipids, respectively; n=28) have earlier been reported. In addition, other POPs (PCBs, HCB and HCHs) were found in SA breast milk, at relatively low levels. To conclude, measurable levels of PBDEs and HBCD, and a specific BDE congener pattern, were found in breast milk from the Limpopo province, SA. A number of other POPs, including DDTs in high levels, were also present.

Large variation in breast milk levels of organohalogenated compounds is dependent on mother's age, changes in body composition and exposures early in life.

We identified factors that are important determinants of body burdens (breast milk levels) of polychlorinated biphenyls (PCBs), dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)) and polybrominated diphenyl ethers (PBDEs). PCBs, PCDD/Fs and PBDEs were analysed in breast milk from up to 325 first-time mothers in Uppsala, Sweden, who delivered between 1996 and 2006. Hierarchical clustering was used as a method for identification of groups of compounds with common sources of exposure and similar toxicokinetics. Based on correlations between levels of single compounds/congeners in breast milk, distinctly separated clusters were formed, strongly dependent on structural similarities of the organohalogen molecules. In a multiple regression model, levels of PCBs (except PCB 28), PCDD/Fs and BDE-153 were positively associated with age of the mother and weight loss after delivery and inversely associated with pre-pregnancy BMI (body mass index) and weight gain during pregnancy. Higher levels of mono-ortho PCB TEQ, non-ortho PCB TEQ and BDE-153 in milk were found among women with high physical activity. Women who were breastfed during infancy and grew up on the Baltic coast of Sweden, with high availability of contaminated fish from the Baltic sea, had higher levels of PCBs and PCDD/Fs in breast milk indicating that exposure early in life from breast milk and contaminated fish may still affect body burdens at the time of pregnancy. The importance of current consumption of fatty Baltic fish as a source of exposure was supported by the positive association with breast milk levels of mono-ortho PCB TEQ, PCDF TEQ and BDE-153. The results show that, in contrast to the lower brominated PBDE congeners, the hexa-brominated BDE-153 resembles the chlorinated compounds with regards to determinants in breast milk. This suggests that some of the PBDEs may have toxicokinetic properties and that are similar to the PCBs and PCDD/Fs. Our results show that a few simple advices to women regarding weight changes in connection with pregnancy and consumption of contaminated fatty fish during the whole lifetime may lower the levels of dioxins in breast milk by up to 60%.

PCDD/F, PCB, PBDE, HBCD and chlorinated pesticides in a Swedish market basket from 2005--levels and dietary intake estimations.

Based on consumption data statistics, food items from four regions in Sweden were sampled in a so-called market basket study. Food items from five food groups, i.e. fish, meat, dairy products, eggs and fat/oils, were analyzed for persistent organic pollutants (POPs) followed by per capita intake calculations. The highest levels of PCDD/F, PCB, PBDE, HBCD and chlorinated pesticides were found in the fish/fish products. The estimated market basket per capita intake of PCDD/F and dl-PCB was 0.7pg WHO-TEQ kg bw(-1) d(-1) (TEFs from 1998). The intake of ∑PCB was estimated to 4.9 ng kg bw(-1) d(-1) and fish was found to be the major contributor with 64%. The intake of ∑PBDE was found to be 0.7 ng kg bw(-1) d(-1). Fish (38%) and dairy products (31%) were the largest contributors to the total PBDE intake. The intake of HBCD was estimated to 0.14 ng kg bw(-1) d(-1). HBCD mainly came from fish (65%), but also dairy products (24%) and meat (10%) contributed. Also regarding the chlorinated pesticides, fish was found to be the major contributor, with 51% of the ∑DDT coming from fish. The intake of ∑DDT, ∑HCH and HCB was 4.0, 1.0 and 1.1 ng kg bw(-1) d(-1), respectively. Most of the ∑HCH and HCB originate from dairy products (43% and 55%, respectively). This study shows that the levels, and intake, of different POPs from food of animal origin in the market basket of 2005 seem to have decreased since the market basket study in 1999.

Changes in serum concentrations of polychlorinated biphenyls (PCBs), hydroxylated PCB metabolites and pentachlorophenol during pregnancy.

We studied pregnancy-related changes in serum concentrations of five polychlorinated biphenyls (PCBs, CB 118, CB 138, CB 153, CB 156, CB 180), three hydroxylated PCB metabolites (4-OH-CB107, 4-OH-CB146, 4-OH-CB187), and pentachlorophenol (PCP). Median serum lipid content increased 2-fold between early (weeks 9-13) and late pregnancy (weeks 35-36) (N=10), whereas median PCB levels in serum lipids decreased 20-46%, suggesting a dilution of PCB concentrations in serum lipids. Nevertheless, strong positive intra-individual correlations (Spearman's r=0.61-0.99) were seen for PCBs during the whole study period. Thus, if samples have been collected within the same relative narrow time window during pregnancy, PCB results from one single sampling occasion can be used in assessment of relative differences in body burdens during the whole pregnancy period. Concentrations of OH-PCBs in blood serum tended to decline as pregnancy progressed, although among some women the concentrations increased at the end of pregnancy. Positive intra-individual correlations (r=0.66-0.99) between OH-PCB concentrations were observed during the first and second trimester, whereas correlations with third trimester concentrations were more diverging (r=-0.70-0.85). No decline in PCP concentrations was observed during pregnancy and no significant correlations were found between concentrations at different sampling periods. Our results suggest that for both OH-PCBs and PCP, sampling has to be more specifically timed depending on the time period during pregnancy that is of interest. The differences in patterns of intra- and inter-individual variability of the studied compounds may be due to a combination of factors, including lipid solubility, persistence of the compounds, distribution in blood, metabolic formation, and pregnancy-related changes in body composition and physiological processes.