Associations of PFAS-related plasma metabolites with cholesterol and triglyceride concentrations.

The wide-spread environmental pollutants per- and polyfluoroalkyl substances (PFAS) have repeatedly been associated with elevated serum cholesterol in humans. However, underlying mechanisms are still unclear. Furthermore, we have previously observed inverse associations with plasma triglycerides. To better understand PFAS-induced effects on lipid pathways we investigated associations of PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations. We used 290 PFAS-related metabolite features that we previously discovered from untargeted liquid chromatography-mass spectometry metabolomics in a case-control study within the Swedish Västerbotten Intervention Programme cohort. Herein, we studied associations of these PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations in plasma samples from 187 healthy control subjects collected on two occasions between 1991 and 2013. The PFAS-related features did not associate with cholesterol, but 50 features were associated with triglycerides. Principal component analysis on these features indicated that one metabolite pattern, dominated by glycerophospholipids, correlated with longer chain PFAS and associated inversely with triglycerides (both cross-sectionally and prospectively), after adjustment for confounders. The observed time-trend of the metabolite pattern resembled that of the longer chain PFAS, with higher levels during the years 2004-2010. Mechanisms linking PFAS exposures to triglycerides may thus occur via longer chain PFAS affecting glycerophospholipid metabolism. If the results reflect a cause-effect association, as implied by the time-trend and prospective analyses, this may affect the general adult population.

Predictors of Beta-Hexachlorocyclohexane blood levels among people living close to a chemical plant and an illegal dumping site.

BACKGROUND: Hexachlorocyclohexane is a synthetic chemical with several isomers, including ß-Hexachlorocyclohexane (ß-HCH). In 2005, a large contamination of crude milk from some bovine farms along the Sacco River (Central Italy) was detected; it was related to the illegal disposal of large quantities of processing waste by a chemical industry of the area. A biomonitoring study, conducted in 2007 on a sample of the residing population, found high values of ß-HCH in people living close to the river. These results led to the establishment of a clinical and epidemiological surveillance program on all the exposed population. The aim of the study was to evaluate the determinants of ß-HCH blood levels in people living within 1 Km of the Sacco River, focusing on the role of specific foods, body mass index and risk factors not yet identified. METHODS: The program involved all people living within 1 km of the river. A descriptive analysis of ß-HCH blood levels was done in relation to the potential determinants including specific foods. Regression analysis was used to study the association between potential determinants and (natural log) ß-HCH haematic concentration. The results were expressed as geometric mean ratios (GMR). To take into account similarities within the families we adjusted for family clustering. RESULTS: A total of 602 subjects (87.2%) agreed to participate in the surveillance. The ß-HCH geometric mean serum concentration was 72 ng/g lipid. The regression analysis showed that being female (GMR: 1.32, 95%CI: 1.14-1.53), elderly (GMR> 70yy: 10.04, 95%CI: 6.65-15.15), obese (GMR: 1.63, 95%CI: 1.28-2.08), eating food of local/own production (GMR 1.47, 95%CI: 1.15-1.88) and using water from private wells (GMRdrink:1.47, 95%CI: 1.00-2.14 and GMRwash: 1.48, 95%CI: 1.17-1.87) were associated with higher ß-HCH values. There was inverse association with breastfeeding (GMR: 0.64, 95%CI: 0.47-0.86). The focus on specific foods showed that the most important factors were eggs and beef. CONCLUSIONS: The study indicated a greater contamination for older people, and those drinking and washing with water from private wells and consuming locally produced food, especially eggs and beef.

Associations between persistent organic pollutants and metabolic syndrome in morbidly obese individuals.

BACKGROUND AND AIMS: Persons with "metabolically healthy" obesity may develop cardiometabolic complications at a lower rate than equally obese persons with evident metabolic syndrome. Even morbidly obese individuals vary in risk profile. Persistent organic pollutants (POPs) are widespread environmental chemicals that impair metabolic homeostasis. We explored whether prevalence of metabolic syndrome in morbidly obese individuals is associated with serum concentrations of POPs. METHODS AND RESULTS: A cross-sectional study among 161 men and 270 women with BMI >35 kg/m2 and comorbidity, or >40 kg/m2. Circulating concentrations of 15 POPs were stratified by number of metabolic syndrome components. In multiple logistic regression analysis odds ratios between top quartile POPs and metabolic risk factors versus POPs below the top quartile were calculated adjusting for age, gender, body mass index, smoking status, alcohol consumption and cholesterol concentrations. Age-adjusted concentrations of trans-nonachlor and dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs) increased with number of metabolic syndrome components in both genders (p < 0.001), while the organochlorine pesticides HCB, ß-HCH and p,p'DDE increased only in women (p < 0.008). Organochlorine pesticides in the top quartile were associated with metabolic syndrome as were dioxin-like and non-dioxin-like PCBs (OR 2.3 [95% CI 1.3-4.0]; OR 2.5 [95% CI 1.3-4.8] and 2.0 [95% CI 1.1-3.8], respectively). Organochlorine pesticides were associated with HDL cholesterol and glucose (OR = 2.0 [95% CI = 1.1-3.4]; 2.4 [95% CI = 1.4-4.0], respectively). Dioxin-like PCBs were associated with diastolic blood pressure, glucose and homeostatic model assessment-insulin resistance index (OR = 2.0 [95% CI = 1.1-3.6], 2.1 [95% CI = 1.2-3.6] and 2.1 [95% CI = 1.0-4.3], respectively). CONCLUSION: In subjects with morbid obesity, metabolic syndrome was related to circulating levels of organochlorine pesticides and PCBs suggesting that these compounds aggravate clinically relevant complications of obesity.

Biomonitoring of selected persistent organic pollutants (PCDD/Fs, PCBs and PBDEs) in Finnish and Russian terrestrial and aquatic animal species.

BACKGROUND: The Finnish and Russian animal species (semi-domesticated reindeer, Finnish wild moose, Baltic grey seal and Baltic herring) samples were biomonitored in terrestrial and aquatic environments for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs). RESULTS: Grey seal (Halichoerus grypus) was clearly the most contaminated species. The mean PBDE concentration in grey seal was 115 ng/g fat, and the highest WHO-PCDD/F-PCB-TEQ (toxic equivalent set by WHO) was 327 pg/g fat. In Finnish, reindeer WHO-PCDD/F-TEQ varied from 0.92 pg/g fat in muscle to 90.8 pg/g fat in liver. WHO-PCDD/F-TEQ in moose liver samples was in the range of 0.7-4.26 pg/g fat, and WHO-PCB-TEQ in the range of 0.42-3.34 pg/g fat. Overall moose had clearly lower PCDD/F and DL-PCB concentrations in their liver than reindeer. CONCLUSIONS: Terrestrial animals generally had low POP concentrations, but in reindeer liver dioxin levels were quite high. All Finnish and Russian reindeer liver samples exceeded the EU maximum level [8] for PCDD/Fs (10 pg/g fat), which is currently set for bovine animals.

Biological responses of midge (Chironomus riparius) and lamprey (Lampetra fluviatilis) larvae in ecotoxicity assessment of PCDD/F-, PCB- and Hg-contaminated river sediments.

We evaluated the utility of chironomid and lamprey larval responses in ecotoxicity assessment of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/F)-, polychlorinated biphenyls (PCB)- and mercury (Hg)-contaminated river sediments. Sediment samples were collected from the River Kymijoki with a known industrial pollution gradient. Sediment for the controls and lamprey larvae were obtained from an uncontaminated river nearby. Contamination levels were verified with sediment and tissue PCDD/F, PCB and Hg analyses. Behaviour of sediment-exposed chironomid and lamprey larvae were measured with Multispecies Freshwater Biomonitor© utilizing quadrupole impedance conversion technique. In addition, mortality, growth and head capsule deformity incidence of chironomids were used as ecotoxicity indicators. WHOPCDD/F+PCB-TEQ in the R. Kymijoki sediments ranged from the highest upstream 22.36 ng g(-1) dw to the lowest 1.50 ng g(-1) near the river mouth. The sum of PCDD/Fs and PCBs correlated strongly with Hg sediment concentrations, which ranged from <0.01 to 1.15 µg g(-1). Lamprey tissue concentrations of PCDD/Fs were two orders and PCBs one order of magnitude higher in the R. Kymijoki compared to the reference. Chironomid growth decreased in contaminated sediments and was negatively related to sediment ∑PCDD/Fs, WHOPCDD/F+PCB-TEQ and Hg. There were no significant differences in larval mortality or chironomid mentum deformity incidence between the sediment exposures. The distinct behavioural patterns of both species indicate overall applicability of behavioural MFB measurements of these species in sediment toxicity bioassays. Chironomids spent less and lampreys more time in locomotion in the most contaminated sediment compared to the reference, albeit statistically significant differences were not detected. Lamprey larvae had also a greater activity range in some of the contaminated sediments than in the reference. High pollutant levels in lamprey indicate risks for biomagnification in the food webs, with potential health risks to humans consuming fish.

Prenatal exposure to persistent organic pollutants and offspring allergic sensitization and lung function at 20 years of age.

BACKGROUND: Prenatal exposures to persistent organic pollutants (POPs) have been associated with asthma medication use and self-reported symptoms, but associations with lung function and allergic sensitization have been minimally explored. The aim of the study was to examine the associations between prenatal exposures to POPs and allergic sensitization and lung function in 20-year-old offspring. METHODS: In a Danish cohort of 965 pregnant women established in 1988-1989, six polychlorinated biphenyl (PCB) congeners, hexachlorobenzene (HCB), and dichlorodiphenyldichloroethylene (p,p'-DDE) were quantified in archived maternal serum drawn in gestational week 30 (n = 872). Among those with available maternal exposure information, at age 20, 421 offspring attended attended a clinical examination including measurements of allergic sensitization (serum-specific IgE ≥ 0.35 kUA /L) (n = 418) and lung function [forced expiratory volume in one second (FEV1 ) and forced vital capacity (FVC)] (n = 414). RESULTS: There were no associations between maternal concentrations of POPs and offspring allergic sensitization at 20 years of age. Maternal concentrations of POPs were, however, positively associated with offspring airway obstruction (FEV1 /FVC < 75%). Compared to offspring in the first tertile of exposure, offspring in the third tertile of dioxin-like PCB exposure had an OR of 2.96 (95% CI: 1.14-7.70). Similar associations for non-dioxin-like PCBs, HCB, and p,p'-DDE were 2.68 (1.06-6.81), 2.63 (1.07, 6.46), and 2.87 (1.09, 7.57), respectively. No associations were observed with reduced lung function (FEV1 % of predicted value < 90%). CONCLUSION AND CLINICAL RELEVANCE: Our data indicate that prenatal exposure to POPs appears to be associated with airway obstruction but not allergic sensitization at 20 years of age. The findings support that chronic obstructive lung diseases may have at least part of their origins in early life.

Organic anion transporter 4 (OAT 4) modifies placental transfer of perfluorinated alkyl acids PFOS and PFOA in human placental ex vivo perfusion system.

INTRODUCTION: Perfluorinated alkyl acids (PFAAs) are widely used in industry and consumer products. Pregnant women are exposed to PFAAs and their presence in umbilical cord blood represents fetal exposure. Interestingly, PFAAs are substrates for organic anion transporters (OAT) of which OAT4 is expressed in human placenta. METHODS: To evaluate the contribution of OAT4 and ATP-binding cassette transporter G2 (ABCG2) proteins in the transplacental transfer of perfluoro octane sulfonate (PFOS) and perfluoro octanoate (PFOA) an ex vivo dual recirculating human placental perfusion was used. Altogether 8 placentas from healthy mothers with uncomplicated pregnancies were successfully perfused. RESULTS: Both PFOS and PFOA crossed the placenta as suggested by in vivo data in the literature. The expression of OAT4 and ABCG2 proteins were studied by immunoblotting and correlation with the transfer index %(TI %) of PFOS and PFOA at 120 and 240 min (n = 4) was studied. The expression of OAT4 was in negative correlation with TI % of PFOA (R(2) = 0.92, p = 0.043) and PFOS (R(2) = 0.99, p = 0.007) at 120 min while at 240 min the correlation was statistically significant only with PFOA. The expression of ABCG2 did not correlate with TI% of PFOS or PFOA. DISCUSSION: Data obtained in this study suggest the involvement of OAT4 in placental passage of PFAAs. Placental passage of PFOS and PFOA is modified by the transporter protein OAT4 but not by ABCG2. This is the first study indicating that OAT4 may decrease the fetal exposure to PFAAs and protect the fetus after maternal exposure to PFAAs but further studies are needed to confirm our findings.

Time trends and congener profiles of PCDD/Fs, PCBs, and PBDEs in Baltic herring off the coast of Finland during 1978-2009.

In Finland, consumption of Baltic fatty fish may lead to high exposure to persistent organic pollutants (POPs), which might have hazardous health effects. Monitoring of POPs in Baltic fish enables the health authorities to keep dietary advice on fish consumption up to date. In this study, which is a compilation of analytical data from earlier studies, time trends and congener profiles of polychlorinated dioxins and furans (PCDD/Fs) and biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) in Baltic herring are reported. Altogether 344 samples of Baltic herring from 1978-2009 were collected across the Finnish coast of the Baltic Sea. The chemical analysis was performed in an accredited testing laboratory with high resolution gas chromatography mass spectrometry. During the 31-year period, PCDD/F and PCB concentrations decreased on approximately 80%, from approximately 20 to 5 pg/g fw, expressed as WHO2005 TEQ. The PBDE concentrations experienced a 4-10 fold increase during late 1980s-early 1990s, and declined to 1978s levels of approximately 2 ng/g fw by 2009. The current concentrations of PCDD/Fs, PCBs and PBDEs in Baltic herring are relatively low, and mostly below EU maximum accepted levels, and are expected to continue decreasing. In the future, it may be possible to re-evaluate the consumption restrictions for this specific Baltic fatty fish.

Persistent organic pollutant levels in semi-domesticated reindeer (Rangifer tarandus tarandus L.), feed, lichen, blood, milk, placenta, foetus and calf.

A study concerning persistent organic pollutants in Finnish semi-domesticated reindeer was conducted in northern Finland. The aim of this study was to explore POP presence in different tissues of reindeer. In addition, it was studied how POPs are transported from food concentrates and lichen to reindeer hind tissues and further to the placenta, foetus, milk and calf. Concentrations of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/Fs), 37 polychlorinated biphenyls (PCBs) (including 12 dioxin-like PCBs), and 15 polybrominated diphenyl ethers (PBDEs) were analysed. In most of the reindeer muscle tissue samples PCBs were clearly dominating compounds (on average 58% of the total WHO-TEQ). The total WHO-TEQ was higher in the muscle tissue of reindeer calves than in their corresponding hinds (on average 1.7 pg/g fat vs. 1.1 pg/g fat, respectively). The total WHO-TEQ concentrations were higher in the muscle and liver tissues of reindeer hinds than in their blood or placentas. The foetuses had clearly lower WHO-TEQ concentrations than their corresponding hinds. The contribution of WHO-PCDD/F-TEQ to the total WHO-TEQ was somewhat higher in the liver than in the muscle tissue. The reindeer hind-calf pair, which had gone through the lichen diet, had on average higher WHO-PCDD/F- and PCB-TEQ concentrations in their tissues than the hind-calf-pair that had gone through the reindeer food concentrate diet. WHO-PCB-TEQs in the reindeer foetuses were equal with the concentrations of placentas. The reindeer foetuses contained generally more PBDEs than their corresponding hinds and placentas. This may indicate effective transport of these compounds through the placenta of reindeer.

Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis.

BACKGROUND: Fish consumption and omega-3 polyunsaturated fatty acid (PUFA) intake are shown to protect from cardiovascular diseases (CVD). However, most fish contain environmental contaminants such as dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and methylmercury (MeHg) that may have adverse effects on cardiovascular health. OBJECTIVE: Our aim was to elucidate the associations of fish consumption, omega-3 PUFAs, environmental contaminants with low-grade inflammation, early atherosclerosis, and traditional CVD risk factors. METHODS: The Health 2000 survey participants (n=1173) represented the general Finnish population and the Fishermen study participants (n=255) represented a population with high fish consumption and high exposure to environmental contaminants. Model-adjusted geometric means and tests for linear trend were calculated for CVD risk factors by tertiles of fish consumption and serum omega-3 PUFAs, and additionally in the Fishermen study only, by tertiles of serum PCDD/F+PCB, and blood MeHg. RESULTS: Serum triglyceride decreased across omega-3 PUFA tertiles in both sexes and studies. Insulin resistance, C-reactive protein, tumour necrosis factor α, and interleukin 6 decreased across omega-3 PUFA tertiles among the Health 2000 survey participants. Among the Fishermen study men, insulin resistance and arterial stiffness indicated by ß-stiffness index tended to increase and the RR estimate for carotid artery plaque tended to decrease across tertiles of PCDD/F+PCB and MeHg. CONCLUSION: Previously established hypotriglyceridemic and anti-inflammatory effects of omega-3 PUFAs were seen also in this study. The hypothesised favourable effect on insulin sensitivity and arterial elasticity was suggested to be counteracted by high exposure to environmental contaminants but the effect on plaque prevalence appeared not to be harmful.

Pollutant concentrations in placenta.

Unborn children are exposed to environmental pollutants via the placenta, and there is a causal relationship between maternal intake of pollutants and fetal exposure. Placental examination is an effective way for acquiring data for estimating fetal exposure. We analyzed the concentrations of 104 congeners of persistent organic pollutants, seven organotin compounds, five heavy metals, and methylmercury in 130 randomly selected placentas. Additionally, we examined similarities between pollutant concentrations by analyzing correlations between their placental concentrations. Our results yield new information for conducting contaminant risk assessments for the prenatal period. Out of the 117 individual persistent organic pollutants or metals assayed, 46 could be detected in more than half of the placentas. Moreover, dichlorodiphenyldichloroethylene (p,p'-DDE) was found in all placentas. The data indicates that fetal exposure to dioxins and furans (PCDD/Fs), polychlorinated biphenyls (PCBs), p,p'-DDE, and methylmercury depends on the mother's parity, and age. We also conclude that sources of the above four pollutants are similar but differ from the sources of polybrominated diphenyl ethers.

Association between chemical pattern in breast milk and congenital cryptorchidism: modelling of complex human exposures.

During the past four decades, there has been an increase in the incidence rate of male reproductive disorders in some, but not all, Western countries. The observed increase in the prevalence of male reproductive disorders is suspected to be ascribable to environmental factors as the increase has been too rapid to be explained by genetics alone. To study the association between complex chemical exposures of humans and congenital cryptorchidism, the most common malformation of the male genitalia, we measured 121 environmental chemicals with suspected or known endocrine disrupting properties in 130 breast milk samples from Danish and Finnish mothers. Half the newborns were healthy controls, whereas the other half was boys with congenital cryptorchidism. The measured chemicals included polychlorinated biphenyls (PCBs), polybrominated diphenyl-ethers, dioxins (OCDD/PCDFs), phthalates, polybrominated biphenyls and organochlorine pesticides. Computational analysis of the data was performed using logistic regression and three multivariate machine learning classifiers. Furthermore, we performed systems biology analysis to explore the chemical influence on a molecular level. After correction for multiple testing, exposure to nine chemicals was significantly different between the cases and controls in the Danish cohort, but not in the Finnish cohort. The multivariate analysis indicated that Danish samples exhibited a stronger correlation between chemical exposure patterns in breast milk and cryptorchidism than Finnish samples. Moreover, PCBs were indicated as having a protective effect within the Danish cohort, which was supported by molecular data recovered through systems biology. Our results lend further support to the hypothesis that the mixture of environmental chemicals may contribute to observed adverse trends in male reproductive health.

Associations between congenital cryptorchidism in newborn boys and levels of dioxins and PCBs in placenta.

In animal studies, exposure to dioxins has been associated with disrupted development of the male reproductive system, including testicular maldescent. Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition, one previous case-control study has reported an association between congenital cryptorchidism and colostrum PCB levels. We performed a case-control study to evaluate whether congenital cryptorchidism in boys was associated with increased levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition, associations between placenta levels of these chemicals and reproductive hormone levels in boys at 3 months were studied. Placentas were collected in a Danish-Finnish joint prospective cohort study on cryptorchidism (1997-2001). The boys were examined for cryptorchidism at birth and at 3 months. Altogether, 280 placentas [112 Finnish (56 cases, 56 controls) and 168 Danish (39 cases, 129 controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum samples taken at 3 months were analysed for reproductive hormones. No significant differences between cases and controls were observed in either country in dioxin WHO-TEq levels (median 9.78 vs. 8.47 pg/g fat, respectively, in Finland, and 11.75 vs. 10.88 pg/g fat in Denmark) or PCB WHO-TEq levels (median 2.12 vs. 2.15 pg/g fat in Finland, 2.34 vs. 2.10 pg/g fat in Denmark) or total-TEq levels (median 11.66 vs. 10.58 pg/g fat in Finland, 13.94 vs. 13.00 pg/g fat in Denmark). Placenta WHO-TEq levels of dioxins were not associated with infant reproductive hormone levels at 3 months. In Finland, PCB WHO-TEq levels in placenta associated positively with infant LH levels. WHO-TEq levels of dioxins and PCBs and total-TEq levels were higher in Danish than Finnish samples. In conclusion, no association between placenta levels of dioxins or PCBs and congenital cryptorchidism was found. Significant country differences in chemical levels were observed.

Occurrence of PCDD/F, PCB, PBDE, PFAS, and organotin compounds in fish meal, fish oil and fish feed.

We analysed polychlorinated dibenzo-p-dioxins and furans (PCDD/F, dioxins), and polychlorinated biphenyls (PCB) in 13 fish meal, five fish oil, and seven fish feed samples. Polybrominated diphenyl ethers (PBDE), organotin compounds (OTC), and perfluoroalkylated substances (PFAS) were analysed in ten fish meal, two fish oil, and two fish feed samples. All measured TEQ concentrations of PCDD/F and PCB were below the maximum levels set by Directive 2002/32/EC. There was no correlation between concentrations of WHOPCDD/F-TEQ and indicator PCB in our samples. The most common congeners among PBDEs were BDE-47 and BDE-100. BDE-209 was present in five fish meals of the ten analysed. Tributyltin (TBT) was the predominant congener in all samples except in three fish meals, where monobutyltin (MBT) was the major congener. Perfluorooctane sulphonate (PFOS) was the predominant congener in six fish meals of the ten analysed. There was large variation in concentrations and congener distributions of the studied compounds between our samples. Our results underline a need to pay special attention to the origin and purity of feed raw material of marine origin.

Dioxins, polychlorinated biphenyls, methyl mercury and omega-3 polyunsaturated fatty acids as biomarkers of fish consumption.

BACKGROUND/OBJECTIVES: To assess biomarkers and frequency questions as measures of fish consumption. SUBJECTS/METHODS: Participants in the Fishermen substudy numbered 125 men and 139 women (aged 22-74), and in the Health 2000 substudy, 577 men and 712 women (aged 45-74) participated. The aim of the Fishermen study was to examine the overall health effect of fish consumption in a high-consumption population, whereas the aim of the Health 2000 substudy was to obtain in-depth information on cardiovascular diseases and diabetes. Fish consumption was measured by the same validated food frequency questionnaire (FFQ) in both the studies, with a further two separate frequency questions used in the Fishermen substudy. Dioxins, polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) (in the Fishermen substudy alone), and omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (in both studies) were analyzed from fasting serum/blood samples. RESULTS: The Spearman's correlation coefficients between FFQ fish consumption and dioxins, PCBs, MeHg and omega-3 PUFAs were respectively 0.46, 0.48, 0.43 and 0.38 among the Fishermen substudy men, and 0.28, 0.36, 0.45 and 0.31 among women. Similar correlation coefficients were observed between FFQ fish consumption and serum omega-3 PUFAs in the Health 2000 substudy, and also between FFQ fish consumption and the frequency questions on fish consumption in the Fishermen substudy. According to multiple regression modeling and LMG metrics, the most important fish consumption biomarkers were dioxins and PCBs among the men and MeHg among the women. CONCLUSIONS: Environmental contaminants seemed to be slightly better fish consumption biomarkers than omega-3 PUFAs in the Baltic Sea area. The separate frequency questions measured fish consumption equally well when compared with the FFQ.

Country-specific chemical signatures of persistent environmental compounds in breast milk.

Recent reports have confirmed a worldwide increasing trend of testicular cancer incidence, and a conspicuously high prevalence of this disease and other male reproductive disorders, including cryptorchidism and hypospadias, in Denmark. In contrast, Finland, a similarly industrialized Nordic country, exhibits much lower incidences of these disorders. The reasons behind the observed trends are unexplained, but environmental endocrine disrupting chemicals (EDCs) that affect foetal testis development are probably involved. Levels of persistent chemicals in breast milk can be considered a proxy for exposure of the foetus to such agents. Therefore, we undertook a comprehensive ecological study of 121 EDCs, including the persistent compounds dioxins, polychlorinated biphenyls (PCBs), pesticides and flame retardants, and non-persistent phthalates, in 68 breast milk samples from Denmark and Finland to compare exposure of mothers to this environmental mixture of EDCs. Using sophisticated, bioinformatic tools in our analysis, we reveal, for the first time, distinct country-specific chemical signatures of EDCs with Danes having generally higher exposure than Finns to persistent bioaccumulative chemicals, whereas there was no country-specific pattern with regard to the non-persistent phthalates. Importantly, EDC levels, including some dioxins, PCBs and some pesticides (hexachlorobenzene and dieldrin) were significantly higher in Denmark than in Finland. As these classes of EDCs have been implicated in testicular cancer or in adversely affecting development of the foetal testis in humans and animals, our findings reinforce the view that environmental exposure to EDCs may explain some of the temporal and between-country differences in incidence of male reproductive disorders.

Molar-incisor-hypomineralisation and dioxins: new findings.

AIM: According to our earlier study, molar-incisor-hypomineralisation (MIH) was associated with the exposure of a child via mother's milk to polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) in a group of Finnish children born in 1987. Since the levels of PCDD/Fs and PCBs in mother's milk/placenta have remarkably decreased, it was important to find out if an association still exists. METHODS: The study group was composed of 167 mothers and their children. Placental samples from the mothers were collected in maternity hospitals in Helsinki and Oulu in 1995--1999 and concentrations of the 17 most toxic PCDD/PCDF and 36 PCB congeners were measured. After 7-10 years the children were examined for MIH and the mothers were interviewed on the duration of breast-feeding. RESULTS: MIH was found in 24 children (14.4%). The duration of breast-feeding ranged from 0 to 30 months (mean=7.2+/-4.7). WHOPCDD/FTEQ ranged from 2.5 to 39.1 pg/g fat (mean=13.7+/-6.8) and WHOPCBTEQ from 0.7 to 9.8 pg/g fat (mean=2.7+/-1.4). The mean sum of PCDD/Fs was 196+/-105 pg/g fat and that of PCBs was 57.2+/-28.1ng/g fat. The total exposure to PCDD/Fs, which was calculated from the placental concentration (used as a proxy for the milk concentration) and duration of breastfeeding, was not associated with the occurrence or severity of MIH. Neither was the total exposure to PCBs associated with the occurrence or severity of MIH. CONCLUSION: At prevailing levels, exposure of a child via placenta/mother's milk to PCDD/Fs and PCBs is not associated with MIH.

Dioxins in adipose tissue of women in Southern Spain.

Seventeen polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were quantified in adipose tissue samples of non-occupationally exposed women living in Southern Spain. Geometric mean levels of sum of congeners and WHO(PCDD/F)-TEQ(2005) were 410 and 17.9pgg(-1) fat, respectively. Among PCDDs, octachlorodibenzo-p-dioxin (OCDD) showed the highest concentration with a mean value of 265pgg(-1) fat, followed by 1,2,3,6,7,8-HxCDD (49.3pgg(-1) fat) and 1,2,3,4,6,7,8-HpCDD (45.2pgg(-1) fat). These three congeners were responsible for around 90% of the sum of all PCDD/F congeners in adipose tissue. The geometric mean 2,3,7,8-TCDD value was 1.87pgg(-1) fat. 2,3,4,7,8-PeCDF (8.43pgg(-1) fat) showed the highest concentration among the PCDFs, followed by 1,2,3,4,7,8-HxCDF (4.17pgg(-1) fat) and 1,2,3,6,7,8-HxCDF (3.28pgg(-1) fat), and these three congeners were responsible for 4% of the sum of all studied PCDD/F congeners in adipose tissue and 76% of the sum of ten PCDFs. 1,2,3,7,8,9-HxCDF was the only congener not quantified in any sample, while 1,2,3,4,7,8,9-HpCDF, 1,2,3,7,8-PeCDF, OCDF and 2,3,7,8-TCDF were found in 5, 16, 16 and 19 samples, respectively. All other congeners were quantifiable in all 20 samples. Congeners contributing most to the WHO(PCDD/F)-TEQ(2005) were 1,2,3,7,8-PeCDD (31.6%), 1,2,3,6,7,8-HxCDD (28.3%) and 2,3,4,7,8-PeCDF (14.6%). The body burden of log-transformed WHO(PCDD/F)-TEQ(2005) levels increased with age (B=0.02; 95% CI=0.01, 0.03; p=0.02). Although these adipose tissue PCDD/F levels are similar to previously published findings in Spain and other European countries, further research is needed to determine trends in the exposure of women to these chemical residues.

Polychlorinated biphenyls (PCBs) and hydroxy-PCBs in adipose tissue of women in Southeast Spain.

Polychlorinated biphenyls (PCBs) and hydroxylated PCBs (OH-PCBs) were investigated in human adipose tissue samples collected from 20 women undergoing surgery. Mean sum of PCB and sum of OH-PCB levels were 737ng/g of lipid and 8pg/g of lipid, respectively. Among PCBs, congeners 180, 153, 138 and 170 were the most frequent and abundant, and together constituted 72% of the total amount of PCBs in adipose tissue. The PCB congener pattern and the frequencies and concentrations of non-dioxin-like and non-hydroxylated congeners observed in adipose tissue were similar in distribution and order of magnitude to the profile previously published in Spain but lower than that found in other European countries. Among OH-PCB congeners studied, 4-OH-PCB 107/118 was found at the highest concentrations followed by 3'-OH-PCB 180 and 3-OH-PCB 138. To date, no information on levels of PCB metabolites in the Spanish population is available for comparison. These three predominant OH-PCBs contributed 97% of all OH-PCBs. Twelve dioxin-like PCBs contributed around 8% of the total PCB exposure, and all were present in all study subjects. Further research is required to determine trends in human exposure to PCBs and OH-PCBs and how existing banning measures affect exposure.

Concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in milk of women from Catalonia, Spain.

In this study, the concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in milk from women living in the vicinity of a new hazardous waste incinerator (HWI) in Catalonia, Spain, were determined. The study was performed after 4 years of regular operations in the facility and the present PCB levels were compared with baseline concentrations obtained in a pre-operational program. PCBs and PBDEs levels were determined by HRGC/HRMS in 15 samples. In the present study planar PCBs ranged from 1.3 to 6.3 pg WHO-TEQ/g fat with a mean value of 3.8 pg WHO-TEQ/g fat. After adding dioxin-like mono-ortho-PCBs the total PCB-TEQ concentrations ranged from 3.8 to 13.3 pg WHO-TEQ/g fat (mean value: 8.7 pg WHO-TEQ/g fat). A comparison of the current data with those obtained in the baseline study showed significant decreases for both planar and total WHO-TEQ of PCBs: 47.9% and 44.6%, respectively. PCB concentrations in milk of women living in urban zones were higher than those living near industrial areas (10.1 and 7.4 pg WHO-TEQ/g fat, respectively). Mean PBDE concentrations were 2.2 and 2.5 ng/g fat for women living in urban and industrial zones, respectively. Dietary intake of PCBs and PBDEs for a standard adult woman samples were 898 and 843 ng/day for PCBs, and 72 and 63 ng/day for PBDEs, for residents in urban and industrials areas, respectively. This study suggests that dietary intake is more relevant for human exposure to PCBs and PBDEs than living near the HWI.