Helle Katrine Knutsen

Diet and particularly seafood are major sources of perfluorinated compounds in humans

Commercially used perfluorinated compounds (PFCs) have been widely detected in wildlife and humans, but the sources of human exposure are not fully characterized. The objectives of this study were to explore possible associations between concentrations of PFCs in serum and consumption of food with particular focus on seafood, and to compare estimated dietary intakes with determined serum PFC concentrations. Concentrations of 19 PFCs were determined in serum from 175 participants in the Norwegian Fish and Game Study and evaluated with respect to food consumption using multiple linear regression analysis. Associations between estimated individual total dietary intakes of PFCs and serum concentrations were also explored. PFC concentrations in serum were significantly associated (p<0.05) with the consumption of lean fish, fish liver, shrimps and meat, as well as age, breastfeeding history and area of residence (R(2) 0.35-0.63). The estimated dietary intakes of perfluorooctanoic acid (PFOA), perfluoroundecanoic acid (PFUnDA) and perfluorooctane sulfonic acid (PFOS) were 0.60, 0.34 and 1.5 ng/kg body weight/day, respectively. Seafood (fish and shellfish) was the major dietary source contributing 38% of the estimated dietary intakes of PFOA, 93% of PFUnDA and 81% of PFOS. The estimated dietary intakes of these three selected PFCs were significantly associated with the corresponding serum PFC concentrations (p<0.05). In conclusion, our results show that consumption of fish and shellfish is a major determinant of serum PFC concentrations. Further, significant relationships between estimated dietary intakes and serum concentrations have been demonstrated for the first time.

Dietary exposure to brominated flame retardants correlates with male blood levels in a selected group of Norwegians with a wide range of seafood consumption.

This study investigates dietary exposure and serum levels of polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) in a group of Norwegians (n = 184) with a wide range of seafood consumption (4-455 g/day). Mean dietary exposure to Sum 5 PBDEs (1.5 ng/kg body weight/day) is among the highest reported. Since concentrations in foods were similar to those found elsewhere in Europe, this may be explained by high seafood consumption among Norwegians. Oily fish was the main dietary contributor both to Sum PBDEs and to the considerably lower HBCD intake (0.3 ng/kg body weight/day). Milk products appeared to contribute most to the BDE-209 intake (1.4 ng/kg body weight/day). BDE-209 and HBCD exposures are based on few food samples and need to be confirmed. Serum levels (mean Sum 7 PBDEs = 5.2 ng/g lipid) and congener patterns (BDE-47 > BDE-153 > BDE-99) were comparable with other European reports. Correlations between individual congeners were higher for the calculated dietary exposure than for serum levels. Further, significant but weak correlations were found between dietary exposure and serum levels for Sum PBDEs, BDE-47, and BDE-28 in males. This indicates that other sources in addition to diet need to be addressed.

Consumption of fish from a contaminated lake strongly affects the concentrations of polybrominated diphenyl ethers and hexabromocyclododecane in serum

Very high concentrations of polybrominated diphenyl ethers (PBDE) have been reported in fish from Lake Mjøsa in Norway. This study was performed to examine the serum concentrations of PBDE and hexabromocyclododecane (HBCD) in consumers of fish from this lake and to investigate possible relationships between serum concentrations, self-reported fish intake and calculated total dietary PBDE exposure. Serum concentrations of the sum of the seven PBDE (BDE-28, 47, 99, 100, 153, 154 and 183) were significantly higher than those of a reference group of Norwegians eating only food with background levels of contamination (medians: 18 ng/g lipids men, 8.4 ng/g lipids women). The median dietary intake of Sum 7 PBDE was 2549 ng/day (30 ng/kg body weight/day), the highest dietary intake of PBDE reported. The contribution from fish caught from the contaminated lake comprised 98.7% of the total dietary exposure. For men, serum levels of PBDE were strongly correlated with the calculated dietary exposure, except for BDE-209. This suggests that sources other than the diet are important for human BDE-209 exposure. The median serum HBCD concentration was 4.1 and 2.6 ng/g lipids for men and women, respectively, and was also found to be associated with consumption of fish from Lake Mjøsa.

Determinants of plasma concentrations of perfluoroalkyl substances in pregnant Norwegian women.

BACKGROUND Perfluoroalkyl substances (PFASs) are widespread pollutants that have been associated with adverse health effects although not on a consistent basis. Diet has been considered the main source of exposure. The aim of the present study was to identify determinants of four plasma PFASs in pregnant Norwegian women. METHODS This study is based in the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Our sample included 487 women who enrolled in MoBa from 2003 to 2004. A questionnaire regarding sociodemographic, medical, and reproductive history was completed at 17 weeks of gestation and a dietary questionnaire was completed at 22 weeks of gestation. Maternal plasma samples were obtained around 17 weeks of gestation. Plasma concentrations of four PFASs (perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA)) were examined in relation to demographic, lifestyle, dietary, and pregnancy-related covariates. Predictors were identified by optimizing multiple linear regression models using Akaikes information criterion (AIC). RESULTS Parity was the determinant with the largest influence on plasma PFAS concentrations, with r(2) between 0.09 and 0.32 in simple regression models. In optimal multivariate models, when compared to nulliparous women, parous women had 46%, 70%, 19%, and 62% lower concentrations of PFOS, PFOA, PFHxS, and PFNA respectively (p<0.001 except for PFHxS, p<0.01). In all these models, duration of breastfeeding was associated with reduced PFAS levels. PFOA showed the largest reduction from breastfeeding, with a 2-3% reduction per month of breastfeeding in typical cases. Levels of PFOS, PFOA, and PFNA increased with time since most recent pregnancy. While pregnancy-related factors were the most important predictors, diet was a significant factor explaining up to 4% of the variance. One quartile increase in estimated dietary PFAS intake was associated with plasma PFOS, PFOA, PFHxS, and PFNA concentration increases of 7.2%, 3.3%, 5.8% and 9.8%, respectively, resulting in small, although non-trivial absolute changes in PFAS concentrations. CONCLUSION Previous pregnancies and breastfeeding duration were the most important determinants of PFASs in this sample of pregnant women.

Recent advances in the risk assessment of melamine and cyanuric acid in animal feed

Melamine can be present at low levels in food and feed mostly from its legal use as a food contact material in laminates and plastics, as a trace contaminant in nitrogen supplements used in animal feeds, and as a metabolite of the pesticide cyromazine. The mechanism of toxicity of melamine involves dose-dependent formation of crystals with either endogenous uric acid or a structural analogue of melamine, cyanuric acid, in renal tubules resulting in potential acute kidney failure. Co-exposure to melamine and cyanuric acid in livestock, fish, pets and laboratory animals shows higher toxicity compared with melamine or cyanuric acid alone. Evidence for crystal formation between melamine and other structural analogs i.e. ammelide and ammeline is limited. Illegal pet food adulterations with melamine and cyanuric acid and adulteration of milk with melamine resulted in melamine-cyanuric acid crystals, kidney damage and deaths of cats and dogs and melamine-uric acid stones, hospitalisation and deaths of children in China respectively. Following these incidents, the tolerable daily intake for melamine was re-evaluated by the U.S. Food and Drug Administration, the World Health Organisation, and the Scientific Panel on Contaminants in the Food Chain of the European Food Safety Authority (EFSA). This review provides an overview of toxicology, the adulteration incidents and risk assessments for melamine and its structural analogues. Particular focus is given to the recent EFSA risk assessment addressing impacts on animal and human health of background levels of melamine and structural analogues in animal feed. Recent research and future directions are discussed.

Essential and toxic element concentrations in blood and urine and their associations with diet: Results from a Norwegian population study including high-consumers of seafood and game

The first aim of the study was to evaluate calculated dietary intake and concentrations measured in blood or urine of essential and toxic elements in relation to nutritional and toxicological reference values. The second aim was to identify patterns of the element concentrations in blood and urine and to identify possible dietary determinants of the concentrations of these elements. Adults with a known high consumption of environmental contaminants (n=111), and a random sample of controls (n=76) answered a validated food frequency questionnaire (FFQ). Complete data on biological measures were available for 179 individuals. Blood and urine samples were analyzed for selenium, iodine, arsenic, mercury, cadmium and lead. Principal component analysis was used to identify underlying patterns of correlated blood and urine concentrations. The calculated intakes of selenium, iodine, inorganic arsenic and mercury were within guideline levels. For cadmium 24% of the high consumer group and 8% of the control group had intakes above the tolerable weekly intake. Concentrations of lead in blood exceeded the bench-mark dose lower confidence limits for some participants. However, overall, the examined exposures did not give rise to nutritional or toxicological concerns. Game consumption was associated with lead in blood (B(ln) 0.021; 95%CI:0.010, 0.031) and wine consumption. Seafood consumption was associated with urinary cadmium in non-smokers (B(ln) 0.009; 95%CI:0.003, 0.015). A novel finding was a distinct pattern of positively associated biological markers, comprising iodine, selenium, arsenic and mercury (eigenvalue 3.8), reflecting seafood intake (B 0.007; 95%CI:0.004, 0.010). The study clearly demonstrates the significance of seafood as a source of both essential nutrients and toxic elements simultaneously and shows that exposure to various essential and toxic elements can be intertwined.

Prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet may be associated with immunosuppressive effects that persist into early childhood.

We investigated whether prenatal exposure from the maternal diet to the toxicants polychlorinated biphenyls (PCBs) and dioxins is associated with the development of immune-related diseases in childhood. Children participating in BraMat, a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), were followed in the three first years of life using annual questionnaires (0-3years; n=162, 2-3years; n=180), and blood parameters were examined at three years of age (n=114). The maternal intake of the toxicants was calculated using a validated food frequency questionnaire from MoBa. Maternal exposure to PCBs and dioxins was found to be associated with an increased risk of wheeze and more frequent upper respiratory tract infections. Furthermore, maternal exposure to PCBs and dioxins was found to be associated with reduced antibody response to a measles vaccine. No associations were found between prenatal exposure and immunophenotype data, allergic sensitization and vaccine-induced antibody responses other than measles. Our results suggest that prenatal dietary exposure to PCBs and dioxins may increase the risk of wheeze and the susceptibility to infectious diseases in early childhood.

Dietary mercury exposure in a population with a wide range of fish consumption — Self-capture of fish and regional differences are important determinants of mercury in blood

Human, low level, chronic exposure to mercury (Hg) from fish is of concern because of potential neurodevelopmental and cardiovascular toxicity. The purpose of the study was to 1) measure total mercury (THg) in blood and estimate dietary exposure in a population group with a wide range of seafood consumption, 2) assess the intake and blood concentration in relation to tolerable intake values, 3) characterise dietary sources, and 4) to investigate the relationship between dietary THg with THg in blood (BTHg), including factors that can explain the variance in BTHg concentrations. The participants (n=184) filled in an extensive food frequency questionnaire which was combined with a database on THg concentrations in Norwegian food, and donated blood and urine. Median consumption of seafood was 65 g/day (range 4 to 341 g/day). The calculated mean dietary THg exposure was 0.35 (median 0.30) μg/kg body weight/week. Seafood contributed on average 95% to the exposure. The JECFA Provisional Tolerable Weekly Intake (PTWI) of 1.6 μg MeHg/kg bw/week was not exceeded by any of the participants. BTHg ranged from 0.6 to 30 μg/L, with a mean of 5.3 (median 4.0 μg/L). There was a strong relationship between total seafood consumption and BTHg concentrations (r=0.58 95%CI: 0.48, 0.67) and between estimated THg dietary exposure and BTHg (r=0.46 95%CI: 0.35, 0.57). Fish consumption, sex, catching >50% of their seafood themselves, and living in coastal municipalities were significant factors in linear regression models with lnBTHg. Including urinary Hg in the regression model increased the explained variance from 54% to 65%. In a toxicokinetic model, the calculated dietary intake appeared to moderately underestimate the measured BTHg among the participants with the highest BTHg. Only two of the participants had BTHg slightly above a value equivalent to the JECFA PTWI, but none of them were women in fertile age.

Maternal dietary intake of dioxins and polychlorinated biphenyls and birth size in the Norwegian Mother and Child Cohort Study (MoBa)

Maternal diet not only provides essential nutrients to the developing fetus but is also a source of prenatal exposure to environmental contaminants. We investigated the association between dietary intake of dioxins and PCBs during pregnancy and birth size. The study included 50,651 women from the Norwegian Mother and Child Cohort Study (MoBa). Dietary information was collected by FFQs and intake estimates were calculated by combining food consumption and food concentration of dioxins, dioxin-like PCBs and non-dioxin-like PCBs. We used multivariable regression models to estimate the association between dietary intake of dioxins and PCBs and fetal growth. The contribution of fish and seafood intake during pregnancy was 41% for dietary dioxins and dioxin-like PCBs and 49% for dietary non-dioxin-like PCBs. Further stratified analysis by quartiles of seafood intake during pregnancy was conducted. We found an inverse dose-response association between dietary intake of dioxins and PCBs and fetal growth after adjustment for confounders. Newborns of mothers in the upper quartile of dioxin and dioxin-like PCBs intake had 62g lower birth weight (95% CI: -73, -50), 0.26cm shorter birth length (95% CI: -0.31, -0.20) and 0.10cm shorter head circumference (95% CI: -0.14, -0.06) than newborns of mothers in the lowest quartile of intake. Similar negative associations for intake of dioxins and dioxin-like PCBs were found after excluding women with intakes above the tolerable weekly intake (TWI=14pg TEQ/kg bw/week). The negative association of dietary dioxins and PCBs with fetal growth was weaker as seafood intake was increasing. No association was found between dietary dioxin and PCB intake and the risk for small-for-gestational age neonate. In conclusion, dietary intakes of dioxins and PCBs during pregnancy were negatively associated with fetal growth, even at intakes below the TWI.

Prenatal mercury exposure and infant birth weight in the Norwegian Mother and Child Cohort Study.

OBJECTIVE To examine the association between calculated maternal dietary exposure to Hg in pregnancy and infant birth weight in the Norwegian Mother and Child Cohort Study (MoBa). DESIGN Exposure was calculated with use of a constructed database of Hg in food items and reported dietary intake during pregnancy. Multivariable regression models were used to explore the association between maternal Hg exposure and infant birth weight, and to model associations with small-for-gestational-age offspring. SETTING The study is based on data from MoBa. SUBJECTS The study sample consisted of 62 941 women who answered a validated FFQ which covered the habitual diet during the first five months of pregnancy. RESULTS Median exposure to Hg was 0·15 μg/kg body weight per week and the contribution from seafood intake was 88 % of total Hg exposure. Women in the highest quintile compared with the lowest quintile of Hg exposure delivered offspring with 34 g lower birth weight (95 % CI -46 g, -22 g) and had an increased risk of giving birth to small-for-gestational-age offspring, adjusted OR = 1·19 (95 % CI 1·08, 1·30). Although seafood intake was positively associated with increased birth weight, stratified analyses showed negative associations between Hg exposure and birth weight within strata of seafood intake. CONCLUSIONS Although seafood intake in pregnancy is positively associated with birth weight, Hg exposure is negatively associated with birth weight. Seafood consumption during pregnancy should not be avoided, but clarification is needed to identify at what level of Hg exposure this risk might exceed the benefits of seafood.