Design, Methods, and Participation in Riksmaten Young Children-A Swedish National Dietary Survey.

Background: National dietary surveys provide essential data for risk benefit assessments of foods and nutrients, for management and policy development. Physical activity measurement and biomonitoring can provide important complementary data but are less commonly included. Objectives: This study aimed to describe the study design and methods of the cross-sectional Swedish national dietary survey Riksmaten Young Children (Riksmaten småbarn), of children aged 9 mo, 18 mo, and 4 y. Participation/dropout rates for the 2 older age groups are also presented. The impact of different recruitment strategies is discussed. Methods: Children (N = 16,655) were randomly selected from the population register; invitations to guardians were sent by post and where possible, followed up by telephone. Food intake was assessed by a 2-d food diary and/or questionnaire. Height and weight were reported after measurement. Physical activity (accelerometery, 7 d) and stool, blood, and urine samples were assessed in subgroups. Results: Food consumption data were collected in 1828 children (11% of the invited; 18 mo: n = 1078, and 4 y: n = 750). Of participants also in subgroups, 71% provided physical activity data (n = 1307), 60% stool samples (n = 630), and 51% blood and/or urine samples (n = 593). The study population represented all geographic regions and types of municipalities in Sweden, but participating households had both higher education level and higher income than the target population. Only minor differences were seen in participation rates between recruitment via post and telephone compared with those through post only (12% compared with 10%). Repeated contact attempts were needed for the majority of participants (65%). Despite the low-participation rate, 99% of the participants completed the study once started. Conclusions: Although it was a challenge to recruit participants, Riksmaten Young Children provides a substantial amount of information at national level, representative in terms of sex, geography, and family structure. The underrepresentation of households with lower socioeconomic position must be considered when generalizing results.

Socio-demographic inequalities influence differences in the chemical exposome among Swedish adolescents.

Relatively little is known about the relationship between socio-demographic factors and the chemical exposome in adolescent populations. This knowledge gap hampers global efforts to meet certain UN sustainability goals. The present work addresses this problem in Swedish adolescents by discerning patterns within the chemical exposome and identify demographic groups susceptible to heightened exposures. Enlisting the Riksmaten Adolescents 2016-17 (RMA) study population (N = 1082) in human-biomonitoring, and using proportional odds ordinal logistic regression models, we examined the associations between concentrations of a diverse array of substances (N = 63) with the determinants: gender, age, participant/maternal birth country income per capita level, parental education levels, and geographic place of living (longitude/latitude). Participant/maternal birth country exhibited a significant association with the concentrations of 46 substances, followed by gender (N = 41), and longitude (N = 37). Notably, individuals born in high-income countries by high-income country mothers demonstrated substantially higher estimated adjusted means (EAM) concentrations of polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs) and per- and polyfluoroalkyl substances (PFASs) compared to those born in low-income countries by low-income country mothers. A reverse trend was observed for cobalt (Co), cadmium (Cd), lead (Pb), aluminium (Al), chlorinated pesticides, and phthalate metabolites. Males exhibited higher EAM concentrations of chromium (Cr), mercury (Hg), Pb, PCBs, chlorinated pesticides, BFRs and PFASs than females. In contrast, females displayed higher EAM concentrations of Mn, Co, Cd and metabolites of phthalates and phosphorous flame retardants, and phenolic substances. Geographical disparities, indicative of north-to-south or west-to-east substance concentrations gradients, were identified in Sweden. Only a limited number of lifestyle, physiological and dietary factors were identified as possible drivers of demographic inequalities for specific substances. This research underscores birth country, gender, and geographical disparities as contributors to exposure differences among Swedish adolescents. Identifying underlying drivers is crucial to addressing societal inequalities associated with chemical exposure and aligning with UN sustainability goals.

Low concentrations of perfluoroalkyl acids (PFAAs) in municipal drinking water associated with serum PFAA concentrations in Swedish adolescents.

While highly contaminated drinking water (DW) is a major source of exposure to perfluoroalkyl acids (PFAAs), the contribution of low-level contaminated DW (i.e. < 10 ng/L of individual PFAAs) to PFAA body burdens has rarely been studied. To address this knowledge gap, we evaluated the association between concentrations of perflurooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS), and their sum (∑4PFAAs) in DW and serum in Swedish adolescents using weighted least squares regression. We paired serum PFAA concentrations in adolescents (age 10-21 years, n = 790) from the dietary survey Riksmaten Adolescents 2016-17 (RMA) with mean PFAA concentrations in water samples collected in 2018 from waterworks (n = 45) supplying DW to the participant residential and school addresses. The median concentrations of individual PFAAs in DW were < 1 ng/L. Median concentrations of PFNA and PFHxS in serum were < 1 ng/g, while those of PFOA and PFOS were 1-2 ng/g. Significant positive associations between PFAA concentrations in DW and serum were found for all four PFAAs and ∑4PFAAs, with estimated serum/DW concentration ratios ranging from 210 (PFOA) to 670 (PFHxS), taking exposure from sources other than DW (background) into consideration. The mean concentrations of PFHxS and ∑4PFAA in DW that would likely cause substantially elevated serum concentrations above background variation were estimated to 0.9 ng/L and 2.4 ng/L, respectively. The European Food Safety Authority has determined a health concern concentration of 6.9 ng ∑4PFAAs/mL serum. This level was to a large degree exceeded by RMA participants with DW ∑4PFAA concentrations above the maximum limits implemented in Denmark (2 ng ∑4PFAAs/L) and Sweden (4 ng ∑4PFAAs/L) than by RMA participants with DW concentrations below the maximum limits. In conclusion, PFAA exposure from low-level contaminated DW must be considered in risk assessment for adolescents.

PFAS and Phthalate/DINCH Exposure in Association with Age at Menarche in Teenagers of the HBM4EU Aligned Studies.

Early puberty has been found to be associated with adverse health outcomes such as metabolic and cardiovascular diseases and hormone-dependent cancers. The decrease in age at menarche observed during the past decades has been linked to an increased exposure to endocrine-disrupting compounds (EDCs). Evidence for the association between PFAS and phthalate exposure and menarche onset, however, is inconsistent. We studied the association between PFAS and phthalate/DINCH exposure and age at menarche using data of 514 teenagers (12 to 18 years) from four aligned studies of the Human Biomonitoring for Europe initiative (HBM4EU): Riksmaten Adolescents 2016-2017 (Sweden), PCB cohort (follow-up; Slovakia), GerES V-sub (Germany), and FLEHS IV (Belgium). PFAS concentrations were measured in blood, and phthalate/DINCH concentrations in urine. We assessed the role of each individual pollutant within the context of the others, by using different multi-pollutant approaches, adjusting for age, age- and sex-standardized body mass index z-score and household educational level. Exposure to di(2-ethylhexyl) phthalate (DEHP), especially mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), was associated with an earlier age at menarche, with estimates per interquartile fold change in 5OH-MEHP ranging from -0.34 to -0.12 years in the different models. Findings from this study indicated associations between age at menarche and some specific EDCs at concentrations detected in the general European population, but due to the study design (menarche onset preceded the chemical measurements), caution is needed in the interpretation of causality.

Exposure of Swedish adolescents to elements, persistent organic pollutants (POPs), and rapidly excreted substances - The Riksmaten adolescents 2016-17 national survey.

Adolescence is a period of significant physiological changes, and likely a sensitive window to chemical exposure. Few nation-wide population-based studies of chemical body burdens in adolescents have been published. In the national dietary survey Riksmaten Adolescents (RMA) 2016-17, over 13 chemical substance groups, including elements, chlorinated/brominated/fluorinated persistent organic pollutants (POPs) were analysed in blood, and in urine metabolites of phthalates/phthalate alternatives, phosphorous flame retardants, polycyclic aromatic hydrocarbons (PAHs), and pesticides, along with bisphenols and biocide/preservative/antioxidant/UV filter substances (N = 1082, ages 11-21). The aim was to characterize the body burdens in a representative population of adolescents in Sweden, and to compare results with human biomonitoring guidance values (HBM-GVs). Cluster analyses and Spearman's rank order correlations suggested that concentrations of substances with known common exposure sources and similar toxicokinetics formed obvious clusters and showed moderate to very strong correlations (r ≥ 0.4). No clusters were formed between substances from different matrices. Geometric mean (GM) concentrations of the substances were generally less than 3-fold different from those observed among adolescents in NHANES (USA 2015-16) and GerES V (Germany 2014-17). Notable exceptions were brominated diphenyl ethers (PBDEs) with >20-fold lower GM concentrations, and the biocide triclosan and ultraviolet (UV) filter benzophenone-3 with >15-fold lower mean concentrations in RMA compared to NHANES. Exceedance of the most conservative HBM-GVs were observed for aluminium (Al, 26% of subjects), perfluorooctanesulfonic acid (PFOS, 19%), perfluorooctanoic acid (PFOA, 12%), lead (Pb, 12%), MBP (dibutyl phthalate metabolite, 4.8%), hexachlorobenzene (HCB, 3.1%) and 3-phenoxybenzoic acid (PBA, pyrethroid metabolite, 2.2%). Males showed a higher proportion of exceedances than females for Pb, HCB and PFOS; otherwise no gender-related differences in exceedances were observed. A higher proportion of males than females had a Hazard Index (HI) of substances with liver and kidney toxicity and neurotoxicity >1. Industrialized countries with similarly high standards of living, with some exceptions, show comparable average body burdens of a variety of toxic chemicals among adolescents from the general population. The exceedances of HBM-GVs and HIs strongly suggests that further efforts to limit chemical exposure are warranted.

Harmonized human biomonitoring in European children, teenagers and adults: EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014-2021).

As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6-12 years, (ii) 3,117 teenagers aged 12-18 years and (iii) 4,102 young adults aged 20-39 years. The participants were recruited between 2014 and 2021 in 11-12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures.

Current exposure to phthalates and DINCH in European children and adolescents - Results from the HBM4EU Aligned Studies 2014 to 2021.

Phthalates are mainly used as plasticizers for polyvinyl chloride (PVC). Exposure to several phthalates is associated with different adverse effects most prominently on the development of reproductive functions. The HBM4EU Aligned Studies (2014-2021) have investigated current European exposure to ten phthalates (DEP, BBzP, DiBP, DnBP, DCHP, DnPeP, DEHP, DiNP, DiDP, DnOP) and the substitute DINCH to answer the open policy relevant questions which were defined by HBM4EU partner countries and EU institutions as the starting point of the programme. The exposure dataset includes ∼5,600 children (6-11 years) and adolescents (12-18 years) from up to 12 countries per age group and covering the North, East, South and West European regions. Study data from participating studies were harmonised with respect to sample size and selection of participants, selection of biomarkers, and quality and comparability of analytical results to provide a comparable perspective of European exposure. Phthalate and DINCH exposure were deduced from urinary excretions of metabolites, where concentrations were expressed as their key descriptor geometric mean (GM) and 95th percentile (P95). This study aims at reporting current exposure levels and differences in these between European studies and regions, as well as comparisons to human biomonitoring guidance values (HBM-GVs). GMs for children were highest for ∑DEHP metabolites (33.6 µg/L), MiBP (26.6 µg/L), and MEP (24.4 µg/L) and lowest for∑DiDP metabolites (1.91 µg/L) and ∑DINCH metabolites (3.57 µg/L). In adolescents highest GMs were found for MEP (43.3 µg/L), ∑DEHP metabolites (28.8 µg/L), and MiBP (25.6 µg/L) and lowest for ∑DiDP metabolites (= 2.02 µg/L) and ∑DINCH metabolites (2.51 µg/L). In addition, GMs and P95 stratified by European region, sex, household education level, and degree of urbanization are presented. Differences in average biomarker concentrations between sampling sites (data collections) ranged from factor 2 to 9. Compared to the European average, children in the sampling sites OCC (Denmark), InAirQ (Hungary), and SPECIMEn (The Netherlands) had the lowest concentrations across all metabolites and ESTEBAN (France), NAC II (Italy), and CROME (Greece) the highest. For adolescents, comparably higher metabolite concentrations were found in NEB II (Norway), PCB cohort (Slovakia), and ESTEBAN (France), and lower concentrations in POLAES (Poland), FLEHS IV (Belgium), and GerES V-sub (Germany). Multivariate analyses (Survey Generalized Linear Models) indicate compound-specific differences in average metabolite concentrations between the four European regions. Comparison of individual levels with HBM-GVs revealed highest rates of exceedances for DnBP and DiBP, with up to 3 and 5%, respectively, in children and adolescents. No exceedances were observed for DEP and DINCH. With our results we provide current, detailed, and comparable data on exposure to phthalates in children and - for the first time - in adolescents, and - for the first time - on DINCH in children and adolescents of all four regions of Europe which are particularly suited to inform exposure and risk assessment and answer open policy relevant questions.

Human urinary arsenic species, associated exposure determinants and potential health risks assessed in the HBM4EU Aligned Studies.

The European Joint Programme HBM4EU coordinated and advanced human biomonitoring (HBM) in Europe in order to provide science-based evidence for chemical policy development and improve chemical management. Arsenic (As) was selected as a priority substance under the HBM4EU initiative for which open, policy relevant questions like the status of exposure had to be answered. Internal exposure to inorganic arsenic (iAs), measured as Toxic Relevant Arsenic (TRA) (the sum of As(III), As(V), MMA, DMA) in urine samples of teenagers differed among the sampling sites (BEA (Spain) > Riksmaten adolescents (Sweden), ESTEBAN (France) > FLEHS IV (Belgium), SLO CRP (Slovenia)) with geometric means between 3.84 and 8.47 µg/L. The ratio TRA to TRA + arsenobetaine or the ratio TRA to total arsenic varied between 0.22 and 0.49. Main exposure determinants for TRA were the consumption of rice and seafood. When all studies were combined, Pearson correlation analysis showed significant associations between all considered As species. Higher concentrations of DMA, quantitatively a major constituent of TRA, were found with increasing arsenobetaine concentrations, a marker for organic As intake, e.g. through seafood, indicating that other sources of DMA than metabolism of inorganic As exist, e.g. direct intake of DMA or via the intake of arsenosugars or -lipids. Given the lower toxicity of DMA(V) versus iAs, estimating the amount of DMA not originating from iAs, or normalizing TRA for arsenobetaine intake could be useful for estimating iAs exposure and risk. Comparing urinary TRA concentrations with formerly derived biomonitoring equivalent (BE) for non-carcinogenic effects (6.4 µg/L) clearly shows that all 95th percentile exposure values in the different studies exceeded this BE. This together with the fact that cancer risk may not be excluded even at lower iAs levels, suggests a possible health concern for the general population of Europe.

Cross-sectional associations between exposure to per- and polyfluoroalkyl substances and body mass index among European teenagers in the HBM4EU aligned studies.

Per- and polyfluoroalkyl substances (PFAS) are widespread pollutants that may impact youth adiposity patterns. We investigated cross-sectional associations between PFAS and body mass index (BMI) in teenagers/adolescents across nine European countries within the Human Biomonitoring for Europe (HBM4EU) initiative. We used data from 1957 teenagers (12-18 yrs) that were part of the HBM4EU aligned studies, consisting of nine HBM studies (NEBII, Norway; Riksmaten Adolescents 2016-17, Sweden; PCB cohort (follow-up), Slovakia; SLO CRP, Slovenia; CROME, Greece; BEA, Spain; ESTEBAN, France; FLEHS IV, Belgium; GerES V-sub, Germany). Twelve PFAS were measured in blood, whilst weight and height were measured by field nurse/physician or self-reported in questionnaires. We assessed associations between PFAS and age- and sex-adjusted BMI z-scores using linear and logistic regression adjusted for potential confounders. Random-effects meta-analysis and mixed effects models were used to pool studies. We assessed mixture effects using molar sums of exposure biomarkers with toxicological/structural similarities and quantile g-computation. In all studies, the highest concentrations of PFAS were PFOS (medians ranging from 1.34 to 2.79 µg/L). There was a tendency for negative associations with BMI z-scores for all PFAS (except for PFHxS and PFHpS), which was borderline significant for the molar sum of [PFOA and PFNA] and significant for single PFOA [ß-coefficient (95% CI) per interquartile range fold change = -0.06 (-0.17, 0.00) and -0.08 (-0.15, -0.01), respectively]. Mixture assessment indicated similar negative associations of the total mixture of [PFOA, PFNA, PFHxS and PFOS] with BMI z-score, but not all compounds showed associations in the same direction: whilst [PFOA, PFNA and PFOS] were negatively associated, [PFHxS] associated positively with BMI z-score. Our results indicated a tendency for associations of relatively low PFAS concentrations with lower BMI in European teenagers. More prospective research is needed to investigate this potential relationship and its implications for health later in life.

Harmonization of Human Biomonitoring Studies in Europe: Characteristics of the HBM4EU-Aligned Studies Participants.

Human biomonitoring has become a pivotal tool for supporting chemicals' policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical's risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6-12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL® DINCH, and flame retardants. Samples from 2950 teenagers aged 12-18 years are collected for the analysis of biomarkers for phthalates, Hexamoll® DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20-39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children's group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers' group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0-2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe's strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed.

Healthy eating index and diet diversity score as determinants of serum perfluoroalkyl acid (PFAA) concentrations in a national survey of Swedish adolescents.

Food is an important source of perfluoroalkyl acid (PFAA) exposure for the general adult population, but few data exist for adolescents. Healthy food habits established during adolescence may positively influence health later in life. Associations between serum PFAA concentrations and a healthy eating index (SHEIA15), as well as a diet diversity score (RADDS), were determined in a nationally representative adolescent population from Sweden (Riksmaten Adolescents 2016-2017, RMA). Using consumption data from food registrations and frequency questionnaires, we additionally analyzed associations with commonly consumed food groups. Associations were analyzed by fitting a cumulative probability model using ordinal regression. Among the seven PFAAs detected in ≥70% of the 1098 participants (age 10-21 years), median concentrations ranged from <1 ng/g serum of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perflurorundecanoic acid (PFUnDA), linear (lin-) perfluorohexanesulfonic acid (PFHxS) and branched (br-) perfluorooctanesulfonic acid (PFOS) to 1-2 ng/g serum of lin-perfluorooctanoic acid (PFOA) and lin-PFOS. PFNA, PFDA, PFUnDA and lin-PFOS concentrations were positively associated with both SHEIA15 and RADDS, a finding most likely driven by higher consumption of seafood. PFDA, PFUnDA and lin-PFOS concentrations were positively related to commonly consumed fish/shellfish groups, such as lean marine fish and shellfish. Inverse associations between PFAA concentrations and dairy consumption suggest an underlying factor behind dairy consumption that similarly affects adolescent exposure to the different PFAAs. Isomeric differences in dietary exposure between lin-PFOS and br-PFOS were suggested, as br-PFOS concentrations, in contrast to lin-PFOS, were not associated with SHEIA15, RADDS and consumption of different food groups. We conclude that Swedish adolescents, adhering to a diverse and healthy diet, appears to be more highly exposed to legacy PFAAs than those eating less healthy. Additional research is necessary for a better understanding of the health implications of healthy eating from a PFAA exposure perspective.

Demographic, life-style and physiological determinants of serum per- and polyfluoroalkyl substance (PFAS) concentrations in a national cross-sectional survey of Swedish adolescents.

PER: and polyfluoroalkyl substances (PFAS) may affect adolescent health, yet factors related to PFAS concentrations in serum are poorly understood. We studied demographic, life-style and physiological determinants of serum PFAS concentrations in Swedish adolescents from a nation-wide survey, Riksmaten Adolescents 2016-17 (RMA, age 10-21 years, n = 1098). Serum samples were analyzed for 42 PFAS, using liquid chromatography-tandem mass spectrometry. The cumulative probability model was used to estimate associations between serum PFAS and determinants, using ordinal logistic regression. Legacy linear (lin-) perfluorooctanoic acid (PFOA), perfluorononaoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), lin-perfluorohexanesulfonic acid (PFHxS) and lin-/branched (br-) perfluorooctanesulfonic acid (PFOS) were quantifiable in ≥70% of the samples. The emerging PFAS 9-chlorohexanedecafluoro-3-oxanone-1-sulfonic acid (9Cl-PF3ONS) was quantified in 5.4% of the samples, suggesting initiation of long-range transport far from production sites. Median concentrations of all legacy PFAS were <2 ng/g serum, with a few participants having very high (>100 ng/g serum) lin-PFHxS and lin-/br-PFOS concentrations due to previous high exposure from PFAS-contaminated drinking water. Legacy PFAS exposure was strongly associated with birth country of the participants and their mothers. 2-fold higher estimated adjusted mean (EAM) concentrations were seen among high income country participants with mothers from high income countries than among low/lower-middle income country participants with mothers from the same category. Menstruating females had lower br-PFOS EAM concentrations than those who were not. Iron status (plasma ferritin) among females may be a marker of intensity of menstrual bleeding, but it was not significantly associated with legacy PFAS concentrations among females. Further studies are needed to determine how physiological changes occurring around menstruation affect the toxicokinetics of PFAS in females. In conclusion, PFAS are pollutants of the industrialized world and some of the identified determinants may be overlooked confounders/effect modifiers that should be included in future PFAS/health studies among adolescents.

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.

Cadmium, total mercury, and lead in blood and associations with diet, sociodemographic factors, and smoking in Swedish adolescents.

BACKGROUND: Despite their vulnerability to the toxic effects of certain metals, biomonitoring data on adolescents are limited. In the present study, we assessed blood concentrations of toxic metals (cadmium [Cd], total mercury [Hg], and lead [Pb] in a national representative sample of Swedish adolescents. We also examined the associations of Cd, total Hg and Pb with habitual intakes of major energy-providing food groups and other possible determinants such as age, sex, household education, Nordic or non-Nordic origin, and smoking. METHODS: We analysed blood concentrations of Cd, total Hg, and Pb in a sample of 1099 adolescents from the Riksmaten Adolescents 2016-17 study in three age groups (mean age of 12, 15, and 18 years) using inductively coupled plasma mass spectrometry. The participants completed web-based questionnaires on food consumption frequency, sociodemographic factors and health status. Dietary data from two web-based 24-h dietary recalls were used to estimate the habitual intake of 10 major food groups. RESULTS: Almost all participants had detectable concentrations of Cd, total Hg, and Pb in whole blood. The median blood concentrations were 0.12 µg/L for Cd, 0.72 µg/L for total Hg, and 7.1 µg/L for Pb. Higher blood concentrations of Cd were observed in girls than in boys, whereas concentrations of total Hg and Pb were higher in boys. We observed an inverse association between Cd and meat intake. Total Hg concentrations were positively associated with intakes of fish, eggs, meat, and vegetables, and Pb concentrations were inversely associated with intakes of dairy products. Furthermore, smokers had higher concentrations of Cd and Pb. CONCLUSIONS: We found that fish was a potentially important source of exposure to total Hg in Swedish adolescents. No other food group was identified to have a strong impact on the blood levels of Cd, total Hg and Pb. Thirteen per cent of the adolescents had blood Pb concentrations above 12 µg/L, the reference point used in the risk assessment of Pb by the European Food Safety Authority (EFSA).

Total mercury in hair as biomarker for methylmercury exposure among women in central Sweden- a 23 year long temporal trend study.

Exposure to methylmercury (MeHg) through fish is a global public health problem. Exposure monitoring is essential for health risk assessment, especially in pregnant women and children due to the documented neurotoxicity. Herein, we evaluate a time series of MeHg exposure via fish in primiparous Swedish women, covering a time period of 23 years (1996-2019). The 655 included mothers were part of the POPUP study (Persistent Organic Pollutants in Uppsala Primiparas) conducted by the Swedish Food Agency (SFA). MeHg exposure was assessed via measurements of total mercury (Hg) in hair using either cold vapor atomic fluorescence spectrophotometry or inductively coupled plasma mass spectrometry, showing very good linear agreement (R2 = 0.97). Maternal characteristics and fish consumption were obtained via questionnaires. The median concentration of total Hg in hair was 0.38 mg/kg (range 0.17-1.5) in 1996 and 0.25 mg/kg (range 0.03-1.1) in 2019. On average the women consumed 11 ± 8.2 meals of fish per month, and fish consumption was positively correlated with total Hg in hair (Spearman correlation: 0.39; p < 0.001). In multiple regression analyses, the geometric mean annual decrease of total Hg in hair was -2.5% (95% CI: -3.2, -1.8%). Total fish consumption increased up to 2011 (B: 0.32 times/month per year; 95% CI 0.17, 0.46) after which it started to decline (B: -0.66 times/month per year; 95% CI -0.92, -0.40). Moreover, both total Hg in hair and fish consumption was positively associated with maternal age and education, and inversely associated with pre-pregnancy BMI. In conclusion, the exposure to MeHg via fish appears to be slowly declining among Swedish pregnant women.

Temporal trends of suspect- and target-per/polyfluoroalkyl substances (PFAS), extractable organic fluorine (EOF) and total fluorine (TF) in pooled serum from first-time mothers in Uppsala, Sweden, 1996-2017.

A combined method for quantitative analysis, along with suspect and non-target screening of per- and polyfluoroalkyl substances (PFAS) was developed using ultra-high pressure liquid chromatography-ultra-high resolution (Orbitrap) mass spectrometry. The method was applied together with measurements of total- and extractable organofluorine (TF and EOF, respectively), to pooled serum samples from 1996-2017 from first-time mothers living in the county of Uppsala, Sweden, some of which (i.e. 148 of 472 women sampled 1996-2012) were exposed to drinking water contaminated with perfluorohexane sulfonate (PFHxS) and other PFAS until mid-2012. Declining trends were observed for all target PFAS as well as TF, with homologue-dependent differences in year of onset of decline. Only 33% of samples displayed detectable EOF, and amongst these samples the percentage of EOF explained by target PFAS declined significantly (-3.5% per year) over the entire study period. This finding corroborates prior observations in Germany after the year 2000, and may reflect increasing exposure to novel PFAS which have not yet been identified. Suspect screening revealed the presence of perfluoro-4-ethylcyclohexanesulfonate (PFECHS), which displayed declining trends since the year 2000. Non-target time trend screening revealed 3 unidentified features with time trends matching PFHxS. These features require further investigation, but may represent contaminants which co-occurred with PFHxS in the contaminated drinking water.

Determinants of serum concentrations of perfluoroalkyl acids (PFAAs) in school children and the contribution of low-level PFAA-contaminated drinking water.

Little is known about the demographic/life-style/physiological determinants explaining the variation of serum perfluoroalkyl acid (PFAA) concentrations in children. We identified significant determinants in children and investigated the influence of low-level PFAA-contaminated drinking water (DW) (<10 ng L-1 of single PFAAs) on serum concentrations. Four perfluorosulfonic acids (PFSAs) and 11 perfluorocarboxylic acids (PFCAs) were analyzed in serum from 5th grade children from 11 Swedish schools (N = 200; average age: 12 years) using liquid chromatography-tandem-mass-spectrometry. Data on demography and life-style/physiological factors were obtained by questionnaires. PFAA concentrations in raw and drinking water (DW) were obtained from the water works supplying DW to the schools. In multiple regression analyses school was the determinant contributing most to the variation in PFAA concentrations, with the lowest contribution for PFHpA (10%) and the highest for PFHxS (81%). Girls had lower adjusted mean concentrations of PFHxS, PFOS, PFNA and PFDA than boys, but a higher concentration of PFHxA. Girls reporting onset of menstruation had lower PFHxS and PFOA concentrations than other girls, suggesting menstrual bleeding elimination. Children born by mothers from less industrialized countries had lower mean concentrations of both PFSAs and PFCAs than children with mothers from highly industrialized countries, suggesting differences in early-life exposure. Life-style factors associated with paternal education levels appeared to influence PFAA concentrations differently than maternal education level. Already at an average DW PFHxS concentration of 2 ng L-1, children had a significantly higher adjusted mean serum PFHxS concentration than at an average DW concentration of <1.6 ng PFHxS L-1. Similar results were observed for PFOS and PFOA. The DW variable explained 16% (PFOA) to 78% (PFHxS) of the variation in serum PFAA concentrations, suggesting that low-level-contaminated DW is a significant source of exposure for children in Sweden. Although some of the associations, especially those with menstruation and maternal birth country, should be interpreted with extra caution due to the small size of the study, the results contribute to future work on identifying populations of children at risk of elevated PFAA exposures.

Perfluoroalkyl Acids (PFAAs) in Children's Serum and Contribution from PFAA-Contaminated Drinking Water.

We investigated associations between serum perfluoroalkyl acid (PFAA) concentrations in children aged 4, 8, and 12 years (sampled in 2008-2015; n = 57, 55, and 119, respectively) and exposure via placental transfer, breastfeeding, and ingestion of PFAA-contaminated drinking water. Sampling took place in Uppsala County, Sweden, where the drinking water has been historically contaminated with perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS), perfluorooctanesulfonate (PFOS), perfluoroheptanoate (PFHpA), and perfluorooctanoate (PFOA). PFOS showed the highest median concentrations in serum (3.8-5.3 ng g-1 serum), followed by PFHxS (1.6-5.0 ng g-1 serum), PFOA (2.0-2.5 ng g-1 serum), and perfluorononanoate (PFNA) (0.59-0.69 ng g-1 serum) in children. Including all children, serum PFOA, PFHxS, and PFOS concentrations in children increased 10, 10, and 1.3% (adjusted mean), respectively, per unit (ng g-1 serum) of increase in the maternal serum level (at delivery), the associations being strongest for 4 year-old children. PFHxS and PFOS significantly increased 3.9 and 3.8%, respectively, per month of nursing, with the highest increase for 4 year-olds. PFOA, PFBS, PFHxS, and PFOS increased 1.2, 207, 7.4, and 0.93%, respectively, per month of cumulative drinking water exposure. Early life exposure to PFOA, PFHxS, and PFOS is an important determinant of serum concentrations in children, with the strongest influence on younger ages. Drinking water with low to moderate PFBS, PFHxS, PFOS, and PFOA contamination is an important source of exposure for children with background exposure from other sources.

Increased urinary excretion of aluminium after ingestion of the food additive sodium aluminium phosphate (SALP) - a study on healthy volunteers.

Food is an important source of human aluminium (Al) exposure and regular consumption of foods containing Al-based food additives may result in high Al intakes above health-based tolerable intakes. However, some additives are Al salts with low solubility, and little is known about bioavailability of Al in these additives. We investigated urine Al concentrations in healthy adult volunteers (N = 18, women/men) before (base-line) and after 7 days of ingestion of pancakes with a low Al content (median: <0.5 mg Al/kg) and high Al content (median: 860 mg/kg). The high-Al pancakes contained the common additive sodium aluminium phosphate (SALP). The participants did not know if the pancakes contained SALP or not during the experiment. After adjusting for creatinine content of the urine samples, median base-line Al concentrations before pancake ingestion were in the range 30-40 µmol Al/mol creatinine. Urine Al concentrations after ingestion of low-Al pancakes (average intake: <0.042 Al mg/day) did not differ significantly from the base-line levels. After ingestion of high-Al pancakes (72 mg Al/day) the median Al concentration in urine was more than 2-fold higher than at the base-line sampling before the high-Al pancake ingestion. At the end of the experiment the volunteers ingested an Al-containing antacid (Al-OH, 1800 mg Al/day) for 7 days as a positive control of Al absorption. This caused a 10-fold increase in median urine Al concentration compared to base-line. Our results strongly suggest that Al in the form of SALP in a pancake mix is bioavailable for absorption in humans, which should be taken into account in risk assessment of Al in food in countries with a high use of SALP as a food additive.

Perfluoroalkyl Acids (PFAAs) in Serum from 2-4-Month-Old Infants: Influence of Maternal Serum Concentration, Gestational Age, Breast-Feeding, and Contaminated Drinking Water.

Little is known about factors influencing infant perfluorinated alkyl acid (PFAA) concentrations. Associations between serum PFAA concentrations in 2-4-month-old infants ( n = 101) and determinants were investigated by multiple linear regression and general linear model analysis. In exclusively breast-fed infants, maternal serum PFAA concentrations 3 weeks after delivery explained 13% (perfluoroundecanoic acid, PFUnDA) to 73% (perfluorohexanesulfonate, PFHxS) of infant PFAA concentration variation. Median infant/maternal ratios decreased with increasing PFAA carbon chain length from 2.8 for perfluoroheptanoic acid and perfluorooctanoic acid (PFOA) to 0.53 for PFUnDA and from 1.2 to 0.69 for PFHxS and perfluorooctanesulfonate (PFOS). Infant PFOA, perfluorononanoic acid (PFNA), and PFOS levels increased 0.7-1.2% per day of gestational age. Bottle-fed infants had mean concentrations of PFAAs 2 times lower than and a mean percentage of branched (%br) PFOS isomers 1.3 times higher than those of exclusively breast-fed infants. PFOA, PFNA, and PFHxS levels increased 8-11% per week of exclusive breast-feeding. Infants living in an area receiving PFAA-contaminated drinking water had 3-fold higher mean perfluorobutanesulfonate (PFBS) and PFHxS concentrations and higher mean %br PFHxS. Prenatal PFAA exposure and postnatal PFAA exposure significantly contribute to infant PFAA serum concentrations, depending on PFAA carbon chain length. Moderately PFBS- and PFHxS-contaminated drinking water is an important indirect exposure source.