•POPs and PFAAs are determined from a single 200μl aliquot of serum.•Method performance compares acceptable with methods published for POPs and PFAAs.•Dispersive solid phase extraction (DSPE) is used ...to separate PFAAs from POPs.•Care is taken to make the manual sample pre-treatment as simple and fast as possible.•New compounds can easily be added to the method if needed.
A simple and fast method is presented for the determination of selected persistent organic pollutants (POPs) and perfluorinated alkyl acids (PFAAs), a subgroup of per- and polyfluorinated alkyl substances (PFAS) from a single 200μl aliquot of serum. Sample pretreatment starts with dispersive solid phase extraction of POPs to dichloromethane–hexane, which is immediately poured to cleanup column. POPs are eluted from column and concentrated for GC–MS/MS analysis. PFAAs are trapped to dispersant and are then extracted with ammonium acetate in methanol, concentrated and analysed with LC–MS/MS. For POPs, the limit of detection (LOD) ranged from 1.6 to 17pg/ml. Oxychlordane and dichlorodiphenyltrichloroethane had LODs in the upper end of this range as they were more labile and prone for interferences in the GC–MS/MS. For PFAAs, the LOD range from 0.027 to 0.068ng/ml. For POPs, the accuracy from Standard Reference Materials SRM 1589a and Arctic Monitoring and Assessment Programme (AMAP) intercalibration samples range from 74 to 127% and the repeatability (relative standard deviation, RSD%) from 2.0 to 15%. For PFAAs, the accuracy from AMAP samples ranged from 90 to 110% and from LOQ level spiked serum samples from 72 to 133%. Repeatability from AMAP and LOQ samples ranged from 1.6 to 7.3% and 5.5 to 15%, respectively. The presented method is useful in epidemiological studies where only limited amount of serum is available.
Perfluoroalkyl substances (PFAS) are persistent synthetic chemicals that may affect components of metabolic risk through the peroxisome proliferator-activated receptor but epidemiological data remain ...scarce and inconsistent.
To estimate associations between repeated measurements of the main PFAS in plasma and total cholesterol, triglycerides and hypertension among the control subjects from a population-based nested case-control study on diabetes type 2 in middle-aged women and men.
Participants (n = 187) were free of diabetes at both baseline and follow-up visits to the Västerbotten Intervention Programme, 10 years apart: during 1990 to 2003 (baseline) and 2001 to 2013 (follow-up). Participants left blood samples, completed questionnaires on diet and lifestyle factors, and underwent medical examinations, including measurement of blood pressure. PFAS and lipids were later determined in stored plasma samples. Associations for the repeated measurements were assessed using generalized estimating equations.
Six PFAS exceeded the limit of quantitation. Repeated measures of PFAS in plasma, cardiometabolic risk factors and confounders, showed an average decrease of triglycerides from −0.16 mmol/l (95% confidence interval CI: −0.33, 0.02 for PFOA) to −0.26 mmol/l (95% CI: −0.50, −0.08 for PFOS), when comparing the highest tertile of PFAS plasma levels with the lowest. Associations based on average PFAS measurements and follow-up triglycerides revealed similar inverse associations, although attenuated. The estimates for cholesterol and hypertension were inconsistent and with few exception non-significant.
This study found inverse associations between PFAS and triglycerides, but did not support any clear link with either cholesterol or hypertension.
•PFAS activate PPARs and may affect cardiometabolic risk factors, such as increased cholesterol•We performed repeated assessments of PFAS and cardiometabolic risk factors, 10 years apart•There were no indications of any PFAS-associated increase in blood lipids or hypertension•We observed inverse associations of PFAS with triglycerides, but inconclusive findings for cholesterol or hypertension•Confounding from dietary sources of PFAS may explain conflicting results of the studies reported to date
Phenolic acids, flavonoids, proanthocyanidins, and ellagitannins are polyphenols that may have beneficial effects on human health and provide protection against chronic diseases. To date, limited ...data exist on quantitative intake of polyphenols. The aims of this study were to estimate the quantitative intakes of polyphenols by using analyzed concentrations together with individual food consumption records and to determine major dietary sources. Analyzed concentrations of phenolic acids, anthocyanidins, and other flavonoids, proanthocyanidins, and ellagitannins (44 total polyphenol compounds) were entered into the national food composition database, Fineli. The absolute intakes of the polyphenols and the corresponding food sources were calculated on the basis of 48-h dietary recalls of 2007 Finnish adults. The mean total intake of polyphenols was 863 ± 415 mg/d. Phenolic acids comprised the dominant group of polyphenols (75% of total intake) followed by proanthocyanidins (14%) and anthocyanidins and other flavonoids (10%). Due to their high consumption and high concentrations of phenolic acids, coffee and cereals were the main contributors to total polyphenol intake. Berries and berry products were the main source for anthocyanidins, ellagitannins, and proanthocyanidins, and fruits were the main source for flavonols, flavones, and flavanones. The results give additional support to the recommendations for a varied diet with fruits, berries, cereals, and vegetables.
•The phthalate metabolite levels were mostly comparable to the published levels in adult populations in Europe and the US.•The exposure of the Finnish population to DnBP was higher than that in the ...German, Austrian, Norwegian and US populations.•The levels of individual phthalate metabolites did not often correlate very well with each other.•The 95th percentile levels of individual phthalate metabolites remained below the respective biomonitoring equivalents.•Combined exposure to DnBP, DiBP, DEHP and BBP resulted in the risk characterization ratio exceeding 1.
The aim of this study was to assess phthalate exposure of non-occupationally exposed working aged population in Finland. Studied phthalates included diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), benzyl butyl phthalate (BzBP), dicyclohexyl phthalate (DCHP), di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP), di(2-propylheptyl) phthalate (DPHP), and di-n-octyl phthalate (DnOP). Sample collection campaign took place in 2015.
Metabolites of DEP, DnBP and DiBP were detected in all the first morning void urine samples of the non-occupationally exposed volunteers (n = 60; 42 women and 18 men; aged 25–63). Metabolite of BBP and secondary metabolites of DEHP and DiNP were detected in >90% of the samples. MCHP (1.7%), MEHP (18.3%), cx-MiNP (8.3%) and MnOP (1.7%) were less frequently detected. MiNP and OH-MPHP were not detected in any of the urine samples.
The observed levels were mostly comparable to the levels published in the adult population in Europe and the US. One notable difference was the observed higher exposure of the Finnish study population to DnBP in comparison to the German, Austrian, Norwegian and US populations. The levels of individual phthalates did not often correlate very well with each other. In most cases, higher exposure to phthalates was seen in females in comparison to males, which is in accordance with other studies.
The urinary levels were compared to the biomonitoring equivalents (BEs), which were calculated on the basis of published DNELs (derived no-effect levels). The P95 levels of individual phthalates remained below the respective BEs, the highest risk characterization ratio (RCR) being 0.88 for DnBP and the second highest 0.34 for DiBP. For other phthalates, the RCRs were below 0.2. Using the P95 levels, combined exposure to DnBP, DiBP, DEHP and BBP resulted in risk characterization ratio exceeding 1. This suggests a need to limit the exposure to these phthalates.
Numerous in vitro and in vivo studies have suggested that dietary anthocyanins and ellagitannins or ellagic acid might have beneficial health effects. Epidemiological evidence on the ...disease-preventing potential of these polyphenols is lacking, due to the absence of reliable data on their contents in foods. In this study was analyzed the content of anthocyanins and ellagitannins (as ellagic acid equivalents after acid hydrolysis) in foods consumed in Finland, including berries, fruits, vegetables, and processed products, using high-performance liquid chromatographic (HPLC) methods. Anthocyanins were detected in 41 of 54 selected food items. The total anthocyanin content varied in berries from 1 to 611 mg/100 g, in fruits from 2 to 66 mg/100 g, and in vegetables from 3 to 75 mg/100 g of fresh weight as the weight of the aglycone. Ellagitannins were screened in 33 food items, but were detected only in 5 species of berries, that is, in cloudberry, raspberry, rose hip, strawberry, and sea buckthorn, the content ranging from 1 to 330 mg/100 g. The results underscore the superiority of berries, especially dark blue or red berries, as excellent sources of anthocyanins and certain berries of the Rosaceae family as the major source of ellagitannins in the Finnish diet.
Perfluoroalkyl substances (PFAS) have drawn much attention due to bioaccumulation potential and their current omnipresence in human blood. We assessed whether plasma PFAS, suspected to induce ...endocrine-disrupting effects, were prospectively associated with clinical type 2 diabetes (T2D) risk.
We established a nested case-control study within the Swedish prospective population-based Västerbotten Intervention Programme cohort. Several PFAS were measured in plasma from a subset of 124 case-control pairs at baseline (during 1990–2003) and at 10-year follow-up. T2D cases were matched (1:1) according to gender, age and sample date with participants without T2D (controls).
Conditional logistic regressions were used to prospectively assess risk of T2D by baseline PFAS plasma concentrations. Associations between long-term PFAS plasma levels (mean of baseline and follow-up) and insulin resistance (HOMA2-IR) and beta-cell function (HOMA2-B%) at follow-up were prospectively explored among 178 and 181 controls, respectively, by multivariable linear regressions.
After adjusting for gender, age, sample year, diet and body mass index, the odds ratio of T2D for the sum of PFAS (Σ z-score PFAS) was 0.52 (95% confidence interval, CI: 0.20, 1.36), comparing third with first tertile; and 0.92 (95% CI: 0.84, 1.00) per one standard deviation increment of sum of log-transformed PFAS. Among the controls, the adjusted β of HOMA2-IR and HOMA-B% for the sum of PFAS were −0.26 (95% CI: −0.52, −0.01) and −9.61 (95% CI: −22.60, 3.39) respectively comparing third with first tertile.
This prospective nested case-control study yielded overall inverse associations between individual PFAS and risk of T2D, although mostly non-significant. Among participants without T2D, long-term PFAS exposure was prospectively associated with lower insulin resistance.
•PFAS have endocrine-disrupting properties, activate PPARs and may affect T2D risk•We observed weak indications of PFAS-associated lower T2D risk.•Long-term PFAS were inversely associated with insulin resistance in non-diabetics•Confounding from dietary sources of PFAS may explain overall conflicting results•Further research to tease out the true impact of PFAS in human T2D is warranted
Studies suggest negative health impacts from early life exposure to per- and polyfluoroalkyl substances (PFASs). However, information on longitudinal exposure to PFASs during childhood is scarce for ...background-exposed individuals. This study sought to fill this gap by investigating children's longitudinal exposure trends through measurement of PFAS serum concentrations and calculation of body burdens (μg, total in body). Blood of 54 Finnish children was sampled 2005–2015 and analyzed for 20 PFASs at 1, 6 and 10.5 years of age. The body burden was calculated by multiplying the serum concentration by the volume of distribution and the bodyweight for each individual. Associations between serum concentrations or body burdens and parameters, such as sex, breastfeeding duration, body mass index as well as indoor dust and air PFAS concentrations, were evaluated. Serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) decreased significantly (p < 0.001) with age. In contrast to serum concentrations, body burdens stayed unchanged or even increased significantly (p < 0.05), except for PFOA in female children. Breastfeeding duration was positively correlated (p < 0.001) with serum concentrations of PFHxS, PFOS, PFOA and PFNA at 1 year of age. Some associations were found at 10.5 years with sex and indoor PFAS concentrations. Observations of longitudinal decreasing trends of serum concentrations can be misleading for understanding exposure levels from external media during childhood, as the serum concentration is influenced by parallel temporal changes and growth dilution. Body burdens account for growth dilution and thus better reflect differences in early-life to adolescence exposure than serum concentrations.
•Body burden is better marker for early life exposure than serum concentration.•Serum concentrations of PFAAs decreased significantly with children's age.•PFAA body burdens stayed unchanged or increased significantly with children's age.•Breastfeeding duration was positively correlated with children's serum PFAAs.
•PFAS may impact Type 2 Diabetes (T2D) development, but findings are inconsistent.•We found PFAS-related metabolites from untargeted metabolomics using random forest.•PFAS correlated positively with ...diacylglycerols and glycerophospholipids.•These two metabolite groups showed opposite associations with T2D risk.•The findings may help to explain the conflicting results found for PFAS and T2D.
Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations.
We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Västerbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D.
PFAS levels correlated with 171 metabolite features (0.16 ≤ |r| ≤ 0.37, false discovery rate (FDR) adjusted p < 0.05). Out of these, 35 associated with T2D (p < 0.05), with 7 remaining after multiple testing adjustment (FDR < 0.05). PCA of the 35 PFAS- and T2D-related metabolite features revealed two patterns, dominated by glycerophospholipids and diacylglycerols, with opposite T2D associations. The glycerophospholipids correlated positively with PFAS and associated inversely with risk for T2D (Odds Ratio (OR) per 1 standard deviation (1-SD) increase in metabolite PCA pattern score = 0.2; 95% Confidence Interval (CI) = 0.1–0.4). The diacylglycerols also correlated positively with PFAS, but they associated with increased risk for T2D (OR per 1-SD = 1.9; 95% CI = 1.3–2.7). These results suggest that PFAS associate with two groups of lipid species with opposite relations to T2D risk.
The aim of this study was to assess occupational exposure to diisononyl phthalate (DiNP) and di(2-propylheptyl) phthalate (DPHP in Finland. Four companies took part in the research project: A cable ...factory, a plastic producing company, a producer of coated textiles, and a tarpaulin producer. The cable factory used DPHP (and occasionally also diisodecyl phthalate, DiDP), the plastic producing company used both DPHP and DiNP, and the latter two companies used DiNP in their production. Exposure was assessed by measuring phthalate metabolites in urine samples (biomonitoring) and by performing air measurements. Low-level occupational exposure to DiNP was observed in the company that produced coated textiles-out of eight workers, one extruder operator was exposed to DiNP at levels exceeding the non-occupationally exposed population background levels. Some workers in the cable factory and the plastics producing company were occupationally exposed to DPHP. Air levels of phthalates were generally low, mostly below the limit of quantification. All phthalate metabolite concentrations were, however, well below the calculated biomonitoring equivalents, which suggests that the health risks related to the exposure are low.
Multiple studies have shown associations between exposure to endocrine disrupting chemicals (EDCs) and reduced fertility in women. However, little is known about the target organs of chemical ...disruption of female fertility. Here, we focus on the hormone-sensitive uterine lining, the endometrium, as a potential target. Decidualization is the morphological and functional change that endometrial stromal cells undergo to support endometrial receptivity, which is crucial for successful implantation, placentation, and pregnancy. We investigated the effect of nine selected EDCs on primary human endometrial stromal cell decidualization
in vitro.
The cells were exposed to a decidualization-inducing mixture in the presence or absence of 1 μM of nine different EDCs for nine days. Extent of decidualization was assessed by measuring the activity of cAMP dependent protein kinase, Rho-associated coiled-coil containing protein kinase, and protein kinase B in lysates using photoluminescent probes, and secretion of prolactin into the media by using ELISA. Decidualization-inducing mixture upregulated activity of protein kinases and prolactin secretion in cells derived from all women. Of the tested chemicals, dichlorodiphenyldichloroethylene (p,p’-DDE), hexachlorobenzene (HCB) and perfluorooctanesulfonic acid (PFOS) significantly reduced decidualization as judged by the kinase markers and prolactin secretion. In addition, bisphenol A (BPA) reduced prolactin secretion but did not significantly affect activity of the kinases. None of the EDCs was cytotoxic, based on the assessment of total protein content or activity of the viability marker casein kinase 2 in lysates. These results indicate that EDCs commonly present in the blood circulation of reproductive-aged women can reduce decidualization of human endometrial stromal cells
in vitro
. Future studies should focus on detailed hazard assessment to define possible risks of EDC exposure to endometrial dysfunction and implantation failure in women.
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