Environmental contamination and human exposure to PFASs near a fluorochemical production plant: Review of historic and current PFOA and GenX contamination in the Netherlands

Fluorochemical production plants (FPP) are primary emission sources of per- and polyfluoroalkyl substances (PFASs) to the local environment. An FPP located in the Netherlands has historically used perfluorooctanoic acid (PFOA) for fluoropolymer production and is currently using GenX (HFPO-DA; 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propionic acid) as a replacement. This study reviewed existing data from open access reports and peer reviewed publications on the environmental presence of PFOA and GenX in environmental matrices such as surface water, groundwater, soil and vegetation. Published data on human exposure to PFOA and GenX (i.e. via drinking water and food as well as blood monitoring) were reviewed in order to assess the influence of the FPP on contamination of the local population. Concentrations in environmental and human exposure samples were compared to (inter)national quality standards or risk limits. The data showed higher PFOA and GenX concentrations in surface water, groundwater, soil and vegetation samples taken close to point sources, and the highest observed concentrations exceeded these standards and limits (except for PFOA in soil). Drinking water and food also contained higher PFOA and GenX concentrations in samples taken close to point sources compared to samples further away. Tolerable daily intake (TDIs) for both PFASs were exceeded, however, only in a maximum exposure scenario. Blood monitoring of the local population near the FPP, and FPP workers, confirmed high exposure can occur as blood concentrations of several individuals exceeded the safe level. This paper provides a comprehensive overview on PFOA and GenX contamination close to point sources in the Netherlands.</p

Review of analytical approaches for the identification of non-intentionally added substances in paper and board food contact materials

Background: Food contact materials (FCM) may contain non-intentionally added substances (NIAS) as a result of reaction by-products, oligomers, degradation processes, chemical reactions between packaging materials and foodstuff, or as impurities from the raw materials used for their production. Scope and approach: In this review, current approaches for the detection and identification of NIAS from paper and board FCM are presented. Reviewed are the definition of NIAS, approaches for NIAS identification and quantification, the comprehensive analysis of NIAS and the role of in silico tools and bioassays. Key Findings and Conclusions: NIAS in paper and board are mostly components from printing inks, adhesives, sizing agents and surface coatings. Recycled paper contains overall more NIAS than fresh paper. Targeted analysis is generally performed for predicted NIAS, whereas an untargeted, or full-scan screening method is applied to detect and identify unpredicted NIAS. Sample preparation and contact conditions fall in two categories; migration and extraction. Migration studies are performed with food simulants while extraction studies are Soxhlet or ultrasound assisted solvent extraction. In untargeted analysis in silico tools are gaining importance in the identification of NIAS. Bioassays are used to determine the bioactivity of extracts or fractions in order to assess the potential toxicity of NIAS present in the mixture. A combination of bioassays and chemical analysis is used to direct the identification of unknown bioactive NIAS in complex mixtures like those from paper and board FCM. However, future research is required into the selection of bioassays since these should not only be sensitive enough for detecting all compounds of concern but should also have a relevance with human health.</p

Influence of green tea consumption on endoxifen steady-state concentration in breast cancer patients treated with tamoxifen

Background: Many cancer patients use additional herbs or supplements in combination with their anti-cancer therapy. Green tea—active ingredient epigallocatechin-3-gallate (EGCG)—is one of the most commonly used dietary supplements among breast cancer patients. EGCG may alter the metabolism of tamoxifen. Therefore, the aim of this study was to investigate the influence of green tea supplements on the pharmacokinetics of endoxifen; the most relevant active metabolite of tamoxifen. Methods: In this single-center, randomized cross-over trial, effects of green tea capsules on endoxifen levels were evaluated. Patients treated with tamoxifen for at least 3 months were eligible for this study. After inclusion, patients were consecutively treated with tamoxifen monotherapy for 28 days and in combination with green tea supplements (1 g twice daily; containing 300 mg EGCG) for 14 days (or vice versa). Blood samples were collected on the last day of monotherapy or combination therapy. Area under the curve (AUC0–24h), maximum concentration (Cmax) and minimum concentration (Ctrough) were obtained from individual plasma concentration–time curves. Results: No difference was found in geometric mean endoxifen AUC0–24h in the period with green tea versus tamoxifen monotherapy (− 0.4%; 95% CI − 8.6 to 8.5%; p = 0.92). Furthermore, no differences in Cmax (− 2.8%; − 10.6 to 5.6%; p = 0.47) nor Ctrough (1.2%; − 7.3 to 10.5%; p = 0.77) were found. Moreover, no severe toxicity was reported during the whole study period. Conclusions: This study demonstrated the absence of a pharmacokinetic interaction between green tea supplements and tamoxifen. Therefore, the use of green tea by patients with tamoxifen does not have to be discouraged

Haplotype reference consortium panel: Practical implications of imputations with large reference panels

Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and HRC imputations. We compared the results of the meta-analysis using 1000GP to the meta-analysis results using HRC. Overall, we found that using HRC imputation significantly improved P values (P = 3.07 × 10-61), particularly for suggestive variants. Both meta-analyses were performed in the same sample size, yet we found eight genome-wide significant loci in the HRC-based meta-analysis versus seven genome-wide significant loci in the 1000GP-based meta-analysis. This study provides supporting evidence of the new avenues for gene discovery and fine mapping that the HRC imputation panel offers

Congener patterns of polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls as a useful aid to source identification during a contamination incident in the food chain

Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) are still considered among the most important groups of contaminants in the food chain. Self-control by food producers and official control by authorities are important activities that allow contaminant sources to be traced and promote further reduction in food and feed levels. Strict but feasible maximum levels were set by the EU Commission for food and feed to support this strategy, as well as action levels and thresholds. When products exceed these levels, it is important to trace the source of contamination and take measures to remove it. Congener patterns of PCDD/Fs and PCBs differ between sources and are important tools for source identification. Therefore, patterns associated with different sources and incidents relating to various feed matrices and certain agricultural chemicals were collated from published scientific papers, with additional ones available from some laboratories. The collection was evaluated for completeness by presentations at workshops and conferences. Primary sources appear to derive from 5 categories, i) by-products from production of organochlorine chemicals (e.g. PCBs, chlorophenols, chlorinated pesticides, polyvinyl chloride (PVC)), ii) the result of combustion of certain materials and accidental fires, iii) the use of inorganic chlorine, iv) recycling/production of certain minerals, and v) certain naturally occurring clays (ball clay, kaolinite). A decision tree was developed to assist in the identification of the source

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

Discrimination of processing grades of olive oil and other vegetable oils by monochloropropanediol esters and glycidyl esters

In this study, the processing derived contaminants 2- and 3-monochloropropanediol (2- and 3-MCPD) esters and glycidyl esters (GEs) were analysed in 84 oil samples by GC–MS/MS for the discrimination of processing grades of olive oils as a potential authentication tool. Concentrations of 2- and 3-MCPD esters and GEs varied in the ranges 0–6 mg/kg, 0–1.5 mg/kg, and 0–1 mg/kg oil, respectively. The concentrations of the three compounds in lower grade olive oils were significantly higher (P &lt;.001) than that in EVOO. A similar difference was observed for other refined and cold-pressed vegetable oils. The limit of fraud detection of lower grade oils in EVOO was 2% when using 3-MCPD esters, 5% for 2-MCPD esters, and 13–14% for GEs based on calculations of virtual mixtures of the current sample set. Especially the MCPD esters appear very specific and promising for the detection of lower processing grade oils in EVOO

Presence of Emerging Per- and Polyfluoroalkyl Substances (PFASs) in River and Drinking Water near a Fluorochemical Production Plant in the Netherlands

The present study investigated the presence of legacy and emerging per- and polyfluoroalkyl substances (PFASs) in river water collected in 2016 up- and downstream from a fluorochemical production plant, as well as in river water from control sites, in The Netherlands. Additionally, drinking water samples were collected from municipalities in the vicinity from the production plant, as well as in other regions in The Netherlands. The PFOA replacement chemical GenX was detected at all downstream river sampling sites with the highest concentration (812 ng/L) at the first sampling location downstream from the production plant, which was 13 times higher than concentrations of sum perfluoroalkylcarboxylic acids and perfluoroalkanesulfonates (-PFCA+-PFSA). Using high resolution mass spectrometry, 11 polyfluoroalkyl acids belonging to the C2nH2nF2nO2, C2nH2n+2F2nSO4 or C2n+1H2nF2n+4SO4 homologue series were detected, but only in downstream water samples. These emerging PFASs followed a similar distribution as GenX among the downstream sampling sites, suggesting the production plant as the source. Polyfluoroalkyl sulfonates (C2nH2F4nSO3) were detected in all collected river water samples, and therefore appear to be ubiquitous contaminants in Dutch rivers. GenX was also detected in drinking water collected from 3 out of 4 municipalities in the vicinity of the production plant, with highest concentration at 11 ng/L. Drinking water containing the highest level of GenX also contained two C2nH2nF2nO2 homologues.</p

Non-targeted identification of per- and polyfluoroalkyl substances at trace level in surface water using fragment ion flagging

The extent of unidentified Per- and Poly-fluoroalkyl substances (PFASs) found in environmental samples has led to the development of non-targeted screening methods. The study presented here reports the use of liquid chromatography hyphenated with high resolution mass spectrometry to detect and identify unknown and unexpected PFASs by fragment ion flagging (FIF). By exploring all ion fragmentation spectra for several characteristic fragments including CnF2n+1−, CnF2n-1−, CnF2n-3−, CnF2n-7−, CnF2n-11− and CnF2n+1O− the presence of widely different PFAS species can be anticipated without the need for targeted screening methods. These fragments are then related to their precursor ion by retention time matching and subsequently identified. With this methodology 40 PFASs were (tentatively) identified in four surface water samples sampled throughout the Netherlands. To the best of the authors’ knowledge, four PFASs found through FIF are newly discovered species and have not been mentioned in any database or literature. This methodology eliminates the dependence on commonly reported full scan feature selection techniques such as mass defect filtering, homologous series detection and intensity threshold filtering, allowing the identification of PFASs at trace levels. Additionally, eight of the (tentatively) identified PFASs are not part of homologous series, stressing the shortcomings of commonly reported non-targeted PFASs screening methods and demonstrating the importance of more effective identification strategies such as FIF. Moreover, we like to emphasise that this approach is applicable to real-life environmental samples with PFASs at background concentration levels.</p

Occurrence of dietary advanced glycation end-products in commercial cow, goat and soy protein based infant formulas

Thermal treatment is a key step during infant formula (IF) processing which causes protein glycation and formation of dietary advanced glycation end-products (dAGEs). This study aimed to evaluate the glycation degree in IF in relation to the ingredients of the formula. dAGEs concentrations have been determined by UPLC-MS/MS in a range of commercial cow-based, goat-based, and soy-based IF. Results indicated that the protein source, protein composition, and amount and type of carbohydrates determines the level of protein glycation in IFs. The investigated soy-based formula had significant higher concentrations of arginine and arginine-derived dAGEs than cow-based and goat-based formulas. IF containing hydrolyzed proteins had higher dAGEs concentrations than those containing intact proteins. Lactose-containing formula was more prone to glycation than those containing sucrose and maltodextrin. Data showed glycation degree in IF cannot be estimated by a single compound, but the complete picture of the dAGEs should be considered