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•Bisphenol analogs like BPS and BPF are increasingly used to replace BPA.•Aggregate and cumulative exposure assessments are needed to assess risks.•To test model plausibility, model ...results are compared to biomonitoring (BM) data.•144 Norwegian adults in BM study: detailed diaries and urine collection for 24 h.•BPS and BPF: underestimation of modeled exposure, BPA: good agreement.
Bisphenol A (BPA) and, with increasing occurrence, its analogs bisphenol S (BPS) and bisphenol F (BPF) are applied in many consumer products, leading to humans being exposed from a vast number of sources and via several routes. Estrogenic and anti-androgenic effects are exerted by the chemical BPA, and also by its analogs. Therefore, realistic exposure assessments are needed for assessing risks related to cumulative exposure.
Biomonitoring for BPA, BPS, and BPF was conducted in a human study embedded in the EU project EuroMix and the measured urinary concentrations were compared to source-to-dose calculations for source allocation and plausibility test of the model.
For two 24-hour study periods separated by 2–3 weeks, 144 adult volunteers in Norway kept detailed diaries on food consumption, personal care product (PCP) use, and thermal paper (TP) handling. Concurrently, 24 h urine was collected and urinary levels of BPA, BPS, and BPF were analyzed using ultra-high performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS). In line with the information obtained from the first study day, bisphenol exposure from food, PCPs, TP, and dust was modeled primarily individual-based with probabilistic models. Estimates for BP excretion over 24 h were obtained with the models and compared to measured amounts.
Modeled aggregate internal exposures covered the full range of measured urinary amounts for all BP analogs. In general, individual-based medians of modeled BPA exposures were in good agreement with the measurements, but individual-specific correlation was lacking. Modeled exposures mostly underestimated BPS and BPF levels in participants with positive measurements (53% and 8%), except for the P95 values of modeled BPS exposure that were higher than measured amounts if TP was handled. Most likely, diet and TP were the sources contributing the most to BP exposure in this study. Urinary measurements did not reveal a significant correlation between the amounts of canned food consumed, the number of PCPs used, or the number of TP handling events and levels of BPA, BPS, or BPF.
The good agreement between the ranges of modeled BPA exposure and measured BPA amounts indicates that available concentrations, especially from the main exposure source food, mirror the exposure situation realistically, and suggests that the exposure model considers the relevant exposure sources. The lack of individual-specific correlations means that the individual measured amounts and modeled exposures did not vary in parallel, e.g. due to mismatch of BP concentrations in food, TP, and other sources, or delayed internal exposure. The underestimation of modeled BPS and BPF exposure suggests that not all relevant sources were included in the respective exposure models. This could be due to a lack of input data, e.g. for food items, or due to an increased replacement of BPA with structural analogs compared to the used concentration and occurrence data.
Acrylamide is a probable human carcinogen with widespread exposure via food. The present study compared acrylamide intake measurements obtained from haemoglobin adduct levels and self-registered ...dietary consumption data in a group of 144 Norwegian healthy adults. Acrylamide adducts to N-terminal valine in haemoglobin were measured and used to estimate the intake via the internal dose approach which showed a median (interquartile range) of 0.24 (0.19–0.30) μg/kg bw/day. Data from weighed food records and food frequency questionnaires from the same individuals were used for probabilistic modelling of the intake of acrylamide. The median acrylamide intake was calculated to be 0.26 (0.16–0.39) and 0.30 (0.23–0.39) μg/kg bw/day, respectively from the two sources of self-registered dietary consumption data. Overall, a relatively good agreement was observed between the methods in pairwise comparison in Bland-Altman plots, with the methods disagreeing with 7% or less of the values. The intake estimates obtained with the two dietary consumption methods and one biomarker method are in line with earlier dietary estimates in the Norwegian population. The Margin of Exposure indicate a possible health risk concern from dietary acrylamide. This is the first study with a comparison in the same individuals of acrylamide intake estimates obtained with these methods.
•High-dimensional single cell analyses/immune cell profiling of human PBMC.•Urinary phthalate levels (∑DEHP + DiNP) associated with specific immune cell clusters.•Phthalates may stimulate/activate ...subsets of innate cells and suppress adaptive cells.•A novel approach to study effects of environmental factors on the immune system.
Phthalate exposure has been associated with immune-related diseases such as asthma and allergies, but there is limited knowledge on mechanisms, effect biomarkers and thus biological support of causality.
To investigate associations between exposure to the phthalates DEHP (di(2-ethylhexyl) phthalate) and DiNP (diisononyl phthalate) and functional immune cell profiles.
Peripheral blood mononuclear cells (PBMCs) from 32 healthy adult Norwegian participants in the EuroMix biomonitoring study were selected based on high or low (n = 16) levels of urine metabolites of DEHP and DiNP. High-dimensional immune cell profiling including phenotyping and functional markers was performed by mass cytometry (CyTOF) using two broad antibody panels after PMA/ionomycin-stimulation. The CITRUS algorithm with unsupervised clustering was used to identify group differences in cell subsets and expression of functional markers, verified by manual gating.
The group of participants with high phthalate exposure had a higher proportion of some particular innate immune cells, including CD11c positive NK-cell and intermediate monocyte subpopulations. The percentage of IFNγ TNFα double positive NK cells and CD11b expression in other NK cell subsets were higher in the high exposure group. Among adaptive immune cells, however, the percentage of IL-6 and TNFα expressing naïve B cell subpopulations and the percentage of particular naïve cytotoxic T cell populations were lower in the high exposure group.
Cell subset percentages and expression of functional markers suggest that DEHP and DiNP phthalate exposure may stimulate subsets of innate immune cells and suppress adaptive immune cell subsets. By revealing significant immunological differences even in small groups, this study illustrates the promise of the broad and deep information obtained by high-dimensional single cell analyses of human samples to answer toxicological questions regarding health effects of environmental exposures.
Phthalates are a group of diesters of phthalic acid and have been widely used by the industry as plasticisers giving flexibility and durability to polyvinyl chloride (PVC) plastics. Commonly their ...uses vary from plasticisers in food contact materials and toys to emulsifying agents in personal care products. Phthalates are not covalently bound to PVC, thus they can migrate into the air, skin, water, food and the environment. The omnipresence of phthalates results in human exposure via multiple pathways such as dermal, oral and inhalation for prolonged periods. There is evidence that phthalates can induce disruption in oestrogenic activity, reproductive, developmental and liver toxicity both in experimental animals and potentially in humans. The aim of this technical report is to summarise the activities of the fellow performed at the Norwegian Institute of Public Health (NIPH). The goals of the work programme were collecting concentration levels on five specific phthalates from the scientific literature and combining them with consumption/use data reported in a biomonitoring study part of a Horizon 2020 project (EuroMix), and finally, estimate the aggregate phthalate exposure from food and personal care products and compare them with the measured phthalate levels in urine samples collected in the biomonitoring study.
Observed associations between consumption of diet foods and obesity have sparked controversy over whether intense sweeteners may promote weight gain, despite their negligible energy contribution. We ...conducted a scoping review of reviews, to obtain an overview of hypotheses, research approaches and features of the evidence on intense sweeteners' potential relationships to appetite and weight changes. We searched for reviews of the scientific literature published from 2006 to May 2017. Two reviewers independently assessed title and abstracts, and full text publications. Arksey and O'Malley's framework for scoping reviews guided the process. We extracted and charted data on characteristics of the reviews and the evidence presented. The 40 included reviews present hypotheses both on how intense sweeteners can reduce or maintain body weight and on how these can promote weight gain. We classified only five publications as systematic reviews; another nine presented some systematic approaches, while 26 reviews did not describe criteria for selecting or assessing the primary studies. Evidence was often presented for intense sweeteners as a group or unspecified, and against several comparators (e.g. sugar, water, placebo, intake levels) with limited discussion on the interpretation of different combinations. Apart from the observational studies, the presented primary evidence in humans is dominated by small studies with short follow-up-considered insufficient to assess weight change. Systematic reviews of animal studies are lacking in this topic area. The systematic evidence only partly explore forwarded hypotheses found in the literature. Primary studies in humans seem to be available for systematic exploration of some hypotheses, but long-term experimental studies in humans appear sparse. With few exceptions, the reviews on intense sweeteners and weight change underuse systematic methodology, and thus, the available evidence. Further studies and systematic reviews should be explicit about the hypothesis explored and elucidate possible underlying mechanisms.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Occurrence data for chemical compounds in foods are critical for food safety.•Linear semi-quantitative method to rank chemicals in foods for monitoring was devised.•The ranking of ...chemical substances for monitoring was based on risk and knowledge gaps.•The method can be used for the prioritisation of all classes of chemicals in foods.
Chemical contaminants are present in all foods. Data on the occurrence of contaminants in foods that are often consumed or contain high contaminant concentrations are critical for the estimation of exposure and evaluation of potential negative health effects. Due to limited resources for the monitoring of contaminants and other chemical substances in foods, methods for prioritisation are needed. We have developed a straightforward semi-quantitative method to rank chemical substances in foods for monitoring as part of a risk-based food control. The method is based on considerations of toxicity, level of exposure including both occurrence in food and dietary intake, vulnerability of one or more population groups due to high exposure because of special food habits or resulting from specific genetic variants, diseases, drug use or age/life stages, and the adequacy of both toxicity and exposure data. The chemical substances ranked for monitoring were contaminants occurring naturally, unintentionally or incidentally in foods or formed during food processing, and the inclusion criteria were high toxicity, high exposure and/or lack of toxicity or exposure data. In principle, this method can be used for all classes of chemical substances that occur in foods, both unintended contaminants and deliberately added chemical substances. Foods considered relevant for monitoring of the different chemical substances were also identified. The outcomes of ranking exercises using the new method including considerations of vulnerable groups and adequacy of data and a shortened version based on risk considerations only were compared. The results showed that the resolution between the contaminants was notably increased with the extended method, which we considered as advantageous for the ranking of chemical substances for monitoring in foods.
The dietary exposure to the mycotoxin deoxynivalenol (DON) can be assessed by human biomonitoring (HBM). Here, we assessed the relation between dietary DON intake and the excretion of its major ...metabolite DON-15-glucuronide (DON15GlcA) through time, in an everyday situation. For 49 volunteers from the EuroMix biomonitoring study, the intake of DON from each meal was calculated and the excretion of DON and its metabolites was analyzed for each urine void collected separately throughout a 24-h period. The relation between DON and DON15GlcA was analyzed with a statistical model to assess the residence time and the excreted fraction of ingested DON as DON15GlcA (f
). F
was treated as a random effect variable to address its heterogeneity in the population. The estimated time in which 97.5% of the ingested DON was excreted as DON15GlcA was 12.1 h, the elimination half-life was 4.0 h. Based on the estimated f
, the mean reversed dosimetry factor (RDF) of DON15GlcA was 2.28. This RDF can be used to calculate the amount of total DON intake in an everyday situation, based on the excreted amount of DON15GlcA. We show that urine samples collected over 24 h are the optimal design to study DON exposure by HBM.
Glyoxal is formed endogenously and at a higher rate in the case of hyperglycemia. Glyoxal is also a food processing contaminant and has been shown to be mutagenic and genotoxic in vitro. The ...tumourigenic potential of glyoxal was investigated using the multiple intestinal neoplasia (Min) mouse model, which spontaneously develops intestinal tumours and is susceptible to intestinal carcinogens.
C57BL/6J females were mated with Min males. Four days after mating and throughout gestation and lactation, the pregnant dams were exposed to glyoxal through drinking water (0.0125%, 0.025%, 0.05%, 0.1%) or regular tap water. Female and male offspring were housed separately from PND21 and continued with the same treatment. One group were only exposed to 0.1% glyoxal from postnatal day (PND) 21.
There was no difference in the number of intestinal tumours between control and treatment groups. However, exposure to 0.1% glyoxal starting in utero and at PND21 caused a significant increase in tumour size in the small intestine for male and female mice in comparison with respective control groups. This study suggests that glyoxal has tumour growth promoting properties in the small intestine in Min mice.
•Dietary glyoxal exposure did not increase number of tumours.•Dietary glyoxal exposure did increase the average tumour size.•Maternal glyoxal exposure did not affect tumour number and size.
In this opinion, the EFSA Panel on Food Additives and Flavourings (FAF Panel) was requested by the European Commission to carry out a scientific evaluation of an extended one‐generation reproductive ...toxicity study (EOGRTS) to determine whether it would allow reconsideration of the temporary group acceptable daily intake (ADI) for sorbic acid (E 200) and potassium sorbate (E 202), established by the Panel on Food Additives and Nutrient Sources added to Food (ANS Panel) in 2015. From the EOGTRS, the FAF Panel identified a lower confidence limit of the benchmark dose (BMDL) of 1,110 mg sorbic acid/kg body weight (bw) per day. By applying a default uncertainty factor of 100, the Panel established a group ADI expressed as 11 mg sorbic acid/kg bw per day for sorbic acid (E 200) and its potassium salt (E 202). In addition, European Commission asked EFSA to review a report on the ‘Stability of sorbic acid (E 200) and its potassium salt (E 202) during food processing and storage’ provided by industry. No new information was provided in this report, and therefore, in this opinion, there was no re‐assessment of the EFSA ANS opinion conclusions from 2015 regarding the stability of sorbates in food.
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