Background Dioxin and per- and polyfluoroalkyl substances (PFAS) exposure in fetal life and early infancy may be harmful for the male reproductive system. Objectives We investigated the associations between pre- and postnatal dioxin/PFAS exposure and semen quality in young adulthood. Methods The Ulm Birth Cohort Study is a population-based longitudinal birth cohort study (recruited 11/2000-11/2001). Maternal serum was collected shortly after delivery (mostly taken within the first two days) and maternal milk 6 weeks postpartum, immediately aliquoted, and stored at -80 ⁰C. Concentrations of dioxins (PCDDs, PCFDs and dioxin-like PCBs) were analyzed in milk in the year 2022 and PFAS in maternal serum in the year 2023. Semen provided by male offspring in 2021/22 was analyzed according to the 2010 WHO manual. Multivariable linear regression models were used to analyze the associations of (1) maternal dioxin/PFAS concentrations and of (2) cumulative dioxin/PFAS exposure with semen quality. Results Semen was available for n=98 males (age 20.4 ± 0.4 years; 86% were breastfed at 6 weeks). Median WHO2005-PCDD/F+PCB-TEQ concentration was 0.516 pg/g milk (n=77, IQR 0.296-0.715), median serum PFAS level (EFSA sum) was 10.8 µg/L (n=92, IQR 8.3-13.8). In adjusted analyses, we found no associations between concentrations of dioxin on a continuous scale with various measures of semen quality. For the continuous analysis of PFAS, a positive association with sperm concentration was seen in the partly adjusted cumulative exposure model, which was, however, not present after full adjustment. The mutual adjustment for dioxins and PFAS in statistical analysis revealed a significant negative association between dioxin levels in milk with sperm concentration and %-progressive motility and a significant positive association between PFAS levels in postpartum serum and sperm concentration. Conclusion While our data do not suggest an adverse association between early PFAS exposure and semen quality in adulthood, an adverse association with early dioxin exposure cannot be excluded. The small sample size and potential sources of bias or confounding call for cautious interpretation.

Fatty acid esters of 3-monochloropropane-1,2-diol (3-MCPD) are heat-induced contaminants formed from fats and sodium chloride. The mode of action for the 3-MCPD mediated induction of renal tubule neoplasms in rats is still unclear, which is in part due to lacking metabolism data. In the current study, urinary metabolites were identified by one- and two-dimensional 13C nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry following oral administration of 3-MCPD or [13C3]3-MCPD in rats. In addition to 3-MCPD itself, nine metabolites were identified. Four of those, N-acetyl-S-(2,3-dihydroxypropyl)cysteine (DHPMA), 3-MCPD sulfate, β-chlorolactic acid (β-ClLA) and oxalic acid have been reported before. Five novel metabolites in rat urine were thiodiglycolic acid (TDGA), thionyldiglycolic acid (TNDGA), 3-MCPD glucuronide (at least three isomers), 3-carboxy-2-hydroxypropyl mercapturic acid (CHPMA), and 3-(S-carboxymethyl)mercaptolactic acid (CMMLA). Only three metabolites were excreted at mean dose ratios > 1

To review recent advances in research on per- and polyfluoroalkyl substances (PFAS) and outline priority steps for risk assessment in consumer health protection, the German Federal Institute for Risk Assessment (BfR) organized the 'International PFAS Conference' in Berlin in October 2025. Building on the European Food Safety Authority's (EFSA) opinion in 2020, global research activities on PFAS have intensified. The conference was attended by 200 participants from 18 countries and covered topics such as analytical methods, human exposure, toxicokinetics, toxicity, and future perspectives. Given that there are more than 21,000 different PFAS in use, discussions highlighted the need for further data collection and a basis for prioritizing substances. Robust exposure assessment requires improved analytical methods combined with newly developed predictive tools to quantify, identify, and make better use of non-target data. Hazard characterization may benefit from the combined use of classic experimental data sets, epidemiological data, and new approach methodologies (NAMs) data. The participants emphasized the continuous need for refined data and proposed a systematic consolidation of global data on shared data platforms, accompanied by corresponding guidelines for data usage. In the final panel discussion, effective risk communication was identified as a critical challenge, necessitating clear and consistent messaging for the public and policymakers. The conference concluded with five key recommendations for future health risk assessments: prioritizing PFAS; improving analytical methods; promoting generation of robust data and data gap filling; promoting open science, including the development of shared data infrastructure and cross-institutional knowledge exchange; and strengthening risk communication. These recommendations aim to support transparent, evidence-based and effective PFAS consumer health risk management in the decades ahead.

Per- and polyfluoroalkyl substances (PFAS) may elevate blood lipids, suggesting that PFAS may also target the cardiovascular system. This systematic review aimed to investigate the relationship between internal human exposure to main PFAS, i.e., perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) and ischemic heart diseases (IHD). Two systematic literature searches were performed in MEDLINE and EMBASE - most recently on January 8, 2025. Eligible studies analyzed associations between individual blood PFAS exposure and IHD among humans. Risk of bias was assessed using the OHAT Risk of Bias Rating Tool and evidence was synthesized using structured tables and vote counting based on direction of effect, as meta-analyses and dose-response analyses did not provide meaningfully interpretable results. The 16 studies included comprised 79,313 participants. Seven studies estimated rate ratios (RR) and nine estimated odds ratios (OR). Associations between PFOA exposure and IHD (RR) were small and exposure levels were heterogeneous. In the vote counting analysis of the association between PFOA exposure and IHD, 82.4% (95%-CI: 56.6%-96.2%) of effect estimates (RR) pointed in the harmful direction (low certainty). A harmful tendency was less pronounced for PFOS and IHD, with 60.0% (95%-CI: 14.7%-94.7%) of RR and 46.4% (95%-CI 27.5%-66.1%) of OR indicating a harmful relationship. For PFHxS, PFNA, and the sum of PFAS, the overall direction of the vote counting results differed between RR and OR (very low or low certainty). The relationship between PFAS and IHD remains unclear, so further longitudinal studies investigating dose-dependent effects are required.

The widespread application of per- and polyfluoroalkyl substances (PFAS) resulted in ubiquitous environmental contamination. Understanding the PFAS tissue distribution in mammals and humans is crucial for the assessment of potential health risks. The levels of eleven PFAS were determined by UPLC-MS/MS in plasma and various tissues of wild boar (n = 82) hunted in Germany. The most prevalent PFAS (PFOA, PFNA, PFHxS and PFOS) were detected in all analyzed samples. The median level of the sum (Σ 4PFAS) was highest in liver (90.2 μg/kg), followed by kidney (9.45 μg/kg), plasma (7.63 μg/L), lung (6.84 μg/kg), heart muscle (2.60 μg/kg), spleen (2.46 μg/kg), and skeletal muscle (1.03 μg/kg). Consumption of a single portion (125 g) of liver containing the Σ 4PFAS median level would result in a 36.6-fold exceedance of the tolerable weekly intake (TWI) of EFSA in a 70 kg-person. The accumulation (calculated as tissue/plasma ratio) of perfluoroalkyl carboxylic acids with ηpfc = 8-13 in lung, spleen, muscle and heart tissues increased with molecule size, indicating passive mechanisms of distribution driven by hydrophobicity. In contrast, liver and kidney distribution coefficients scattered, indicating additional involvement of chain-length dependent active transport processes. The highest accumulation was observed for PFOS in the liver (median tissue/plasma ratio 18.0). The shortest PFAS included in the study (PFHxA, PFHpA, PFOA, PFBS and PFHxS) did not accumulate in any of the tissues, probably due to strong binding to blood proteins like serum albumin and their relative polarity impeding passive membrane diffusion.

BACKGROUND & AIMS:Previous studies have described benefits and risks on human health associated with a vegan diet. Although it is recognized that diet affects the gut microbiota, there is no consensus on the effects of a vegan diet compared to omnivorous diet on the gut microbiota. We have conducted a pilot study to assess the differences between the gut microbiome of vegans and omnivores in 2017 and 2021. METHODS:Fecal samples of 23 vegans and 23 omnivores (n = 46) were collected in 2017 and 2021 together with more than 300 dietary, lifestyle, and health related characteristics. The fecal microbiome was assessed comparing both amplicon sequencing and metagenome sequencing, to determine robust signals agnostic of sequencing approaches. RESULTS:Dietary grouping itself explained a small (∼4 %) but significant proportion of the individual variation between microbiota. Natural clustering of microbiomes explained an even larger proportion. We found Ruminococcus torques to be relatively enriched in omnivores compared to vegans across methods and years. Interestingly, this species has been previously associated with unfavorable health outcomes. Despite a low sample size, we found some consistent differences between microbiota of individuals consuming either a vegan or omnivorous diet. CONCLUSIONS:These results were consistent with recently published gut microbiome signatures of vegans and omnivores across three different countries. Therefore, this small dataset allows a first insight into the gut microbiota of another county's omnivores and vegans whereby detailed and relevant dietary, lifestyle and health related characteristics collected in this study aid in understanding of the connection between respective diets and the microbiome.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants with half-lives in humans in the range of years in case of the long-chain compounds, leading to accumulation and measurable levels in plasma. In contrast, short-chain and "alternative" PFAS have lower levels or are not detectable in humans with background exposure. This may be due to lower exposure, but also due to much shorter half-lives compared to long-chain compounds. To get better data on kinetics, a healthy volunteer orally ingested a mixture of fifteen predominantly 13C-labeled PFAS ("MPFAS") in a pilot investigation (MPFBA, MPFPeA, MPFHxA, MPFHpA, MPFOA, MPFNA, MPFDA, MPFUdA, MPFDoA, PFBS, MPFHxS, MPFOS, DONA, HFPO-DA, 6:2FTS). After application, concentrations were measured over 450 days in plasma, urine and feces, using UHPLC-MS/MS analysis after extraction. The compounds were absorbed quickly and almost completely. Data analysis revealed volumes of distribution between 110 and 177 mL/kg bw for most compounds, but higher values for MPFDA, MPFUdA and MPFDoA (maximum of 354 mL/kg bw). Half-lives were found to vary extremely, from 0.5 days (MPFPeA) and 1.5 days (MPFHxA) to 51 days (PFBS) and 152 days (MPFHpA) in case of the short-chain and "alternative" compounds. For the long-chain compounds, half-lives in the range of several years were confirmed for MPFOA, MPFNA, MPFHxS and MPFOS, but with even higher chain-lengths of the carboxylic acids, the halflives were found to decrease, with the shortest half-life for MPFDoA (295 days). Elimination from the body was completely explained by the urinary losses in case of the short-chain and "alternative" PFAS, and in part by the fecal losses in case of the long-chain PFCA. Overall, elimination kinetics seem to be determined by several different renal and gastrointestinal factors (fraction unbound in plasma, binding affinity to organic anion transporters causing netto secretion or reabsorption, fecal loss with mechanisms to be clarified).

Fatty acid esters of 2/3-monochloropropanediol (2/3-MCPD) and glycidol are formed mainly during heat processing (deodorization) of vegetable oils, and are hydrolyzed by lipases in the gastrointestinal tract leading to the absorption of 2/3-MCPD and glycidol. The International Agency for Research on Cancer (IARC) has classified 3-MCPD as possibly and glycidol as probably carcinogenic to humans. The aims of the current work were to clarify the exposure to 2/3-MCPD and glycidol associated with different dietary habits (omnivore, vegan, raw-food eating), and the exposure development between 2017 and 2021 in German study participants. The questions were addressed using the daily urinary excretion of 2/3-MCPD and the hemoglobin adduct N-(2,3-dihydroxypropyl)-Val (DHP-Val) formed from glycidol as biomarkers of exposure, which were determined in two dietary studies including 36 omnivores, 36 vegans and 16 strict raw food eaters (abstaining from any heated food for at least four months). The median urinary excretion of 2- and 3-MCPD in non-smoking omnivores and vegans was 0.87 and 1.35 µg/day (2-MCPD), respectively, and 0.79 and 1.03 µg/day (3-MCPD), respectively. The 2/3-MCPD concentrations in urine samples of raw food eaters were usually below the limit of detection. The median DHP-Val levels in non-smoking vegans and omnivores were 3.9 pmol/g Hb each, and 1.9 pmol/g Hb in raw food eaters. Between 2017 and 2021, the exposure to 3-MCPD and glycidol did not change, however, the median 2-MCPD excretion decreased (p = 0.02, omnivores and vegans combined). The correlation between daily excretions of 2/3-MCPD determined 4 years apart was weak, whereas a moderate correlation was observed for DHP-Val (rS = 0.66) in this timeframe. In conclusion, the exposure to glycidol in omnivores and vegans was alike, whereas the 2/3-MCPD exposure was somewhat (albeit not significantly) higher in vegans. While 2/3-MCPD were hardly detectable in urine samples of raw food eaters, the median DHP-Val level (about 50

The urinary mercapturic acids N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) are short-term biomarkers of exposure from acrylamide and its metabolite glycidamide, respectively. The medium-term exposure to acrylamide and glycidamide is monitored by the adducts N-(2-carbamoylethyl)-Val (AA-Val) and N-(2-carbamoyl-2-hydroxyethyl)-Val (GA-Val) in hemoglobin (Hb), respectively. Three questions were addressed by application of these biomarkers in two diet studies including 36 omnivores, 36 vegans and 16 strict raw food eaters (abstaining from any warmed or heated food for at least four months): first, what is the internal acrylamide exposure following a vegan or a raw food diet in comparison to that in omnivores? Second, did the exposure change between 2017 and 2021? And third, what is the stability over time of AAMA/GAMA excretion compared to that of AA-Val/GA-Val levels in Hb between both time points? Median urinary AAMA excretion per day in non-smoking omnivores, vegans and raw food eaters were 62.4, 85.4 and 15.4 µg/day, respectively; the corresponding median AA-Val levels were 27.7, 39.7 and 13.3 pmol/g Hb, respectively. Median levels in strict raw food eaters were about 25

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants. Studying the bioaccumulation in mammalian tissues requires a considerable effort for the PFAS extraction from complex biological matrices. The aim of the current work was to select and optimize the most efficient among common extraction strategies for eleven perfluoroalkyl acids (PFAA). Primary extractions from wild boar tissues (liver, kidney, and lung) were performed with methanol at neutral, acidic, or alkaline conditions, or with methyl-tert-butyl ether (MTBE) after ion-pairing with tetrabutylammonium (TBA) ions. A second purification step was chosen after comparing different solid-phase extraction (SPE) cartridges (Oasis WAX, ENVI-Carb, HybridSPE Phospholipid) and various combinations thereof or dispersive SPE with C18 and ENVI-Carb material. The best extraction efficiencies of the liquid PFAA extraction from tissue homogenates were achieved with methanol alone (recoveries from liver 86.6-114.4%). Further purification of the methanolic extracts using dispersive SPE or Oasis WAX columns decreased recoveries of most PFAA, whereas using pairs of two SPE columns connected in series proved to be more efficient albeit laborious. Highest recoveries for ten out of eleven PFAA were achieved using ENVI-Carb columns (80.3-110.6%). In summary, the simplest extraction methods using methanol and ENVI-Carb columns were also the most efficient. The technique was validated and applied in a proof of principle analysis in human tissue samples.

3-Chloro-1,2-propanediol (3-MCPD) and its fatty acid esters (FE) are present as contaminants in different pro-cessed foods. Based on the available toxicological data the potential risk of 3-MCPD and its FE to human health was assessed by risk assessment authorities, including the European Food Safety Authority (EFSA). Considering the available data, EFSA concluded that 3-MCPD is a non-genotoxic compound exhibiting secondary carcino-genic effects in rodents. A tolerable daily intake of 2 mu g/kg body weight and day was derived by EFSA for free and ester-bound 3-MCPD in 2018. However, there are still different pending issues that have remained unclear until now. Here, we summarize the current knowledge regarding 3-MCPD and its FE with a focus on pending issues regarding exposure assessment via biomarkers as well as the identification of (toxic) metabolites formed after exposure to FE of 3-MCPD and their modes of action.

[This corrects the article DOI: 10.1016/j.fochx.2022.100459.].

LebensmittelchemieVolume 77, Issue S3 p. S3-044-S3-044 Posterflashtalks Solvent and solid-phase extraction of per- and polyfluoroalkyl substances (PFASs) from mammalian tissues homogenates for UPLC-MS/MS analysis H. Junk, H. Junk Berlin/D German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin/DSearch for more papers by this authorB. Noll, B. Noll Berlin/DSearch for more papers by this authorT. Schwerdtle, T. Schwerdtle Berlin/DSearch for more papers by this authorK. Abraham, K. Abraham Berlin/DSearch for more papers by this authorB.H. Monien, B.H. Monien Berlin/DSearch for more papers by this author H. Junk, H. Junk Berlin/D German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin/DSearch for more papers by this authorB. Noll, B. Noll Berlin/DSearch for more papers by this authorT. Schwerdtle, T. Schwerdtle Berlin/DSearch for more papers by this authorK. Abraham, K. Abraham Berlin/DSearch for more papers by this authorB.H. Monien, B.H. Monien Berlin/DSearch for more papers by this author First published: 01 August 2023 https://doi.org/10.1002/lemi.202359038AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume77, IssueS3Supplement: Abstracts der Vorträge, Posterflashtalks und Poster von den 51. Deutschen Lebensmittelchemietagen 2023August 2023Pages S3-044-S3-044 RelatedInformation

Dietary biomarkers can potentially overcome the limitations of self-reported dietary data. While in ecology and archaeology, stable isotope ratios of carbon and nitrogen are widely used as biomarkers, this is not the case in nutrition research. Since the abundance of the 13C and the 15N isotope differ in food sources from plant and animal origin, stable isotope ratios of carbon and nitrogen (δ13C and δ15N) may differ in human biological material. Here, we investigated the stable isotope ratios of nitrogen and carbon in serum and urine from vegans and omnivores. Measurement of δ15N and δ13C in serum and 24 h urine was performed by Elemental Analyzer–Isotope Ratio Mass Spectrometer in the cross-sectional study “Risks and Benefits of a Vegan Diet”. The study included 36 vegans and 36 omnivores with a median age of 37.5 years (matched for age and sex), who adhered to their diet for at least 1 year. Both δ15N and δ13C were significantly lower in both the serum and 24 h urine of vegans compared to omnivores. δ15N either in serum or urine had 100

The aim of this work is to describe the development of a web-based, interactive tool of maximum tolerable consumption levels for selected foods that might be contaminated ('' ContamCalculator ''). The scientific application criteria for the ContamCalculator are described. As an example, we present the fipronil event in summer 2017.

Introduction Persistent organic pollutants (POPs) are a heterogeneous group of ubiquitous environmental pollutants with a high persistence accumulating in the food chain. Despite external background exposures being relatively low, the long biological half-lives of these compounds in humans lead to considerable accumulation, with measurable levels of internal exposure in the general population. With respect to possible effects, fetal exposure may be especially critical (expected highest susceptibility), and postnatal exposure from breastfeeding, in the case of a long duration, is expected to be the highest exposure period over a lifetime. In this context, two groups of POPs are in the focus of scientific and public concern, namely dioxins and perand polyfluorinated alkyl substances (PFAS). One possible effect of exposure is an impact on the male reproductive system in fetal life and/or early childhood resulting in reduced semen quality in adulthood. In the case of dioxins, evidence comes not only from animal experiments,1,2 but also from high-dose exposure to tetrachlorodibenzop-dioxin (TCDD) following the Seveso accident in 1976.3 The European Food Safety Authority (EFSA) used data from a study of high ambient exposure in a Russian industrial city4 to lower the tolerable weekly intake (TWI) in 2018.1 Investigations into the effect of early PFAS exposure on male semen quality in laboratory animals are missing, but epidemiological support comes from a study of 864 participants,5 which focused on the exposure to PFAS in early pregnancy only. With respect to the latter study, the question of the correlation of dioxins and PFAS was raised in a comment,6 showing data of dioxin international toxicity equivalents (I-TEq) and perfluorooctanoic acid (PFOA) in 11-month-old children predominantly breastfed for at least 4 months,7 with a Spearman’s rank correlation coefficient of r=0:77. In their response,8 the authors argued that they expect low correlations of dioxins and PFAS with respect to prenatal exposure (i.e., concentrations in the mothers). Data on the correlations are available from our study,7 not only for the children,6 but also for the mothers, the latter of which are presented in this article.

Biomarker measurements in spot urine are often adjusted for creatinine to control for dilution resulting from individual hydration. We here report on results of a study involving age- and sex-matched vegans and omnivores (n = 36 each). The daily urinary excretion of 2,3-dihydroxypropylmercapturic acid (DHPMA, a diet-independent endogenous C3-metabolite used as an example compound) was found not to be different in vegans and omnivores (median 433 mu g/24 h each), however, creatinine-adjusted levels were 26% lower in omnivores (median 285 mu g/g creatinine) than in vegans (median 383 mu g/g creatinine, p = 0.003). This difference results from the higher urinary excretion of creatinine in the omnivores compared to vegans (median 1.51 vs. 1.21 g/24 h, p = 0.009). Linear regression showed - besides the fat-free mass - a significant impact of the factor diet (vegans vs. omnivores). This may be due to the consumption of meat and fish as exogenous sources of creatinine. A literature search revealed broad evidence for this interpretation, as creatinine is formed from creatine during heating of meat and fish. Accordingly, consumption leads to temporary increase of serum/plasma creatinine and urinary creatinine excretion, resulting in higher levels in omnivores compared to vegans/vegetarians. An adjustment of the urinary DHPMA concentrations using specific gravity revealed 13% lower values in omnivores (median 225 mu g/L) than in vegans (median 260 mu g/L, p = 0.07). Compared to creatinine-adjustment, adjustment for specific gravity introduces a smaller but still obvious difference between omnivores and vegans. Especially with respect to future studies comparing vegans, vegetarians and omnivores, researchers should be aware of the risks of severe misinterpretations if biomarker measurements in spot urine are adjusted for creatinine.

Fatty acid esters of glycidol (glycidyl esters, GE) are processing contaminants in vegetable oils and fats. GE release the carcinogenic glycidol in the gastrointestinal tract. The assessment of health risks associated with dietary GE uptake is hindered by the inaccuracy of exposure estimations based on consumption and food content data. Alternatively, the internal exposure can be approximated by monitoring of human biomarkers of glycidol, for example, the hemoglobin adduct N-(2,3-dihydroxypropyl)-valine (DHP-Val). The quantification of DHP-Val levels in blood samples showed that human adults are exposed principally by foodstuffs and tobacco smoke. Reverse dosimetry allowed calculating the mean oral exposure for 11 German adults (0.94 μg/kg body weight) and 50 Swedish adolescents (1.4 μg/kg body weight). These values exceeded the median chronic exposure estimated from dietary surveys for the adult population (0.2 μg/kg body weight) and for adolescents (0.3 μg/kg body weight), which may be due to hitherto unknown sources of glycidol/GE. Data on DHP-Val in strict raw food eaters, who do not consume food heated to more than 42 °C, suggests that DHP-Val is also formed independently from the oral exposure to GE.