Internal exposure to heat-induced food contaminants in omnivores, vegans and strict raw food eaters: biomarkers of exposure to acrylamide (hemoglobin adducts, urinary mercapturic acids) and new insights on its endogenous formation.

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% (AAMA excretion) and 48% (AA-Val) of those in omnivores. In comparison to 2017, AAMA and GAMA excretion levels were hardly altered in 2021, however, levels of AA-Val and GA-Val in 2021 slightly increased. There was a weak correlation between AAMA excretion levels determined four years apart (rS = 0.30), and a moderate correlation between levels of AA-Val (rS = 0.55) in this timeframe. Our data in strict raw food eaters confirm a significant endogenous formation to acrylamide in a size range, which is-based on the levels of AA-Val-distinctly higher than reported previously based on levels of urinary AAMA excretion. The relatively lower AAMA excretion in raw food eaters likely represents a lower extent of glutathione conjugation due to missing hepatic first-pass metabolism in case of endogenous formation of acrylamide, which leads to a higher systemic exposure.

Urinary Excretion of Mercapturic Acids of the Rodent Carcinogen Methyleugenol after a Single Meal of Basil Pesto: A Controlled Exposure Study in Humans.

Methyleugenol (ME), found in numerous plants and spices, is a rodent carcinogen and is classified as "possibly carcinogenic to humans". The hypothesis of a carcinogenic risk for humans is supported by the observation of ME-derived DNA adducts in almost all human liver and lung samples examined. Therefore, a risk assessment of ME is needed. Unfortunately, biomarkers of exposure for epidemiological studies are not yet available. We hereby present the first detection of N-acetyl-l-cysteine conjugates (mercapturic acids) of ME in human urine samples after consumption of a popular ME-containing meal, pasta with basil pesto. We synthesized mercapturic acid conjugates of ME, identified the major product as N-acetyl-S-[3'-(3,4-dimethoxyphenyl)allyl]-l-cysteine (E-3'-MEMA), and developed methods for its extraction and LC-MS/MS quantification in human urine. For conducting an exposure study in humans, a basil cultivar with a suitable ME content was grown for the preparation of basil pesto. A defined meal containing 100 g of basil pesto, corresponding to 1.7 mg ME, was served to 12 participants, who collected the complete urine at defined time intervals for 48 h. Using d6-E-3'-MEMA as an internal standard for LC-MS/MS quantification, we were able to detect E-3'-MEMA in urine samples of all participants collected after the ME-containing meal. Excretion was maximal between 2 and 6 h after the meal and was completed within about 12 h (concentrations below the limit of detection). Excreted amounts were only between 1 and 85 ppm of the ME intake, indicating that the ultimate genotoxicant, 1'-sulfooxy-ME, is formed to a subordinate extent or is not efficiently detoxified by glutathione conjugation and subsequent conversion to mercapturic acids. Both explanations may apply cumulatively, with the ubiquitous detection of ME DNA adducts in human lung and liver specimens arguing against an extremely low formation of 1'-sulfooxy-ME. Taken together, we hereby present the first noninvasive human biomarker reflecting an internal exposure toward reactive ME species.

Less is more: a methodological assessment of extraction techniques for per- and polyfluoroalkyl substances (PFAS) analysis in mammalian tissues.

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.

Corrigendum to "The first German total diet study (BfR MEAL Study) confirms highest levels of dioxins and dioxin-like polychlorinated biphenyls in foods of animal origin title of article" [Food Chem.: X 16 (2022) 100459].

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

Risks of misinterpretation of biomarker measurements in spot urine adjusted for creatinine - A problem especially for studies comparing plant based with omnivorous diets.

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 µg/24 h each), however, creatinine-adjusted levels were 26% lower in omnivores (median 285 µg/g creatinine) than in vegans (median 383 µg/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 µg/L) than in vegans (median 260 µg/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.

Stable isotope ratios of nitrogen and carbon as biomarkers of a vegan diet.

PURPOSE: 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. METHOD: 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. RESULTS: 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% specificity and sensitivity to discriminate between vegans and omnivores. Specificity of δ13C was also > 90%, while sensitivity was 93% in serum and 77% in urine. CONCLUSION: δ15N both in serum and urine was able to accurately identify vegans and thus appears to be a promising marker for dietary habits.

3-MCPD as contaminant in processed foods: State of knowledge and remaining challenges.

3-Chloro-1,2-propanediol (3-MCPD) and its fatty acid esters (FE) are present as contaminants in different processed 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 carcinogenic effects in rodents. A tolerable daily intake of 2 µg/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.

Urinary Potential Renal Acid Load (uPRAL) among Vegans Versus Omnivores and Its Association with Bone Health in the Cross-Sectional Risks and Benefits of a Vegan Diet Study.

Both veganism and high dietary acid load are linked to unfavorable bone health. However, the specific role of dietary alkali or acid load for the bone health of vegans is so far unknown. Thus, the renal biomarker for dietary acid or alkali load, i.e., urinary potential renal acid load (uPRAL), was measured in 24 h urine samples of 34 vegans and 35 omnivores (50.7% males). Bone health was assessed via calcaneal quantitative ultrasound. Associations between uPRAL and bone health indices were examined using multivariable general linear models. Compared to omnivores, vegans had a significantly lower uPRAL (mean difference = −34.5 mEq/24 h, p < 0.0001), a lower 24 h urinary phosphate excretion (p = 0.0004), a lower 24 h urinary sulfate excretion (p = 0.01), and a higher urine pH value (p < 0.0001). Broadband ultrasound attenuation (BUA) was lower among vegans versus omnivores (p = 0.037), yet it was not associated with uPRAL irrespective of adjustments. This study confirms different acid-base profiles of vegans and omnivores, with a pronounced alkaline excess among vegans and a rather low acid load among a group of omnivores with moderate protein intake. Within this spectrum of alkaline to low acid load, no association with bone health was found.

Transdermal absorption of 13C4-perfluorooctanoic acid (13C4-PFOA) from a sunscreen in a male volunteer - What could be the contribution of cosmetics to the internal exposure of perfluoroalkyl substances (PFAS)?

Per- and polyfluoroalkyl substances (PFAS) are a complex group of man-made chemicals with high stability and mobility leading to ubiquitous environmental contamination and accumulation especially of some long-chain perfluoroalkyl acids (PFAA) in humans. While dietary intake is the main route of exposure, transdermal uptake from cosmetic products usually is considered negligible. However, PFAS are present in a part of these products, and recent epidemiological studies have provided evidence for relevant uptake via this route. The crucial question is whether PFAA in cosmetic products can cross the human skin barrier. A defined amount (110 µg) of 13C4-perfluorooctanoic acid (13C4-PFOA) was mixed into a sunscreen (30 g) which was applied on the whole skin of a volunteer. The plasma concentrations of 13C4-PFOA were determined in serial blood samples taken over 115 days using UHPLC-MS/MS and 13C2-PFOA as internal standard. After application, 13C4-PFOA plasma levels increased continuously, reaching levels of 3, 56 and 118 ng/L after 6 h, 3 days and 10 days, respectively. A maximum level of 132 ng/L was measured 22 days after application, representing 9.4 % of the PFOA level resulting from the volunteer's background exposure (1400 ng/L, equivalent to 1.4 ng/mL). In the following weeks, the levels slightly decreased with an estimated half-life of 1.8 years. The best estimate for the fraction absorbed may be 1.6 % of the dose, using a volume of distribution of 0.17 L/kg body weight. For PFOA mixed into a sunscreen, this experimental approach demonstrates a significant uptake of a PFAA via transdermal absorption in humans. In the past, some cosmetic products contained relevant PFAA levels as contaminants/impurities of PFAS added as active ingredients. Depending on these levels and the use (frequency, skin area involved), it is plausible that this route of exposure has contributed to the internal exposure to PFAA, as already suggested by epidemiological observations.

The first German total diet study (BfR MEAL Study) confirms highest levels of dioxins and dioxin-like polychlorinated biphenyls in foods of animal origin.

The first German Total Diet Study, called the BfR MEAL Study, generated a comprehensive dataset of polychlorinated dibenzo-p-dioxins and -furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in foods representative for the consumption habits in households in Germany. PCDD/Fs and dl-PCBs are persistent organic pollutants. Dietary intake is considered to be the most relevant exposure pathway for humans. Levels were examined in 300 foods that were prepared as typically consumed by the population in Germany. Highest PCDD/F and dl-PCB levels were detected in animal-based foods such as fish, butter, dairy products, liver, and meat. The comparison of conventionally and organically produced foods revealed a trend to slightly higher contents in organically produced foods. Sampling discriminated by region and season showed no major differences. Analysed occurrence data will improve future dietary exposure and food safety assessments in Germany.

Dietary and Plasma Phospholipid Profiles in Vegans and Omnivores-Results from the RBVD Study.

Over the last few years, the vegan diet has become increasingly popular in Germany. It has been proposed that this diet is generally lower in fat, but less is known about the impact on fatty acid (FA) profiles. Therefore, the cross-sectional "Risks and Benefits of a Vegan Diet" (RBVD) study (n = 72) was used to investigate dietary FA intake as well as plasma phospholipid FA in vegans (n = 36) compared to omnivores (n = 36). Vegans had a significantly lower dietary intake of total fat (median 86 g/day, IQR 64−111) in comparison to omnivores (median 104 g/day, IQR 88−143, p = 0.004). Further, vegans had a lower intake of saturated fatty acids (SFA) (p < 0.0001) and monounsaturated fatty acids (MUFA) (p = 0.001) compared to omnivores. Vegans had a higher intake in total polyunsaturated fatty acids (PUFA), omega-3 and omega-6 PUFA compared to omnivores, but without statistical significance after Bonferroni correction. According to plasma phospholipid profiles, relatively lower proportions of SFA (p < 0.0001), total trans fatty acids (TFA) (p = 0.0004) and omega-3-FA (p < 0.0001), but higher proportions of omega-6-FA (p < 0.0001) were observed in vegans. With the exception of omega-3 PUFA, a vegan diet is associated with a more favorable dietary fat intake and more favorable plasma FA profiles and therefore may reduce cardiovascular risk.

Comparison of Five Oxidative Stress Biomarkers in Vegans and Omnivores from Germany and Finland.

When the amount of reactive oxygen species produced by human metabolism cannot be balanced by antioxidants, this phenomenon is commonly referred to as oxidative stress. It is hypothesised that diets with high amounts of plant food products may have a beneficial impact on oxidative stress status. However, few studies have examined whether a vegan diet is associated with lower oxidative stress compared to an omnivorous diet. The present cross-sectional study aimed to compare the levels of five oxidative stress biomarkers in vegans and omnivores. Data of 36 vegans and 36 omnivores from Germany and of 21 vegans and 18 omnivores from Finland were analysed. HPLC coupled with mass spectrometry or fluorescence detection and ELISA methods were used to measure the oxidative stress biomarkers malondialdehyde (MDA), protein carbonyls and 3-nitrotyrosine in plasma and 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in 24 h urine. Analyses of variance and covariance, considering potential confounders, were used. Vegans and omnivores showed no differences in MDA and protein carbonyl concentrations. In Finnish but not in German vegans, the concentrations of 3-nitrotyrosine were lower compared to those in omnivores (p = 0.047). In Germany, vegans showed lower excretion levels of 8-iso-PGF2α than omnivores (p = 0.002) and with a trend also of 8-OHdG (p = 0.05). The sensitivity analysis suggests lower 8-iso-PGF2α excretion levels in women compared to men, independently of the dietary group. The present study contributes to expanding our knowledge of the relationship between diet and oxidative stress and showed that 3-nitrotyrosine, 8-OHdG and 8-iso-PGF2α tended to be lower in vegans. Furthermore, studies are recommended to validate the present findings.

Simultaneous quantification of eight hemoglobin adducts of genotoxic substances by isotope-dilution UHPLC-MS/MS.

Various genotoxic carcinogens ubiquitously present in the human environment or respective reactive metabolites form adducts in DNA and proteins, which can be used as biomarkers of internal exposure. For example, the mass spectrometric determination of Val adducts at the N-termini of hemoglobin (Hb) peptide chains after cleavage by an Edman degradation has a long tradition in occupational medicine. We developed a novel isotope-dilution UHPLC-MS/MS method for the simultaneous quantification of Val adducts of eight genotoxic substances in Hb after cleavage with fluorescein-5-isothiocyanate (FIRE procedure™). The following adducts were included [sources in square brackets]: N-(2,3-dihydroxypropyl)-Val [glycidol], N-(2-carbamoylethyl)-Val [acrylamide], N-(2-carbamoyl-2-hydroxyethyl)-Val [glycidamide], N-((furan-2-yl)methyl)-Val [furfuryl alcohol], N-(trans-isoestragole-3'-yl)-Val [estragole/anethole], N-(3-ketopentyl)-Val [1-penten-3-one], N-(3-ketooctanyl)-Val [1-octene-3-one], and N-benzyl-Val [benzyl chloride], each of which was quantified with a specific isotope-labeled standard. The limits of quantification were between 0.014 and 3.6 pmol/g Hb (using 35 mg Hb per analysis); other validation parameters were satisfactory according to guidelines of the U.S. Food and Drug Administration. The quantification in erythrocyte samples of human adults (proof of principle) showed that the median levels of Hb adducts of acrylamide, glycidamide, and glycidol were found to be significantly lower in six non-smokers (25.9, 12.2, and 4.7 pmol/g Hb, respectively) compared to those of six smokers (69.0, 44.2, and 8.6 pmol/g Hb, respectively). In summary, the method surpasses former techniques of Hb adduct quantification due to its simplicity, sensitivity, and accuracy. It can be extended continuously with other Hb adducts and will be used in epidemiological studies on internal exposure to carcinogens.

Nutritional Intake and Biomarker Status in Strict Raw Food Eaters.

Following a strict raw food diet (primarily based on fresh fruit and raw vegetables, waiving any consumption of heated or processed food) has the risk of undersupply of energy and certain macro- and micronutrients. In this cross-sectional study, we compared 16 non-smoking strict raw food eaters (5 women and 11 men, age 44.6 ± 12.3 years, duration of following the diet 11.6 ± 10.8 years) with the non-smoking participants (32 vegans, 27 omnivores) of the "Risk and Benefits of a Vegan Diet" (RBVD) study. We investigated body composition, dietary intake from 3-day weighed food records, and relevant fasting blood and serum parameters. Food choice and dietary behavior were very heterogenic in raw food eaters. They had lower mean values of BMI and percentage of body fat than the respective RBVD participants. The same holds true for energy supply and intakes of protein, carbohydrate, calcium and iodine. Serum levels revealed lower levels of HDL cholesterol, triglycerides, zinc, and vitamin D3. The raw food eaters with (n = 9) and without (n = 7) supplementation of vitamin B12 had median vitamin B12 levels of 399 and 152 ng/L, respectively. Accordingly, eight raw food eaters (50%) had homocysteine levels above 12 µmol/L. The study allows a close look at strict raw food eaters with respect to possible dietary deficiencies, but also provides insights into motivations and daily life.

Mycotoxins in Serum and 24-h Urine of Vegans and Omnivores from the Risks and Benefits of a Vegan Diet (RBVD) Study.

SCOPE: Vegans might have a higher exposure to mycotoxins due to their heightened consumption of typical mycotoxin containing food sources. Yet, data on internal exposure among vegans in comparison to omnivores are currently lacking. METHODS AND RESULTS: This cross-sectional study includes 36 vegans and 36 omnivores (50% females, 30-60 years). A set of 28 and 27 mycotoxins is analyzed in 24-h urine and serum samples, respectively, by validated multi-mycotoxin methods (HPLC-MS/MS). Ochratoxin A (OTA), 2'R-OTA, and enniatin B in serum as well as deoxynivalenol-glucuronide in 24-h urine are quantified in 57-100% of the samples. Serum OTA levels are twofold higher in vegans than in omnivores (median 0.24 ng mL-1 vs 0.12 ng mL-1 ; p < 0.0001). No further significant differences were observed. Serum OTA levels are associated with intake of "vegan products" (r = 0.50, p < 0.0001) and "pasta & rice" (r = 0.33, p = 0.006). Sensitivity analyses advise cautious interpretation. Furthermore, serum levels of 2'R-OTA are related to coffee consumption (r = 0.64, p < 0.0001). CONCLUSION: The results indicate a higher exposure of vegans to OTA, but not to other mycotoxins. However, larger studies with repeated measurements are required to better evaluate the exposure to mycotoxins from plant-based diets.

Amino acid intake and plasma concentrations and their interplay with gut microbiota in vegans and omnivores in Germany.

PURPOSE: It has been estimated that most vegans meet the total protein requirements, but whether this is also true for individual essential amino acids (AAs) is unclear. Furthermore, a shift in protein intake is suggested to alter microbiota composition, but this association is unknown in terms of veganism or individual AAs. This cross-sectional study compared vegans and omnivores regarding dietary intake and plasma concentration of AAs. The prevalence of insufficient intake of essential AAs among vegans was determined using estimated average requirements (EAR) of WHO. Moreover, correlations between AAs intake and gut microbiota were investigated. METHODS: Data of 36 vegans and 36 omnivores (30-60 years) were analysed. AA intake, AA plasma concentrations and gut microbiota were ascertained by three-day weighed food protocols, gas/liquid chromatography-tandem mass spectrometry and 16S rRNA sequencing, respectively. RESULTS: At almost the same energy intake, the intake of 9 AAs in vegans was significantly lower than in omnivores, with median differences of - 27.0% to - 51.9%. However, only one female vegan showed total protein and lysine intake below the EAR. Vegans showed lower lysine (- 25.0%), but higher glycine (+ 25.4%) and glutamate (+ 13.1%) plasma concentrations than omnivores. Correlation patterns between AA intake and bacterial microbiota differed between vegans and omnivores. In vegans 19 species and in omnivores 5 species showed correlations with AA intake. CONCLUSION: Vegans consumed apparently sufficient but lower AAs than omnivores. In addition, the different AAs intake seems to influence the microbiota composition. The use of short-term dietary data without considering usual intake limits these findings.

Detection of a Hemoglobin Adduct of the Food Contaminant Furfuryl Alcohol in Humans: Levels of N-((Furan-2-yl)methyl)-valine in Two Epidemiological Studies.

SCOPE: Furfuryl alcohol is a heat-induced food contaminant, classified as possibly carcinogenic to humans. The proximal carcinogen 2-sulfoxymethylfuran leads to adduct formation in DNA and proteins (e.g., N-((furan-2-yl)methyl)-Val (FFA-Val) in hemoglobin). METHODS AND RESULTS: This study analyzed human erythrocyte samples from two studies for the presence of FFA-Val: the Risks and Benefits of a Vegan Diet study (RBVD; 72 adults) and the ENVIRonmental influence ON early AGEing birth cohort study (ENVIRONAGE; 100 mother-newborn pairs). In the RBVD study, FFA-Val levels are lower in vegans compared to omnivores (median 13.0 vs 15.8 pmol g-1 hemoglobin, p = 0.008), and lower in non-smokers compared to smokers (median 14.1 vs 17.0 pmol g-1 hemoglobin, p = 0.003). In the birth cohort, FFA-Val levels are distinctly higher in maternal compared to newborn samples (median 15.2 vs 2.2 pmol g-1 hemoglobin, p < 0.001). CONCLUSIONS: FFA-Val, hitherto detected only in blood samples of mice, is quantifiable in all human samples, indicating a general exposure to furfuryl alcohol. The low adduct levels in blood samples from newborn children suggested that the placenta is a barrier to furfuryl alcohol. Dietary habits and tobacco smoking are two main influencing factors on the formation of FFA-Val, which may be of use as a biomarker of exposure to furfuryl alcohol.