Probabilistic Estimation of Airborne Micro- and Nanoplastic Intake in Humans.

Little research exists on the magnitude, variability, and uncertainty of human exposure to airborne micro- and nanoplastics (AMNPs), despite their critical role in human exposure to MNPs. We probabilistically estimate the global intake of AMNPs through three main pathways: indoor inhalation, outdoor inhalation, and ingestion during indoor meals, for both children and adults. The median inhalation of AMPs is 1,207.7 (90% CI, 42.5-8.48 × 104) and 1,354.7 (90% CI, 47.4-9.55 × 104) N/capita/day for children and adults, respectively. The annual intake of AMPs is 13.18 mg/capita/a for children and 19.10 mg/capita/a for adults, which is approximately one-fifth and one-third of the mass of a standard stamp, assuming a consistent daily intake of medians. The majority of AMP number intake occurs through inhalation, while the ingestion of deposited AMPs during meals contributes the most in terms of mass. Furthermore, the median ANP intake through outdoor inhalation is 9,638.1 N/day (8.23 × 10-6 µg/d) and 5,410.6 N/day (4.62 × 10-6 µg/d) for children and adults, respectively, compared to 5.30 × 105 N/day (5.79 × 10-4 µg/d) and 6.00 × 105 N/day (6.55 × 10-4 µg/d) via indoor inhalation. Considering the increased toxicity of smaller MNPs, the significant number of ANPs inhaled warrants great attention. Collaborative efforts are imperative to further elucidate and combat the current MPN risks.

In Vitro and In Vivo Biotransformation Profiling of 6PPD-Quinone toward Their Detection in Human Urine.

The antioxidant N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its oxidized quinone product 6PPD-quinone (6PPD-Q) in rubber have attracted attention due to the ecological risk that they pose. Both 6PPD and 6PPD-Q have been detected in various environments that humans cohabit. However, to date, a clear understanding of the biotransformation of 6PPD-Q and a potential biomarker for exposure in humans are lacking. To address this issue, this study presents a comprehensive analysis of the extensive biotransformation of 6PPD-Q across species, encompassing both in vitro and in vivo models. We have tentatively identified 17 biotransformation metabolites in vitro, 15 in mice in vivo, and confirmed the presence of two metabolites in human urine samples. Interestingly, different biotransformation patterns were observed across species. Through semiquantitative analysis based on peak areas, we found that almost all 6PPD-Q underwent biotransformation within 24 h of exposure in mice, primarily via hydroxylation and subsequent glucuronidation. This suggests a rapid metabolic processing of 6PPD-Q in mammals, underscoring the importance of identifying effective biomarkers for exposure. Notably, monohydroxy 6PPD-Q and 6PPD-Q-O-glucuronide were consistently the most predominant metabolites across our studies, highlighting monohydroxy 6PPD-Q as a potential key biomarker for epidemiological research. These findings represent the first comprehensive data set on 6PPD-Q biotransformation in mammalian systems, offering insights into the metabolic pathways involved and possible exposure biomarkers.

Combining Advanced Analytical Methodologies to Uncover Suspect PFAS and Fluorinated Pharmaceutical Contributions to Extractable Organic Fluorine in Human Serum (Tromsø Study).

A growing number of studies have reported that routinely monitored per- and polyfluoroalkyl substances (PFAS) are not sufficient to explain the extractable organic fluorine (EOF) measured in human blood. In this study, we address this gap by screening pooled human serum collected over 3 decades (1986-2015) in Tromsø (Norway) for >5000 PFAS and >300 fluorinated pharmaceuticals. We combined multiple analytical techniques (direct infusion Fourier transform ion cyclotron resonance mass spectrometry, liquid chromatography-Orbitrap-high-resolution mass spectrometry, and total oxidizable precursors assay) in a three-step suspect screening process which aimed at unequivocal suspect identification. This approach uncovered the presence of one PFAS and eight fluorinated pharmaceuticals (including some metabolites) in human serum. While the PFAS suspect only accounted for 2-4% of the EOF, fluorinated pharmaceuticals accounted for 0-63% of the EOF, and their contribution increased in recent years. Although fluorinated pharmaceuticals often contain only 1-3 fluorine atoms, our results indicate that they can contribute significantly to the EOF. Indeed, the contribution from fluorinated pharmaceuticals allowed us to close the organofluorine mass balance in pooled serum from 2015, indicating a good understanding of organofluorine compounds in humans. However, a portion of the EOF in human serum from 1986 and 2007 still remained unexplained.

Nationwide Investigation on Organophosphate Flame Retardants in Tea from China: Migration from Packaging Materials and Implications for Global Risk Assessment.

In this study, we measured 15 common organophosphate flame retardants (OPFRs) in six categories of tea samples across China. OPFRs were found in all the tea samples, with the total concentrations of OPFRs (∑OPFRs) at 3.44-432 ng/g [geometric mean (GM): 17.6 ng/g]. Triphenyl phosphate (TPhP) was the dominant OPFR, accounting for 39.0-76.2% of ∑OPFRs across all tea categories. The potential factors influencing the residual OPFRs in tea were thoroughly examined, including the agricultural environment, fermentation, and packaging of teas. Tea packaging materials (TPMs) were then identified as the primary sources of OPFRs in teas. The migration test revealed that OPFRs with lower molecular weights and log Kow values exhibited a higher propensity for facilitating the migration of OPFRs from TPMs to teas. The estimated daily intakes of OPFRs from teas were relatively higher for the general populations in Mauritania, Gambia, Togo, Morocco, and Senegal (3.18-9.79 ng/kg bw/day) than China (3.12 ng/kg bw/day). The health risks arising from OPFRs in Chinese teas were minor. This study established a baseline concentration and demonstrated the contamination sources of OPFRs in Chinese tea for the first time, with an emphasis on enhancing the hygiene standards for TPMs.

In Vitro Metabolism of Quaternary Ammonium Compounds and Confirmation in Human Urine by Liquid Chromatography Ion-Mobility High-Resolution Mass Spectrometry.

Quaternary ammonium compounds (QACs) are high-production chemicals used as cleaning and disinfecting agents. Due to their ubiquitous presence in the environment and several toxic effects described, human exposure to these chemicals gained increasing attention in recent years. However, very limited data on the biotransformation of QACs is available, hampering exposure assessment. In this study, three QACs (dimethyl dodecyl ammonium, C10-DDAC; benzyldimethyl dodecylammonium, C12-BAC; cetyltrimethylammonium, C16-ATMAC) commonly detected in indoor microenvironments were incubated with human liver microsomes and cytosol (HLM/HLC) simulating Phase I and II metabolism. Thirty-one Phase I metabolites were annotated originating from 19 biotransformation reactions. Four metabolites of C10-DDAC were described for the first time. A detailed assessment of experimental fragmentation spectra allowed to characterize potential oxidation sites. For each annotated metabolite, drift-tube ion-mobility derived collision cross section (DTCCSN2) values were reported, serving as an additional identification parameter and allowing the characterization of changes in DTCCSN2 values following metabolism. Lastly, eight metabolites, including four metabolites of both C12-BAC and C10-DDAC, were confirmed in human urine samples showing high oxidation states through introduction of up to four oxygen atoms. This is the first report of higher oxidized C10-DDAC metabolites in human urine facilitating future biomonitoring studies on QACs.

Micro(nano)plastics in the Human Body: Sources, Occurrences, Fates, and Health Risks.

The increasing global attention on micro(nano)plastics (MNPs) is a result of their ubiquity in the water, air, soil, and biosphere, exposing humans to MNPs on a daily basis and threatening human health. However, crucial data on MNPs in the human body, including the sources, occurrences, behaviors, and health risks, are limited, which greatly impedes any systematic assessment of their impact on the human body. To further understand the effects of MNPs on the human body, we must identify existing knowledge gaps that need to be immediately addressed and provide potential solutions to these issues. Herein, we examined the current literature on the sources, occurrences, and behaviors of MNPs in the human body as well as their potential health risks. Furthermore, we identified key knowledge gaps that must be resolved to comprehensively assess the effects of MNPs on human health. Additionally, we addressed that the complexity of MNPs and the lack of efficient analytical methods are the main barriers impeding current investigations on MNPs in the human body, necessitating the development of a standard and unified analytical method. Finally, we highlighted the need for interdisciplinary studies from environmental, biological, medical, chemical, computer, and material scientists to fill these knowledge gaps and drive further research. Considering the inevitability and daily occurrence of human exposure to MNPs, more studies are urgently required to enhance our understanding of their potential negative effects on human health.

Disposable Plastic Waste and Associated Antioxidants and Plasticizers Generated by Online Food Delivery Services in China: National Mass Inventories and Environmental Release.

China's online food delivery (OFD) services consume enormous amounts of disposable plastics. Here, we investigated and modeled the national mass inventories and environmental release of plastics and chemical additives in the plastic. The extra-tree regression identified six key descriptors in determining OFD sales in Chinese cities. Approximately 847 kt of OFD plastic waste was generated in 2021 (per capita 1.10 kg/yr in the megacities and 0.39 kg/yr in other cities). Various additives were extensively detected, with geomean concentrations of 140.96, 4.76, and 0.25 µg/g for ∑8antioxidants, ∑21phthalates, and bisphenol A (BPA), respectively. The estimated mass inventory of these additives in the OFD plastics was 164.7 t, of which 51.1 t was released into the atmosphere via incineration plants and 51.0 t was landfilled. The incineration also released 8.07 t of polycyclic aromatic hydrocarbons and 39.1 kt of particulate matter into the atmosphere. Takeout food may increase the dietary intake of phthalates and BPA by 30% to 50% and raise concerns about considerable exposure to antioxidant transformation products. This study provides profound environmental implications for plastic waste in the Chinese OFD industry. We call for a sustainable circular economy action plan for waste disposal, but mitigating the hazardous substance content and their emissions is urgent.

Ubiquity of Synthetic Phenolic Antioxidants in Children's Cerebrospinal Fluid from South China: First Evidence for Their Penetration across the Blood-Cerebrospinal Fluid Barrier.

Synthetic phenolic antioxidants (SPAs) and relevant transformation products (TPs) are potentially neurotoxic pollutants to which humans are widely exposed. However, their penetration behavior across the brain barrier and associated exposure to the central nervous system (CNS) remain unknown. This study is the first to investigate a wide range of 30 SPAs and TPs, including emerging SPAs, in matched serum and cerebrospinal fluid (CSF) samples from children in Guangzhou, China. Sixty-two children of either sex aged <14 years with nonbloody CSF and complete clinical information were included. The findings demonstrated the ubiquitous occurrence of many SPAs and TPs, particularly BHT, 2,4-di-tert-butylphenol (DBP), AO 1010, AO 1076, BHT-Q, and BHT-quinol, not only in serum but also in the CSF. Median total concentrations of SPAs and TPs were up to 22.0 and 2.63 ng/mL in serum and 14.5 and 2.11 ng/mL in CSF, respectively. On calculating the penetration efficiencies across the blood-CSF barrier (BCSFB) (RCSF/serum, CCSF/Cserum) for selected SPAs and TPs, their RCSF/serum values (median 0.52-1.41) were highly related to their physicochemical properties, indicating that passive diffusion may be the potential mechanism of BCSFB penetration. In addition, the RCSF/serum values were positively correlated with the barrier permeability index RAlb (AlbuminCSF/Albuminserum), indicating that barrier integrity is an important determinant of BCSFB penetration. Overall, these results will improve our perception of human internal exposure to SPAs and lay a solid foundation for assessing the risk of CNS exposure to various SPAs.

Are We Justified in Modeling Human Exposure to Chlorinated Paraffin Mixtures Using the Average Properties of Congeners and Homologues?

Concern over human exposure to chlorinated paraffin (CP) mixtures keeps increasing. The absence of a comprehensive understanding of how human exposure varies with the physicochemical properties of CP constituents has hindered the ability to determine at what level of aggregation exposure to CPs should be assessed. We answer this question by comparing exposure predicted with either a "complex" method that utilizes isomer-specific properties or "simplified" methods that rely on median properties of congener, homologue, or short-/medium-/long-chain CP groups. Our results demonstrate the wide range of physicochemical properties across CP mixtures and their dependence on molecular structures. Assuming unit emissions in the environment, these variances translate into an extensive disparity in whole-body concentrations predicted for different isomers, spanning ∼11 orders of magnitude. CPs with 13-19 carbons and 6-10 chlorines exhibit the highest human exposure potential, primarily owing to moderate to high hydrophobicity and slow environmental degradation and biotransformation. Far-field exposure is dominant for most CP constituents. Our study underscores that using average properties of congener, homologue, or S/M/LCCP groups yields results that are consistent with those derived from isomer-based modeling, thus offering an efficient and practical framework for future risk assessments and human exposure studies of CPs and other complex chemical mixtures.

Impact of Legislation on Brominated Flame Retardant Concentrations in UK Indoor and Outdoor Environments: Evidence for Declining Indoor Emissions of Some Legacy BFRs.

Concentrations of polybrominated diphenyl ethers, hexabromocyclododecane (HBCDD), and novel brominated flame retardants (NBFRs) were measured in indoor dust, indoor air, and outdoor air in Birmingham, UK. Concentrations of ΣBFRs ranged from 490 to 89,000 ng/g, 46-14,000 pg/m3, and 22-11,000 pg/m3, respectively, in UK indoor dust, indoor air, and outdoor air. BDE-209 and decabromodiphenyl ethane (DBDPE) were the main contributors. The maximum concentration of DBDPE (10,000 pg/m3) in outdoor air is the highest reported anywhere to date. In contrast with previous studies of outdoor air in Birmingham, we observed significant correlations between concentrations of tri- to hepta-BDEs and HBCDD and temperature. This may suggest that primary emissions from ongoing use of these BFRs have diminished and that secondary emissions (e.g., evaporation from soil) are now a potentially major source of these BFRs in outdoor air. Conversely, the lack of significant correlations between temperature and concentrations of BDE-209 and DBDPE may indicate that ongoing primary emissions from indoor sources remain important for these BFRs. Further research to clarify the relative importance of primary and secondary sources of BFRs to outdoor air is required. Comparison with earlier studies in Birmingham reveals significant (p < 0.05) declines in concentrations of legacy BFRs, but significant increases for NBFRs over the past decade. While there appear minimal health burdens from BFR exposure for UK adults, dust ingestion of BDE-209 may pose a significant risk for UK toddlers.

Flame Retardant Exposure in Vehicles Is Influenced by Use in Seat Foam and Temperature.

Flame retardants (FRs) are added to vehicles to meet flammability standards, such as US Federal Motor Vehicle Safety Standard FMVSS 302. However, an understanding of which FRs are being used, sources in the vehicle, and implications for human exposure is lacking. US participants (n = 101) owning a vehicle of model year 2015 or newer hung a silicone passive sampler on their rearview mirror for 7 days. Fifty-one of 101 participants collected a foam sample from a vehicle seat. Organophosphate esters (OPEs) were the most frequently detected FR class in the passive samplers. Among these, tris(1-chloro-isopropyl) phosphate (TCIPP) had a 99% detection frequency and was measured at levels ranging from 0.2 to 11,600 ng/g of sampler. TCIPP was also the dominant FR detected in the vehicle seat foam. Sampler FR concentrations were significantly correlated with average ambient temperature and were 2-5 times higher in the summer compared to winter. The presence of TCIPP in foam resulted in ∼4 times higher median air sampler concentrations in winter and ∼9 times higher in summer. These results suggest that FRs used in vehicle interiors, such as in seat foam, are a source of OPE exposure, which is increased in warmer temperatures.

Silicone wristbands reveal ubiquitous human exposure to ortho-phthalates and non-ortho-phthalate plasticizers in Southern California.

In the United States and abroad, ortho-phthalates and non-ortho-phthalate plasticizers continue to be used within a diverse array of consumer products. Prior California-specific biomonitoring programs for ortho-phthalates have focused on rural, agricultural communities and, to our knowledge, these programs have not measured the potential for exposure to non-ortho-phthalate plasticizers. Therefore, the potential for human exposure to ortho-phthalates and non-ortho-phthalate plasticizers have not been adequately addressed in regions of California that have higher population density. Since there are numerous sources of ortho-phthalates and non-ortho-phthalate plasticizers in population-dense, urban regions, the objective of this study was to leverage silicone wristbands to quantify aggregate ortho-phthalate and non-ortho-phthalate plasticizer exposure over a 5-day period across two different cohorts (2019 and 2020) of undergraduate students at the University of California, Riverside (UCR) that commute from all over Southern California. Based on 5 d of aggregate exposure across two different cohorts, total ortho-phthalate plus non-ortho-phthalate plasticizer concentrations ranged, on average, from ∼100,000-1,000,000 ng/g. Based on the distribution of individual ortho-phthalate and non-ortho-phthalate plasticizer concentrations, the concentrations of di-isononyl phthalate (DiNP, a high molecular weight ortho-phthalate), di (2-ethylhexyl) phthalate (DEHP, a high molecular weight ortho-phthalate), and di-2-ethylhexyl terephthalate (DEHT, a non-ortho-phthalate plasticizer) detected within wristbands were higher than the remaining seven ortho-phthalates and non-ortho-phthalate plasticizers measured, accounting for approximately 94-97% of the total mass depending on the cohort. Overall, our findings raise concerns about chronic DiNP, DEHP, and DEHT exposure in urban, population-dense regions throughout California.

Presence of N, N'-Substituted p-Phenylenediamine Quinones in Tap Water: Implication for Human Exposure.

Monitoring studies have demonstrated the wide presence of N, N'-substituted p-phenylenediamine-derived quinones (PPDQs) in environmental matrices. The general population may be potentially exposed to PPDQs through the consumption of tap water. While, the existence of PPDQs in tap water has not been well examined. To fill this gap, in this study we collected tap water samples from Hangzhou, China, and examined seven homologues of PPDQs in collected samples. All target PPDQs were identified in the collected tap water samples, with distinct detection frequencies (38-89%). PPDQs detected in tap water was dominated by N-(1, 3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPDQ; mean 0.56 ng/L, < LOD-4.0 ng/L). The profiles of PPDQs concentrations in tap water from the four districts of Hangzhou city were slightly different. The daily intake (DI) was found highest for 6PPDQ (mean 14-22 pg/kg bw/day, median 10-15 pg/kg bw/day) through tap water intake. The relatively higher DIs of various PPDQs were displayed for infants (mean 10-22 pg/kg bw/day, median 6.5-15 pg/kg bw/day), relative to the children (8.0-18 pg/kg bw/day, 5.4-12 pg/kg bw/day) and adults (6.7-14 pg/kg bw/day, 4.5-10 pg/kg bw/day). These data are crucial for assessing the overall human exposure to PPDQs. This study first, to our knowledge, reveals the concentrations and profiles of PPDQs in tap water.

Human exposure to methyl and butyl parabens and their transformation products in settled dust collected from urban, semi-urban, rural, and tribal settlements in a tropical environment.

The present study involved monitoring the distribution of two widely consumed parabens (methyl paraben (MeP) and butyl paraben (BuP)) and their transformation products in indoor dust from different categories of settlement (urban, semi-urban, rural, and tribal homes). The results revealed a prevalent occurrence of parabens in all the settlement categories. A non-normal distribution pattern for MeP and BuP levels across the sampling sites was noted. While comparing the residence time of parabens in dust samples, it was found that the half-lives of the analytes were greater in the dust from urban (MeP t1/2: 47.510 h; BuP t1/2: 22.354 h) and rural (MeP t1/2: 27.725 h and BuP t1/2: 31.500 h) areas. The presence of paraben metabolites, such as hydroxy methylparaben (OH-MeP), para hydroxy benzoic acid (p-HBA), and benzoic acid (BA) in dust samples supports their transformation within indoor spaces. The average daily intake of parabens through dust ingestion and dermal absorption by children was higher than adults. BuP was the prime contributor (>85%) to the total estradiol equivalency quotient (tEEQ) in all the settlement categories.

Levels and health risk assessment of twenty-one current-use pesticides in urban and riverside waters of the Brazilian Amazon Basin.

In Brazil, the favorable weather conditions and abundant land contribute to the thriving agricultural production. Brazilian crops extensively employ pesticides due to their high efficacy, cost-effectiveness, and permissive regulatory framework. However, pesticide use also endangers water resources, animal organisms, and human health. Due to the lack of data on pesticide use in the Amazonas forest-based Brazil, the present study aimed to assess the levels of twenty-one current-use pesticides (CUPs) from five different classes in river waters collected from urban and riverside areas in this region. Moreover, the non-carcinogenic risks associated with water consumption were also characterized. Thirteen CUPs were detected in concentrations above the limit of detection (LOD) in at least one of the water samples, and most pesticides were detected in riverside areas. In contrast, only 18% of the analyzed samples were considered "clean," with only one compound detected. Fenitrothion showed the highest concentration, with a mean value of 4.86 ng/mL (0.30-14.3 ng/mL). Up to 33% of the samples showed levels of fipronil above the LOD, an issue of environmental and human health concern, mainly because of the adverse effects observed in honeybees. Despite this, the human health risk assessment showed a target hazard quotient below one (HQ < 1) in adults for all substances, suggesting that pesticide exposure through water consumption should not mean risk for the riverside populations. Taking into account the large extension of Brazil, as well as its different agricultural practices throughout the country, it would be of great importance to conduct extensive research in other areas. It would help to gain knowledge in this field and to promote eco-friendly alternatives to mitigate pesticide use and, consequently, to reduce their potential adverse effects on human health and the ecosystems.

Phthalate alternatives and their monoesters in indoor dust from several regions, China and implications for human exposure.

Household products, in response to regulations, increasingly incorporate phthalate (PAE) alternatives instead of traditional PAEs. However, limited information exists regarding the fate and exposure risk of these PAE alternatives and their monoesters in indoor environments. The contamination levels of PAE alternatives and their monoesters in indoor dust might vary across regions due to climate, population density, industrial activities, and interior decoration practices. By analyzing indoor dust samples from six geographical regions across China, this study aims to shed light on concentrations, profiles, and human exposure to 12 PAE alternatives and 9 their monoesters. Bis(2-ethylhexyl) benzene-1,4-dicarboxylate (DEHTP), tributyl 2-acetyloxypropane-1,2,3-tricarboxylate (ATBC), and tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate (TOTM) were the main PAE alternatives in dust across all regions. The total concentrations of 12 PAE alternatives ranged from 0.125 to 4160 µg/g in indoor dust. High molecular weight PAE alternatives had significantly correlated concentrations (p < 0.05) based on Spearman analysis, suggesting their co-use in heat-resistant plastic products. A collective of nine monoesters were identified in most samples, with total concentrations ranging from 0.048 to 29.6 µg/g. The median concentrations of PAE alternatives were highest in North China (66.8 µg/g), while those of monoesters were highest in Southwest China (6.93 µg/g). A significant correlation (p < 0.05) between the concentrations of DEHTP and its monoester suggested that degradation could be a potential source of monoesters. Although hazard quotients (HQs) have been calculated to suggest that the current exposure is unlikely to pose a significant health risk, the lack of toxicity threshold data and the existence of additional exposure pathways necessitate a further confirmation.

Presence of benzotriazole ultraviolet stabilizers in human urine.

Health exposure to benzotriazole ultraviolet stabilizers (BUVSs) may pose diverse toxic impacts on health. Presently, the occurrence of BUVSs in human urine remains inadequately understood. This study analyzed 13 kinds of BUVSs in human urine (n = 182) from the general Chinese adult participants. Totally, nine BUVSs were measurable in these human urine samples. Among the detected BUVSs, 2-(2H-benzotriazol-2-yl)-p-cresol (UV-P) was the most predominant BUVS in the human urine, with the mean concentration of 1.6 µg/g creatinine (

Occurrence of short- and ultra-short chain PFAS in drinking water from Flanders (Belgium) and implications for human exposure.

SHORT: and ultra-short chain perfluoroalkyl substances (S- and US-PFAS) are alternatives for the long-chain PFAS which have been more regulated over time. They are highly mobile in the environment and can easily reach drinking water sources which can become an important human exposure route. Furthermore, there have been growing concerns about the presence of PFAS in Flanders. Because of this, human exposure to S- and US-PFAS through Flemish drinking water was evaluated in this study. For this purpose, the presence of 2 S-PFAS (PFBS and PFBA) and 5 US-PFAS (PFPrS, PFEtS, TFMS, PFPrA and TFA) was investigated in 47 tap water samples, collected from different Flemish provinces, and 16 bottled waters purchased in Flanders. Out of the 7 target PFAS, 4 (PFBA, PFBS, PFPrS and PFEtS) were detected at concentrations above LOQ in tap water. In bottled water, only TFMS was present above its LOQ. PFAS concentrations in all analyzed water samples ranged from <0.7 to 7.3 ng/L for PFBS, <0.03-15.0 ng/L for TFMS and <0.9-12.0 ng/L for PFBA. PFPrS was only detected once above its LOQ, at 0.6 ng/L. No value could be reported for PFPrA due to high procedural blanks resulting in a high LOQ, nor for TFA due to high matrix effect. No significant differences in PFAS concentrations were seen in tap water among different drinking water companies, provinces, nor between the two types of analyzed bottled water (natural mineral water vs spring water). The use of a commercial carbon filter significantly reduced the median concentrations of the studied compounds in tap water. Finally, it was estimated that the presence of S- and US-PFAS in Flemish drinking water does not pose an immediate threat to human health, as concentrations were at least two orders of magnitude below the available guidance values.

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.

Biotransformation and toxicokinetics of 2-phenoxyethanol after oral exposure in humans: a volunteer study.

2-Phenoxyethanol (PhE) is an aromatic glycol ether and is used in a variety of functions and applications, e.g., as preservative in pharmaceuticals, cosmetic and personal care products, as biocide in disinfectants (e.g. human hygiene), or as a solvent in formulations (e.g. coatings, functional fluids). Despite its widespread use, little is yet known on its biotransformation and toxicokinetics in humans. Therefore, a pilot study was conducted with oral administration of PhE (5 mg/kg body weight) to five volunteers. Blood and urine samples were collected and analyzed for PhE and three of its presumed metabolites up to 48 h post-exposure. Additionally, one volunteer was dermally exposed to PhE and monitored until 72 h post-exposure. PhE was rapidly resorbed following both oral and dermal application with tmax-levels in blood of about 1 h and 3 h, respectively. Metabolism of PhE was observed to be rather extensive with phenoxyacetic acid (PhAA) and 4-hydroxyphenoxyacetic acid (4-OH-PhAA) as the main metabolites found in blood and urine following oral and dermal exposure. PhE was excreted rapidly and efficiently via urine mostly in metabolized form: following oral exposure, on average 77% and 12% of the applied dose was excreted within 48 h as PhAA and 4-OH-PhAA, respectively. A similar metabolism pattern was observed following the single dermal exposure experiment. The obtained data on biotransformation and toxicokinetics of PhE in humans provide valuable information on this important chemical and will be highly useful for pharmacokinetic modelling and evaluation of human PhE exposure.