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.

UNASSIGNED: Arsenic, a widely recognized and highly toxic carcinogen, is regarded as one of the most hazardous metalloids globally. However, the precise assessment of acute and chronic human exposure to arsenic and its contributing factors remains unclear in Ethiopia.
UNASSIGNED: The primary goal of this study was to assess the levels of acute and chronic arsenic exposure, as well as the contributing factors, using urine and nail biomarkers.
UNASSIGNED: A community-based analytical cross-sectional study design was employed for this study. Agilent 7900 series inductively coupled plasma mass spectrometry was used to measure the concentrations of arsenic in urine and nail samples. We performed a multiple linear regression analysis to assess the relationships between multiple predictors and outcome variables.
UNASSIGNED: The concentration of arsenic in the urine samples ranged from undetectable (<0.01) to 126.13, with a mean and median concentration of 16.02 and 13.5 μg/L, respectively. However, the mean and median concentration of arsenic in the nails was 1.01, ranging from undetectable (<0.01 μg/g) to 2.54 μg/g. Furthermore, Pearson\'s correlation coefficient analysis showed a significant positive correlation between arsenic concentrations in urine and nail samples (r = 0.432, P < .001). Also, a positive correlation was observed between urinary (r = 0.21, P = .007) and nail (r = 0.14, P = .044) arsenic concentrations and the arsenic concentration in groundwater. Groundwater sources and smoking cigarettes were significantly associated with acute arsenic exposure. In contrast, groundwater sources, cigarette smoking, and the frequency of showers were significantly associated with chronic arsenic exposure.
UNASSIGNED: The study\'s findings unveiled the widespread occurrence of both acute and chronic arsenic exposure in the study area. Consequently, it is crucial to prioritize the residents in the study area and take further measures to prevent both acute and chronic arsenic exposure.

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.

Over the past decade, our understanding of the impact of air pollution on short- and long-term population health has advanced considerably, focusing on adverse effects on cardiovascular and respiratory systems. There is, however, increasing evidence that air pollution exposures affect cognitive function, particularly in susceptible groups. Our study seeks to assess and hazard rank the cognitive effects of prevalent indoor and outdoor pollutants through a single-centre investigation on the cognitive functioning of healthy human volunteers aged 50 and above with a familial predisposition to dementia. Participants will all undertake five sequential controlled exposures. The sources of the air pollution exposures are wood smoke, diesel exhaust, cleaning products, and cooking emissions, with clean air serving as the control. Pre- and post-exposure spirometry, nasal lavage, blood sampling, and cognitive assessments will be performed. Repeated testing pre and post exposure to controlled levels of pollutants will allow for the identification of acute changes in functioning as well as the detection of peripheral markers of neuroinflammation and neuronal toxicity. This comprehensive approach enables the identification of the most hazardous components in indoor and outdoor air pollutants and further understanding of the pathways contributing to neurodegenerative diseases. The results of this project have the potential to facilitate greater refinement in policy, emphasizing health-relevant pollutants and providing details to aid mitigation against pollutant-associated health risks.

BACKGROUND: Polychlorinated alkanes (PCAs) constitute a large group of individual congeners originating from commercial chlorinated paraffin (CP) products with carbon chain lengths of PCAs-C10-13, PCAs-C14-17, and PCAs-C18-32, occasionally containing PCAs-C6-9 impurities. The extensive use of CPs has led to global environmental pollution of PCAs. This study aimed to quantify PCAs in paired serum and breast milk of lactating Swedish mothers, exploring their concentration relationship.
METHODS: Twenty-five paired samples of mothers\' blood serum and breast milk were analysed and concentrations were determined for PCAs C6-32 and compared to 4,4\'-DDE, the PCB congener 2,2\',4,4\',5,5\'-hexachlorobiphenyl (CB-153), and hexachlorobenzene (HCB).
RESULTS: The median concentrations of PCAs-C6-9, PCAs-C10-13, PCAs-C14-17, PCAs-C18-32 and ΣPCAs in serum were 14, 790, 520, 16 and 1350 ng/g lipid weight (lw), respectively, and in breast milk 0.84, 36, 63, 6.0 and 107 ng/g lw. Levels of 4,4\'-DDE, CB-153 and HCB were comparable in the two matrices, serum and breast milk at 17, 12 and 4.9 ng/g lw. The results show significant differences of PCAs-C10-13 and PCAs-C14-17 in breast milk with 22- and 6.2-times lower lw-based concentrations than those measured in serum. On wet weight the differences serum/breast milk ratios of PCAs-C6-9, PCAs-C10-13, PCAs-C14-17, PCAs-C18-32 and ΣPCAs were 1.7, 3.2, 1.0, 0.4 and 1.6, respectively, while the ratio for 4,4\'-DDE, CB-153 and HCB were each close to 0.1.
CONCLUSIONS: Swedish lactating mothers had high serum concentrations of PCAs-C10-13 and PCAs-C14-17, with the ΣPCAs median serum concentration of 1350 ng/g lw. The breast milk concentration, although considerably lower at 107 ng/g lw, still surpassed those of 4,4\'-DDE, CB-153 and HCB, suggesting an exposure risk of infants to PCAs. The variation in blood and breast milk accumulation between PCAs and studied legacy POPs, is rarely discussed but warrants further studies on partitioning properties as well as associated toxicological implications.

BACKGROUND: Diesel exhaust (DE) exposures pose concerns for serious health effects, including asthma and lung cancer, in California communities burdened by multiple stressors.
OBJECTIVE: To evaluate DE exposures in disproportionately impacted communities using biomonitoring and compare results for adults and children within and between families.
METHODS: We recruited 40 families in the San Francisco East Bay area. Two metabolites of 1-nitropyrene (1-NP), a marker for DE exposures, were measured in urine samples from parent-child pairs. For 25 families, we collected single-day spot urine samples during two sampling rounds separated by an average of four months. For the 15 other families, we collected daily spot urine samples over four consecutive days during the two sampling rounds. We also measured 1-NP in household dust and indoor air. Associations between urinary metabolite levels and participant demographics, season, and 1-NP levels in dust and air were evaluated.
RESULTS: At least one 1-NP metabolite was present in 96.6% of the urine samples. Detection frequencies for 1-NP in dust and indoor air were 97% and 74%, respectively. Results from random effect models indicated that levels of the 1-NP metabolite 6-hydroxy-1-nitropyrene (6-OHNP) were significantly higher in parents compared with their children (p-value = 0.005). Urinary 1-NP metabolite levels were generally higher during the fall and winter months. Within-subject variability was higher than between-subject variability (~60% of total variance versus ~40%, respectively), indicating high short-term temporal variability.
CONCLUSIONS: Biomonitoring, coupled with air monitoring, improves understanding of hyperlocal air pollution impacts. Results from these studies will inform the design of effective exposure mitigation strategies in disproportionately affected communities.

Animal studies have pointed at the liver as a hotspot for per- and polyfluoroalkyl substances (PFAS) accumulation and toxicity; however, these findings have not been replicated in human populations. We measured concentrations of seven PFAS in matched liver and plasma samples collected at the time of bariatric surgery from 64 adolescents in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Liver:plasma concentration ratios were perfectly explained (r2 > 0.99) in a multilinear regression (MLR) model based on toxicokinetic (TK) descriptors consisting of binding to tissue constituents and membrane permeabilities. Of the seven matched plasma and liver PFAS concentrations compared in this study, the liver:plasma concentration ratio of perfluoroheptanoic acid (PFHpA) was considerably higher than the liver:plasma concentration ratio of other PFAS congeners. Comparing the MLR model with an equilibrium mass balance model (MBM) suggested that complex kinetic transport processes are driving the unexpectedly high liver:plasma concentration ratio of PFHpA. Intratissue MBM modeling pointed to membrane lipids as the tissue constituents that drive the liver accumulation of long-chain, hydrophobic PFAS, whereas albumin binding of hydrophobic PFAS dominated PFAS distribution in plasma. The liver:plasma concentration data set, empirical MLR model, and mechanistic MBM modeling allow the prediction of liver from plasma concentrations measured in human cohort studies. Our study demonstrates that combining biomonitoring data with mechanistic modeling can identify underlying mechanisms of internal distribution and specific target organ toxicity of PFAS in humans.

There is insufficient knowledge about the systemic health effects of exposure to fine (PM2.5) and ultrafine particles emitted from typical indoor sources, including cooking and candlelight burning. We examined whether short-term exposure to emissions from cooking and burning candles cause inflammatory changes in young individuals with mild asthma. Thirty-six non-smoking asthmatics participated in a randomized controlled double-blind crossover study attending three exposure sessions (mean PM2.5 µg/m3; polycyclic aromatic hydrocarbons ng/m3): (a) air mixed with emissions from cooking (96.1; 1.1), (b) air mixed with emissions from candles (89.8; 10), and (c) clean filtered air (5.8; 1.0). Emissions were generated in an adjacent chamber and let into a full-scale exposure chamber where participants were exposed for five hours. Several biomarkers were assessed in relation to airway and systemic inflammatory changes; the primary outcomes of interest were surfactant Protein-A (SP-A) and albumin in droplets in exhaled air - novel biomarkers for changes in the surfactant composition of small airways. Secondary outcomes included cytokines in nasal lavage, cytokines, C-reactive protein (CRP), epithelial progenitor cells (EPCs), genotoxicity, gene expression related to DNA-repair, oxidative stress, and inflammation, as well as metabolites in blood. Samples were collected before exposure start, right after exposure and the next morning.
SP-A in droplets in exhaled air showed stable concentrations following candle exposure, while concentrations decreased following cooking and clean air exposure. Albumin in droplets in exhaled air increased following exposure to cooking and candles compared to clean air exposure, although not significant. Oxidatively damaged DNA and concentrations of some lipids and lipoproteins in the blood increased significantly following exposure to cooking. We found no or weak associations between cooking and candle exposure and systemic inflammation biomarkers including cytokines, CRP, and EPCs.
Cooking and candle emissions induced effects on some of the examined health-related biomarkers, while no effect was observed in others; Oxidatively damaged DNA and concentrations of lipids and lipoproteins were increased in blood after exposure to cooking, while both cooking and candle emissions slightly affected the small airways including the primary outcomes SP-A and albumin. We found only weak associations between the exposures and systemic inflammatory biomarkers. Together, the results show the existence of mild inflammation following cooking and candle exposure.

This paper explores Wastewater-Based Epidemiology (WBE) as a tool enabling understanding of city\'s pain treatment in an intercity longitudinal study. An intensive 13-month monitoring programme was undertaken in two adjacent urban areas in South-West England: a small commuter town Keynsham and the city of Bath (>180 samples collected). The study has shown a great potential of using triangulated WBE and National health Service (NHS) prescription data in understanding pain treatment in two contrasting communities with strong apparent seasonal patterns of short pain medications vs chronic pain treatment as well as the type of treatment used (e.g. oral vs topical). Community-wide usage of Non-Steroidal Anti-inflammatory Drugs (NSAIDs) and paracetamol in the intercity study is population size and season driven with the highest usage recorded in winter months. This contrasts with other pain pharmaceuticals, especially those used for chronic pain, where no/limited seasonal usage was recorded. Unmetabolized NSAIDs are, to a large extent, directly disposed of into the sewerage system bypassing metabolism due to their topical application. This is particularly apparent in winter months with naproxen showing the highest seasonal variability. Pharma/met (ratio of pharmaceutical and its metabolite concentration) analysis allows for tracking topical (non-metabolic) application/down-the-drain disposal of pharmaceuticals with frequent instances of direct disposal of NSAIDs into the sewerage system observed. Normalisation of pharma markers to population size shows comparable estimates of pharma usage in the two cities confirming population as the main driver of pharma loads in wastewater. Variable application patterns of pain pharmaceuticals make back-calculation of intake more convoluted. Intake calculated using percentage excretion of parent NSAIDs will likely lead to overestimation, as it is assumed that NSAIDs are subject to extensive metabolism (this is not the case for topical applications). Intake calculated using percentage excretion of metabolites (or parent compound) as consumption markers leads to underestimation of NSAIDs usage due to contributions from topical application not being accounted for. Prescription data indicates cumulative internal and topical usage, but the data ignores large proportion of over-the-counter usage. Therefore, we have proposed a combined approach allowing for estimation of total usage including, and differentiating between, topical application and oral administration.

Benzophenone-3 (BP-3) has been widely used as a typical ultraviolet (UV) filter in various personal care products. While BP-3 and its derivatives (BPs) have been detected in various environmental matrices, very little is known about the concentration profile of BPs in human hair. The associations of BPs in human hair with those in indoor dust samples collected from the same locations remain largely unclear. In this study, a total of 258 indoor dust samples and 66 human hair samples were collected across China and analyzed to determine the presence of BP-3 and its derivatives. The BP-3 concentrations ranged from 0.386 to 1230 ng/g dw in indoor dust and from 0.149 to 696 ng/g dw in human hair. No difference was found between BPs in indoor dust samples from different geographic regions (p > 0.05), whereas relatively higher BP concentrations were observed for dust from urban regions than dust from rural ones (p < 0.05). A positive correlation was found between the BP-3 concentrations of indoor dust and human hair samples (p < 0.05). The estimated daily intake (EDI) of BPs for humans from indoor dust showed a gender difference (females > males; p < 0.05), with the highest EDI value being found in Southwest China (males: 35.5 pg/kg bw/day; females: 40.6 pg/kg bw/day). This study provides the concentration profiles of BPs in human hair and elucidates the associations between the BP concentrations in indoor dust samples and human hair samples collected across China.