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A washed suspension of the bacteria Escherichia coli, pre-grown on a complex culture medium, was stored in sterilized drinking water for 21 days at 25°C in glass flasks in order to assess the effect of iron corrosion products on the persistence of the bacteria in drinking water. Four conditions were tested: aerobic with 50 mM lepidocrocite (γ-FeOOH, an insoluble iron corrosion product), anaerobic with 50 mM lepidocrocite, aerobic without lepidocrocite and anaerobic without lepidocrocite. The survival of E. coli was monitored by their cultivability and their membrane integrity (propidium iodide staining). When the samples were not supplemented with the iron oxide, the cultivability and cell integrity of the bacteria were dramatically altered: from the 107 initially added, only 10 CFU ml-1 remained after 21 days; 90% of the cells exhibited membrane alteration after 2 weeks of storage. In contrast, bacteria with lepidocrocite preserved their cultivability and integrity over the 21 days of storage. In the presence of di-oxygen and without iron oxide, the alteration of cell cultivability was more pronounced than that in anaerobic conditions, suggesting that oxidative stress was part of the phenomenon. When the cells were pre-grown in a growth medium supplemented by a large excess of an easily available form of iron (ferric-citrate), the cells stored a higher amount of iron and persisted one week longer in the iron-free drinking water than cells pre-grown in the standard growth medium. Therefore, in an oligotrophic environment like drinking water, E. coli cells can find the ability to survive a long time through the presence of iron corrosion products. The necessity of controlling the corrosiveness of drinking water for sanitary reasons is therefore emphasized by this study. [ABSTRACT FROM AUTHOR]

Little is known about exposure determinants of acrylamide (AA), a genotoxic food-processing contaminant, in Europe. We assessed determinants of AA exposure, measured by urinary mercapturic acids of AA (AAMA) and glycidamide (GAMA), its main metabolite, in 3157 children/adolescents and 1297 adults in the European Human Biomonitoring Initiative. Harmonized individual-level questionnaires data and quality assured measurements of AAMA and GAMA (urine collection: 2014-2021), the short-term validated biomarkers of AA exposure, were obtained from four studies (Italy, France, Germany, and Norway) in children/adolescents (age range: 3-18 years) and six studies (Portugal, Spain, France, Germany, Luxembourg, and Iceland) in adults (age range: 20-45 years). Multivariable-adjusted pooled quantile regressions were employed to assess median differences (β coefficients) with 95% confidence intervals (95% CI) in AAMA and GAMA (µg/g creatinine) in relation to exposure determinants. Southern European studies had higher AAMA than Northern studies. In children/adolescents, we observed significant lower AA associated with high socioeconomic status (AAMA:β =  - 9.1 µg/g creatinine, 95% CI - 15.8, - 2.4; GAMA: β =  - 3.4 µg/g creatinine, 95% CI - 4.7, - 2.2), living in rural areas (AAMA:β =  - 4.7 µg/g creatinine, 95% CI - 8.6, - 0.8; GAMA:β =  - 1.1 µg/g creatinine, 95% CI - 1.9, - 0.4) and increasing age (AAMA:β =  - 1.9 µg/g creatinine, 95% CI - 2.4, - 1.4; GAMA:β =  - 0.7 µg/g creatinine, 95% CI - 0.8, - 0.6). In adults, higher AAMA was also associated with high consumption of fried potatoes whereas lower AAMA was associated with higher body-mass-index. Based on this large-scale study, several potential determinants of AA exposure were identified in children/adolescents and adults in European countries., (© 2023. The Author(s).)

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000-2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011-2012, biobanked samples from the DEMOCOPHES project were used. For 2014-2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5-12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24-52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM.

As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6-12 years, (ii) 3,117 teenagers aged 12-18 years and (iii) 4,102 young adults aged 20-39 years. The participants were recruited between 2014 and 2021 in 11-12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures., Competing Interests: Declarations of competing interest The authors declare no conflict of interest. José V. Tarazona is employed by the European Food Safety Authority (EFSA). The views expressed in this publication are those of the authors and should not be interpreted as representing the official position of EFSA., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Knowledge gaps regarding the potential role of pesticides in the loss of agricultural biodiversity worldwide and mixture-related issues hamper proper risk assessment of unintentional impacts of pesticides, rendering essential the monitoring of wildlife exposure to these compounds. Free-ranging mammal exposure to legacy (Banned and Restricted: BRPs) and currently used (CUPs) pesticides was investigated, testing the hypotheses of: (1) a background bioaccumulation for BRPs whereas a "hot-spot" pattern for CUPs, (2) different contamination profiles between carnivores and granivores/omnivores, and (3) the role of non-treated areas as refuges towards exposure to CUPs. Apodemus mice (omnivore) and Crocidura shrews (insectivore) were sampled over two French agricultural landscapes (n = 93). The concentrations of 140 parent chemicals and metabolites were screened in hair samples. A total of 112 compounds were detected, showing small mammal exposure to fungicides, herbicides and insecticides with 32 to 65 residues detected per individual (13-26 BRPs and 18-41 CUPs). Detection frequencies exceeded 75% of individuals for 13 BRPs and 25 CUPs. Concentrations above 10 ng/g were quantified for 7 BRPs and 29 CUPs (in 46% and 72% of individuals, respectively), and above 100 ng/g for 10 CUPs (in 22% of individuals). Contamination (number of compounds or concentrations) was overall higher in shrews than rodents and higher in animals captured in hedgerows and cereal crops than in grasslands, but did not differ significantly between conventional and organic farming. A general, ubiquitous contamination by legacy and current pesticides was shown, raising issues about exposure pathways and impacts on ecosystems. We propose a concept referred to as "biowidening", depicting an increase of compound diversity at higher trophic levels. This work suggests that wildlife exposure to pesticide mixtures is a rule rather than an exception, highlighting the need for consideration of the exposome concept and questioning appropriateness of current risk assessment and mitigation processes., (© 2022. The Author(s).)

The objectives of the study were to estimate the current exposure to cadmium (Cd) in Europe, potential differences between the countries and geographic regions, determinants of exposure and to derive European exposure levels. The basis for this work was provided by the European Human Biomonitoring Initiative (HBM4EU) which established a framework for alignment of national or regional HBM studies. For the purpose of Cd exposure assessment, studies from 9 European countries (Iceland, Denmark, Poland, Czech Republic, Croatia, Portugal, Germany, France, Luxembourg) were included and urine of 20-39 years old adults sampled in the years 2014-2021 (n = 2510). The measurements in urine were quality assured by the HBM4EU quality assurance/quality control scheme, study participants' questionnaire data were post-harmonized. Spatially resolved external data, namely Cd concentrations in soil, agricultural areas, phosphate fertilizer application, traffic density and point source Cd release were collected for the respective statistical territorial unit (NUTS). There were no distinct geographic patterns observed in Cd levels in urine, although the data revealed some differences between the specific study sites. The levels of exposure were otherwise similar between two time periods within the last decade (DEMOCOPHES - 2011-2012 vs. HBM4EU Aligned Studies, 2014-2020). The age-dependent alert values for Cd in urine were exceeded by 16% of the study participants. Exceedances in the different studies and locations ranged from 1.4% up to 42%. The studies with largest extent of exceedance were from France and Poland. Association analysis with individual food consumption data available from participants' questionnaires showed an important contribution of vegetarian diet to the overall exposure, with 35% higher levels in vegetarians as opposed to non-vegetarians. For comparison, increase in Cd levels due to smoking was 25%. Using NUTS2-level external data, positive associations between HBM data and percentage of cropland and consumption of Cd-containing mineral phosphate fertilizer were revealed, which indicates a significant contribution of mineral phosphate fertilizers to human Cd exposure through diet. In addition to diet, traffic and point source release were identified as significant sources of exposure in the study population. The findings of the study support the recommendation by EFSA to reduce Cd exposure as also the estimated mean dietary exposure of adults in the EU is close or slightly exceeding the tolerable weekly intake. It also indicates that regulations are not protecting the population sufficiently., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

More than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children.

Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014-2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000-2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years.

In studies investigating the effects of endocrine disruptors (ED) such as phthalates, bisphenols and some pesticides on human health, exposure is usually characterized with urinary metabolites. The variability of biomarkers concentration, due to rapid elimination from the body combined with frequent exposure is however pointed out as a major limitation to exposure assessment. This study was conducted to assess variability of urinary metabolites of ED, and to investigate how sampling time and number of samples analyzed impacts exposure assessment. Urine samples were collected over 6 months from 16 volunteers according to a random sampling design, and analyzed for 16 phthalate metabolites, 9 pesticide metabolites and 4 bisphenols. The amount of biomarkers excreted in urine at different times of the day were compared. In parallel, 2 algorithms were developed to investigate the effect of the number of urine samples analyzed per subject on exposure assessment reliability. In the 805 urine samples collected from the participants, all the biomarkers tested were detected, and 18 were present in >90% of the samples. Biomarkers variability was highlighted by the low intraclass correlation coefficients (ICC) ranging from 0.09 to 0.51. Comparing the amount of biomarkers excreted in urine at different time did not allow to identify a preferred moment for urine collection between first day urine, morning, afternoon and evening. Algorithms demonstrated that between 10 (for monobenzyl (MBzP) phthalate) and 31 (for bisphenol S) samples were necessary to correctly classify 87.5% of the subjects into quartiles according to their level of exposure. The results illustrate the high variability of urinary biomarkers of ED over time and the impossibility to reliably classify subjects based on a single urine sample (or a limited number). Results showed that classifying individuals based on urinary biomarkers requires several samples per subject, and this number is highly different for different biomarkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The skin exposome, defined as the totality of environmental exposures from conception to death that can induce or modify various skin conditions, compiles environmental, lifestyle and psychosocial exposures, as well as the resulting internal biological and physiological responses to these exposures. Biomonitoring can be used to obtain information on the internal dose of pollutants. The concentration of biomarkers in body fluids is highly variable over time due to differential elimination kinetics of chemicals, whereas they accumulate in hair. Hair analysis thus provides information on cumulative exposure over a longer period of time, and so can be used for assessing chronic exposure to pollutants. Studies on hair samples collected from 204 women living in two cities in China with different levels of pollution demonstrated that hair damage and the skin microbiome are biomarkers of a polluted city and long-term exposure to pollution and UV can increase signs of facial ageing. Adopting an exposome approach to skin health requires assessing multiple exposures and biological consequences, possibly in relation to longitudinally followed-up health outcomes. Leveraging "omics" data (e.g. metabolomics, proteomics, genomics and microbiome) and big data analytics, in particular multivariate analysis, will help to further understand the impact of pollution on skin and the combined effects with other exposome factors, including solar radiation and other environmental exposures., (© 2020 European Academy of Dermatology and Venereology.)

Hair is increasingly used as a biological matrix of interest for the assessment of hormone secretion over extended periods of time. This study described the development and the validation of a sensitive UPLC-MS/MS method for simultaneous analysis of steroid and thyroid hormones in human hair. The gradient designed in this method enables to obtain a satisfactory separation of 9 hormones of interest: cortisol, cortisone, THE, THF, α-THF, triiodothyronine (T3) and thyroxine (T4), estradiol, and testosterone. Several methodological parameters of extraction (such as the used of "cut hair" versus "pulverized hair", the extraction time, the incubation solvent purification on SPE column and hydrolysis) that may influence the determination of hormones levels in human hair, have thus been tested here. Therefore, the results obtained highlighted the necessity of using a C 18 SPE purification method for the determination of both steroid and thyroid hormones in hair. This method allows reaching suitable levels of sensitivity for cortisol and cortisone since the results obtained pointed out concentration levels of cortisol in hair of volunteers similar to those observed in the literature. This method could also offer an important impact in the field of hormone analysis since it allows, for the first time, the quantification of both T3 and T4 in human hair., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier B.V.)

Background: It is challenging to manage data collection as planned and creation of opportunities to adapt during the course of enrolment may be needed. This paper aims to summarize the different sampling strategies adopted in the second wave of Observation of Cardiovascular Risk Factors (ORISCAV-LUX, 2016-17), with a focus on population coverage and sample representativeness., Methods: Data from the first nationwide cross-sectional, population-based ORISCAV-LUX survey, 2007-08 and from the newly complementary sample recruited via different pathways, nine years later were analysed. First, we compare the socio-demographic characteristics and health profiles between baseline participants and non-participants to the second wave. Then, we describe the distribution of subjects across different strategy-specific samples and performed a comparison of the overall ORISCAV-LUX2 sample to the national population according to stratification criteria., Results: For the baseline sample (1209 subjects), the participants (660) were younger than the non-participants (549), with a significant difference in average ages (44 vs 45.8 years; P = 0.019). There was a significant difference in terms of education level (P < 0.0001), 218 (33%) participants having university qualification vs. 95 (18%) non-participants. The participants seemed having better health perception (p < 0.0001); 455 (70.3%) self-reported good or very good health perception compared to 312 (58.2%) non-participants. The prevalence of obesity (P < 0.0001), hypertension (P < 0.0001), diabetes (P = 0.007), and mean values of related biomarkers were significantly higher among the non-participants. The overall sample (1558 participants) was mainly composed of randomly selected subjects, including 660 from the baseline sample and 455 from other health examination survey sample and 269 from civil registry sample (constituting in total 88.8%), against only 174 volunteers (11.2%), with significantly different characteristics and health status. The ORISCAV-LUX2 sample was representative of national population for geographical district, but not for sex and age; the younger (25-34 years) and older (65-79 years) being underrepresented, whereas middle-aged adults being over-represented, with significant sex-specific difference (p < 0.0001)., Conclusion: This study represents a careful first-stage analysis of the ORISCAV-LUX2 sample, based on available information on participants and non-participants. The ORISCAV-LUX datasets represents a relevant tool for epidemiological research and a basis for health monitoring and evidence-based prevention of cardiometabolic risk in Luxembourg.

Due to the presence of pollutants in the environment and food, the assessment of human exposure is required. This necessitates high-throughput approaches enabling large-scale analysis and, as a consequence, the use of high-performance analytical instruments to obtain highly informative metabolomic profiles. In this study, direct introduction mass spectrometry (DIMS) was performed using a Fourier transform ion cyclotron resonance (FT-ICR) instrument equipped with a dynamically harmonized cell. Data quality was evaluated based on mass resolving power (RP), mass measurement accuracy, and ion intensity drifts from the repeated injections of quality control sample (QC) along the analytical process. The large DIMS data size entails the use of bioinformatic tools for the automatic selection of common ions found in all QC injections and for robustness assessment and correction of eventual technical drifts. RP values greater than 10 6 and mass measurement accuracy of lower than 1 ppm were obtained using broadband mode resulting in the detection of isotopic fine structure. Hence, a very accurate relative isotopic mass defect (RΔm) value was calculated. This reduces significantly the number of elemental composition (EC) candidates and greatly improves compound annotation. A very satisfactory estimate of repeatability of both peak intensity and mass measurement was demonstrated. Although, a non negligible ion intensity drift was observed for negative ion mode data, a normalization procedure was easily applied to correct this phenomenon. This study illustrates the performance and robustness of the dynamically harmonized FT-ICR cell to perform large-scale high-throughput metabolomic analyses in routine conditions. Graphical abstract Analytical performance of FT-ICR instrument equipped with a dynamically harmonized cell.

Even though clinical, epidemiological and toxicological studies have progressively provided a better knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects, further in vitro studies on relevant cell systems are still needed. Hence, aiming of getting closer to the human in vivo conditions, primary human bronchial epithelial cells derived from normal subjects (NHBE) or sensitive chronic obstructive pulmonary disease (COPD)-diseased patients (DHBE) were differentiated at the air-liquid interface. Thereafter, they were repeatedly exposed to air pollution-derived PM 2.5 to study the occurrence of some relevant genetic and/or epigenetic endpoints. Concentration-, exposure- and season-dependent increases of OH-B[a]P metabolites in NHBE, and to a lesser extent, COPD-DHBE cells were reported; however, there were more tetra-OH-B[a]P and 8-OHdG DNA adducts in COPD-DHBE cells. No increase in primary DNA strand break nor chromosomal aberration was observed in repeatedly exposed cells. Telomere length and telomerase activity were modified in a concentration- and exposure-dependent manner in NHBE and particularly COPD-DHBE cells. There were a global DNA hypomethylation, a P16 gene promoter hypermethylation, and a decreasing DNA methyltransferase activity in NHBE and notably COPD-DHBE cells repeatedly exposed. Changes in site-specific methylation, acetylation, and phosphorylation of histone H3 (i.e., H3K4me3, H3K9ac, H3K27ac, and H3S10ph) and related enzyme activities occurred in a concentration- and exposure-dependent manner in all the repeatedly exposed cells. Collectively, these results highlighted the key role played by genetic and even epigenetic events in NHBE and particularly sensitive COPD-DHBE cells repeatedly exposed to air pollution-derived PM 2.5 and their different responsiveness. While these specific epigenetic changes have been already described in COPD and even lung cancer phenotypes, our findings supported that, together with genetic events, these epigenetic events could dramatically contribute to the shift from healthy to diseased phenotypes following repeated exposure to relatively low doses of air pollution-derived PM 2.5 ., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A gas chromatography tandem mass-spectrometry method dedicated to the analysis of 50 metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) was applied to urine specimens collected from female Long Evans rats under controlled exposure to a mixture of PAHs (at 7 doses ranging from 0.01 to 0.8 mg/kg, by gavage, 3 times per week for 90 days). On four occasions (day 1, 28, 60 and 90), urine samples were collected over a 24 h period. Among these 50 OH-PAHs, 41 were detected in urine samples. Seven additional OH-PAHs were identified for the first time: 1 corresponding to metabolite of pyrene and 3 of anthracene. Strong linear dose versus urinary concentration relationships were observed for 25 of the 41 OH-PAHs detected in rat urine, confirming their suitability for assessing exposure to their respective parent compound. In addition, some isomers (e.g. 1-OH-pyrene, 3-OH-/4-OH-chrysene, 10-OH-benz[a]anthracene, 8-OH-benzo[k]fluoranthene, 11-OH-benzo[b]fluoranthene and 3-OH-benzo[a]pyrene) that were detected starting from the lowest levels of exposure or even in controls were considered particularly relevant biomarkers compared to metabolites only detected at higher levels of exposure. Finally, on the basis of the excretion profiles (on days 1, 28, 60 and 90) and urinary elimination kinetics of each OH-PAH detected at days 1 and 60, this study highlighted the fact that sampling time may influence the measurement of metabolites in urine. Taken together, these results provide interesting information on the suitability of the analysis of OH-PAHs in urine for the assessment of PAH exposure, which could be taken into consideration for the design of epidemiological studies in the future., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Most tumors undergo metabolic reprogramming towards glycolysis, the so-called Warburg effect, to support growth and survival. Overexpression of IF1, the physiological inhibitor of the F0F1ATPase, has been related to this phenomenon and appears to be a relevant marker in cancer. Environmental contributions to cancer development are now widely accepted but little is known about the underlying intracellular mechanisms. Among the environmental pollutants humans are commonly exposed to, benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons (PAHs), is a well-known human carcinogen. Besides apoptotic signals, B[a]P can also induce survival signals in liver cells, both likely involved in cancer promotion. Our previous works showed that B[a]P elicited a Warburg-like effect, thus favoring cell survival. The present study aimed at further elucidating the molecular mechanisms involved in the B[a]P-induced metabolic reprogramming, by testing the possible involvement of IF1. We presently demonstrate, both in vitro and in vivo, that PAHs, especially B[a]P, strongly increase IF1 expression. Such an increase, which might rely on β2-adrenergic receptor activation, notably participates to the B[a]P-induced glycolytic shift and cell survival in liver cells. By identifying IF1 as a target of PAHs, this study provides new insights about how environmental factors may contribute to related carcinogenesis.

While the knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects is still incomplete, detailed in vitro studies are highly needed. With the aim of getting closer to the human in vivo conditions and better integrating a number of factors related to pre-existing chronic pulmonary inflammatory, we sought to develop primary cultures of normal human bronchial epithelial (NHBE) cells and chronic obstructive pulmonary disease (COPD)-diseased human bronchial epithelial (DHBE) cells, grown at the air-liquid interface. Pan-cytokeratin and MUC5AC immunostaining confirmed the specific cell-types of both these healthy and diseased cell models and showed they are closed to human bronchial epithelia. Thereafter, healthy and diseased cells were repeatedly exposed to air pollution-derived PM 4 at the non-cytotoxic concentration of 5 μg/cm 2 . The differences between the oxidative and inflammatory states in non-exposed NHBE and COPD-DHBE cells indicated that diseased cells conserved their specific physiopathological characteristics. Increases in both oxidative damage and cytokine secretion were reported in repeatedly exposed NHBE cells and particularly in COPD-DHBE cells. Diseased cells repeatedly exposed had lower capacities to metabolize the organic chemicals-coated onto the air-pollution-derived PM 4 , such as benzo[a]pyrene (B[a]P), but showed higher sensibility to the formation of OH-B[a]P DNA adducts, because their diseased state possibly affected their defenses. Differential profiles of epigenetic hallmarks (i.e., global DNA hypomethylation, P16 promoter hypermethylation, telomere length shortening, telomerase activation, and histone H3 modifications) occurred in repeatedly exposed NHBE and particularly in COPD-DHBE cells. Taken together, these results closely supported the highest responsiveness of COPD-DHBE cells to a repeated exposure to air pollution-derived PM 4 . The use of these innovative in vitro exposure systems such as NHBE and COPD-DHBE cells could therefore be consider as a very useful and powerful promising tool in the field of the respiratory toxicology, taking into account sensitive individuals., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Dyslipidemia associated with obesity often manifests as increased plasma LDL and triglyceride-rich lipoprotein levels suggesting changes in hepatic lipoprotein receptor status. Persistent organic pollutants have been recently postulated to contribute to the obesity etiology by increasing adipogenesis, but little information is available on their potential effect on hepatic lipoprotein metabolism., Objective: The objective of this study was to investigate the effect of the common environmental pollutant, benzo[α]pyrene (B[α]P) on two lipoprotein receptors, the LDL-receptor and the lipolysis-stimulated lipoprotein receptor (LSR) as well as the ATP-binding cassette transporter A1 (ABCA1) using cell and animal models., Results: LSR, LDL-receptor as well as ABCA1 protein levels were significantly decreased by 26-48% in Hepa1-6 cells incubated (<2 h) in the presence of B[α]P (≤1 µM). Real-time PCR analysis and lactacystin studies revealed that this effect was due primarily to increased proteasome, and not lysosomal-mediated degradation rather than decreased transcription. Furthermore, ligand blots revealed that lipoproteins exposed to 1 or 5 µM B[α]P displayed markedly decreased (42-86%) binding to LSR or LDL-receptor. B[α]P-treated (0.5 mg/kg/48 h, i.p. 15 days) C57BL/6J mice displayed higher weight gain, associated with significant increases in plasma cholesterol, triglycerides, and liver cholesterol content, and decreased hepatic LDL-receptor and ABCA1 levels. Furthermore, correlational analysis revealed that B[α]P abolished the positive association observed in control mice between the LSR and LDL-receptor. Interestingly, levels of other proteins involved in liver cholesterol metabolism, ATP-binding cassette transporter G1 and scavenger receptor-BI, were decreased, while those of acyl-CoA:cholesterol acyltransferase 1 and 2 were increased in B[α]P-treated mice., Conclusions: B[α]P demonstrates inhibitory action on LSR and LDL-R, as well as ABCA1, which we propose leads to modified lipid status in B[α]P-treated mice, thus providing new insight into mechanisms underlying the involvement of pollutants in the disruption of lipid homeostasis, potentially contributing to dyslipidemia associated with obesity.

Humans are exposed to polycyclic aromatic hydrocarbons (PAHs), a family of ubiquitous neurotoxic pollutants, mainly through ingestion of contaminated food. Developing organisms can be exposed also to PAHs due to the ability of these compounds to pass through the placental barrier as well as through the breast milk. Previous animal studies have reported that the exposure of rats to a 16 PAH mixture at environmental doses strictly limited to gestation did not induce any long-lasting consequences, whereas gestational and lactational PAH exposure induced long-term behavioral and cerebral metabolic effects. In the present study, short-term effects of exposures to the same PAH mixture during gestation, or during gestation and lactation, were assessed by evaluating motor and sensory development of rat pups, and by measuring cerebral cytochrome oxidase activity (a marker of energetic metabolism) in different brain areas. Brain levels of PAHs and some monohydroxylated metabolites were also evaluated in pups at birth and at 21 days of postnatal life. No significant short-term modifications of behavioral development and of cerebral metabolism were observed following an early PAH exposure whatever the dose and the period of exposure. Surprisingly, the same brain levels of concentration of PAHs and metabolites were observed in control and exposed pups in both studies. These analytical results raise the difficulty in overcoming environmental contamination of control animals and the choice of such controls in experimental studies which focus on neurotoxicity of exposure to low levels of pollutants., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Previous studies have indicated that the use of high-ethanol-content (>65%) hair-care products may elevate fatty acid ethyl ester (FAEE) concentrations in hair. In this case series, nine individuals were identified by FAEE analysis to be chronic alcohol abusers in the context of child-welfare substance abuse monitoring. Based on patient claims of moderate or no alcohol consumption, the presence of ethanol in the patients' hair-care regimens was investigated. Samples were additionally tested for the presence of ethyl glucuronide (EtG). From a total of nine patients, 12 hair samples were submitted for analysis. Patient histories were obtained as well as Material Safety Data Sheets (MSDS) listing hair-care product ethanol content. Hair samples were pre-washed to remove external contamination and analyzed for FAEE and EtG by GC-MS. According to the Society of Hair Testing consensus guidelines, FAEE levels exceeding 0.50 ng/mg and/or EtG levels exceeding 30 pg/mg indicate chronic excessive alcohol consumption. Upon initial analysis, the nine samples exhibited positive FAEE findings ranging from 0.496 to 4.984 ng/mg. MSDS review revealed the presence of ethanol from 10% to 95% by volume in at least one hair-care product used by each individual. Results of the EtG analysis ranged from 1.9 to 23.5 pg/mg. These findings indicate that regular use of products with ethanol content as low as 10% can impact FAEE results. EtG analysis should be used to confirm FAEE findings and appears to be unaffected by hair-care products, likely due to alternative mechanisms of incorporation.

Background: Severe nicotine intoxication occurred in a patient after ingestion of a tobacco extract made from a recipe found on a freely available Internet site., Objectives: To determine the levels of nicotine and cotinine in the plasma of a patient who tried to commit suicide by drinking a highly concentrated tobacco extract., Case Report: A 67-year-old man tried to commit suicide by following guidelines found on an Internet site. He soaked 300 grams of tobacco for 3 days in water, evaporated most of the extract, and drank the rest of it. He felt sick immediately, with the following signs: respiratory depression, hypothermia, hypersalivation, bradycardia, and myoclonic jerks. Soon after the ingestion he vomited most of the extract. Toxicological analysis revealed potentially life-threatening nicotine and cotinine serum concentrations. Surprisingly, nicotine peak levels (322 microg/L) and cotinine peak levels (9092 microg/L) were reached more than 3 h after ingestion of the extract. Estimated nicotine and cotinine half-lives were 200 min and 1185 min, respectively. Treatment consisted of gastric lavage, ventilation, and monitoring of vital functions. The patient recovered and was discharged from the Emergency Department 4 days later without sequelae., Conclusion: Nicotinergic intoxication is not always easy to recognize, and without clues from the patient and the toxicologic analysis, might well have been missed in the present case., (Copyright 2010 Elsevier Inc. All rights reserved.)

Fentanyl is a synthetic opioid used to treat intense chronic pain. In this study, the authors report detection and quantification of fentanyl in sweat and hair of a patient receiving fentanyl (25 microg/h) via a transdermal therapeutic system (TTS) for 22 days. Sweat was collected using sweat patches every night on days 13-21 of the therapy, and hair was collected 12 weeks after the end of the treatment. Detection and quantification was performed with liquid chromatography-tandem mass spectrometry using electron spray ionization in selected reaction monitoring mode. Alfentanyl was used as internal standard for quantification in hair and in sweat. Sodium ions have been used as endogenous internal reference for determination of volume of sweat excreted on each patch. Results show presence of fentanyl in both matrices. Fentanyl concentrations in sweat varied from 0.17 to 1.02 ng/microL, and time-resolved segmented hair analysis showed a maximum fentanyl concentration of 0.48 ng/mg of hair during the period of the therapy.

A washed suspension of the bacteria Escherichia coli, pre-grown on a complex culture medium, was stored in sterilized drinking water for 21 days at 25 degrees C in glass flasks in order to assess the effect of iron corrosion products on the persistenceof the bacteria in drinking water. Four conditions were tested: aerobic with 50 mM lepidocrocite (gamma-FeOOH, an insoluble iron corrosion product), anaerobic with 50 mM lepidocrocite, aerobic without lepidocrocite and anaerobic without lepidocrocite. The survival of E. coli was monitored by their cultivability and their membrane integrity (propidium iodide staining). When the samples were not supplemented with the iron oxide, the cultivability and cell integrity of the bacteria were dramatically altered: from the 10(7) initially added, only 10 CFU ml(-1) remained after 21 days; 90% of the cells exhibited membrane alteration after 2 weeks of storage. In contrast, bacteria with lepidocrocite preserved their cultivability and integrity over the 21 days of storage. In the presence of di-oxygen and without iron oxide, the alteration of cell cultivability was more pronounced than that in anaerobic conditions, suggesting that oxidative stress was part of the phenomenon. When the cells were pre-grown in a growth medium supplemented by a large excess of an easily available form of iron (ferric-citrate), the cells stored a higher amount of iron and persisted one week longer in the iron-free drinking water than cells pre-grown in the standard growth medium. Therefore, in an oligotrophic environment like drinking water, E. coli cells can find the ability to survive a long time through the presence of iron corrosion products. The necessity of controlling the corrosiveness of drinking water for sanitary reasons is therefore emphasized by this study.

The effect of phosphate addition in drinking water was tested under static conditions as batch tests and under dynamic conditions using continuously fed reactors. Phosphate supplements in batch tests from 0.1 to 2 mg P-PO4 L(-1) did not show any relationship between bacterial growth and phosphate concentration. Dynamic tests in slightly corroded reactor (stainless steel) treated at 1 mg P-PO4 L(-1) showed only a moderate improvement in the growth of microorganisms. On the contrary, phosphate treatment applied to the highly corroded reactor (unlined cast iron) led to an immediate, drastic drop in iron oxide release and bacterial production. Phosphate uptake by the reactor wall was less than 14% with the stainless-steel reactor and 70-90% with the corroded cast iron reactor. Moreover, about 5% of the phosphate associated to corroded iron pipe walls was released for 20 days after the end of treatment.