Coupling of Homologous Recombination and the Checkpoint by ATR.

ATR is a key regulator of cell-cycle checkpoints and homologous recombination (HR). Paradoxically, ATR inhibits CDKs during checkpoint responses, but CDK activity is required for efficient HR. Here, we show that ATR promotes HR after CDK-driven DNA end resection. ATR stimulates the BRCA1-PALB2 interaction after DNA damage and promotes PALB2 localization to DNA damage sites. ATR enhances BRCA1-PALB2 binding at least in part by inhibiting CDKs. The optimal interaction of BRCA1 and PALB2 requires phosphorylation of PALB2 at S59, an ATR site, and hypo-phosphorylation of S64, a CDK site. The PALB2-S59A/S64E mutant is defective for localization to DNA damage sites and HR, whereas the PALB2-S59E/S64A mutant partially bypasses ATR for its localization. Thus, HR is a biphasic process requiring both high-CDK and low-CDK periods. As exemplified by the regulation of PALB2 by ATR, ATR promotes HR by orchestrating a "CDK-to-ATR switch" post-resection, directly coupling the checkpoint to HR.

HBM4EU E-waste study: Assessing persistent organic pollutants in blood, silicone wristbands, and settled dust among E-waste recycling workers in Europe.

E-waste recycling is an increasingly important activity that contributes to reducing the burden of end-of-life electronic and electrical apparatus and allows for the EU's transition to a circular economy. This study investigated the exposure levels of selected persistent organic pollutants (POPs) in workers from e-waste recycling facilities across Europe. The concentrations of seven polychlorinated biphenyls (PCBs) and eight polybrominated diphenyl ethers (PBDEs) congeners were measured by GC-MS. Workers were categorized into five groups based on the type of e-waste handled and two control groups. Generalized linear models were used to assess the determinants of exposure levels among workers. POPs levels were also assessed in dust and silicone wristbands (SWB) and compared with serum. Four PCB congeners (CB 118, 138, 153, and 180) were frequently detected in serum regardless of worker's category. With the exception of CB 118, all tested PCBs were significantly higher in workers compared to the control group. Controls working in the same company as occupationally exposed (Within control group), also displayed higher levels of serum CB 180 than non-industrial controls with no known exposures to these chemicals (Outwith controls) (p < 0.05). BDE 209 was the most prevalent POP in settled dust (16 µg/g) and SWB (220 ng/WB). Spearman correlation revealed moderate to strong positive correlations between SWB and dust. Increased age and the number of years smoked cigarettes were key determinants for workers exposure. Estimated daily intake through dust ingestion revealed that ΣPCB was higher for both the 50th (0.03 ng/kg bw/day) and 95th (0.09 ng/kg bw/day) percentile exposure scenarios compared to values reported for the general population. This study is one of the first to address the occupational exposure to PCBs and PBDEs in Europe among e-waste workers through biomonitoring combined with analysis of settled dust and SWB. Our findings suggest that e-waste workers may face elevated PCB exposure and that appropriate exposure assessments are needed to establish effective mitigation strategies.

Incorporation of Fast-Elimination Chemicals in Hair Is Governed by Pharmacokinetics-Implications for Exposure Assessment.

Mechanisms governing chemicals' incorporation in hair are incompletely understood, and gaps remain to link the concentration of chemicals in hair to level of exposure and internal dose present in the body. This study assesses the relevance of hair analysis for the biomonitoring of exposure to fast-elimination compounds and investigates the role of pharmacokinetics (PK) in their incorporation in hair. Rats were administered with pesticides, bisphenols, phthalates, and DINCH over 2 months. Hairs were analyzed for 28 chemicals/metabolites to investigate correlations between their concentration in hair and the dose administered to the animals. Urine collected over 24 h after gavage was used to determine chemicals' PK and to investigate their influence on incorporation into hair by means of linear mixed models (LMMs). Eighteen chemicals presented a significant correlation between concentration in hair and level of exposure. In models combining all chemicals, agreement between concentration in hair predicted by LMM and experimental values was moderate (R2 = 0.19) but significantly increased when PK were included in the models (R2 = 0.37), and even more when chemical families were considered separately (e.g., R2 = 0.98 for pesticides). This study shows that pharmacokinetics mediate incorporation of chemicals in hair and suggests the relevance of hair for assessing exposure to fast-elimination chemicals.

MICROSCOPE Mission: Final Results of the Test of the Equivalence Principle.

The MICROSCOPE mission was designed to test the weak equivalence principle (WEP), stating the equality between the inertial and the gravitational masses, with a precision of 10^{-15} in terms of the Eötvös ratio η. Its experimental test consisted of comparing the accelerations undergone by two collocated test masses of different compositions as they orbited the Earth, by measuring the electrostatic forces required to keep them in equilibrium. This was done with ultrasensitive differential electrostatic accelerometers onboard a drag-free satellite. The mission lasted two and a half years, cumulating five months worth of science free-fall data, two-thirds with a pair of test masses of different compositions-titanium and platinum alloys-and the last third with a reference pair of test masses of the same composition-platinum. We summarize the data analysis, with an emphasis on the characterization of the systematic uncertainties due to thermal instabilities and on the correction of short-lived events which could mimic a WEP violation signal. We found no violation of the WEP, with the Eötvös parameter of the titanium and platinum pair constrained to η(Ti,Pt)=[-1.5±2.3(stat)±1.5(syst)]×10^{-15} at 1σ in statistical errors.

HBM4EU chromates study - Usefulness of measurement of blood chromium levels in the assessment of occupational Cr(VI) exposure.

Occupational exposures to hexavalent Chromium (Cr(VI)) can occur in welding, hot working stainless steel processing, chrome plating, spray painting and coating activities. Recently, within the human biomonitoring for Europe initiative (HBM4EU), a study was performed to assess the suitability of different biomarkers to assess the exposure to Cr(VI) in various job tasks. Blood-based biomarkers may prove useful when more specific information on systemic and intracellular bioavailability is necessary. To this aim, concentrations of Cr in red blood cells (RBC-Cr) and in plasma (P-Cr) were analyzed in 345 Cr(VI) exposed workers and 175 controls to understand how these biomarkers may be affected by variable levels of exposure and job procedures. Compared to controls, significantly higher RBC-Cr levels were observed in bath plating and paint application workers, but not in welders, while all the 3 groups had significantly greater P-Cr concentrations. RBC-Cr and P-Cr in chrome platers showed a high correlation with Cr(VI) in inhalable dust, outside respiratory protective equipment (RPE), while such correlation could not be determined in welders. In platers, the use of RPE had a significant impact on the relationship between blood biomarkers and Cr(VI) in inhalable and respirable dust. Low correlations between P-Cr and RBC-Cr may reflect a difference in kinetics. This study showed that Cr-blood-based biomarkers can provide information on how workplace exposure translates into systemic availability of Cr(III) (extracellular, P-Cr) and Cr(VI) (intracellular, RBC-Cr). Further studies are needed to fully appreciate their use in an occupational health and safety context.

HBM4EU chromates study - Overall results and recommendations for the biomonitoring of occupational exposure to hexavalent chromium.

Exposure to hexavalent chromium [Cr(VI)] may occur in several occupational activities, e.g., welding, Cr(VI) electroplating and other surface treatment processes. The aim of this study was to provide EU relevant data on occupational Cr(VI) exposure to support the regulatory risk assessment and decision-making. In addition, the capability and validity of different biomarkers for the assessment of Cr(VI) exposure were evaluated. The study involved nine European countries and involved 399 workers in different industry sectors with exposures to Cr(VI) such as welding, bath plating, applying or removing paint and other tasks. We also studied 203 controls to establish a background in workers with no direct exposure to Cr(VI). We applied a cross-sectional study design and used chromium in urine as the primary biomonitoring method for Cr(VI) exposure. Additionally, we studied the use of red blood cells (RBC) and exhaled breath condensate (EBC) for biomonitoring of exposure to Cr(VI). Personal measurements were used to study exposure to inhalable and respirable Cr(VI) by personal air sampling. Dermal exposure was studied by taking hand wipe samples. The highest internal exposures were observed in the use of Cr(VI) in electrolytic bath plating. In stainless steel welding the internal Cr exposure was clearly lower when compared to plating activities. We observed a high correlation between chromium urinary levels and air Cr(VI) or dermal total Cr exposure. Urinary chromium showed its value as a first approach for the assessment of total, internal exposure. Correlations between urinary chromium and Cr(VI) in EBC and Cr in RBC were low, probably due to differences in kinetics and indicating that these biomonitoring approaches may not be interchangeable but rather complementary. This study showed that occupational biomonitoring studies can be conducted successfully by multi-national collaboration and provide relevant information to support policy actions aiming to reduce occupational exposure to chemicals.

Hair analysis for the biomonitoring of polycyclic aromatic hydrocarbon exposure: comparison with urinary metabolites and DNA adducts in a rat model.

Alongside the analysis of urinary metabolites which are traditional biomarkers of polycyclic aromatic hydrocarbons (PAH) exposure, the possibility of detecting PAH as well as their metabolites in hair has also recently been demonstrated. As the concentration of pollutants detected in hair is not impacted by short-term variations in exposure as can be observed with urine, it accurately represents an individual's average level of exposure, which is the most relevant information when investigating possible linkages with biological effects. In the current study, based on a rat model exposed to a mixture of PAHs for a 90-day period, the linkage between the PAH exposure level and the resulting concentration of their metabolites in hair was then investigated. The linkage between exposure levels and the concentrations of OH-PAH in hair collected at the end of the experiment were compared to those obtained using urinary concentration of OH-PAH collected from the same animals. Linear relationship between levels of exposure and the concentration of OH-PAH in the rats' hair (R2 0.722-0.965, p < 0.001) was observed for 28 OH-PAH out of the 54 investigated. The difference in PAH concentration between the different groups of exposure and the possibility to back determine the animals' level of exposure on the basis of PAH-metabolite concentrations in both hair and urine was also demonstrated. In addition to the strong linear relation observed between the doses of exposure and the levels of concentration of hydroxylated metabolites in hair (p < 0.001), the analysis of a subset of animals demonstrated a linkage between 3-OH-benzo[a]pyrene concentration levels in hair and the levels of B[a]P-DNA adduct formed (p < 0.05), thereby suggesting the potential of their analysis to predict genetic alteration.

MICROSCOPE Mission: First Results of a Space Test of the Equivalence Principle.

According to the weak equivalence principle, all bodies should fall at the same rate in a gravitational field. The MICROSCOPE satellite, launched in April 2016, aims to test its validity at the 10^{-15} precision level, by measuring the force required to maintain two test masses (of titanium and platinum alloys) exactly in the same orbit. A nonvanishing result would correspond to a violation of the equivalence principle, or to the discovery of a new long-range force. Analysis of the first data gives δ(Ti,Pt)=[-1±9(stat)±9(syst)]×10^{-15} (1σ statistical uncertainty) for the titanium-platinum Eötvös parameter characterizing the relative difference in their free-fall accelerations.

Hair analysis for the biomonitoring of pesticide exposure: comparison with blood and urine in a rat model.

Urine and plasma have been used to date for the biomonitoring of exposure to pollutants and are still the preferred fluids for this purpose; however, these fluids mainly provide information on the short term and may present a high level of variability regarding pesticide concentrations, especially for nonpersistent compounds. Hair analysis may provide information about chronic exposure that is averaged over several months; therefore, this method has been proposed as an alternative to solely relying on these fluids. Although the possibility of detecting pesticides in hair has been demonstrated over the past few years, the unknown linkage between exposure and pesticides concentration in hair has limited the recognition of this matrix as a relevant tool for assessing human exposure. Based on a rat model in which there was controlled exposure to a mixture of pesticides composed of lindane, ß-hexachlorocyclohexane, ß-endosulfan, p,p'-DDT, p,p'-DDE, dieldrin, pentachlorophenol, diazinon, chlorpyrifos, cyhalothrin, permethrin, cypermethrin, propiconazole, fipronil, oxadiazon, diflufenican, trifluralin, carbofuran, and propoxur, the current work demonstrates the association between exposure intensity and resulting pesticide concentration in hair. We also compared the results obtained from a hair analysis to urine and plasma collected from the same rats. Hair, blood, and urine were collected from rats submitted to 90-day exposure by gavage to the aforementioned mixture of common pesticides at different levels. We observed a linear relationship between exposure intensity and the concentration of pesticides in the rats' hair (R Pearson 0.453-0.978, p < 0.01). A comparison with results from urine and plasma samples demonstrated the relevance of hair analysis and, for many chemicals, its superiority over using fluids for differentiating animals from different groups and for re-attributing animals to their correct groups of exposure based on pesticide concentrations in the matrix. Therefore, this study strongly supports hair analysis as a reliable tool to be used during epidemiological studies to investigate exposure-associated adverse health effects.

Influence of pesticide physicochemical properties on the association between plasma and hair concentration.

Although the relationship between chemical intake and resulting concentration in hair remains incompletely elucidated, the transfer from blood to hair bulb living cells is generally considered the main route of incorporation. The present work investigated the correlation between blood and hair concentration of 23 pesticides/metabolites from different chemical classes in rats submitted to chronic controlled exposure. Long-Evans rats were administered pesticides by gavage three times per week over a 90-day period. After hair sample decontamination, pulverization, and extraction, compounds were analyzed by gas chromatography tandem mass spectrometry (GC-MS/MS). Blood was collected at sacrifice, immediately turned into plasma, and analyzed after extraction for the same compounds by GC-MS/MS. The data obtained for all the investigated compounds demonstrated significant association between plasma and hair concentrations (P value of 2.97E-45 and R(Pearson) of 0.875), with the exception of three outliers. For all the target compounds, water solubility, lipophilicity, molecular weight, and charge were therefore investigated in order to understand the role of these parameters in outliers' specific behavior. Although a possible change in the charge through the transfer from blood to hair might be suspected for two outliers, on the whole the physicochemical parameters investigated here did not seem to influence incorporation of chemicals into hair. Our results support that the concentration of chemicals in hair mainly depends on the respective concentration in plasma and suggest that for most compounds, the transfer from blood to hair would not represent a limiting step in the incorporation.

Analysis of tetrahydroxylated benzo[a]pyrene isomers in hair as biomarkers of exposure to benzo[a]pyrene.

A first gas chromatography-tandem mass spectrometry (GC-MS/MS) method was designed for analysis of four tetrahydroxylated benzo[a]pyrene metabolites (benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, benzo[a]pyrene-r-7,t-8,t-9,t-10-tetrahydrotetrol, benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol, and benzo[a]pyrene-r-7,t-8,c-9,t-10-tetrahydrotetrol) in hair. Hair powder extract was submitted to liquid-solid extraction, followed by C18 solid-phase purification. The analytes were derivatized with use of N-methyl-N-(trimethylsilyl)trifluoroacetamide and then analyzed by GC-MS/MS in negative chemical ionization mode. The calibration curve was linear from the limit of quantification (LOQ) to 20 pg/mg in hair. The coefficient of determination of the calibration curve was more than 0.975 for all the analytes investigated. The LOQs ranged from 0.075 to 0.2 pg/mg in hair. The method was afterward applied to the analysis of hair of 16 rats randomly allocated to experimental groups receiving 16 polycyclic aromatic hydrocarbons solubilized in oil at 0 or 0.8 mg/kg body weight by oral administration three times per week for 90 days. The analysis of monohydroxylated and dihydroxylated benzo[a]pyrenes was conducted in parallel by GC-MS/MS on the same samples. All tetrahydroxylated benzo[a]pyrene isomers were detected in hair samples collected from rats exposed to polycyclic aromatic hydrocarbons. Benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, the most abundant isomer in hair of treated rats, was also the principal isomer released in DNA adduct hydrolysis in humans. Moreover, the benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol concentrations in hair were significantly greater than those of 2-hydroxybenzo[a]pyrene, 1-hydroxybenzo[a]pyrene, 7-hydroxybenzo[a]pyrene, and 4-hydroxybenzo[a]pyrene and similar to those of 9-hydroxybenzo[a]pyrene and 3-hydroxybenzo[a]pyrene. The method was also sufficiently sensitive to monitor environmental levels of exposure because two hair specimens in the eight analyzed from smokers were above the LOQ for benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol and benzo[a]pyrene-r-7,t-8,c-9,t-10-tetrahydrotetrol. This study therefore demonstrated that tetrahydroxylated benzo[a]pyrenes in hair might be a useful biomarker for the assessment of both the general population and occupationally exposed workers.

Exposure of children to brominated flame retardants and heavy metals in Morocco: Urine and blood levels in association with global cytosine and adenine methylation.

Persistent pollutants, namely brominated flame retardants (BFRs) and heavy metals, are compounds that are added to a wide range of products and materials for preventing ignition, increasing the functionality of materials or improving their performance, e.g. electric conductivity. The exposure of children might consequently be inferred, through indoor dust and hand-to-mouth or toy-chewing behaviors. The current study is aimed at assessing the exposure of Moroccan children to BFRs and heavy metal elements, and evaluating their associations with global DNA methylation. First, parents responded to a questionnaire pertaining to children's lifestyle, then blood and urine samples were collected from (n = 93) children aged between 5 and 11 years for biomonitoring and DNA methylation analysis. BFRs were detected in 54.84% of samples with a median concentration of 0.01 nmol/mL (range: 0.004-0.051 nmol/mL) while metal elements were detected in more than 90% of samples. BFRs showed no variations with global DNA methylation, unlike metal elements, which revealed significant associations with global DNA methylation markers, namely 5-mC, 5-hmC and N6-mA levels. Moroccan children may be exposed to flame retardants and heavy metals through several routes. Further research is required to assess the exposure and the health impacts of environmental pollutants and ultimately protect the Moroccan population by the prevention of adverse health effects.

Crumbs controls epithelial integrity by inhibiting Rac1 and PI3K.

Drosophila Crumbs (Crb) and its mammalian ortholog CRB3 control epithelial polarity through poorly understood molecular mechanisms. Elucidating these mechanisms is crucial, because the physiology of epithelia largely depends on the polarized architecture of individual epithelial cells. In addition, loss of CRB3 favors tumor cell growth, metastasis and epithelial to mesenchymal transition (EMT). Using Drosophila embryos, we report that Rac1 sustains PI3K signaling, which is required for Rac1 activation. Crb represses this positive-feedback loop. Notably, this property confers to Crb its ability to promote epithelial integrity in vivo, because attenuation of either Rac1 or PI3K activity rescues the crb mutant phenotype. Moreover, inhibition of Rac1 or PI3K results in Crb-dependent apical membrane growth, whereas Rac1 activation restricts membrane localization of Crb and interferes with apical domain formation. This illustrates that Crb and the Rac1-PI3K module are antagonists, and that the fine balance between the activities of these proteins is crucial to maintain epithelial organization and an appropriate apical to basolateral ratio. Together, our results elucidate a mechanism that mediates Crb function and further define the role of PI3K and Rac1 in epithelial morphogenesis, allowing for a better understanding of how distinct membrane domains are regulated in polarized epithelial cells.

Surveillance of Indoor Air Concentration of Volatile Organic Compounds in Luxembourgish Households.

Exposure to air pollution is a well-known health risk. For instance, volatile and very volatile organic compounds (VOCs and VVOCs) are known to cause respiratory, haematologic or immune diseases, and even cancer. Based on the Luxembourgish indoor pollution surveillance program, we performed an exploratory analysis for the period 2014-2019, in order (1) to evaluate the prevalence of VOCs and VVOCs in households, and (2) to estimate the risks of lifelong exposure to selected VOCs on the health of the adult population. The database included 715 indoor air samples from 159 different households. Observed VOC and VVOC levels were similar to those in neighbouring countries. Our health impact assessment identified some health risks associated with the observed concentrations in Luxembourg. Furthermore, this study shows the major public health importance of having a national indoor pollution surveillance system in place. Highlights: (1) This study provides an overview of the domestic indoor pollution in Luxembourg. (2) (V)VOCs levels in Luxembourg were similar to those in neighbouring countries. (3) The results clearly show the importance of having a surveillance system in place.

Adaptation to host cell environment during experimental evolution of Zika virus.

Zika virus (ZIKV) infection can cause important developmental and neurological defects in Humans. Type I/III interferon responses control ZIKV infection and pathological processes, yet the virus has evolved various mechanisms to defeat these host responses. Here, we established a pipeline to delineate at high-resolution the genetic evolution of ZIKV in a controlled host cell environment. We uncovered that serially passaged ZIKV acquired increased infectivity and simultaneously developed a resistance to TLR3-induced restriction. We built a mathematical model that suggests that the increased infectivity is due to a reduced time-lag between infection and viral replication. We found that this adaptation is cell-type specific, suggesting that different cell environments may drive viral evolution along different routes. Deep-sequencing of ZIKV populations pinpointed mutations whose increased frequencies temporally coincide with the acquisition of the adapted phenotype. We functionally validated S455L, a substitution in ZIKV envelope (E) protein, recapitulating the adapted phenotype. Its positioning on the E structure suggests a putative function in protein refolding/stability. Taken together, our results uncovered ZIKV adaptations to the cellular environment leading to accelerated replication onset coupled with resistance to TLR3-induced antiviral response. Our work provides insights into Zika virus adaptation to host cells and immune escape mechanisms.

Pervasive exposure of wild small mammals to legacy and currently used pesticide mixtures in arable landscapes.

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.

Biomonitoring of fast-elimination endocrine disruptors - Results from a 6-month follow up on human volunteers with repeated urine and hair collection.

BACKGROUND: The assessment of human exposure to fast-elimination endocrine disruptors (ED) such as phthalates, bisphenols or pesticides is usually based on urinary biomarkers. 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. Other matrices such as hair, less sensitive to short-term variations in the exposure, have been proposed as possible alternatives. Nevertheless, no study compared the information obtained from hair and urine respectively in a follow-up allowing to assess biomarkers variability over time in these two matrices, and to compare the correlation between them. METHODS: In the present study, hair and urine samples were collected from 16 volunteers over a 6 months follow-up. All in all, 92 hair samples and 805 urines samples were collected and analyzed for the presence of 16 phthalate metabolites, 4 bisphenols and 8 pesticides/metabolites. RESULTS: All the biomarkers analyzed were detected in at least one of the two matrices. 21 biomarkers were more frequently detected in hair, 6 in urine, and 1 was equivalent. Biomarkers intraclass correlation coefficients (ICC) ranged from 0.1 to 0.8 (ten above 0.4) in hair, and from 0.09 to 0.51 in urine (two above 0.4). The concentrations of biomarkers in hair and urine were significantly correlated for only one compound. CONCLUSION: This study highlights the complexity of assessing exposure to fast-elimination ED and suggests considering with caution the specificity of the matrix in data interpretation. The results document the respective advantages and limitations of urine and hair, and provide new insight in the understanding of the information provided by these biological matrices and their relevance for the assessment of human exposure to fast elimination contaminants. CAPSULE: 92 hair and 805 urine samples collected from 16 volunteers over 6 months, tested for phthalate metabolites, bisphenols and pesticides. 19 biomarkers (in hair) and 24 (in urine) were detected in >50% of the samples.

Impact of Protein-Enriched Plant Food Items on the Bioaccessibility and Cellular Uptake of Carotenoids.

Carotenoids are lipophilic pigments which have been associated with a number of health benefits, partly related to antioxidant effects. However, due to their poor solubility during digestion, carotenoid bioavailability is low and variable. In this study, we investigated the effect of frequently consumed proteins on carotenoid bioaccessibility and cellular uptake. Whey protein isolate (WPI), soy protein isolate (SPI), sodium caseinate (SC), gelatin (GEL), turkey and cod, equivalent to 0/10/25/50% of the recommended dietary allowance (RDA, approx. 60g/d), were co-digested gastro-intestinally with carotenoid-rich food matrices (tomato and carrot juice, spinach), and digesta further studied in Caco-2 cell models. Lipid digestion, surface tension and microscopic visualization were also carried out. Co-digested proteins positively influenced the micellization of carotenes (up to 3-fold, depending on type and concentration), especially in the presence of SPI (p < 0.001). An increased cellular uptake was observed for xanthophylls/carotenes (up to 12/33%, p < 0.001), which was stronger for matrices with an initially poor carotenoid micellization (i.e., tomato juice, p < 0.001), similar to what was encountered for bioaccessibility. Turkey and cod had a weaker impact. Significant interactions between carotenoids, lipids and proteins were observed during digestion. Co-digested proteins generally improved lipid digestion in all matrices (p < 0.001), especially for carrot juice, though slight decreases were observed for GEL. Protein impact on the surface tension was limited. In conclusion, proteins generally improved both carotenoid bioaccessibility and cellular uptake, depending on the matrices and carotenoid-type (i.e., carotene vs. xanthophylls), which may be relevant under specific circumstances, such as intake of carotenoid-rich food items low in lipids.

Population-based biomonitoring of exposure to persistent and non-persistent organic pollutants in the Grand Duchy of Luxembourg: Results from hair analysis.

Environmental exposure of humans to pollutants has been associated with adverse health outcomes, but few studies have evaluated the multiple exposure of general populations. In the present study, we used hair analysis to assess the exposure of a general adult population (n = 497) in Luxembourg to 34 persistent and 33 non-persistent organic pollutants from 11 chemical families, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), and pyrethroid pesticides (PYRs). We detected 24 persistent and 29 non-persistent organic pollutants, with 17 pollutants being detected in more than 50% of hair samples. The median concentrations for pollutants detected in 100% of the samples were 0.37 pg/mg for lindane (γ-HCH), 0.15 pg/mg for hexachlorobenzene (HCB), 14.1 pg/mg for p-nitrophenyl (PNP), and 0.10 pg/mg for trifluralin. Each participant in this study had detectable levels of at least 10 of the pollutants analyzed, and 50% of participants had 19 or more, suggesting the simultaneous exposure to numerous different pollutants among our study population. Significant correlations were often found between pollutants from the same family, with the strongest being found between two PYR metabolites, trans/cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-carboxylic acid (Cl2CA) and 3-phenoxybenzoic acid (3-PBA). Results from multiple linear regression analyses showed that sex, age and/or body mass index were significantly associated with 15 out of the 17 frequently detected pollutants. The current study is the first nationwide biomonitoring investigating organic contaminants in the Luxembourg population using hair analysis.

Hair versus urine for the biomonitoring of pesticide exposure: Results from a pilot cohort study on pregnant women.

BACKGROUND/AIM: The quantitative assessment of human exposure to contaminants such as pesticides is a crucial step in the characterization of exposure-associated risk. For this purpose, biomonitoring is often privileged as it presents the advantage of integrating all the possible sources and routes of exposure and of being representative of the internal dose resulting from exposure. Although biological fluids such as urine and blood have been used to date for this purpose, increasing interest has also been observed over the past decade for hair analysis. The present work aimed at comparing the information obtained from the analysis of urine versus hair regarding exposure to pesticides in a pilot cohort of pregnant women. METHODS: In ninety-three pregnant women included in the pilot of the French cohort ELFE, one urine and one hair sample were collected simultaneously from each subject at the maternity. Samples were analyzed using GC-MS/MS analytical methods allowing for the detection of both parent pesticides and metabolites, and designed to be as similar as possible between urine and hair for reliable inter-matrix comparison. Fifty-two biomarkers of exposure were targeted, including parents and metabolites of organochlorines, organophosphates, pyrethroids, carbamates, phenylpyrazoles and other pesticides. RESULTS: The number of different compounds detected ranged from 16 to 27 (median = 22) in hair, and from 3 to 22 (median = 12) in urine. In hair, 24 compounds were found in > 40% of the individuals, whereas only 12 compounds presented the same frequency of detection in urine. Among the chemicals detected in > 80% of both hair and urine samples, only one (pentachlorophenol) showed a signification correlation between hair and urine concentrations. CONCLUSIONS: The present results highlight the multiple exposure of the pregnant women included in this cohort and suggest that hair provides more comprehensive information on pesticide exposure than urine analysis. This study thus supports the relevance of hair analysis in future epidemiological studies investigating association between exposure and adverse health effects.