Review of environmental airborne pyrene/benzo[a]pyrene levels from industrial emissions for the improvement of 1-hydroxypyrene biomonitoring interpretation.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants of significant public health concern, with several that are highly toxic to humans, including some proven or suspected carcinogens. To account for the high variability of PAH mixtures encountered in occupational settings, adjusting urinary 1-hydroxypyrene (1-OHP) levels by the total airborne pyrene (PyrT)/benzo[a]pyrene (BaP) ratio is essential for human biomonitoring (HBM). Given the complexity and cost of systematically monitoring atmospheric levels, alternative approaches to simultaneous airborne and HBM are required. The aim of this review was to catalog airborne PyrT/BaP ratios measured during different industrial activities and recommend 1-OHP-dedicated biological guidance values (BGV). A literature search was conducted. Seventy-one studies were included, with 5619 samples pertaining to 15 industrial sectors, 79 emission processes, and 213 occupational activities. This review summarized more than 40 years of data from almost 20 countries and highlighted the diversity and evolution of PAH emissions. PyrT/BaP ratios were highly variable, ranging from 0.8 in coke production to nearly 40 in tire and rubber production. A single PyrT/BaP value cannot apply to all occupational contexts, raising the question of the relevance of defining a single biological limit value for 1-OHP in industrial sectors where the PyrT/BaP ratio variability is high. Based upon the inventory, a practical approach is proposed for systematic PAH exposure and risk assessment, with a simple frame to follow based upon specific 1-OHP BGVs depending upon the occupational context and setup of a free PAH HBM interactive tool.

Bitumen fumes and PAHs in asphalt road paving: Emission characteristics, determinants of exposure and environmental impact.

BACKGROUND: Asphalt road paving and its subsequent complex airborne emissions have raised concerns about occupational exposures and environmental impacts. Although several studies described bitumen fumes or Polycyclic Aromatic Hydrocarbons (PAH) emissions at specific worksites, no comprehensive studies have characterised road paving emissions and identified the main determinants of exposure. METHODS: A 10-year study from 2012 to 2022 was performed to examine the pollutants resulting from bitumen fume emissions and covering the main processes used in road paving (asphalt production, mechanical rolled asphalt paving, manual paving, mastic asphalt paving, emulsion paving, and coal-tar asphalt milling). A total of 623 air samples were collected at 63 worksites (on 290 workers, in the environment and near emission sources), and bitumen fumes, PAHs, aldehydes and volatile organic compounds were analysed. Biomonitoring campaigns were performed on 130 workers to assess internal exposure to PAHs. RESULTS: Fume emissions revealed complex mixtures of C10-C30 compounds, including linear saturated hydrocarbons (C6-C12), alicyclic hydrocarbons and aliphatic ketones. PAHs were dominated by 2-3 aromatic ring compounds (naphthalene, fluorene, and phenanthrene), and C1-C13 aldehydes were identified. Binder proportion, paving temperature, outdoor temperature, workload and job category influenced airborne concentrations. A significant temporal trend was observed over the time period of the study, with decreasing BF and PAH exposures. PAH biomonitoring was consistent with air samples, and urinary metabolites of 2-3 ring PAHs dominated over 4-5 ring PAHs. Occupational exposures were generally far lower than exposure limits, except coal-tar asphalt milling activities. Very low environmental concentrations were measured, which highlights a negligible contribution of paving emissions to global environmental pollution. CONCLUSION: The present study confirmed the complex nature of bitumen fumes and characterised the main determinants of exposure. The results highlight the need to reduce the paving temperature and binder proportion. Recycled asphalt pavement use was not associated with higher emissions. The impact of paving activities on environmental airborne pollution was deemed negligible.

Metabolism of benzo[a]pyrene after low-dose subchronic exposure to an industrial mixture of carcinogenic polycyclic aromatic hydrocarbons in rats: a cocktail effect study.

Polycyclic aromatic hydrocarbons (PAHs) are interesting environmental pollutants for understanding cocktail effects. High-molecular-weight-PAHs (HMW-PAHs) are classified as probable or possible carcinogens; only benzo[a]pyrene (B[a]P) is a certain carcinogen in humans. Their toxicity depends on their metabolic activation. While 3-hydroxybenzo[a]pyrene (3-OHB[a]P) represents its detoxification pathway, trans-anti-7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (tetrol-B[a]P) represents the carcinogenicity pathway. The objective was to study the metabolism of B[a]P and HMW-PAHs during chronic low-dose exposure to B[a]P or a PAH mixture. Rats were exposed orally 5 times/week for 10 weeks to low-levels of B[a]P (0.02 and 0.2 mg.kg-1.d-1) or to an industrial mixture extracted from coal tar pitch (CTP) adjusted to 0.2 mg.kg-1.d-1 B[a]P. Urinary levels of monohydroxy-, diol-, and tetrol-PAH were measured during weeks 1 and 10 by HPLC-fluorescence and GC‒MS/MS. After 1 week, the percentages of B[a]P eliminated as 3-OHB[a]P and tetrol-B[a]P were not different depending on the dose of B[a]P, whereas they were reduced by half in the CTP group. Repeated exposure led to an increase in the percentages of the 2 metabolites for the 0.02-B[a]P group. Moreover, the percentage of B[a]P eliminated as 3-OHB[a]P was equal in the 0.2-B[a]P and CTP groups, whereas it remained halved for tetrol-B[a]P in the CTP group. The percent elimination of HMW-PAH metabolites did not vary between weeks 1 and 10. Thus, dose, duration of exposure and chemical composition of the mixture have a major influence on PAH metabolism that goes beyond a simple additive effect. This work contributes to the reflection on determination of limit values and risk assessments in a context of poly-exposures.

Detecting Phylogenetic Signal and Adaptation in Papionin Cranial Shape by Decomposing Variation at Different Spatial Scales.

Phylogenetic reconstruction based on morphometric data is hampered by homoplasies. For example, many similarities in cranial form between primate taxa more strongly reflect ecological similarities rather than phylogenetic relatedness. However, the way in which the different cranial bones constitute cranial form is, if at all, of less functional relevance and thus largely hidden from selection. We propose that these "constructional details" are better indicators of phylogenetic history than any large-scale shape feature or raw form variable. Within a geometric morphometric context, we show how to analyze the relative extent of bones independently of differences in overall shape. We also show how to decompose total shape variation into small-scale and large-scale shape variation. We apply both methods to the midsagittal cranial morphology of papionin monkeys, which are well known for the discrepancy between morphological similarities and phylogenetic relationships. We study phylogenetic signal and functional adaptation using a molecular phylogeny and contextual data on feeding ecology and locomotor behavior. As expected, total cranial shape, bone outline shape, and large-scale shape features were only weakly associated with phylogenetic distance. But the relative bone contributions and small-scale shape features were both highly correlated with phylogenetic distances. By contrast, the association with ecological and behavioral variables was strongest for the outline shape and large-scale shape features. Studies of morphological adaptation and phylogenetic history thus profit from a decomposition of shape variation into different spatial scales. [Adaptation; canalization; cranial shape; geometric morphometrics; papionini; partial warps; phylogeny.].

Consistency between air and biological monitoring for assessing polycyclic aromatic hydrocarbon exposure and cancer risk of workers.

BACKGROUND: Atmospheric levels of polycyclic aromatic hydrocarbons (PAHs) have been monitored in many companies since 1940. Because of the use of respiratory protective equipment (RPE) and cutaneous absorption, the measurement of urinary 1-hydroxypyrene (1-OHP), metabolite of pyrene (Pyr), and, more recently, 3-hydroxybenzo[a]pyrene (3-OHBaP), metabolite of benzo[a]pyrene (BaP), has been carried out to assess PAH exposure and estimate health risks. OBJECTIVES: This study aimed to investigate the agreement between 523 air and biological levels recorded in the Exporisq-HAP database by taking into account the effectiveness of RPE. METHODS: The agreement/consistency between 523 air and biological exposure levels was assessed by estimating and comparing the probability of exceeding French limit values (LVs) for both BaP and 3-OHBaP and ACGIH LV for 1-OHP, respectively. PAH airborne levels (wPAHs) were weighted by an assigned protection factor (APF) depending on the type of mask worn by workers, while urinary 1-OHP concentrations were adjusted with the wBaP/wPyr ratio of each industrial sector (wadj1-OHP). RESULTS: Within occupational groups, there was an overall agreement between airborne PAH levels and urinary biomarker concentrations. A clear dichotomy was found between "petroleum-derived" and "coal-derived" groups, with much higher exposures in the latest group despite the use of RPEs by two-thirds of the workers. The type of RPE varied from one plant to another, which underlines the importance of taking into account their effectiveness. The analysis of urinary 3-OHBaP was not relevant for low PAH exposure levels. In addition, this biomarker underdiagnosed the exceedance of LV relative to BaP levels for 6% of "coal-derived" groups. CONCLUSIONS: The use of urinary wadj1-OHP seemed to be more protective to assess the exceedance of LVs than those of urinary 3-OHBaP and air wBaP, but adjustment of the 1-OHP concentration by the BaP/Pyr ratio requires air sampling due to highly variable ratios observed in the studied occupational groups.

Morphometric Variation at Different Spatial Scales: Coordination and Compensation in the Emergence of Organismal Form.

It is a classic aim of quantitative and evolutionary biology to infer genetic architecture and potential evolutionary responses to selection from the variance-covariance structure of measured traits. But a meaningful genetic or developmental interpretation of raw covariances is difficult, and classic concepts of morphological integration do not directly apply to modern morphometric data. Here, we present a new morphometric strategy based on the comparison of morphological variation across different spatial scales. If anatomical elements vary completely independently, then their variance accumulates at larger scales or for structures composed of multiple elements: morphological variance would be a power function of spatial scale. Deviations from this pattern of "variational self-similarity" (serving as a null model of completely uncoordinated growth) indicate genetic or developmental coregulation of anatomical components. We present biometric strategies and R scripts for identifying patterns of coordination and compensation in the size and shape of composite anatomical structures. In an application to human cranial variation, we found that coordinated variation and positive correlations are prevalent for the size of cranial components, whereas their shape was dominated by compensatory variation, leading to strong canalization of cranial shape at larger scales. We propose that mechanically induced bone formation and remodeling are key mechanisms underlying compensatory variation in cranial shape. Such epigenetic coordination and compensation of growth are indispensable for stable, canalized development and may also foster the evolvability of complex anatomical structures by preserving spatial and functional integrity during genetic responses to selection.[Cranial shape; developmental canalization; evolvability; morphological integration; morphometrics; phenotypic variation; self-similarity.].

Simultaneous analysis of PAH urinary mono- and dihydroxylated metabolites by GC-MS-MS following SPE and two-stage derivatization.

A new gas chromatography-tandem mass spectrometry method for the determination of mono- and dihydroxylated polycyclic aromatic hydrocarbon metabolites (OH-PAHs and diol-PAHs) in urine was developed and validated. Various sample preparation procedures were compared, namely liquid-liquid extraction (LLE), dispersive solid-phase extraction (dSPE), and SPE, alone or combined. A novel two-stage derivatization approach using 2 silylation reagents was developed, and an experimental procedure design was used to optimize the programmed temperature vaporization-solvent vent injection (PTV-SV) GC parameters. The method focused on 11 target compounds resulting from four- to five-ring suspected carcinogenic PAHs. SPE was identified as an acceptable and more convenient extraction method for all tested metabolites, with extraction rates ranging from 63 to 86% and relative standard deviations lower than 20%. The two-stage derivatization approach successfully allowed first the derivatization of OH-PAHs by MTBSTFA (N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide) and then diol-PAHs by BSTFA (N,O-bis(trimethylsilyl)trifluoroacetamide) in a single run. The limits of quantification were in the range of 0.01-0.02 µg l-1 for OH-PAHs and 0.02-0.2 µg l-1 for diol-PAHs. The intra- and interday precisions were lower than 10%. The method was applied to determine PAH metabolites in urine collected at the beginning and at the end of the working week from 6 workers involved in aluminum production. The mean diol-PAH levels at the end of the week were 10 to 20 times higher (0.86-2.34 µg g-1 creatinine) than those of OH-PAHs (0.03-0.30 µg g-1). These results confirmed the usefulness of this new analytical technique for detecting and characterizing metabolic patterns of PAHs in urine and assessing carcinogenic occupational exposures.

A consensus approach for estimating health risk: Application to inhalation cancer risks.

Conducting a risk assessment is challenging because various and contrasting risk indicators are available, which can lead to discrepancies and, sometimes, conflicting conclusions. Constructing and using a consensus risk indicator (CRI) could provide a reliable alternative that is consistent and supports direct comparisons. The goal of this study is to propose a structured and pragmatic approach for constructing a CRI distribution and demonstrate its feasibility and easy implementation when conducting risk assessments. A CRI distribution is constructed as a weighted combination of existing indicators where the weights are obtained by using the overlapping areas of an individual indicator's distribution and an aggregated reference distribution. The approach is illustrated through an assessment of human cancer risk following inhalation exposure. The CRI is constructed using eight risk indicators. The CRI distribution parameters for 199 human carcinogenic chemicals associated with inhalation exposure were determined and are presented in an interactive table. To aid the wider implementation of the CRI approach, a user-friendly and interactive web application, named InCaRisk, was created to facilitate the cancer risk estimation following inhalation exposure. Our approach could be useful for enhancing the quality of regulatory decisions and protecting human health from environmental pollutants; our approach can be applied for a given health outcome, route of exposure and exposure setting.

Metabolism and genotoxicity of polycyclic aromatic hydrocarbons in human skin explants: mixture effects and modulation by sunlight.

Cutaneous exposure to carcinogenic polycyclic aromatic hydrocarbons (PAH) occurs frequently in the industrialized workplace. In the present study, we addressed this topic in a series of experiments using human skin explants and organic extracts of relevant industrial products. PAH mixtures were applied topically in volumes containing either 10 or 1 nmol B[a]P. We first observed that although mixtures were very efficient at inducing expression of CYP450 1A1, 1A2, and 1B1, formation of adducts of PAH metabolites to DNA, like those of benzo[a]pyrene diol epoxide (BPDE), was drastically reduced as the complexity of the surrounding matrix increased. Interestingly, observation of a nonlinear, dose-dependent response with the least complex mixture suggested the existence of a threshold for this inhibitory effect. We then investigated the impact of simulated sunlight (SSL) on the effects of PAH in skin. SSL was found to decrease the expression of CYP450 genes when applied either after or more efficiently before PAH treatment. Accordingly, the level of DNA-BPDE adducts was reduced in skin samples exposed to both PAH and SSL. The main conclusion of our work is that both increasing chemical complexity of the mixtures and co-exposure to UV radiation decreased the production of adducts between DNA and PAH metabolites. Such results must be taken into account in risk management.

A realistic human skin model to study benzo[a]pyrene cutaneous absorption in order to determine the most relevant biomarker for carcinogenic exposure.

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous pollutants, among which benzo[a]pyrene (B[a]P) is the only compound classified carcinogenic to humans. Besides pulmonary uptake, skin is the major route of PAH absorption during occupational exposure. Health risk due to PAH exposure is commonly assessed among workers using biomonitoring. A realistic human ex vivo skin model was developed to explore B[a]P diffusion and metabolism to determine the most relevant biomarker following dermal exposure. Three realistic doses (0.88, 8.85 and 22.11 nmol/cm2) were topically applied for 8, 24, and 48 h. B[a]P and its metabolites were quantified by liquid chromatography coupled with fluorimetric detection. The impact of time, applied dose, and donor age were estimated using a linear mixed-effects model. B[a]P vastly penetrated the skin within 8 h. The major metabolites were 3-hydroxybenzo[a]pyrene (3-OHB[a]P) and 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P-tetrol). This latter predominantly derives from the most carcinogenic metabolite of B[a]P, benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), as well as benzo[a]pyrene-9,10-diol-7,8-epoxide (reverse-BPDE). Benzo[a]pyrene-trans-7,8-dihydrodiol (B[a]P-7,8-diol) was a minor metabolite, and benzo[a]pyrene-trans-4,5-dihydrodiol (B[a]P-4,5-diol) was never quantified. Unmetabolized B[a]P bioavailability was limited following dermal exposure since less than 3% of the applied dose could be measured in the culture medium. B[a]P was continuously absorbed and metabolized by human skin over 48 h. B[a]P-tetrol production became saturated as the applied dose increased, while no effect was measured on the other metabolic pathways. Age had a slight positive effect on B[a]P absorption and metabolism. This work supports the relevance of B[a]P-tetrol to assess occupational exposure and carcinogenic risk after cutaneous absorption of B[a]P.

Influence of exposure dose, complex mixture, and ultraviolet radiation on skin absorption and bioactivation of polycyclic aromatic hydrocarbons ex vivo.

Combined exposure to complex mixtures of polycyclic aromatic hydrocarbons (PAHs) and ultraviolet radiation (UVR) is suspected to enhance PAH skin permeability and skin cancer risk depending on PAH bioactivation. The impact of PAH mixtures (exposure dose, composition, and complexity) and UVR was assessed for PAH cutaneous absorption and metabolism using realistic exposure conditions and human skin explants. PAH complex mixtures were extracted from the industrial products coal tar pitch (CTP-I) and petroleum coke (PC-I). The synthetic mixture (CTP-S) was identically reconstituted using PAH standards. The applied dose was adjusted to 1 (PC-I, CTP-I) or 10 nmol (CTP-I, CTP-S) of benzo[a]pyrene (B[a]P). Unmetabolized PAHs were recovered from the skin surface, skin and medium, and then quantified by HPLC-fluorescence detection. PAH metabolites were collected from the medium and analyzed by GC-MS/MS. B[a]P and PAH penetration was lower for the highest B[a]P dose, industrial mixtures, and CTP-I compared to PC-I. Skin irradiation increased PAH penetration only for CTP-I. PAH uptake was poorly influenced by the different experimental conditions. PAH metabolism markedly decreased in the application of mixtures, leading to unmetabolized PAH accumulation in human skin. PAH metabolism was similar between CTP-I and PC-I, but was lower for the highest dose and the industrial mixtures, suggesting a saturation of xenobiotic metabolizing enzymes, as confirmed in a time-course study. UVR strongly inhibited all PAH metabolism. Altogether, these results underline the necessity to consider the reality of human exposure (PAH complex mixtures and UVR) during in vitro experiments to properly estimate skin absorption and metabolism.

New data about semicircular canal morphology and locomotion in modern hominoids.

The labyrinth has two functional parts: the cochlea for audition and the vestibular system for equilibrioception. In the latter, the semicircular ducts and the otolithic organs are sensitive to rotational and linear accelerations of the head, respectively. The labyrinthine morphology influences perception accuracy, hence the adaptation to a specific locomotor pattern. The aim of this study is to determine the relationship between locomotion and semicircular canal morphology using geometric morphometrics, and to explain these links with existing functional models. The influence of factors other than functional constraints on labyrinthine morphology is discussed. The left bony labyrinth of 65 specimens was extracted virtually. Five extant hominoid species with various locomotion modes were sampled. A set of 13 landmarks was placed on the semicircular canals. After a Procrustes fit, their coordinates were analyzed using a principal component analysis. It was found that labyrinthine morphology is significantly distinct between species. More specifically, the differences involve a posterolateral projection of the lateral semicircular canal and the rotation of this canal relative to the vertical canals. This rotation occurs in the sagittal plane, which is consistent with previous studies based on traditional morphometrics. Among extant hominoids, the shape of the canals potentially discriminates species based on posture. This result could be used to reconstruct the locomotor pattern of fossil hominoids.

Urinary elimination kinetics of 3-hydroxybenzo(a)pyrene and 1-hydroxypyrene of workers in a prebake aluminum electrode production plant: Evaluation of diuresis correction methods for routine biological monitoring.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous carcinogenic pollutants emitted in complex mixtures in the ambient air and contribute to the incidence of human cancers. Taking into account all absorption routes, biomonitoring is more relevant than atmospheric measurements to health risk assessment, but knowledge about how to use biomarkers is essential. In this work, urinary elimination kinetic of 1-hydroxypyrene (1-OHP) and 3-hydroxybenzo(a)pyrene (3-OHBaP) were studied in six electrometallurgy workers after PAHs exposure. Spot samples were collected on pre- and post-shift of the last workday then the whole urinations were separately sampled during the weekend. Non-linear mixed effects models were built to study inter- and intra-individual variability of both urinary metabolites toxicokinetic and investigate diuresis correction ways. Comparison of models confirmed the diuresis correction requirement to perform urinary biomonitoring of pyrene and BaP exposure. Urinary creatinine was found as a better way than specific gravity to normalize urinary concentrations of 1-OHP and as a good compromise for 3-OHBaP. Maximum observed levels were 1.0 µmol/mol creatinine and 0.8nmol/mol creatinine for 1-OHP and 3-OHBaP, respectively. Urinary 1-OHP concentrations on post-shift were higher than pre-shift for each subject, while 3-OHBaP levels were steady or decreased, and maximum urinary excretion rates of 3-OHBaP was delayed compared to 1-OHP. These results were consistent with the sampling time previously proposed for 3-OHBaP analysis, the next morning after exposure. Apparent urinary half-life of 1-OHP and 3-OHBaP ranged from 12.0h to 18.2h and from 4.8h to 49.5h, respectively. Finally, inter-individual variability of 1-OHP half-life seemed linked with the cutaneous absorption extent during exposure, while calculation of 3-OHBaP half-life required the awareness of individual urinary background level. The toxicokinetic modeling described here is an efficient tool which could be used to describe elimination kinetic and determine diuresis correction way for any other urinary biomarkers of chemicals or metals exposure.

Geographic dimensions of a health network dedicated to occupational and work related diseases.

BACKGROUND: Although introduced nearly 40 years ago, Geographic Information Systems (GISs) have never been used to study Occupational Health information regarding the different types, scale or sources of data. The geographic distribution of occupational diseases and underlying work activities were always analyzed independently. Our aim was to consider the French Network of Occupational Disease (OD) clinics, namely the "French National OD Surveillance and Prevention Network" (rnv3p) as a spatial object in order to describe its catchment. METHODS: We mapped rnv3p observations at the workplace level. We initially analyzed rnv3p capture with reference to its own data, then to the underlying workforce (INSEE "Employment Areas"), and finally compared its capture of one emblematic occupational disease (mesothelioma) to an external dataset provided by a surveillance system thought to be exhaustive (PNSM). RESULTS: While the whole country is covered by the network, the density of observations decreases with increase in the distance from the 31 OD clinics (located within the main French cities). Taking into account the underlying workforce, we show that the probability to capture and investigation of OD (assessed by rates of OD per 10,000 workers) also presents large discrepancies between OD clinics. This capture rate might also show differences according to the disease, as exemplified by mesothelioma. CONCLUSION: The geographic approach to this network, enhanced by the possibilities provided by the GIS tool, allow a better understanding of the coverage of this network at a national level, as well as the visualization of capture rates for all OD clinics. Highlighting geographic and thematic shading zones bring new perspectives to the analysis of occupational health data, and should improve occupational health vigilance and surveillance.

Occupational exposure to polycyclic aromatic hydrocarbons: relations between atmospheric mixtures, urinary metabolites and sampling times.

PURPOSE: Occupational exposure to polycyclic aromatic hydrocarbons (PAHs) can be assessed by either air monitoring or biomonitoring using urinary 1-hydroxypyrene (1-OHP) or 3-hydroxybenzo(a)pyrene (3-OHBaP). The aim of this study was to understand the links between atmospheric PAHs and urinary metabolites, in order to improve the biomonitoring strategy for assessing carcinogenic risk. METHODS: Personal air sampling for pyrene and BaP measurements, and urines for 1-OHP and 3-OHBaP analyses of seven workers from electrode production plant were collected every day of the working week. RESULTS: High variability of atmospheric levels between activities and between days was observed, especially for gaseous pyrene. No correlation was found between urinary metabolites: 1-OHP maximum levels occurred for "electrode extrusion" activity; those of 3-OHBaP occurred for "raw materials dispatcher." Sixty percentage of 3-OHBaP maximum levels were observed in urines collected at the beginning of shift the last workday. Those of 1-OHP occurred at different sampling times, depending on the gaseous pyrene levels (not stopped by P3 respirators). Dermal absorption of PAHs was confirmed by significant effect of particulate pyrene on 1-OHP in the samples collected the morning of the following day (p < 0.02, n = 25). CONCLUSIONS: Lack of correlation between metabolites concentrations emphasizes the non-relevance of 1-OHP, from a non-carcinogenic gaseous and particulate compound, and the great interest of 3-OHBaP, from carcinogenic BaP. Its slower urinary elimination prevents the risk of exposure underestimation, and urinary analysis should be performed at the beginning of shift the end of working week, especially in case of high exposure variability.

Relevance of urinary 3-hydroxybenzo(a)pyrene and 1-hydroxypyrene to assess exposure to carcinogenic polycyclic aromatic hydrocarbon mixtures in metallurgy workers.

OBJECTIVES: In metallurgy, workers are exposed to mixtures of polycyclic aromatic hydrocarbons (PAHs) in which some compounds are carcinogenic. Biomonitoring of PAH exposure has been performed by measuring urinary 1-hydroxypyrene (1-OHP), a metabolite of pyrene which is not carcinogenic. This study investigated the use of 3-hydroxybenzo(a)pyrene (3-OHBaP), a metabolite of benzo(a)pyrene (BaP) which is the main carcinogenic component in PAHs, to improve carcinogen exposure assessment. METHODS: We included 129 metallurgy workers routinely exposed to PAHs during working hours. Urinary samples were collected at three sampling times at the beginning and at the end of the working week for 1-OHP and 3-OHBaP analyses. RESULTS: Workers in anode production showed greater exposure to both biomarkers than those in cathode or silicon production, with respectively, 71, 40, and 30% of 3-OHBaP concentrations exceeding the value of 0.4 nmol mol(-1) creatinine. No difference was observed between the 3-OHBaP levels found at the end of the penultimate workday shift and those at the beginning of the last workday shift. Within these plants, the 1-OHP/3-OHBaP ratios varied greatly according to the workers' activity and emission sources. Using linear regression between these two metabolites, the 1-OHP level corresponding to the guidance value for 3-OHBaP ranged from 0.7 to 2.4 µmol mol(-1) creatinine, depending on the industrial sector. CONCLUSIONS: This study emphasizes the interest of monitoring urinary 3-OHBaP at the end of the last workday shift when working week exposure is relatively steady, and the irrelevance of a single guideline value for 1-OHP when assessing occupational health risk.

Morphology of the Bony Labyrinth Supports the Affinities of Paradolichopithecus with the Papionina.

Discoveries in recent decades indicate that the large papionin monkeys Paradolipopithecus and Procynocephalus are key members of the Late Pliocene - Early Pleistocene mammalian faunas of Eurasia. However, their taxonomical status, phylogenetic relationships, and ecological profile remain unclear. Here we investigate the two latter aspects through the study of the inner ear anatomy, as revealed by applying micro-CT scan imaging techniques on the cranium LGPUT DFN3-150 of Paradolichopithecus from the lower Pleistocene (2.3 Ma) fossil site Dafnero-3 in Northwestern Greece. Using geometric morphometric methods, we quantified shape variation and the allometric and phylogenetic signals in extant cercopithecines (n = 80), and explored the morphological affinities of the fossil specimen with extant taxa. LGPUT DFN3-150 has a large centroid size similar to that of baboons and their relatives. It shares several shape features with Macacina and Cercopithecini, which we interpret as probable retention of a primitive morphology. Overall, its inner ear morphology is more consistent with a stem Papionini more closely related to Papionina than Macacina, or to a basal crown Papionina. Our results, along with morphometrical and ecological features from previous studies, call into question the traditional hypothesis of a Paradolichopithecus-Macacina clade, and provide alternative perspectives in the study of Eurasian primate evolution during the late Neogene-Quaternary. Supplementary Information: The online version contains supplementary material available at 10.1007/s10764-022-00329-4.

Small RNA-sequencing reveals the involvement of microRNA-132 in benzo[a]pyrene-induced toxicity in primary human blood cells.

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed environmental contaminants, triggering deleterious effects such as carcinogenicity and immunosuppression, and peripheral blood mononuclear cells (PBMCs) are among the main cell types targeted by these pollutants. In the present study, we sought to identify the expression profiles and function of miRNAs, gene regulators involved in major cellular processes recently linked to environmental pollutants, in PBMC-exposed to the prototypical PAH, benzo[a]pyrene (B[a]P). Using small RNA deep sequencing, we identified several B[a]P-responsive miRNAs. Bioinformatics analyses showed that their predicted targets could modulate biological processes relevant to cell death and survival. Further studies of the most highly induced miRNA, miR-132, showed that its up-regulation by B[a]P was time- and dose-dependent and required aryl hydrocarbon receptor (AhR) activation. By evaluating the role of miR-132 in B[a]P-induced cell death, we propose a mechanism linking B[a]P-induced miR-132 expression and cytochromes P-450 (CYPs) 1A1 and 1B1 mRNA levels, which could contribute to the apoptotic response of PBMCs. Altogether, this study increases our understanding of the roles of miRNAs induced by B[a]P and provides the basis for further investigations into the mechanisms of gene expression regulation by PAHs.

Modelling occupational inhalation exposure to concentration peaks of chemicals and associated health risk assessment.

OBJECTIVES: The aims of this study were to estimate inhalation exposure to chemicals and the resulting acute health risks for working scenarios characterized by successive peaks of pollutant concentrations. METHODS: A stochastic two-zone model combining a time-varying emission function and field-derived probabilistic distributed input parameter was used to predict both instantaneous and 15-min averaged pollutant concentrations during the decanting operations performed in a pathology laboratory. The location of the workers was taken into account in the model for computing probability distributions of inhalation exposures and for subsequently characterizing hazard quotients (HQ) for health risk purposes. The model was assessed by comparison with repeated individual monitoring performed on the workers during the same tasks. RESULTS: Modelled inhalation exposure profiles revealed 15-min average concentrations of 1.7 and 208 mg m(-) (3) for formaldehyde (FA) and toluene (TOL), respectively. The individual monitoring performed showed similar average concentrations, with 1.2 and 175 mg m(-) (3) for FA and TOL. No more than three to five successive FA concentration peaks were generally sufficient in the modelling exercise to provide 15-min estimated exposures exceeding short-term exposure limits (STEL). Modelled HQ higher than unity and STEL exceedance probabilities higher than 0.5 were found for FA, whereas estimated TOL health risks were notably lower according to high exposure limits. Estimated inhalation exposure distributions frequently ranged over one order of magnitude for the two pollutants, reflecting both the natural exposure variability and the uncertainty of some of the two-zone model input parameters. CONCLUSIONS: These findings indicate that the developed approach may be useful for modelling occupational exposures and acute health risks related to chemicals in situations involving time-varying emission sources. Modelled exposure distributions may also be used within Bayesian decision analysis frameworks for making exposure judgements and refining risk management measures.

Highly sensitive routine method for urinary 3-hydroxybenzo[a]pyrene quantitation using liquid chromatography-fluorescence detection and automated off-line solid phase extraction.

Many workers and also the general population are exposed to polycyclic aromatic hydrocarbons (PAHs), and benzo[a]pyrene (BaP) was recently classified as carcinogenic for humans (group 1) by the International Agency for Research on Cancer. Biomonitoring of PAHs exposure is usually performed by urinary 1-hydroxypyrene (1-OHP) analysis. 1-OHP is a metabolite of pyrene, a non-carcinogenic PAH. In this work, we developed a very simple but highly sensitive analytical method of quantifying one urinary metabolite of BaP, 3-hydroxybenzo[a]pyrene (3-OHBaP), to evaluate carcinogenic PAHs exposure. After hydrolysis of 10 mL urine for two hours and concentration by automated off-line solid phase extraction, the sample was injected in a column-switching high-performance liquid chromatography fluorescence detection system. The limit of quantification was 0.2 pmol L(-1) (0.05 ng L(-1)) and the limit of detection was estimated at 0.07 pmol L(-1) (0.02 ng L(-1)). Linearity was established for 3-OHBaP concentrations ranging from 0.4 to 74.5 pmol L(-1) (0.1 to 20 ng L(-1)). Relative within-day standard deviation was less than 3% and relative between-day standard deviation was less than 4%. In non-occupationally exposed subjects, median concentrations for smokers compared with non-smokers were 3.5 times higher for 1-OHP (p<0.001) and 2 times higher for 3-OHBaP (p<0.05). The two urinary biomarkers were correlated in smokers (ρ=0.636; p<0.05; n=10) but not in non-smokers (ρ=0.09; p>0.05; n=21).