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.

Analytical performance specifications for trace elements in biological fluids derived from six countries federated external quality assessment schemes over 10 years.

OBJECTIVES: This article defines analytical performance specifications (APS) for evaluating laboratory proficiency through an external quality assessment scheme. METHODS: Standard deviations for proficiency assessment were derived from Thompson's characteristic function applied to robust data calculated from participants' submissions in the Occupational and Environmental Laboratory Medicine (OELM) external quality assurance scheme for trace elements in serum, whole blood and urine. Characteristic function was based on two parameters: (1) ß - the average coefficient of variation (CV) at high sample concentrations; (2) α - the average standard deviation (SD) at low sample concentrations. APSs were defined as 1.65 standard deviations calculated by Thompson's approach. Comparison between OELM robust data and characteristic function were used to validate the model. RESULTS: Application of the characteristic function allowed calculated APS for 18 elements across three matrices. Some limitations were noted, particularly for elements (1) with no sample concentrations near analytical technique limit of detection; (2) exhibiting high robust CV at high concentration; (3) exhibiting high analytical variability such as whole blood Tl and urine Pb; (4) with an unbalanced number of robust SD above and under the characteristic function such as whole blood Mn and serum Al and Zn. CONCLUSIONS: The characteristic function was a useful means of deriving APS for trace elements in biological fluids where biological variation data or outcome studies were not available. However, OELM external quality assurance scheme data suggests that the characteristic functions are not appropriate for all elements.

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.

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.

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 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.

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.

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.

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.

Influence of environmental and dietary exposures on metals accumulation among the residents of a major industrial harbour (Fos-sur-Mer, France).

OBJECTIVES: We sought to determine whether the residents living closer to the core industrial zone (Fos-sur-Mer) had higher trace metals blood and urinary levels than residents who lived further away (Saint-Martin-de-Crau). MATERIALS AND METHODS: As part of The INDEX study, we measured the following trace metals into blood and urine samples of 138 participants (80 in the core industrial zone and 58 in the reference area): Antimony, Arsenic, Cadmium, Chromium, Cobalt, Mercury, Nickel, Lead and Vanadium. Participants were recruited using a stratified random sampling method and had to meet the following inclusion criteria: 30-65 years old, living in the area since at least 3 years, not working in the industrial sector, non-smoker. We used single-pollutant multivariate linear regression models, using substitution when censored data were under 15 % and Tobit models alternatively, adjusting for personal physiological, social, dietary, housing characteristics and leisure activities. We also measured these trace metals in samples of lichens (Xanthoria parietina) and atmospheric particles (PM2.5). RESULTS: We showed higher lichen and air levels of several metals (Cd, Cr, Co, Ni and Pb) in the exposed area. Living close to the core industrial zone was significantly associated with an increase in blood levels of lead (adjusted geometric mean = 17.2 [15.8-18.7] vs 15.1 [13.7-16.7] µg.L-1, p < 0.05). We report significant increase of some metals urinary levels among residents of the industrial port zone, as the result of the use of the environment, itself contaminated by industrial activities: dietary history of self-consumption of vegetables (Cadmium), eggs and poultries (Vanadium). However, Vanadium levels were greater among self-consumers of poultry in the reference area and gardeners had circulatory levels of Lead greater than non-gardeners only in the reference area. Consumption of non-local sea-products increased the level of Cadmium. CONCLUSIONS: These results brought interesting clues, in complement to national programs, regarding the exposure to trace metals of residents living in a major industrial harbor.

Modelling the time profiles of organic solvent concentrations for occupational exposure assessment purposes.

OBJECTIVES: Confronted by variable exposure scenarios characterized by intermittent concentration peaks, our study aimed to develop methods and determine mathematical functions reproducing organic solvent concentration profiles in order to assess health risks. METHODS: Two similar repetitive decanting tasks using either formalin or toluene (TOL) were studied at a teaching hospital pathology laboratory. Real-time air monitoring performed in the immediate vicinity of pollutant sources over a 1-year period identified intermittent concentration peaks. In order to describe these specific exposure profiles, two different methods were used. In a first descriptive approach, concentration peaks were either assimilated to an equivalent series of rectangle functions or described by a mathematical bell-shaped function. As an alternative approach, a model based on the schedule of decanting tasks was constructed. To this end, a time-varying emission function was incorporated into three deterministic exposure models of increasing complexity (well-mixed room, two-zone, spherical turbulent diffusion) and field-derived emission parameters were estimated by fitting model outputs to measured concentration profiles. RESULTS: Real-time measurements revealed highly variable concentration profiles, consisting of 1-8 peaks ranging from 5 to 220 s per decanting task, and average concentrations within peaks varying over 1-2 orders of magnitude. Acceptable fits were obtained by both descriptive approaches. The tested emission function seemed relevant in reproducing intermittent pollutant releases. Only advanced models (two-zone and diffusion) gave satisfying fits within assigned input parameter ranges. Average emission rate estimates varied in the range 10-47 mg min(-1) for formaldehyde and 360-1780 mg min(-1) for TOL, depending on the model tested. CONCLUSIONS: Both descriptive approaches and deterministic models accurately reproduced the patterns of measured concentration peaks. However, only deterministic models provided an understanding of the relations between pollutant releases, air movements, and the resulting concentrations and may thus be recommended for exposure variability assessment purposes.

Towards a recommended biomonitoring strategy for assessing the occupational exposure of roofers to PAHs.

The aims of this work were to assess the PAH exposure among roofers and to identify relevant biomarkers for monitoring occupational exposure. Several campaigns were conducted between 2004 and 2017, with 28 individual air samples and 240 urinary samples collected from 73 roofers. Seventeen parent PAHs and 14 urinary biomarkers, metabolites of pyrene (1-OHP), benzo(a)pyrene (3-OHBaP and TetraolBaP), naphthalene (1- and 2-naphtols), fluorene (1- 2- 3- 9-fluorenols) and phenanthrene (1- 2- 3- 4- 9-phenanthrols), were analysed. Three exposure groups were considered: soft-applied roofing using polymer-modified bitumen ("PMB"), hot-applied roofing using oxidized bitumen ("OB") and the tearing off of old roof coatings containing coal tar ("CT"). The PAHs containing 2-3 rings were much more abundant, and the highest airborne levels were observed in the "CT" group. The biomonitoring results were consistent with these results, with a large predominance of 2-3 ring PAH metabolites. 1-OHP, 3-fluorenol and 2-phenanthrol were better correlated with airborne levels and less influenced by smoking than the other metabolites. Conversely, 1-/2-naphtol levels were heavily influenced by smoking and not correlated with airborne naphthalene levels. Moreover, 3-OHBaP and TetraolBaP levels were very low when applying bitumen membranes, and much higher exposures were observed during tear-off activities. In this context, the recommended strategy for roofer biomonitoring should include 1-OHP, fluorenols and phenanthrols, as well as carcinogenic BaP metabolites (3-OHBaP or TetraolBaP) when evaluating the occupational exposure of roofers that are tearing off old roof coatings.

Lung cancer risk assessment for workers exposed to polycyclic aromatic hydrocarbons in various industries.

BACKGROUND: Millions of workers are exposed to carcinogenic polycyclic aromatic hydrocarbon (PAH) mixtures. The toxicity of PAH mixtures is variable and depends on the composition of the mixture, which is related to the emission sources. Although several indicators exist, the cancer risk estimation associated with occupational exposure to PAHs is poorly known. OBJECTIVES: To assess the risk of lung cancer associated with PAHs in several industries using the atmospheric concentrations of benzo[a]pyrene (BaP) as a proxy. METHODS: A total of 93 exposure groups belonging to 9 industries were investigated. Eight indicators found in the literature were compared to assess risks. A consensual indicator was used to estimate lung cancer risks. RESULTS: Approximately 30% of the exposure groups were above the maximal risk level of the European Union (10-4). The risk probabilities were >10-3 for coke and silicon production; >10-4 for the manufacturing of carbon products and aluminum production; >10-5 for foundries and combustion processes; >10-6 for the use of lubricating oils and engine exhaust emissions; and >10-7 for bitumen. The risk probabilities were highly variable within industries (from 1 to 1000 likelihood). A total of 27 (95% CI: 0.1-54) contemporary additional lung cancer cases could be expected per year in the French exposed population based on estimations using published data. CONCLUSION: This study provides an overview of cancer risk estimation in many industries. Despite efforts and changes that had been made to decrease risks, PAHs remain a sanitary threat for people exposed to these pollutants in occupational environments.

Urinary trans-anti-7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene as the most relevant biomarker for assessing carcinogenic polycyclic aromatic hydrocarbons exposure.

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous pollutants present as complex mixtures in the environment. Among them, benzo(a)pyrene (BaP) is classified as carcinogenic to humans by the International Agency of Research on Cancer. Taking into account all absorption ways, human biomonitoring allows PAH exposure assessment, but biomarkers both specific to carcinogenic effect and sufficiently sensitive are lacking. In this work, we proposed the urinary 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene (7,8,9,10-OHBaP) stemming from hydrolysis of BaP-7,8-diol-9,10-epoxide, the ultimate carcinogenic BaP metabolite, as biomarker of PAH exposure. A simple and highly sensitive analytical method, with a limit of quantification (LQ) reaching 0.06pmol/L (0.02ng/L), was described and validated. The relevance of urinary 7,8,9,10-OHBaP concentrations adjustment by creatinine was demonstrated. In a group of 24 non-occupationally PAH exposed subjects, only 15% of 7,8,9,10-OHBaP levels was below the LQ and the last daily void has been found as the best sampling time. Tobacco consumption had a significant positive effect on 7,8,9,10-OHBaP concentrations with a 90e percentile equal to 0.05nmole/mole creatinine (nmol/mol) and 0.03nmol/mol for smokers and non-smokers, respectively. In case of occupational PAH exposure, all the pre- and post-shift urinary 7,8,9,10-OHBaP levels of 7 non-smoking workers in a prebaked electrodes production plant were above the LQ. Concentrations ranged from 0.05 to 0.91nmol/mol and accumulation of 7,8,9,10-OHBaP into organism of workers during the working week was clearly observed. The best sampling time was the post-shift at the end of week but samples should also be collected at pre-shift the beginning of week to assess the background level. Finally, the urinary 7,8,9,10-OHBaP elimination kinetic through the weekend was studied using non-linear mixed effect modelling. Mean apparent urinary half-life was 31.5h with low inter-individual variability. Describing key characteristics of urinary 7,8,9,10-OHBaP as PAH exposure biomarker, this work should promote its use for future large-scale biomonitoring campaigns.

Biomonitoring of styrene occupational exposures: Biomarkers and determinants.

INTRODUCTION: High styrene exposures are still experienced in various occupational settings, requesting regular exposure assessments. The aims of this study were to study occupational exposures in various industrial sectors and to determine factors influencing styrene urinary metabolites levels. METHODS: Biomonitoring was conducted in 141 workers from fiberglass-reinforced plastic (FRP) manufacture, thermoplastic polymers production, vehicle repair shops and cured-in-place pipe lining (CIPP). Urinary styrene (StyU) as well as Mandelic (MA) / Phenyglyoxylic Acids (PGA) were quantified at the beginning and at the end of week, and multivariate linear regression models were used. RESULTS: StyU levels revealed very low, rarely exceeding 3 µg.L-1. Highest concentrations of MA + PGA were observed in FRP sector, with levels reaching up to 1100 mg.g-1 of creatinine. Factors influencing end-of-week MA + PGA concentrations were levels at the beginning of week, open molding processes, proximity to the emission source, respiratory protection, styrene content in raw materials. Elevated levels were also observed during CIPP process, whereas thermoplastic injection and vehicle repair shop workers exhibited much lower exposures. CONCLUSIONS: Intervention on process (decreasing styrene proportion, using closed molding), protective equipment (local exhaust ventilation, respiratory protection) and individual practices (stringent safety rules) are expected to decrease occupational exposures. Urinary MA + PGA remain the most appropriate biomarkers for occupational biomonitoring.

Exporisq-HAP database: 20 years of monitoring French occupational exposure to polycyclic aromatic hydrocarbon mixtures and identification of exposure determinants.

BACKGROUND: Millions of workers are exposed to polycyclic aromatic hydrocarbons (PAHs), a well-known family of carcinogens, but occupational exposure data about PAH mixture compositions are scarce. OBJECTIVES: To provide a detailed picture of airborne PAH exposures encountered in the French industrial landscape over the previous 20 years and to identify determinants driving exposures. METHODS: Results from 1643 airborne samples of 16 gaseous and particulate PAHs implemented into the Exporisq HAP database from 1995 to 2014 were used to describe exposure levels and aerosol chemical composition in many industries and activities. Compliance of benzo[a]pyrene (BaP) levels with several existing occupational exposure limits for long-term exposure was assessed. RESULTS: BaP levels were lower than those reported in the literature, but the level and composition of PAH mixtures were highly variable between and within industries. Numerous exposure determinants (e.g., product composition, type and temperature of process, ventilation and confinement) were assumed to explain these differences. The highest levels were found in industries using products derived from coal (aluminum, silicon, and coke production, manufacturing of carbon products and foundries), with mean BaP levels up to 23 times higher than the French recommended value of 150 ng/m3. Forty-seven percent of the occupational activities exceeded this value. Conversely, exposures resulting from petroleum-derived products were relatively low. CONCLUSIONS: As health effects depend on PAH levels but also on the composition of the mixture, exposure assessments must characterize the entire mixtures and record specific determinants to define homogeneous exposure groups and to accurately assess health risks.

Modeling the exposure functions of atmospheric polycyclic aromatic hydrocarbon mixtures in occupational environments.

BACKGROUND: The health risk assessment associated with polycyclic aromatic hydrocarbon (PAH) mixtures faces three main issues: the lack of knowledge regarding occupational exposure mixtures, the accurate chemical characterization and the estimation of cancer risks. OBJECTIVES: To describe industries in which PAH exposures are encountered and construct working context-exposure function matrices, to enable the estimation of both the PAH expected exposure level and chemical characteristic profile of workers based on their occupational sector and activity. METHODS: Overall, 1729 PAH samplings from the Exporisq-HAP database (E-HAP) were used. An approach was developed to (i) organize E-HAP in terms of the most detailed unit of description of a job and (ii) structure and subdivide the organized E-HAP into groups of detailed industry units, with each group described by the distribution of concentrations of gaseous and particulate PAHs, which would result in working context-exposure function matrices. PAH exposures were described using two scales: phase (total particulate and gaseous PAH distribution concentrations) and congener (16 congener PAH distribution concentrations). RESULTS: Nine industrial sectors were organized according to the exposure durations, short-term, mid-term and long-term into 5, 36 and 47 detailed industry units, which were structured, respectively, into 2, 4, and 7 groups for the phase scale and 2, 3, and 6 groups for the congener scale, corresponding to as much distinct distribution of concentrations of several PAHs. For the congener scale, which included groups that used products derived from coal, the correlations between the PAHs were strong; for groups that used products derived from petroleum, all PAHs in the mixtures were poorly correlated with each other. CONCLUSIONS: The current findings provide insights into both the PAH emissions generated by various industrial processes and their associated occupational exposures and may be further used to develop risk assessment analyses of cancers associated with PAH mixtures.