Renaud Persoons

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.

Determinants of occupational exposure to metals by gas metal arc welding and risk management measures: A biomonitoring study

Welding fumes contain various toxic metals including chromium (Cr), nickel (Ni) and manganese (Mn). An assessment of the risk to health of local and systemic exposure to welding fumes requires the assessment of both external and internal doses. The aims of this study were to test the relevance in small and medium sized enterprises of a biomonitoring strategy based on urine spot-samples, to characterize the factors influencing the internal doses of metals in gas metal arc welders and to recommend effective risk management measures. 137 welders were recruited and urinary levels of metals were measured by ICP-MS on post-shift samples collected at the end of the working week. Cr, Ni and Mn mean concentrations (respectively 0.43, 1.69 and 0.27 μg/g creatinine) were well below occupational health guidance values, but still higher than background levels observed in the general population, confirming the absorption of metals generated in welding fumes. Both welding parameters (nature of base metal, welding technique) and working conditions (confinement, welding and grinding durations, mechanical ventilation and welding experience) were predictive of occupational exposure. Our results confirm the interest of biomonitoring for assessing health risks and recommending risk management measures for welders.

Développement d’une nouvelle méthode d’évaluation des risques chimiques : application dans les laboratoires hospitaliers

Resume Objectif Le contexte reglementaire concernant les risques chimiques et la necessite de prevention de leurs effets sur la sante ont conduit le CHU de Grenoble a mettre en place une demarche d’evaluation des risques toxiques professionnels, en s’interessant dans un premier temps aux laboratoires de biologie. Methode Apres avoir identifie et caracterise les dangers a partir des phrases de risques contenues dans les fiches de donnees de securite des produits commerciaux, un algorithme de hierarchisation des dangers est cree. Seuls les produits les plus dangereux beneficient d’une evaluation de l’exposition par des observations de terrain. A partir du calcul des indices de risques sont identifiees les situations inacceptables. Resultats Pour chaque produit manipule sont definis 9 types de danger : effets locaux respiratoires, cutanes et oculaires, effets systemiques par absorption respiratoire, cutanee ou orale, effets cancerogenes, mutagenes et reprotoxiques. A chaque classe sont affectes 3 niveaux de danger : peu dangereux, dangereux, tres dangereux, les agents CMR etant toujours classes 2 ou 3. Pour les produits dangereux et tres dangereux sont calcules un indice d’exposition (frequence d’utilisation et quantite de produit manipule) et des indices de protection (respiratoire, cutanee et oculaire), chaque variable ayant 3 niveaux croissants ; 11 indices de risques sont calcules a partir du danger, de l’exposition et de la protection. Conclusion L’interet du calcul d’indices de risques reside dans sa possible automatisation. Bien que cette methode necessite un travail important de recueil des donnees, elle apporte des elements precis quant aux programmes d’action.

Constructing a Database of Similar Exposure Groups: The Application of the Exporisq-HAP Database from 1995 to 2015

Background Similar exposure groups (SEGs) are needed to reliably assess occupational exposures and health risks. However, the construction of SEGs can turn out to be rather challenging because of the multifactorial variability of exposures. Objectives The objective of this study is to put forward a semi-empirical approach developed to construct and implement a SEG database for exposure assessments. An occupational database of airborne levels of polycyclic aromatic hydrocarbons (PAHs) was used as an illustrative and working example. Methods The approach that was developed consisted of four steps. The first three steps addressed the construction and implementation of the occupational Exporisq-HAP database (E-HAP). E-HAP was structured into three hierarchical levels of exposure groups, each of which was based on exposure determinants, along 16 dimensions that represented the sampled PAHs. A fourth step was implemented to identify and generate SEGs using the geometric standard deviation (GSD) of PAH concentrations. Results E-HAP was restructured into 16 (for 16 sampled PAHs) 3 × 3 matrices: three hierarchical levels of description versus three degrees of dispersion, which included low (the SEG database: GSD ≤ 3), medium (3 < GSD ≤ 6), and high (GSD > 6). Benzo[a]pyrene (BaP) was the least dispersed particulate PAH with 41.5% of groups that could be considered as SEGs, 48.5% of groups of medium dispersion, and only 8% with high dispersion. These results were comparable for BaP, BaP equivalent toxic, or the sum of all carcinogenic PAHs but were different when individual gaseous PAHs or ∑PAHG were chosen. Conclusion Within the framework of risk assessment, such an approach, based on groundwork studies, allows for both the construction of an SEG database and the identification of exposure groups that require improvements in either the description level or the homogeneity degree toward SEG.

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.

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.

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.

Comparison of gaseous polycyclic aromatic hydrocarbon metabolites according to their specificity as biomarkers of occupational exposure: Selection of 2-hydroxyfluorene and 2-hydroxyphenanthrene

Exposure to Polycyclic Aromatic Hydrocarbons (PAHs) occurs by respiratory, digestive and dermal absorption. Biomonitoring takes all pathways into account but sensitive and specific biomarkers are required. Different gaseous PAHs metabolites were used due to their abundance in the atmospheric mixtures but none of them were selected as better biomarker than the others. To identify the best candidates for assessing occupational airborne exposure, relation between atmospheric levels of Naphtalene, Fluorene and Phenanthrene and urinary metabolites concentrations was studied in a carbon electrode workers group. Linear mixed effects models were built to select explanatory variables and estimate variance component. Urinary creatinine was a predictor of metabolites levels confirming the importance of diuresis for interpreting results. High significance of pre-shift sampling time combined with positive coefficients of post-shift indicated that urine should be sampled at the end of the workday in association with pre-shift urine to avoid misinterpretations. Among the 10 metabolites studied, urinary 2-hydroxyfluorene and 2-hydroxyphenanthrene showed the highest increase of variance explained by models after inclusion of individual atmospheric levels as explanatory variable. Priority could be given to 2-hydroxyfluorene due to higher excretion levels than 2-hydroxyphenanthrene.

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.