Battery-recycling can expose workers to several metals. This study aims to investigate this multiple exposure, by exploring the potential of effect biomarkers to improve risk assessment for workers, and by calculating a hazard index (HI) to assess the risk of cumulative exposure. Urine samples from 86 workers in three French recycling plants were analysed for metal biomarkers (Cd, Co, Cr, Li, Mn, Ni), kidney-injury biomarkers (α1-microglubulin, retinol binding protein, kidney injury molecule-1, N-acetyl-β-D-gluocosaminidase, albumin, total proteins), and oxidative-stress biomarkers (8-hydroxydeoxyguanosine, malondialdehyde). Kidney-injury biomarker levels successfully differentiated exposed recyclers from administrative workers, while oxidative-stress biomarker levels did not allow this differentiation. The calculation of a HI proved effective in detecting the risk associated with multiple metal exposure, offering a better risk assessment than when considering metals individually. This dual approach, combining HI calculation and analyzing kidney-injury biomarkers, should be strongly considered in the risk assessment of workers exposed to multiple metals.

A method for the analysis of essential metals (Fe, Cu, Mg, and Zn) and non-metals (P, S) in single red blood cells was developed by single cell (SC)-ICP-MS. The use of a triple quadrupole configuration (MS/MS) enabled an effective elimination of polyatomic interferences, which affect the accuracy of ICP-MS analysis using a single quadrupole mass analyzer. Fixation with glutaraldehyde for at least 90 days was developed to improve the quantification of elements in a single red blood cell. The experimental conditions were optimized while special attention was paid to the residence time of analytes in the plasma. Addition of a surfactant (0.05% (v/v) Tween80®) improved quantification of elements in fixed red blood cells. The detection limits obtained by SC-ICP-MS/MS were lower than for ICP-MS, especially for S and P (3 fg and 1.7 fg. cell-1 instead of 163 and 6.3 fg. cell-1, respectively).

In battery-recycling facilities, exposure to trace elements may occur through inhalation of contaminated dust or vapor emanating from the treatment processes. Exposure of battery-recycling workers to lead has been quite well covered in the literature. In contrast, we lack data on exposure to other elements contained in batteries. The aim of this study was to characterize the exposure of French battery recyclers to multiple elements using biomonitoring and airborne measurements. Eighty-six workers participated in the study. Inhalable metal concentrations were determined for personal airborne samples, and total exposure was determined from pre-shift and post-shift urine samples collected during the working week. In both types of sample, a total of 33 trace elements were measured using inductively coupled plasma mass spectrometry. Results showed battery recyclers to be mostly exposed to Cd, Co, Cr, Li, Mn, Ni, and Pb. Administrative and sorting workers were exposed at lower levels than maintenance, treatment, and dismantling workers. Cd, Co, Li, Mn, and Ni were detected at high levels in air samples, especially near the treatment facilities, with airborne cadmium levels of up to 79.4 mu g/m3. Urinary sample analysis indicated exposure to Cd and Co, with levels measured at up to 27.6 and 3.34 mu g/g of creatinine, respectively. Concentrations were compared to data reported for e-waste recycling companies. The data presented provide valuable information on exposure to trace elements for workers involved in battery-recycling. They also highlight the need to improve both collective and individual protective measures, which were not sufficient in the participating companies.

A physiologically based pharmacokinetic (PBPK) model with five tissue groups (lung, liver, fat, richly perfused, and poorly perfused tissues plus venous and arterial blood compartments) has been developed from in vitro data and models of primary cell cultures for naphthalene toxicity in mice and rats. It extends a previous naphthalene PBPK model (Sweeney et al., 1996) and demonstrates a possible approach to a predictive mathematical model that requires minimal animal data. Naphthalene metabolism was examined after four exposure routes (intraperitoneal injection (ip), intravenous injection (iv), ingestion (po), and inhalation). Naphthalene and its primary metabolite, naphthalene oxide, are consumed by enzymes in pulmonary and hepatic tissues (cytochrome P450 monooxygenases, epoxide hydrolase, and glutathione-S-transferase). Additionally, the nonenzymatic reactions of naphthalene oxide in all tissues and in blood are included in the model. Kinetic constants for the model were derived primarily from cell fraction and primary cell culture incubations presented in the literature. The mouse model accurately predicts glutathione (GSH) and covalent naphthalene oxide-protein binding levels after a range of ip doses, and the rat model provides excellent estimates for mercapturate excretion following po doses; but neither model simulates well naphthalene blood concentrations after low iv doses. Good prediction of in vivo response using only in vitro data for parameter estimation (except for epoxide-protein binding rates) suggests that the assumed molecular description is a plausible representation of the underlying mechanisms of toxicity. Mice and rats show significant species differences in response to naphthalene. The model results suggest that species differences in toxicity may be explained, in part, by the lower overall rate of enzyme activities in the rat cells. Lower enzyme activities in the rat result in out-of-phase GSH minima in hepatic and lung compartments, while the simultaneous occurrence of these minima in mice results in higher naphthalene oxide concentrations, thereby allowing formation of more metabolites (e.g., covalent binding to proteins) that may be toxic.

BACKGROUND:Hyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced over the last decade for the treatment of peritoneal carcinomatosis. In this procedure, heated cytotoxic drugs are administered directly into the abdominal cavity, ensuring cancer cells to be exposed while reducing systemic toxicity. More recently, pressurized intraperitoneal aerosol chemotherapy (PIPAC), where the chemotherapeutic drug is injected into the peritoneal cavity as an aerosol under pressure, has been proposed to patients in palliative situation, as a new approach. The amount of drug used is up to 10 fold lower than in HIPEC. The use of cytotoxic drugs poses an occupational risk for the operating room personnel. This study investigated the potential exposure of the medical staff by biomonitoring and surface contamination measurements, during a HIPEC procedure and a PIPAC procedure. METHOD:Wipe samples were collected from various locations in operating rooms including gloves, hands, devices and floor. Urines samples were collected from 10 volunteers of the medical staff and from a control group. The platinum analysis was performed by inductively coupled plasma mass spectrometry. RESULTS:Significant contaminations were observed on the floor, gloves, shoes and devices. However, urinary platinum was below the limit of quantification (<10 ng/L) for more than 50% of samples from the healthcare workers performing HIPEC and PIPAC. Concentrations did not differ significantly from those reported for the control group. CONCLUSION:There appears to be little risk of exposure to platinum drugs during HIPEC and PIPAC providing the adequate safety measures are implemented.

La projection thermique est un procédé au cours duquel un revêtement est appliqué à haute température et à grande vitesse sur un objet métallique pour en augmenter sa résistance à la corrosion et pour en améliorer sa conductivité. Plusieurs procédés existent parmi lesquels le flamme-fil, le flamme-poudre, l’arc électrique, l’High Velocity Oxy-Fuel (HVOF) et le plasma. L’étude repose sur l’hypothèse que les salariés métalliseurs seraient exposés de manière différente en fonction des procédés mis en œuvre. Dans cette étude, nous avons caractérisé les émissions et évalué les niveaux d’expositions au chrome (Cr) et au nickel (Ni) à différents postes de projection thermique afin de proposer une stratégie de surveillance biologique utilisable par les services de santé au travail. Six campagnes de prélèvements en entreprise ont été effectuées : des prélèvements atmosphériques individuels et d’ambiance auxquels ont été associés des recueils urinaires de 29 volontaires dont 14 métalliseurs. Les métalliseurs projetant de l’oxyde de Cr par plasma sont exposés à du Cr hexavalent (Cr VI), certaines concentrations étant supérieures à la VLEP-8 h de 1 μg/m3. L’évolution de la chromurie est relativement faible, inférieure à 2 μg/g créatinine, ce qui reste très éloigné de la valeur américaine appliquée aux soudeurs (25 μg/g créatinine) mais proche de la valeur de 1,8 μg/g créatinine proposée par l’ANSES pour le secteur du chromage. Les niveaux d’excrétion de Ni urinaire chez les métalliseurs, tous procédés confondus, sont relativement élevés par rapport à ceux des opérateurs non-exposés, les dernières valeurs étant proches de celles de la population générale (11 μg/g créatinine et 3,8 μg/g créatinine respectivement). Les niveaux d’excrétion urinaire de Cr et Ni mesurés sur le terrain attestent d’une exposition professionnelle des métalliseurs aux aérosols émis lors de l’utilisation des procédés de projection thermique et rappellent l’importance du port d’équipements de protection individuelle adaptés à l’activité. Une analyse statistique descriptive par procédés a montré que le procédé flamme-fil est le plus exposant. Ces premiers résultats seront complétés par des mesures dans d’autres entreprises utilisant des procédés identiques.

Many employees in the aluminum industry are exposed to a range of aluminum compounds by inhalation, and the presence of ultrafine particles in the workplace has become a concern to occupational health professionals. Some metal salts and metal oxides have been shown to enter the brain through the olfactory route, bypassing the blood-brain barrier, but few studies have examined whether aluminum compounds also use this pathway. In this context, we sought to determine whether aluminum was found in rat olfactory bulbs and whether its transfer depended on physicochemical characteristics such as solubility and granulometry. Aluminum salts (chloride and fluoride) and various nanometric aluminum oxides (13nm, 20nm and 40-50nm) were administered to rats by intranasal instillation through one nostril (10μg Al/30μL for 10days). Olfactory bulbs (ipsilateral and contralateral relative to instilled nostril) were harvested and the aluminum content was determined by graphite furnace atomic absorption spectrometry after tissue mineralization. Some transfer of aluminum salts to the central nervous system via the olfactory route was observed, with the more soluble aluminum chloride being transferred at higher levels than aluminum fluoride. No cerebral translocation of any of the aluminas studied was detected.

This paper presents a life history-oriented modeling framework to investigate residential location decisions as a two-tier process of location search and location choice. In the first tier, a stress-based location search model is developed by assuming that households search for a new location due to continual stress at different life-domains. The search model adopts a fuzzy logic-based modeling method that mimics the inter-dependencies between push and pull factors. In the second tier, a location choice model is developed that accommodates how location decisions interact with life-cycle events at different life-domains. The model utilizes a latent segmentation-based logit modeling technique to address the panel effect of the households’ housing career. The model results suggest that households in general show preference for larger lots, and locations closer to work place, transit stop, and health service. Location choice is found to be significantly influenced by the life-cycle events as well as the lead and lagged effects. For example, the birth of a child magnifies the need of larger lots. The life-history effects, however vary across two segments. Suburbanite households in segment two prefer larger lots following a job change; whereas, urbanite households in segment one show a negative relationship. The adjustment period for a job change is longer than that of addition of a new job. A longer adjustment time is also found in the case of the first time vehicle purchase than acquisition of a vehicle. Presence of children influences suburbanite households to reside closer to work place. Urbanite households with children prefer to live closer to school.

Chromium(VI) compounds are classified as carcinogenic to humans. Whereas chromium measurements in urine and whole blood (i.e., including plasma) are indicative of recent exposure, chromium in red blood cells (RBC) is attributable specifically to Cr(VI) exposure. Before recommending Cr in RBC as a biological indicator of Cr(VI) exposure, in-vitro studies must be undertaken to assess its reliability. The present study examines the relationship between the chromium added to a blood sample and that subsequently found in the RBC. After incubation of total blood with chromium, RBC were isolated, counted and their viability assessed. Direct analysis of chromium in RBC was conducted using Atomic Absorption Spectrometry. Hexavalent, but not trivalent Cr, was seen to accumulate in the RBC and we found a strong correlation between the Cr(VI) concentration added to a blood sample and the amount of Cr in RBC. This relationship appears to be independent of the chemical properties of the human blood samples (e.g., different blood donors or different reducing capacities). Even though in-vivo studies are still needed to integrate our understanding of Cr(VI) toxicokinetics, our findings reinforce the idea that a single determination of the chromium concentration in RBC would enable biomonitoring of critical cases of Cr(VI) exposure.

La projection thermique est un procédé au cours duquel un revêtement est appliqué à haute température et grande vitesse sur un objet pour améliorer ses propriétés de surface. Les procédés existants de projection thermique se distinguent par le système de fusion du matériau à projeter. Cette différence influence directement la quantité d’aérosols produits et leur distribution granulométrique (production de particules ultrafines pour les systèmes haute température), et donc leur toxicité. La protection des opérateurs nécessite une évaluation d’exposition atmosphérique et biologique adaptée à ces particularités. Une étude a donc été initiée par le laboratoire Biométrologie du département Toxicologie et Biométrologie de l’INRS et planifiée sur 5 ans à compter de juillet 2016. Les objectifs de cette étude consistent à évaluer les expositions professionnelles au chrome (Cr) et au nickel (Ni) lors des opérations de projection thermique et de soudage, et à proposer une stratégie de surveillance biologique utilisable par la médecine du travail. L’activité de soudage est suivie afin de comparer l’imprégnation biologique des soudeurs et des métalliseurs à exposition quantitative égale. L’intérêt de l’alliage Ni-Cr réside dans le fait qu’il est transversal aux différents procédés existants. De plus, en termes de prévention, le Cr reste un élément d’intérêt notamment à cause de la présence de Cr VI, forme cancérogène du Cr. La campagne d’évaluation des expositions en entreprise reposera sur des mesures atmosphériques, des dosages urinaires de biomarqueurs d’exposition, mais également des biomarqueurs urinaires d’effets précoces d’atteinte rénale tels que la beta-2-microglobuline (β2 M), la N-acétylglucoaminidase (NAG) et la Kidney Injury Molecule 1 (KIM-1) et du stress oxydant comme la malondialdéhyde (MDA) et la 8-hydroxy-2′-deoxyguanosine (8-OHdG). En parallèle, des prélèvements sur les surfaces de travail et dermiques permettront d’objectiver, ou pas, la présence de ces deux métaux sur les surfaces susceptibles d’être une source d’exposition cutanée et sur la peau des opérateurs. Les données issues de cette étude devraient apporter des informations sur les niveaux d’excrétion urinaires du Cr et du Ni utilisés au cours des divers procédés de projection thermique et de soudage, et d’étudier les relations entre les mesures atmosphériques et les niveaux urinaires excrétés, d’une part, et les relations entre les biomarqueurs d’exposition et d’effets précoces, d’autre part. L’objectif final est de proposer des valeurs limites biologiques (VLB) et, a minima, évaluer l’efficacité des systèmes de protection individuelle mis en place.

En plein essor, la chimiothérapie hyperthermique intrapéritonéale (CHIP) est un traitement du cancer pratiqué en bloc opératoire. Elle consiste, après résection de la maladie métastasique péritonéale, à injecter directement dans la cavité péritonéale de fortes concentrations de médicaments cytotoxiques (mitomycine C, 5-fluorouracile, cisplatine, oxaliplatine…) en grande quantité (2 L/m2 de surface corporelle). Ce traitement est réalisé à des températures relativement élevées (40 °C–46 °C) en continu pendant 30 à 90 minutes. Il offre l’avantage de limiter la diffusion systémique des médicaments. En France, les CHIP sont utilisées en routine depuis plusieurs années dans certains centres hospitaliers. Elles sont réalisées par des équipes médicales spécialement formées à ces pratiques. Un nouveau traitement par CHIP pressurisée (pressurized intraperitoneal aerosol chemotherapy [PIPAC]) commence à être utilisé. Il permet une meilleure répartition des produits de chimiothérapie dans la cavité péritonéale. Les conditions de pression utilisées impliquent des risques nouveaux pour le personnel médical. Une bonne maîtrise de ces risques, par une meilleure compréhension des expositions, est nécessaire pour l’administration de ces traitements en toute sécurité. Cette étude a pour objectif d’évaluer l’exposition des équipes médicales durant les CHIP/PIPAC grâce à des analyses biométrologiques. Pour cela, une campagne de prélèvements a été mise en place afin d’échantillonner les urines des salariés dans un centre hospitalier. La quantification des médicaments cytotoxiques dans les urines donne ainsi un état des lieux des expositions réelles des équipes médicales. En parallèle, des prélèvements par frottis ont été effectués avant et après les CHIP/PIPAC sur différentes surfaces ainsi que sur la peau (mains, cou) de l’équipe médicale. Ils apportent des informations complémentaires sur les sources potentielles d’exposition. Le couplage de ces analyses (urinaires et surfaciques) permet ainsi de vérifier l’efficacité des moyens de prévention (EPI, système d’aspiration, organisation…) mis en place.

In order to draw appropriate conclusions about the possible adverse biological effects of titanium dioxide nanoparticles (TiO2—NPs), the so-called “dose?effect” relationship must be explored. This requires proper quantification of titanium in complex matrices such as animal organs for future toxicological studies. This study presents the method development for mineralizing TiO2—NPs for analysis of biological tissues. We compared the recovery and quantification limits of the four most commonly used mineralization methods for metal oxides. Microwave-assisted dissolution in an HNO3–HF mixture followed by H2O2 treatment produced the best results for a TiO2—NPs suspension, with 96 ± 8% recovery and a limit of quantification as low as 0.9 µg/L. This method was then used for the determination of titanium levels in tissue samples taken from rats. However, our tests revealed that even this method is not sensitive enough for quantifying titanium levels in single olfactory bulbs or hippocampus in control animals.

Cadmium and lead are persistent and ubiquitous metals that can cause several deleterious effects in living beings. Apoptosis and necrosis are two types of cell death that can be found after in vivo and in vitro exposure to these metals. In this study, isolated red blood cells from living captive Common buzzard (Buteo buteo) were exposed in vitro to different concentrations of lead, cadmium, and the mixture lead–cadmium in a proportion of 1:10 (similar to that found in previous field studies). Data obtained from dose–response curves were used to evaluate the interactive effects of metal mixtures on cell viability. In general, except for the exposure to NOEC, additivity was the most frequently observed response. As described in human, after in vitro exposure, lead was highly accumulated in buzzard erythrocytes, while cadmium accumulation was scarce. Finally, the type of cell death (apoptosis or necrosis) induced by the exposure to different concentrations of these heavy metals and their mixtures was evaluated in the red blood cells. Apoptosis was found to be the main type of cell death observed after cadmium and/or lead exposure. However, this exposure caused an increase in lysis or necrosis, especially if red blood cells were exposed to high doses.

The potential toxicity of beryllium at low levels of exposure means that a biological and/or air monitoring strategy may be required to monitor the exposure of subjects. The main objective of the work presented in this manuscript was to develop and validate a sensitive and reproducible method for determining levels of beryllium in human urine and to establish reference values in workers and in non-occupationally exposed people. A chelate of beryllium acetylacetonate formed from beryllium(II) in human urine was pre-concentrated on a SPE C18 cartridge and eluted with methanol. After drying the eluate, the residue was solubilised in nitric acid and analysed by atomic absorption spectrometry and/or inductively coupled plasma mass spectrometry. The proposed method is 4 to 100 times more sensitive than other methods currently in routine use. The new method was validated with the concordance correlation coefficient test for beryllium concentrations ranging from 10 to 100 ng/L. Creatinine concentration, urine pH, interfering compounds and freeze-thaw cycles were found to have only slight effects on the performance of the method (less than 6%). The effectiveness of the two analytical techniques was compared statistically with each other and to direct analysis techniques. Even with a detection limit of 0.6 ng/L (obtained with inductively coupled plasma mass spectrometry), the method is not sensitive enough to detect levels in non-occupationally exposed persons. The method performance does however appear to be suitable for monitoring worker exposure in some industrial settings and it could therefore be of use in biological monitoring strategies.