The BMDC model, a performant cell-based test to assess the sensitizing potential and potency of chemicals including pre/pro-haptens.

BACKGROUND: Chemical-induced allergies at workplace represent a significant occupational health issue. These substances must be properly identified as sensitizers. In previous studies, an original model using mouse bone marrow-derived dendritic cells (BMDC) was developed for this purpose. OBJECTIVES: The aim of this study was to evaluate the predictive capacity of the BMDC model with a large panel of sensitizers (including pre- and pro-haptens) and non-sensitizers. METHODS: The readout from the BMDC model is based on expression levels of six phenotypic markers measured by flow cytometry. RESULTS: The results indicate that 29 of the 37 non-sensitizers, and 81 of the 86 sensitizers were correctly classified compared to the Local Lymph Node Assay (LLNA). Statistical analysis revealed the BMDC model to have a sensitivity of 94%, a specificity of 78%, and an accuracy of 89%. The EC2 (Effective Concentration) values calculated with this model allow sensitizers to be categorized into four classes: extreme, strong, moderate and weak. CONCLUSIONS: These excellent predictive performances show that the BMDC model discriminates between sensitizers and non-sensitizers with outstanding precision equal to or better than existing validated alternative models. Moreover, this model allows to predict sensitization potency of chemicals. The BMDC test could therefore be proposed as an additional tool to assess the sensitizing potential and potency of chemicals.

Parameters influencing auditory fatigue among professionals working in the amplified music sector: noise exposure and individual factors.

OBJECTIVE: Hearing disorders are common among music professionals, as they are frequently exposed to sound levels exceeding 100 dB(A). By assessing auditory fatigue, situations that are deleterious for hearing could be identified, allowing the deployment of preventive measures before permanent impairment occurs. However, little is known about the factors contributing to auditory fatigue. The objective is to determine the exposure parameters most influencing auditory fatigue during occupational exposure to amplified music. DESIGN: Auditory fatigue was defined as variations of both pure tone auditory (ΔPTA) and efferent reflex thresholds (ΔER) during the workday. Noise exposure was monitored and information on the volunteers was gathered using a questionnaire. STUDY SAMPLE: The population consisted of 43 adult volunteers exposed to amplified music (sound, light or stage technicians, security agents, barmen) and 24 unexposed administrative agents. RESULTS: ΔPTA and ΔER were positively correlated with the energy of noise exposure and its stability over time, i.e a steady noise tends to create more auditory fatigue. CONCLUSION: In addition to a global decrease of music levels and a systematic use of hearing protection, our results advocate for the provision of quiet periods within noise exposures as they reduce auditory fatigue accumulation and long-term risks for hearing.

Occupational Exposure to Antineoplastic Drugs in Twelve French Health Care Setting: Biological Monitoring and Surface Contamination.

Antineoplastic drugs used in the treatment of cancers have an intrinsic toxicity, because of their genotoxic, teratogenic, and carcinogenic properties. Their use is recognized as an occupational hazard for healthcare workers (HCWs) who may be exposed. The purpose of this article is to present biological- and environmental-monitoring data collected in twelve French hospitals over eight years. Urine samples were collected from a wide range of HCWs (250 participants) from pharmacy and oncology units, including physicians, pharmacists, pharmacy technicians, nurses, auxiliary nurses, and cleaners. The investigated drugs were cyclophosphamide, ifosfamide, methotrexate, and α-fluoro-ß-alanine, the main urinary metabolite of 5-fluorouracil. Wipe samples were collected from various locations in pharmacy and oncology units. More than 50% of participants, from all exposure groups, were contaminated with either drug, depending on the unit, the day, or the task performed. However, workers from oncology units were more frequently exposed than workers from pharmacy units. Significant contamination was detected on various surfaces in pharmacy and oncology units, highlighting potential sources of exposure. Risk-management measures should be implemented to reduce and maintain exposures at lowest-possible levels. In addition, regular exposure assessment, including biological and environmental monitoring, is recommended to ensure the long-term efficiency of the prevention measures.

Occupational exposure to metals among battery recyclers in France: Biomonitoring and external dose measurements.

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 µg/m3. Urinary sample analysis indicated exposure to Cd and Co, with levels measured at up to 27.6 and 3.34 µg/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.

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

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

Do age and work pace affect variability when performing a repetitive light assembly task?

This study examined whether a repetitive light assembly task could be performed according to different movement sequences identified as ways of doing (WoD), and whether the age of the participants or the work pace affected the number of WoDs selected by each participant, or the kinematic parameters for each WoDs. For two work paces, 62 right-handed men in 3 age-groups were asked to fix a handle on a base with 2 nuts without discontinuity for a period of 20 min; no assembly procedure was demonstrated. The WoDs were characterized by a cross tabulation video coding method, and by measuring vertical force applied and the parameters of upper limb kinematics, as well as these measures' approximate entropy (ApEN). Five main different WoDs were used. Although most participants varied their WoD, neither participant age nor work pace affected the number of WoD they used. However, the WoDs differed from each other by the sequence of movements and by the level of ApEn of their kinematic variables without interfering with the production rate. Allowing operators to vary their WoDs when performing repetitive tasks could reduce strain on the locomotor system.

Mycotoxins Exposure of French Grain Elevator Workers: Biomonitoring and Airborne Measurements.

It is now recognized that additional exposure to mycotoxins may occur through inhalation of contaminated dust at a workplace. The aim of this study was to characterize the multi-mycotoxin exposure of French grain elevator workers using biomonitoring and airborne measurements. Eighteen workers participated in the study. Personal airborne dust samples were analyzed for their mycotoxin concentrations. Workers provided multiple urine samples including pre-shift, post-shift and first morning urine samples or 24 h urine samples. Mycotoxin urinary biomarkers (aflatoxin B1, aflatoxin M1, ochratoxin A, ochratoxin α, deoxynivalenol, zearalenone, α-zearalenol, ß-zearalenol, fumonisin B1, HT-2 toxin and T-2 toxin) were measured using a liquid chromatography-high-resolution mass spectrometry method. Grain elevator workers were highly exposed to organic airborne dust (median 4.92 mg.m-3). DON, ZEN and FB1 were frequent contaminants in 54, 76 and 72% of air samples, respectively. The mycotoxin biomarkers quantified were DON (98%), ZEN (99%), α-ZEL (52%), ß-ZEL (33%), OTA (76%), T-2 (4%) and HT-2 (4%). DON elimination profiles showed highest concentrations in samples collected after the end of the work shift and the urinary DON concentrations were significantly higher in post-shift than in pre-shift-samples (9.9 and 22.1 µg/L, respectively). ZEN and its metabolites concentrations did not vary according to the sampling time. However, the levels of α-/ß-ZEL were consistent with an additional occupational exposure. These data provide valuable information on grain worker exposure to mycotoxins. They also highlight the usefulness of multi-mycotoxin methods in assessing external and internal exposures, which shed light on the extent and pathways of exposure occurring in occupational settings.

Is Urinary Chromium Specific to Hexavalent Chromium Exposure in the Presence of Co-exposure to Other Chromium Compounds? A Biomonitoring Study in the Electroplating Industry.

OBJECTIVES: Electroplating processes are widely used in metal industries to improve the resistance properties of manufactured metal parts. Workers in this industry are potentially exposed both to hexavalent chromium (Cr(VI)) and to other chromium compounds [mostly trivalent chromium (Cr(III))], due to the use of chromic acid baths. The goal of this study was to validate urinary chromium as a Cr(VI) exposure biomarker in the presence of exposure to other chromium compounds. METHODS: A biomonitoring study consisted in monitoring airborne chromium exposure and urinary chromium for one working week in 93 workers from nine electroplating companies. Chromium concentrations were measured in all urinations of each volunteer for the working week. Individual airborne soluble and insoluble Cr(VI) as well as Cr(III) concentrations were measured for all of the shifts of the week. The main statistical analysis consisted in modelling, in a Bayesian framework, the pre- and post-shift urinary chromium as a function of airborne Cr(III) and airborne Cr(VI), taking into account the day of the week and the time of collection of the urines (pre- or post-shift). RESULTS: Preliminary descriptions showed an increase in pre-shift urinary chromium during the working week. The model showed an increase in urinary chromium over the shift related to the shift-specific airborne Cr(VI) concentration as well as an increasing trend over the week and a relationship with the mean weekly Cr(VI) thought to reflect chronic exposure. Taking into account the Cr(VI) exposure, there was no evidence of an effect of Cr(III) exposure on urinary chromium. A biological limit value (BLV) was derived from the French occupational exposure limit for Cr(VI) of 1 µg m-3 and was estimated at between 1.9 and 2.6 µg g-1 creatinine for a urinary sample collected at the end of the shift on the last working day of the week. CONCLUSIONS: In the present context of mixed exposure to Cr(III) and Cr(VI) in electroplating, this study showed that urinary chromium depended only on airborne Cr(VI) concentrations, which justifies using a BLV for assessing workers' exposure. The estimated BLV was close to the recommended French BLV, which is 1.8 µg g-1 creatinine, in the electroplating industry.

Simultaneous determination of aromatic and chlorinated compounds in urine of exposed workers by dynamic headspace and gas chromatography coupled to mass spectrometry (dHS-GC-MS).

Mixed exposure to chemical products is a topical issue for occupational health and often includes exposure to volatile organic compounds (VOCs). As very few methods are available for evaluating these mixed exposures, the aim of this work was to develop a simple biomonitoring method to assess simultaneous occupational exposures to chlorinated and aromatic VOCs by analyzing the unmetabolized fraction of the VOCs in the urine of workers. Volatile organic compounds were analyzed using dynamic headspace gas chromatography coupled to mass spectrometry (dHS-GC-MS), and 11 unmetabolized urinary VOCs were measured into headspace phase, without any time-consuming pretreatment. Simultaneously, a standardized collection protocol was designed to avoid VOC losses or the contamination of urinary samples. The calibration samples were real urines, spiked with known amounts of the VOC mixtures studied. Test investigations were performed on potentially exposed workers in three factories in order to assess the effectiveness of both the collection protocol and analytical method. A satisfactory level of sensitivity was achieved, with limits of quantification (LOQ) between 10 and 15 ng/L obtained for all VOCs (except for styrene at 50 ng/L). Calibration curves were linear in the 0-20 µg/L range tested, with R2 correlation coefficients of 0.991 to 0.998. At the lowest concentration tested (0.08 µg/L), within-day precision varied from 2.1 to 5.5% and between-day precision ranged from 2.7 to 8.5%. Sample stability at -20 °C required that urinary samples be analyzed within 3 months. Even though the urinary concentrations of VOCs used in the plants were mostly quite low, significant differences between post-shift and pre-shift were observed. In conclusion, a fast, sensitive, specific and easy-to-use method has been developed for extracting VOCs from human urine using dHS-GC-MS. The method described has proven to be reliable for assessing current occupational exposure to chlorinated and aromatic VOCs in France.

Occupational exposure to beryllium in French industries.

Beryllium (Be) is a metal mainly used in the form of alloys, with copper (Cu) and aluminium (Al) in the metal industry. Be is an extremely toxic element which must be handled under strictly controlled conditions to avoid health hazards to workers. Exposure to Be can be responsible for Chronic Beryllium Disease, a pulmonary disease preceded by sensitization to the element, and for lung cancer. The goals of the current study were to investigate Be exposure in France, to determine the airborne Be occupational exposure levels, the associated impregnation of employees through their urinary Be levels and the factors that might affect them, and finally to study a possible relation between biomonitoring and airborne data. Seventy-five volunteer subjects were thus atmospherically and biologically monitored in five French companies involved in Cu or Al casting, Al smelting, CuBe machining or AlBe general mechanical engineering. Airborne exposure was quite low with only 2% of measurements above the current French Occupational Exposure Limit (2 µg/m3); the population potentially most exposed was foundry workers. Impregnation with Be was also low with only 10% of quantified urinary Be measurements above the current German BAR value (0.05 µg/L). Using a Bayesian statistical modelling approach, the mean subject-specific urinary excretion of Be was found to increase significantly with the mean subject-specific exposure to airborne Be. From this relationship, and based on the current French OEL-8 hr, a Biological Limit Value of 0.08 µg/L (= 0.06 µg/g creatinine) could be proposed.

Occupational exposure of cashiers to bisphenol S via thermal paper.

PURPOSE: In thermal paper, Bisphenol S (BPS) is one of the alternatives for bisphenol A (BPA). Due to its structural similarity to BPA, concern has been raised about the safety of BPS. Indeed, handling thermal paper receipts could be a source of occupational exposure to BPS among cashiers, as it was previously described for BPA. In this study, we investigated whether frequent contacts with thermal paper are associated with an increase in urinary BPS levels in cashiers. METHOD: Total (unconjugated and conjugated forms) and free (unconjugated) BPS were measured in urine samples from 17 cashiers and 15 controls, using LC-MS/MS. Spot urine samples, including pre-shift and post-sift samples and first morning void were collected from each volunteer. BPS concentration in thermal paper was determined and the number of receipts handled by cashiers was estimated as well. RESULTS: The median urinary total BPS concentration was 0.67 µg/L (0.52 µg/g creatinine) for controls and 2.53 µg/L (2.07 µg/g creatinine) for cashiers. Total BPS concentration was significantly higher in cashiers than in controls. Free BPS was detected in less than 20% of urine samples collected from controls and in less than 50% of urine samples collected from cashiers. CONCLUSION: The detectable levels of BPS in urine of controls suggest an exposure to BPS of the general population. In addition, frequent contact with thermal paper could be responsible for an increase in urinary concentration of total BPS in cashiers.

Improving the work environment in the fluorescent lamp recycling sector by optimizing mercury elimination.

One of the main issues in the fluorescent lamp recycling sector is the mercury contamination of output fractions and occupational exposure associated with recycling operations. The aim of this study is to carry out effective mercury mass balance determinations and improve mercury recovery by finding the optimal levels for the recycling process parameters. These optimizations will allow upstream mercury emissions to be reduced, which will help to avoid mercury exposure among WEEE recycling workers. Firstly, the distribution of mercury was assessed in new and spent lamps. For new fluorescent tubes, the mean percentage of mercury in the solid phase is lower in new fluorescent tubes (19.5% with 5.5% in glass, 9.7% in end caps and 4.3% in luminescent powder) than in spent tubes (33.3% with 8.3% in glass, 12.9% in end caps and 12.1% in luminescent powder). The parametric study also shows that the finer the grains of glass, the higher the concentration of mercury (1.2 µg Hg/g for glass size particle >1000 µm and 152.0 µg Hg/g for glass size particle <100 µm); the crushing time required for the optimal removal of mercury from spent tubes is 24 h; on average 71% of the mercury is desorbed at a temperature of 400 °C. The effects of air flow rate, rotation speed and number of balls could not be determined due to wide variations in the results. It is recommended that recycling companies employ processes combining as heating and mixing techniques for the recovery of mercury from lamps in order to both (i) remove as much of the mercury as possible in vapor form and (ii) avoid adsorption of the mercury at new sites created during the crushing process.

Study of potential transfer of aluminum to the brain via the olfactory pathway.

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.

In vitro cell transformation induced by synthetic amorphous silica nanoparticles.

Synthetic amorphous silica nanoparticles (SAS) are among the most widely produced and used nanomaterials, but little is known about their carcinogenic potential. This study aims to evaluate the ability of four different SAS, two precipitated, NM-200 and NM-201, and two pyrogenic, NM-202 and NM-203, to induce the transformation process. For this, we used the recently developed in vitro Bhas 42 cell transformation assay (CTA). The genome of the transgenic Bhas 42 cells contains several copies of the v-Ha-ras gene, making them particularly sensitive to tumor-promoter agents. The Bhas 42 CTA, which includes an initiation assay and a promotion assay, was validated in our laboratory using known soluble carcinogenic substances. Its suitability for particle-type substances was verified by using quartz Min-U-Sil 5 (Min-U-Sil) and diatomaceous earth (DE) microparticles. As expected given their known transforming properties, Min-U-Sil responded positively in the Bhas 42 CTA and DE responded negatively. Transformation assays were performed with SAS at concentrations ranging from 2µg/cm2 to 80µg/cm2. Results showed that all SAS have the capacity to induce transformed foci, interestingly only in the promotion assay, suggesting a mode of action similar to tumor-promoter substances. NM-203 exhibited transforming activity at a lower concentration than the other SAS. In conclusion, this study showed for the first time the transforming potential of different SAS, which act as tumor-promoter substances in the Bhas 42 model of cell transformation.

Epigenetic changes in the early stage of silica-induced cell transformation.

The increasing use of nanomaterials in numerous domains has led to growing concern about their potential toxicological properties, and the potential risk to human health posed by silica nanoparticles remains under debate. Recent studies proposed that these particles could alter gene expression through the modulation of epigenetic marks, and the possible relationship between particle exposure and these mechanisms could represent a critical factor in carcinogenicity. In this study, using the Bhas 42 cell model, we compare the effects of exposure to two transforming particles, a pyrogenic amorphous silica nanoparticle NM-203 to those of the crystalline silica particle Min-U-Sil® 5. Short-term treatment by Min-U-Sil® 5 decreased global DNA methylation and increased the expression of the two de novo DNMTs, DNMT3a and DNMT3b. NM-203 treatment affected neither the expression of these enzymes nor DNA methylation. Moreover, modified global histone H4 acetylation status and HDAC protein levels were observed only in the Min-U-Sil® 5-treated cells. Finally, both types of particle treatment induced strong c-Myc expression in the early stage of cell transformation and this correlated with enrichment in RNA polymerase II as well as histone active marks on its promoter. Lastly, almost all parameters that were modulated in the early stage were restored in transformed cells suggesting their involvement mainly in the first steps of cell transformation.

Bivariate Left-Censored Measurements in Biomonitoring: A Bayesian Model for the Determination of Biological Limit Values Based on Occupational Exposure Limits.

Biological limit values (BLV) are often determined from the occupational exposure limits (OEL) in modelling biological data obtained on a number of exposed subjects based on measurements of air exposure. In order to obtain such BLVs, biomonitoring studies are conducted collecting simultaneously biological and airborne measurements to these substances in exposed workers. One obstacle in the modelling of such data is the often large number of values below the limit of detection (LOD) for both biological and airborne measurements (left-censored measurements). A second difficulty, which is also a strength, is that multiple measurements are obtained for the same workers, leading to non-independence of the data. In this paper, we propose a statistical method based on Bayesian theory making use of measurements below the LOD for both dependent (biological) and independent (air exposure) data, and taking into account multiple measurements on the same worker. This method relies on the modelling of the airborne exposure measurements using standard random effect models adapted for values below LOD and the simultaneous modelling of the biological measurements assumed to be linearly (on the log scale) related to the airborne exposure while accounting for between-worker variability. This method is validated by a simulation study in which up to 50% of the measurements are censored for both variables in realistic settings. This simulation study shows that the proposed method is uniformly more efficient than the candidate alternative we considered (maximum likelihood estimation; MLE method) that did not make use of a data with airborne measurements below the LOD. When the method is applied on a real biomonitoring data set among electroplating workers exposed to chromium with 54% censored airborne measurements and 20% censored urinary measurements, the slope is steeper when incorporating these data using the proposed Bayesian method leading to different BLV estimations depending on the OEL used.

Evaluation of chromium in red blood cells as an indicator of exposure to hexavalent chromium: An in vitro study.

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.

Occupational exposure of cashiers to Bisphenol A via thermal paper: urinary biomonitoring study.

PURPOSE: As an essential component of polycarbonate plastics and epoxy resins, Bisphenol A (BPA) is found in numerous industrial and consumer products. BPA may cause adverse health effects because of its endocrine activity. General population exposure to this compound mainly through diet is well documented. Thermal paper was also identified as a source of BPA through dermal intake. In this study, we investigated whether frequent contact with thermal paper is associated with an increase in urinary BPA excretion. METHODS: We evaluated the exposure to BPA in cashiers and in non-occupationally exposed workers from several workplaces. Urinary BPA was quantified in free (unconjugated) and total (unconjugated plus conjugated) forms in 24-h and spot urine samples using LC-MS/MS. BPA concentration in thermal paper was also measured from each workplace. In addition, participants provided information on job, food and drink, tobacco consumption and hands wash during the sampling period through a questionnaire. RESULTS: Urine samples were collected from 90 cashiers and 44 controls. Free and total BPA were detected in all samples. The median urinary total BPA concentration was 3.54 µg/L (2.89 µg/g creatinine) for controls and 8.92 µg/L (6.76 µg/g creatinine) for cashiers. For the free BPA, the median urinary concentration was 0.20 µg/L (0.21 µg/g creatinine) for controls and 0.28 µg/L (0.22 µg/g creatinine) for cashiers. Any correlation was found between the urinary concentration levels and the number of thermal receipts handled. Hand washes frequency, age, job length of service and tobacco consumption had also no effect on the BPA excretions. CONCLUSION: A significant increase in urinary total BPA concentration was observed for cashiers handling daily thermal paper receipts. However, no significant increase was observed in urinary free BPA concentration. These findings are particularly interesting for risk assessment since all available data on occupational exposure to BPA through thermal paper were obtained from models or from simulated experiments.

Impact of coexposure on toluene biomarkers in rats.

1. Toluene (TOL) is widely used in industry. Occupational exposure to TOL is commonly assessed using TOL in blood, hippuric acid and ortho-cresol. Levels of these biomarkers may depend on factors potentially interfering with TOL biotransformation, such as the presence of other solvents in the workplace. Mercapturic acids (MAs) could be an alternative to the "traditional" TOL biomarkers. 2. This study aims (1) to investigate in rat the effects of an exposure to vapours mixtures on the TOL metabolism, and (2) to assess how well MAs performed in these contexts compared to the traditional TOL biomarkers. 3. Rats were exposed by inhalation to binary mixtures of TOL with n-butanol (BuOH), ethyl acetate (EtAc), methyl ethyl ketone (MEK) or xylenes (XYLs); biological exposure indicators were then measured. 4. Depending on the compounds in the mixture and their concentrations, TOL metabolism was accelerated (with BuOH), unchanged (with EtAc) or inhibited (with XYLs and MEK). Inhibition leads to an increase in blood TOL concentrations, even at authorized atmospheric concentrations, which may potentiate the effect of TOL. 5. MAs excretions are little affected by coexposure scenarios, their levels correlating well with atmospheric TOL levels. They could thus be suitable bioindicators of atmospheric TOL exposure.

Validation of a standardised method for determining beryllium in human urine at nanogram level.

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.