Aurélie Remy

Biomarkers of toluene exposure in rats: mercapturic acids versus traditional indicators (urinary hippuric acid and o-cresol and blood toluene)

Abstract 1. Toluene (TOL) is a neurotoxic, ototoxic and reprotoxic solvent which is metabolized via the glutathione pathway, producing benzylmercapturic, o-, m- and p-toluylmercapturic acids (MAs). These metabolites could be useful as biomarkers of TOL exposure. 2. The aims of this study were (1) to provide data on MAs excretion in rat urine following TOL exposure by inhalation, (2) to compare them to data from traditional TOL biomarkers, i.e. TOL in blood (Tol-B), and urinary hippuric acid (HA) and o-cresol (oCre) and (3) to establish a relationship between these different indicators and the airborne TOL concentration (Tol-A). 3. Sprague–Dawley rats were exposed to a range of TOL concentrations. Blood and urine were collected and analyzed to determine biomarker levels. 4. Levels of the four MAs correlate strongly with Tol-A (comparable to the correlation with Tol-B). 5. MAs are thus clearly superior to oCre and HA as potential markers of exposure to TOL.

Prenatal developmental toxicity studies on diundecyl and ditridecyl phthalates in Sprague-Dawley rats.

This study evaluates the developmental toxicity of two high molecular weight dialkyl phthalate esters, diundecyl phthalate (DUDP) and ditridecyl phthalate (DTDP). Sprague-Dawley rats were administered 0, 0.25, 0.50, or 1g/kg/day of DUDP or DTDP, by gavage, on gestation days 6-20. DUDP and DTDP had no adverse effects on maternal body weight and food consumption. The number of live fetuses, percent of post-implantation loss and of resorptions, fetal sex, and fetal body weights were not affected by either phthalate. There was no evidence of teratogenicity, whatever treatment. Small decreases in the anogenital distance of male fetuses were noted at 0.5 and 1g DUDP/kg/day. The incidence of fetuses with supernumerary lumbar ribs was significantly higher than control at 0.5 and 1g DUDP/kg/day. Thus, DTDP was not developmentally toxic up to 1g/kg/day and there were signs of DUDP-induced fetal effects at 0.5 and 1g/kg/day.

Impact of coexposure on toluene biomarkers in rats

Abstract 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.

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.

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.

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.

Occupational exposure to platinum drugs during intraperitoneal chemotherapy. Biomonitoring and surface contamination

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.

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.