Liquid chromatography-tandem mass spectrometry (LC/APCI-MS/MS) methods for the quantification of captan and folpet phthalimide metabolites in human plasma and urine.

Captan and folpet are fungicides largely used in agriculture. They have similar chemical structures, except that folpet has an aromatic ring unlike captan. Their half-lives in blood are very short, given that they are readily broken down to tetrahydrophthalimide (THPI) and phthalimide (PI), respectively. Few authors measured these biomarkers in plasma or urine, and analysis was conducted either by gas chromatography coupled to mass spectrometry or liquid chromatography with UV detection. The objective of this study was thus to develop simple, sensitive and specific liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) methods to quantify both THPI and PI in human plasma and urine. Briefly, deuterated THPI was added as an internal standard and purification was performed by solid-phase extraction followed by LC/APCI-MS/MS analysis in negative ion mode for both compounds. Validation of the methods was conducted using spiked blank plasma and urine samples at concentrations ranging from 1 to 250 μg/L and 1 to 50 μg/L, respectively, along with samples of volunteers and workers exposed to captan or folpet. The methods showed a good linearity (R (2) > 0.99), recovery (on average 90% for THPI and 75% for PI), intra- and inter-day precision (RSD, <15%) and accuracy (<20%), and stability. The limit of detection was 0.58 μg/L in urine and 1.47 μg/L in plasma for THPI and 1.14 and 2.17 μg/L, respectively, for PI. The described methods proved to be accurate and suitable to determine the toxicokinetics of both metabolites in human plasma and urine

Solid phase microextraction as a short-term sampling technique for BTEX occupational exposure

Solid phase microextraction (SPME) has been widely used for many years in various applications, such as environmental and water samples, food and fragrance analysis, or biological fluids. The aim of this study was to suggest the SPME method as an alternative to conventional techniques used in the evaluation of worker exposure to benzene, toluene, ethylbenzene, and xylene (BTEX). Polymethylsiloxane-carboxen (PDMS/CAR) showed as the most effective stationary phase material for sorbing BTEX among other materials (polyacrylate, PDMS, PDMS/divinylbenzene, Carbowax/divinylbenzene). Various experimental conditions were studied to apply SPME to BTEX quantitation in field situations. The uptake rate of the selected fiber (75 microm PDMS/CAR) was determined for each analyte at various concentrations, relative humidities, and airflow velocities from static (calm air) to dynamic (> 200 cm/s) conditions. The SPME method also was compared with the National Institute of Occupational Safety and Health method 1501. Unlike the latter, the SPME approach fulfills the new requirement for the threshold limit value-short term exposure limit (TLV-STEL) of 2.5 ppm for benzene (8 mg/m(3)

Exposition professionnelle aux hydrocarbures aromatiques polycycliques dans la poussière de bois

Les tumeurs malignes des cavités naso-sinusiennes (CNS) représentent environ 3% des cancers ORL. La poussière de bois est reconnue comme cancérigène pour l'homme (IARC, classe 1A) et la maladie professionnelle formellement identifiée est le CNS ou le cancer de l'ethmoïde. L'adénocarcinome des CNS est une maladie professionnelle admise chez certains travailleurs spécialisés tels les menuisiers et les ébénistes. Selon les enquêtes WOODEX dans les 25 états membres de UE en 2006, environ 3.6 millions de travailleurs sont exposés par voie respiratoire à la poussière de bois, soit 2% de la population active. En France, 307 000 travailleurs sont exposés, et il y a environ 200 cas de cancers sino-nasaux reconnus comme maladie professionnelle par année. La forte proportion de travailleurs du bois développant un adénocarcinome des CNS a suggéré diverses pistes, tel que le tanin pour les bois durs, le formaldéhyde pour les contre-plaqués et le benzo(a)pyrène produit par le bois surchauffé. Il est reconnu que le tanin ne provoque pas de cancer dans l'exposition à la poussière de thé. Le formaldéhyde est un irritant mais il est aussi classé cancérogène. La piste des hydrocarbures aromatiques polycycliques (HAP) cancérogènes provoqués par le bois surchauffé est séduisante. Nous avons étudié leur teneur en fonction des opérations pratiquées sur le bois en cabine d'expérimentation. Les matériaux testés sont du sapin brut, du chêne et chêne imprégné de polyuréthane. La poussière de bois contient des HAP au niveau du µg/g ou ppm. Le bois imprégné de vernis PU produit 100 fois plus de HAP que le bois brut lors des opérations de ponçage

Relative stabilities of cholestadienes calculated by molecular mechanics and semi-empirical methods: application to the acid-catalyzed rearrangement reactions of cholesta-3,5-diene

The study of geochemical transformations undergone by ‘biological markers' after their incorporation into sediments is an important field of organic geochemistry. Combined with laboratory simulation experiments, molecular mechanics calculations have been shown to be very useful to establish the reaction pathways, and to predict intermediate components and stable reaction end products, especially in the case of the acid-catalyzed isomerization reactions of steroid and terpenoid hydrocarbons. Many commercially available softwares are able to optimize (minimize) the geometries of molecules and compute some of their thermodynamical data with either molecular mechanics (MM) or semi-empirical methods of quantum chemistry. In order to verify the reliability of these methods, we have computed the relative thermodynamic stabilities of a large number of steradiene isomers with MM3 (Tripos Inc.), MM+ (HYPERCHEMTM) and MM2 (Chem3D, CambridgeSoft Corp.) empirical force fields, and with AM1 and PM3 (HYPERCHEMTM) semi-empirical methods. The calculation results of thermodynamic stabilities of steradiene isomers are used to explain the compounds produced by the rearrangement of cholesta-3,5-diene when treated with p-toluenesulfonic acid in acetic acid at 70°C. The end products, namely the spirosteradienes 7–8, obtained by this treatment are the most stable steradiene isomers according to all computational methods. The relative thermodynamic stabilities of cholestadienes are also consistent with the mechanism postulated for the spirosteradiene formation proceeding through a pathway including cholestadienes 2–6 as intermediates

Solid-phase microextraction as short-term sampling technique for BTEX occupational exposure

Solid phase microextraction (SPME) has been widely used for many years in various applications, such as environmental and water samples, food and fragrance analysis, or biological fluids. The aim of this study was to suggest the SPME method as an alternative to conventional techniques used in the evaluation of worker exposure to benzene, toluene, ethylbenzene, and xylene (BTEX). Polymethylsiloxane-carboxen (PDMS/CAR) showed as the most effective stationary phase material for sorbing BTEX among other materials (polyacrylate, PDMS, PDMS/divinylbenzene, Carbowax/divinylbenzene). Various experimental conditions were studied to apply SPME to BTEX quantitation in field situations. The uptake rate of the selected fiber (75 μm PDMS/CAR) was determined for each analyte at various concentrations, relative humidities, and airflow velocities from static (calm air) to dynamic (>200 cm/s) conditions. The SPME method also was compared with the National Institute of Occupational Safety and Health method 1501. Unlike the latter, the SPME approach fulfills the new requirement for the threshold limit value-short term exposure limit (TLV-STEL) of 2.5 ppm for benzene (8 mg/m3)

Acid catalysed backbone rearrangement of cholesta-2,4,6-triene: On the origin of ring A and ring B aromatic steroids in recent sediments

Rearrangement of cholesta-2,4,6-triene in the presence of p-toluenesulfonic acid in acetic acid at 70° C leads to 4-methyl-19-nor-cholesta-1,3,5(10)-triene and 1(10 !6)-abeo-14b-cholesta-5,7,9(10)-triene in less than 2 h. Postulated mechanisms of formation of these products are supported by molecular mechanics calculations of the relative stabilities of reaction intermediates. The results suggest that D5,7-sterols, the most common natural precursors of triunsaturated steroidal hydrocarbons in contemporary sediments, constitute another major source for monoaromatic A and B steroids in addition to D5-sterols

Novel instrument to generate representative e-cigarette vapors for physicochemical particle characterization and in-vitro toxicity

The use of “electronic cigarettes” (e-cigs) has exponentially increased during the last decade. This drastic growth has been observed in smokers and never smokers, women and teenagers, with indicators for adverse effects related to nicotine, but also to e-liquid and vapor components. The aerosol characteristics depend on the e-cig features. Therefore, the introduction of many different e-cig types on the market leads to concerns regarding their potential Health effects. Our study aims to develop an instrument to generate representative vapors from e-cigarette devices, characterize the physicochemical properties of the aerosols and elucidate the adverse effects of inhaled vapors on normal human airway epithelia. E-cig vapors were produced using a specially developed aerosol generation instrument mimicking user puffing behavior. Aerosol particle size distribution and concentration were characterized with a Scanning Mobility Particle Sizer. Air-liquid interface cultures of differentiated human bronchial epithelial cells were exposed to 1 puff topography, i.e. to 21 puffs of 3 s with 22-second puff intervals using the Nano-Aerosol Chamber for In-Vitro Toxicity, which simulates particle deposition in the respiratory tract. Cell morphology was evaluated by light microcopy and induction of cell death by release of lactate Dehydrogenase at 4 and 24 h after aerosol exposure. Particle size in e-cig generated aerosols ranged from 20 to 430 nm and concentrations exceeded 1×10^6 particles/cm3. Deposited particle doses were 0.9–3 μg/cm2, depending on e-device type and number of puffs. A single exposure to e-cig vapors caused changes in epithelial cell shape but no massive cell death. We successfully developed an aerosol generation system to produce and deposit realistic vapors from e-cigs. The results obtained indicate that a single exposure to e-cig aerosols affects epithelial morphology and slightly increases cell death. Our interdisciplinary approach combining aerosol Technology and biology allows identifying adverse effects of e-cigs to the respiratory tract in vitro