Occupational exposure to carbon fibers impregnated with epoxy resins and evaluation of their respirability.

Objectives: The study aims to investigate occupational exposure to carbon fibers impregnated with epoxy resins (carbon fiber reinforced [CFR]) in workers at an airplane fuselage section construction plant, by environmental and biological monitoring.Materials and methods: Determination of airborne CFR was done by environmental sampling with active samplers, 11 of which were stationary and 19 personal samplings. The subsequent analyses were performed in the scanning electron microscope fitted with an X-ray microanalysis system (SEM-EDXA). Biological monitoring was carried out by determining CFR in exhaled breath condensate (EBC) collected from 19 male workers who wore personal environmental samplers (exposed workers) and from 10 male workers at the same factory who had no occupational exposure to CFR (internal controls). CFR analysis was done by SEM, applying the method used for determining asbestos fibers in aqueous samples.Results: The airborne CFR concentrations were found to be significantly higher (p = 0.03) at personal samplings (median value 7.01 ff/L, range 1.24-11.16 ff/L) than stationary samplings (median value 1.93 ff/L, range 0.55-10.09 ff/L). The aerodynamic diameters calculated starting from the length and geometric diameter of the sampled CFRs were always higher than 20 µm. CFR was not found in any of the EBC samples collected from the exposed workers and controls.Conclusions: Despite the evidence of occupational exposure to low concentrations of CFR, the absence of such fibers in the EBC in the exposed workers confirms their non-respirability, as expected based on their aerodynamic diameter.

[Serum polychlorinated biphenyls in workers of a second-smelting steel mill]. / Policlorobifenili sierici nei lavoratori di una acciaieria di seconda fusione.

SUMMARY: In the steel industry polychlorodibenzodioxins (PCDD), polychlorinated dibenzofurans (PCDF) and polychlorinated biphenyls (PCBs) may be present deriving from the fusion of ferrous and non-ferrous scrap, as well as for the thermal decomposition of the plastic materials (thermoplastic and thermosetting resins) contained therein and not removed before melting at high temperatures. The aim of the study was to assess in 52 workers of a secondmelting steel plant the PCBs exposure deriving from the manual handling of ferrous scrap waste eventually contaminated. The population was divided by production department (scrap, casting and office). Static air sampling of PCDD, PCDF, PCBs and biological monitoring of serum dioxin-like PCBs (DL-PCBs) were performed. The comparison of serum DL-PCB values between workers from the scrap department and those from the casting did not find any statistically significant differences (Mann- Whitney U test). The range of serum DL-PCBs was 7.74-78.55 ng/g lipids with an average of 24.21 ng/g lipids, much lower than the reference values measured in the Italian general population in 2011. Mean and median TEQ WHO 1998 of DL-PCBs were 0.22 pg/g lipids and 0.15 pg/g lipids respectively. The low concentrations of serum DL-PCBS in the studied population can be explained by the progressive reduction of environmental PCBs contamination.

Validation of cleaning procedures used in an Italian Hospital Pharmacy for antineoplastic drug decontamination: a new tool for industrial hygiene.

BACKGROUND: Current Italian regulations and procedures for surface decontamination of antineoplastic drugs (ADs) are not clear. Therefore, most hospital pharmacies follow internal procedures as an interpretation of the recommended handling guidelines. OBJECTIVES: Our study compared 7 different cleaning procedures after controlled contamination of the work surface of a biological safety cabinet workbench in an Italian hospital oncology pharmacy (HOP) to determine which of them is more efficient and practical. Moreover, in order to approximate operative routine and improve risk awareness, cleaning procedures were carried out by the personnel that usually operate in the HOP. METHODS: Measured quantities, i.e. a drop (100 µL) of 5-FluoroUracil, IPhosfamide, CycloPhosphamide and Gemcitabine, were deposited on the work surface within precisely delimited areas. Following the wipe-test analysis using UPLC-MS/MS, the cleaning efficacy was calculated based on the ratio of the residual concentration of the AD, after the cleaning procedure, to the concentration of each AD before the procedure. RESULTS: Tested cleaning procedures were: 1) Hypo-Chlor®, hot water and Farmecol70®; 2) Hypo-Chlor® and hot water; 3) Farmecol70®; 4) Surfa'Safe SH® and hot water; 5) Amuchina® 10%, hot water and Farmecol70®; 6) Incidin® Oxyfoam and hot water; 7) liquid Marseille soap, hot water and Farmecol70®. Within the studied HOP, the Marseille soap was evaluated to be the optimal choice due to its efficacy, low cost, and the very short contact time needed before rinsing. DISCUSSION: The application of the protocol for procedure validation suggested here could be used in every HOP as a reliable industrial hygiene tool to demonstrate the validity of the chosen cleaning procedure.

[Risk assessment for food preparation, cooking and service]. / Rischi da lavoro nel settore della ristorazione.

The restaurant and food preparation, cooking and distribution sector includes hotels, restaurants, catering, fast food, ecc. The restaurant and food preparation, cooking and distribution sector form a significant part of the Italian economy; they provide employment for a large number of people, both direct employees as well as part-time and contract staff. In this sector there are many hazards that can lead to a broad range of injuries and/or diseases to the workers. For the safety these hazards principally are slick floors, open flames, high temperature cooking surfaces, steam, knives and other cutting instruments and machineries. For the health: cleaning and disinfecting chemicals substances, cooking fumes and vapors, biological agents, heavy loads handling, thermal comfort, ecc. The paper presents an overview of the hazards in the sector and then make a focus on chemical risks identification and assessment to evaluate the workers' exposure (by skin adsorption and inhalation).

[Evolution of technology and occupational exposures in petrochemical industry and in petroleum refining]. / Evoluzioni della tecnologia e delle esposizioni professionali nell'industria petrolchimica e nella raffinazione del petrolio.

The industry of oil refining and petrochemical play an important role in terms of number of employees in the Italian production. Often the terms "petroleum refining" and "petrochemical" are used interchangeably to define processes that occur in complex plants, which grow outdoors on large surfaces and a visual impact is not irrelevant. In reality, the two areas involve potential exposure to different chemical agents, related to raw materials processed and the specific products. The petrochemical uses as raw materials, the oil fractions, obtained by distillation in the refinery, or natural gas; petrochemical products are, usually, single compounds with a specific degree of purity, used as basic raw materials for the entire industry of organic chemistry, from the production of plastics to pharmaceuticals. The oil refining, that is the topic of this paper, processes mainly oil to obtain mixtures of hydrocarbon compounds, the products of which are specified on the basis of aptitude for use. For example gasolines, are obtained by mixing of fractions of the first distillation, reforming products, antiknock. The paper illustrates, necessarily broadly due to the complexity of the productive sectors, the technological and organizational changes that have led to a significant reduction of occupational exposure to chemical agents, the results of environmental monitoring carried out in some refineries both during routine conditions that during scheduled maintenance activities with plant shutdown and a store of petroleum products. The chemical agents measured are typical for presence, physico-chemical properties and toxicological characteristics of the manufacturing processes of petroleum products like benzene, toluene, xylenes, ethyl benzene, n-hexane, Volatile Hydrocarbons belonging to gasoline, kerosene, diesel fuel. Data related to both personal sampling and fixed positions.

Accurate low-dose exposure assessment of benzene and monoaromatic compounds by diffusive sampling: sampling and analytical method validation according to ISO 23320 for radiello® samplers packed with activated charcoal.

The research study aimed at providing an accurate low-dose benzene exposure assessment method, by validating diffusive monitoring techniques for benzene personal exposure measurements at workplaces where benzene concentrations are expected in the low ppb range, such as in the present-day chemical, petrochemical, foundry, and pharmaceutical industry. The project was aimed at addressing the need for a robust and fully validated method to perform personal exposure measurements considering that the occupational exposure limit value for benzene is going to be significantly lowered in the next few years. Diffusive sampling offers a reliable alternative to pumped sampling methods, intrinsic safety in potentially explosive atmospheres, lightness, and ease of use. In this study, the radiello® diffusive sampler, with the packed activated charcoal RAD130 adsorbing substrate [suitable for solvent desorption and analysis by high-resolution gas chromatography-flame ionization detection (HRGC-FID)], was used. The experiments have been conducted following the ISO 23320 standard in the range from 0.005 to 0.1 ppm (16 to 320 µg/m3), yielding a full validation of the sampling and analytical method. The sampler performances have fulfilled all requisites of the ISO 23320 standard, in particular: bias due to the selection of a non-ideal sorbent is lower than 10% (no significant back diffusion of benzene due to concentration change in the atmosphere); bias due to storage of samples for up to 2 months is lower than 10%; nominal uptake rate for benzene on RAD130 is 74.65 mL/min; and expanded uncertainty of the sampling and analytical method is 20.6%. The sampling and analytical method is therefore fit-for-purpose for the personal exposure measurements aimed at testing compliance with occupational exposure limit values for benzene. The method is also fit for short-duration exposure monitoring related to specific tasks, and other volatile organic compounds, usually found in the same workplaces, such as aliphatic and aromatic hydrocarbons and some oxygenated compounds, have also been studied. In particular, n-hexane and isopropyl benzene, whose classification is currently under revision, can be efficiently monitored by this technique.

[Exposure to leather dusts and organic solvents--results of the PPTP-shoe study]. / Esposizione a polveri di cuoio e solventi organici--I risultati dello studio PPTP-calzatura.

In the shoe industry leather dusts and organic solvents present in glues can be identified as a significant chemical risks. To assess the level of occupational exposure a sector study was conducted on small to medium size companies: in 9 were measured the respirable and inhalable dust concentrations and in 13 the solvents. The measurements were performed using personal samplers. The results confirmed the assumed Similar Exposure Group (SEG). The average concentrations of dust were well below the TLV-TWA, the Mixture Index for the solvents is exceeded in 9 out of 67 cases, the "critical" solvent has proven to be cyclohexane.

Occupational Exposure Assessment to Antineoplastic Drugs in Nine Italian Hospital Centers over a 5-Year Survey Program.

In the present study, surface contamination where antineoplastic drugs (ADs) are present was investigated, as occupational exposure risk is still an open debate. Despite recommendations and safety standard procedures being in place in health care settings, quantifiable levels of ADs are being reported in the recent literature. Thus, a survey monitoring program was conducted over five years (2016-2021) in nine Italian hospitals. The repeated surveys produced 8288 data points that have been grouped according to the main hospital settings, such as pharmacy areas and patient care units. Based on the most often prepared ADs, the investigated drugs were cyclophosphamide (CP), gemcitabine (GEM), 5-fluorouracil (5-FU), and platinum compounds (Pt). Patient care units had a frequency of positive wipe samples (59%) higher than pharmacies (44%). Conversely, pharmacies had a frequency of positive pad samples higher (24%) than patient care units (10%). Moreover, by statistical analysis, pad samples had a significantly higher risk of contamination in pharmacy areas than in patient care units. In this study, the 75th and the 90th percentiles of the contamination levels were obtained. The 90th percentile was chosen to describe a suitable benchmark that compares results obtained by the present research with those previously reported in the literature. Based upon surface contamination loads, our data showed that 5-FU had the highest concentration values, but the lowest frequency of positive samples. In pharmacy areas, the 90th percentile of 5-FU data distribution was less than 0.346 ng/cm2 and less than 0.443 ng/cm2 in patient care units. AD levels are higher than those reported for health care settings in other European countries yet trends of contamination in Italy have shown to decrease over time.

Modelling infrared radiation exposure by black body-like sources.

In this work, a method previously proposed in the literature (Sisto R, Pinto I, Stacchini N et al. Infrared radiation exposure in traditional glass factories. AIHAJ 2000; 61: 5-10) to evaluate the exposure to infrared (IR) radiation when the source can be approximated as a black body is implemented in a mathematical code developed in Matlab. Some practical situations are discussed. A comparison between the results obtained by a spectroradiometric technique and that obtained by using a broadband radiometer and the modelling of the source is shown. The IR radiation exposure evaluations in a cement industry and in a steel forge are shown and compared to the exposure limit values.

[Risk assessment of chemical agents]. / La valutazione del rischio da agenti chimici.

The risk assessment of chemical agents is a well known and applied process carried out by Industrial Hygienists and Occupational Physicians based on exposure evaluation. The application of REACH (CE 1907/2006), CLP (CE 1272/2008) and SDS (UE 453/2010) introduces some changes and instruments to carry out the occupational exposure assessment, like new classification of substances, Exposure Scenario, suggested control measures that the Industrial Hygienist and the Occupational Physician must evaluate. If there is not a similar Exposure Scenario to apply a new risk assessment must carried out also by recommended software (ECETOC Targeted Risk Assessment; Easy to use workplace EMKG; Stoffenmanager). Looking at the relevance of the control measures and evaluation of Exposure Scenario we report the flowchart of risk assessment and management by the Method of Organisational Congruencies carried out with the Prevention and Protection Service and Occupational Physician Office of the Health Service of the Azienda Provinciale of Trento.

Development and Validation of a Bioanalytical UHPLC-MS/MS Method Applied to Murine Liver Tissue for the Determination of Indocyanine Green Loaded in H-Ferritin Nanoparticles.

Indocyanine green (ICG) is one of the most commonly used fluorophores in near-infrared fluorescence-guided techniques. However, the molecule is prone to form aggregates in saline solution with a limited photostability and a moderate fluorescence yield. ICG was thus formulated using protein-based nanoparticles of H-ferritin (HFn) in order to generate a new nanostructure, HFn-ICG. In this study, an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) system was employed to develop and validate the quantitative analysis of ICG in liver tissue samples from HFn-ICG-treated mice. To precipitate HFn, cold acetone in acidic solution at pH 5.0 was used. The processed liver samples were injected into the UHPLC-MS/MS system for analysis using the positive electrospray ionization mode. Chromatographic separation was achieved on a Waters Acquity UPLC® HSS T3 Column (1.8 µm, 2.1 × 100 mm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. The selected reaction monitoring transitions of   m / z 753 → m / z 330 and m / z 827 → m / z 330 were applied for ICG and IR-820 (the internal standard, IS), respectively. The method was selective and linear over a concentration range of 50-1,500 ng/ml. The method was validated for sensitivity, accuracy, precision, extraction recovery, matrix effect, and stability in liver tissue homogenates. ICG extraction recoveries ranged between 85 and 108%. The intra- and inter-day precisions were less than 6.28%. The method was applied to a bio-distribution study to compare the amount of ICG levels from mice treated with HFn-ICG and free ICG. The analyses of the homogenate samples from the two types of treatment showed that the concentration levels of ICG is approximately six-fold higher than those of free ICG (1,411 ± 7.62 ng/ml vs. 235 ± 26.0 ng/ml) at 2 h post injection.

Biomarkers of Low-Level Environmental Exposure to Benzene and Oxidative DNA Damage in Primary School Children in Sardinia, Italy.

BACKGROUND: The main anthropic sources of exposure to airborne benzene include vehicular traffic, cigarette smoke, and industrial emissions. METHODS: To detect early genotoxic effects of environmental exposure to benzene, we monitored environmental, personal, and indoor airborne benzene in children living in an urban area and an area near a petrochemical plant. We also used urinary benzene and S-phenylmercapturic acid (S-PMA) as biomarkers of benzene exposure and urinary 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of early genotoxic effects. RESULTS: Although always below the European Union limit of 5 µg/m3, airborne benzene levels were more elevated in the indoor, outdoor, and personal samples from the industrial surroundings compared to the urban area (p = 0.026, p = 0.005, and p = 0.001, respectively). Children living in the surroundings of the petrochemical plant had urinary benzene values significantly higher than those from the urban area in both the morning and evening samples (p = 0.01 and p = 0.02, respectively). Results of multiple regression modelling showed that age was a significant predictor of 8-OHdG excretion, independent of the sampling hour. Moreover, at the low exposure level experienced by the children participating in this study, neither personal or indoor airborne benzene level, nor personal monitoring data, affected 8-OHdG excretion. CONCLUSIONS: Our results suggest the importance of biological monitoring of low-level environmental exposure and its relation to risk of genotoxic effects among children.

Development and validation of a simple and versatile method for the quantification of everolimus loaded in H-ferritin nanocages using UHPLC-MS/MS.

Everolimus (Eve) is an immunosuppressive macrolide that is being analyzed in various biological matrices and fluids. Its antitumor activity makes this drug suitable not only for organ transplantation but also for breast cancer treatments. In the attempt to reduce the incidence and severity of its side effects, Eve was loaded in H-ferritin (HFn), a natural biomolecule that is involved in specific cellular uptake pathways. Thus, Eve pre-complexed with Cu(II) and encapsulated in HFn resulted in an Eve nanoformulation, named HEve. The quantification of HEve was performed using a tailored pH-induced procedure to precipitate H-ferritin. This sample preparation was effective enough to reduce the ion suppression effect on the mass spectrometric responses of Eve in electrospray ionization (ESI). The ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-ESI-MS/MS) system operating in positive ionization mode showed to be a versatile technique in achieving more than 77 % recovery of Eve from the cytoplasmic compartment. This simple, selective and sensitive method enabled the quantification of Eve within the linear range of 2.5-100 ng/mL in matrix spiked with the isotope-labeled internal standard, EveD4. This method was validated according to FDA Guidance. The intracellular distribution of HEve and its accumulation at a cytoplasmic level were studied in breast cancer cell lines. As expected, HEve was more effective than free Eve on sensitive (i.e. BT474) and resistant cell lines, as a result of a better penetration into the target subcellular compartment.

Assessment of airborne microorganism contamination in an industrial area characterized by an open composting facility and a wastewater treatment plant.

In order to assess the potential exposure hazard to workers and people living in the immediate surroundings of an area characterized by an open composting facility and a wastewater treatment plant, a quantitative and a qualitative analysis of airborne microorganisms were carried out. Air sampling was performed once a week for four consecutive weeks in summer and winter. Six sites were selected as air sampling sites: one was upwind at approximately 40 m from the facilities; the other five were downwind at increasing distances from the facilities, with the furthest at 100 m away. Monitoring permitted us to verify the influence that the composting activities and wastewater treatment had on the bacterial and fungal contamination of the air. The results obtained have been expressed by means of contamination indexes that have already been used in previous works: a major microbiological contamination near the plants was evidenced. Near the facilities, mesophilic bacteria, psychrophilic bacteria and microfungi showed the highest median concentrations, respectively, of 307.5, 327.5 and 257.5 CFU/m(3). Moreover, the season generally influenced the concentration of the bacteria as well as of the fungi; higher in summer than in winter. The contamination index global index of microbial contamination (GIMC/m(3)) showed mean values of 4058.9 in summer and 439.7 in winter and the contamination index-amplification index (AI) showed values of 4.5 and 1.1 in the same seasons, respectively. Controlling the seasonal effect, mesophilic bacteria, Pseudomonas spp. and Enterobacteriaceae showed a significant decline in concentration with respect to upwind air samples and with increasing distance. Both GIMC and AI showed a significant decline with respect to upwind air samples by increasing the distance from facilities after adjusting for the seasonal effect. In conclusion, even if these plants do not represent a potential risk for nearby populations, they may pose a potential health risk for workers.

Field evaluation of thermal and chemical desorption BTEX radial diffusive sampler radiello compared with active (pumped) samplers for ambient air measurements.

The performance of two types of radiello diffusive samplers, filled with a thermally desorbable adsorbent (graphitised carbon Carbograph 4) and with a solvent desorbable adsorbent (activated charcoal), respectively, have been evaluated for the monitoring of BTEX in ambient air, by comparison with active (pumped) samplers. A two year survey was carried out in Padua, a medium-sized town, in a traffic site, close to a busy crossroad. The concentrations of BTEX were measured for 15 campaigns, during which four series of radial diffusive samplers were exposed for 2 day, 7 day, 10 day and 14 day time periods, respectively. Every series of chemical desorption samplers included three replicates; thermal desorption samplers included six replicates, three of them filled with freshly conditioned cartridges and three filled with regenerated cartridges. No significant difference in the levels measured either by new or by regenerated cartridges has been found. During three campaigns (summer 2004, winter and spring 2005) two active (pumped) samplers were added for each sampling period. The diffusive uptake rates have been calculated and modelled under various conditions of concentration, temperature and exposure time. The effects of the environmental factors on the performances of both solvent and thermally desorbable samplers have been evaluated. The repeatability of the whole measurement process (sampling and analysis) was calculated for every sampling duration. The comparison of concentration levels measured by diffusive and active sampling methods shows correlation coefficients R >or= 0.98 (p<0.01) for all the compounds. The uncertainty of the diffusive sampling method under field conditions, using active sampling as the reference method, has been assessed according to the ISO 13752 requirements. On field relative expanded uncertainty for benzene has been found below 20%.

Exposure duration and absorbed dose assessment in pesticide-exposed agricultural workers: Implications for risk assessment and modeling.

INTRODUCTION: Absorbed dose assessment from dermal exposure involves multiplying skin contamination by the dermal absorption coefficient, which is usually defined for the standard workday of 8 h. This strategy may suffer from limitations when the duration of exposure is extremely variable, such as in agricultural exposure to pesticides. OBJECTIVES: The aim of this study was to estimate the dose of mancozeb absorbed by agricultural pesticide applicators in a typical working day considering the real duration of exposure, to compare these estimates with those coming from the use of the Fixed Fractional Approach, and to assess the suitability of the dose estimates in the interpretation of biological monitoring results. METHODS: In a series of real-life field studies on 29 workers applying mancozeb in vineyards for 38 work days, three sets of data were collected: information regarding work activities for each work day, potential (on clothes) and actual skin exposure using the "patch" methodology, and excretion of ethylenethiourea (ETU) in the 24-h pre-exposure and 24-h post-exposure urine samples. The statistical analyses were done using the R Language and Environment for Statistical Computing. RESULTS: Accounting for the duration of exposure led to a substantial reduction in the absorbed dose estimates, compared to the estimates coming from the Fixed Fractional Approach. In particular, absorbed dose by the body, hands' and total absorbed dose were reduced by 50%, 81%, and 80% respectively. The body dose estimated considering both approaches still correlated better with post-exposure 24-h urine ETU levels than the hands' dose, although more than 90% of the estimated total absorbed dose comes from the hands. CONCLUSIONS: An accurate estimate of the absorbed dose, carried out considering the real duration of exposure, can result in a higher correlation with a biomarker of occupational exposure, such as urine ETU, or at least yield more accurate results. This can facilitate the interpretation of biological monitoring data in pesticide-exposed agricultural workers despite the absence of biological exposure limits. ETU should be evaluated as a potentially relevant source of exposure due to ethylenebisdithiocarbamates' (EBDCs) degradation in the formulated product or spray mixture.

Paclitaxel-Loaded Silk Fibroin Nanoparticles: Method Validation by UHPLC-MS/MS to Assess an Exogenous Approach to Load Cytotoxic Drugs.

The aim of this work was to load an anticancer drug, paclitaxel (PTX), on Silk Fibroin Nanoparticles (SFNs) by using an exogenous approach. SFNs were produced, freeze-dried and then loaded with PTX. An exogenous method allowed us to reduce both drug loss and environmental impact. In order to quantify PTX loaded in SFNs, a simple and reliable method using reversed phase liquid chromatography coupled to tandem mass spectrometry (rp-UHPLC-MS/MS) was developed. This methodology was validated by the determination of spiked QC samples in three consecutive days. Good accuracy and precision of the method were obtained, while the intra-day and inter-day precisions were less than 10.3%. For PTX, the limit of quantitation (LOQ) was 5.0 ng/mL. Recovery from the matrix (SFNs-PTX pellets) was calculated (81.2% at LOQ value) as PTX was entrapped in a new matrix like the polymer silk fibroin-based. This method was successfully applied to determine the encapsulation efficiency (1.00 ± 0.19%) and the nanoparticle loading (0.12 ± 0.02% w/w). The in vitro anticancer activity of SFNs-PTX was tested against CFPAC-1 cancer cells; results demonstrated a very high cytotoxic activity of SFNs-PTX, with a dose dependent inhibition of CFPAC-1 proliferation, confirmed by the IC50 value of 3450 ± 750 ng/mL.

Environmental and biological monitoring for the identification of main exposure determinants in vineyard mancozeb applicators.

Grapevine is a vulnerable crop to several fungal diseases often requiring the use of ethylenebisdithiocarbamate (EBDC) fungicides, such as mancozeb. This fungicide has been reported to have goitrogenic, endocrine disrupting, and possibly immunotoxic effects. The aim of this study was to assess workers' exposure in two scenarios of mancozeb application and analyse the main determinants of exposure in order to better understand their mechanism of influence. Environmental monitoring was performed using a modified Organisation for Economic Co-operation and Development (OECD) "patch" methodology and by hand-wash collection, while mancozeb's metabolite, ethylenethiourea (ETU), was measured in 24-h preexposure and postexposure urine samples. Liquid chromatography-mass spectrometry was used for determination of mancozeb and ETU in different kinds of samples. Closed tractor use resulted in 40 times lower potential exposure compared with open tractor. Coveralls reduced skin exposure 4 and 10 times in case of open and closed tractors, respectively. Gloves used during application resulted in 10 times lower hand exposure in open but increased exposure in closed tractors. This study has demonstrated that exposure to mancozeb is low if safe occupational hygiene procedures are adopted. ETU is confirmed as suitable biological marker of occupational exposure to mancozeb, but the absence of biological exposure limits significantly reduces the possibility to interpret biological monitoring results in occupationally exposed workers.

A new, sensitive and versatile assay for quantitative determination of α-fluoro-ß-alanine (AFBA) in human urine by using the reversed-phase ultrahigh performance-tandem mass spectrometry (rp-UHPLC-MS/MS) system.

A method for the quantitation of α-fluoro-ß-alanine (AFBA), the main metabolite of capecitabine (Cape) and 5-fluoruracil (5-FU), is described. Among antineoplastic drugs (ADs), 5-FU and Cape (the new oral prodrug) are the most commonly applied drugs in cancer therapy. The main objective of this study was to develop a reliable method that would be easy to run on a reversed-phase UHPLC system coupled to tandem mass spectrometry. AFBA was derivatized with Sanger's reagent to ensure complete yield of a stable 2,4 dinitrophenil-α-fluoro-ß-alanine derivative. This method was based on the use of a mixed-mode anion exchange solid phase extraction enabling urinary extracts to be clear of endogenous interferences affecting quantitative results. The assay was validated in human urine according to FDA criteria with the use of a labeled internal standard (ß-alanine-d4) to minimize experimental error. Good accuracy and precision were demonstrated by determining spiked urine QC samples in four consecutive days. The recovery of AFBA was between 70.0 and 82.6%, with a matrix effect that was 12.8%-18.5%. The lower limit of quantitation (LOQ) was 0.5 ng/mL with a coefficient of variation of 5.3%. This assay was successfully applied to determine the levels of this metabolite in a large number of urine samples taken from personnel who were occupationally exposed to ADs.