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The purpose of this study of the Italian Society of Reference Values (SIVR) was to provide the reference values for metals in the urine of the Italian general population. Thirteen sampling centres situated in the north, centre and south of Italy took part in this project. Each sampling centre selected 20 adult subjects. The sample was made up of 120 male and 140 female non-smokers or smokers who had abandoned the habit at least 5 years previously, aged between 18 and 60 years. Urine samples were obtained from the same subjects in June and again in November of the same year. During collection of these two samples, we administered an ad hoc questionnaire designed to assess factors that might influence exposure and the results of the study such as personal characteristics, occupational or extra-occupational activities, dietary habits, the presence of dental fillings containing amalgam, the frequency and mode of exposure to passive smoking and exhaust gases of motor vehicles (traffic). Therefore, the urinary levels of thirteen trace elements (Be, Cd, Co, Cr, Cu, In, Mn, Ni, Pb, Pt, Sb, Tl and V) were determined by Inductively Coupled Plasma Mass Spectrometry. The concentrations obtained (95 th percentile) are in μg/L: 0.034, 0.900, 2.24, 0.600, 24.0, 0.013, 1.53, 4.44, 2.64, 0.022, 0.095, 0.759 and 0.855 for Be, Cd, Co, Cr, Cu, In, Mn, Ni, Pb, Pt, Sb, Tl and V, respectively. Further studies with a larger number of subjects are needed in order to continue the biomonitoring of the Italian general population and to monitor the modified levels over time., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The aim of the study was to investigate the effect of various factors that modulate the metabolism of benzene, including smoking habits, metabolic genotype of GST and co-exposure to toluene, on the levels of three biomarkers, i.e. urinary benzene (UB), S-phenylmercapturic acid (SPMA) and t,t-muconic acid (t,t-MA), in 146 refinery workers exposed to low levels of air benzene (AB) in the range <1.5-529.2 μg/m 3 (mean value 32.6 μg/m 3 ). The study confirmed the validity of SPMA as a good biomarker of benzene exposure even at low levels of exposure. It was also confirmed that cigarette smoking is the main confounding factor when assessing biological monitoring data of occupational exposure to AB. Our data indicate that the GSTT1, but not the GSTM1 genotype, significantly increases the urinary levels of SPMA, even at low levels of exposure. It is not known, though, whether subjects with a GSTT1 "null" genotype may be more susceptible to the effects of benzene. Finally, environmental toluene appears to inhibit the metabolism of benzene to SPMA even at low concentrations, also resulting in an underestimation by SPMA levels of the actual exposure of workers to benzene., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study aimed to correlate environmental sevoflurane levels with urinary concentrations of sevoflurane (Sev-U) or its metabolite hexafluoroisopropanol (HFIP) in order to assess and discuss the main issues relating to which biomarker of sevoflurane exposure is best, and possibly suggest the corresponding biological equivalent exposure limit values. Individual sevoflurane exposure was measured in 100 healthcare operators at five hospitals in north-east Italy using the passive air sampling device Radiello(®), and assaying Sev-U and HFIP concentrations in their urine collected at the end of the operating room session. All analyses were performed by gas chromatography-mass spectrometry. Environmental sevoflurane levels in the operating rooms were also monitored continuously using an infrared photoacoustic analyzer. Our results showed very low individual sevoflurane exposure levels, generally below 0.5 ppm (mean 0.116 ppm; range 0.007-0.940 ppm). Sev-U and HFIP concentrations were in the range of 0.1-17.28 μg/L and 5-550 μg/L, respectively. Both biomarkers showed a statistically significant correlation with the environmental exposure levels (Sev-U, r=0.49; HFIP, r=0.52), albeit showing fairly scattered values. Sev-U values seem to be influenced by peaks of exposure, especially at the end of the operating-room session, whereas HFIP levels by exposure on the previous day, the data being consistent with the biomarkers' very different half-lives (2.8 and 19 h, respectively). According to our results, both Sev-U and HFIP are appropriate biomarkers for assessing sevoflurane exposure at low levels, although with some differences in times/patterns of exposure. More work is needed to identify the best biomarker of sevoflurane exposure and the corresponding biological equivalent exposure limit values., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The environmental and biological monitoring of benzene exposure is crucial to prevent the toxic effects of this solvent in workers. The degree of correlation, however, between the two and of different biomarkers among them varies, particularly at low levels of exposure, depending on various factors, including variability in metabolizing enzymes and smoking habits. To investigate these further, a cohort of 28 petrochemical workers (6 smokers and 22 non smokers) was monitored throughout ten consecutive days, on two occasions, two years apart, by collecting in total 173 environmental and biological samples. The airborne benzene levels, the urinary t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (S-PMA) concentrations, and the glutathione S-transferases (GST) M1 and T1 genotypes were measured. S-PMA was the only metabolite statistically correlated with airborne benzene levels (r=0.447, P<0.0001), particularly in non smokers (r=0.667, P<0.0001), the smoking habit being the only variable influencing metabolite excretion. Finally, a reduced S-PMA excretion was found to be associated with the GSTT1, but not the GSTM1, null genotype. In conclusion, the results show that S-PMA, but not t,t-MA, is able to monitor exposure to low benzene concentrations and confirm that the GSTT1 null genotype has a significant influence on metabolite excretion. The influence of the GSTT1 null genotype, however, was low, even when studying each subject with several urine samples., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The present work was aimed to study in petrochemical industry operators the correlation, if any, between environmental exposure to low levels of benzene and two biological exposure indexes in end-shift urine, i.e. trans, trans-muconic acid (t,t-MA) and S-phenylmercapturic acid (SPMA). Exposure to benzene was assessed in 133 male subjects employed in outdoor operations in a petrochemical plant, using personal passive-diffusive air samplers worn at the breathing zone; adsorbed benzene was determined by GC-FID analysis. S-PMA was determined by a new HPLCMS/MS method, after (quantitative) acidic hydrolysis of the cysteine conjugate precursor. t,t-MA was measured by an HPLC-UV method. Smoking habits were assessed by means of a self-administered questionnaire. Both environmental and biological monitoring data showed that benzene exposure of petrochemical industry operators was low (mean values were 0.014ppm, 101mug/g creat, and 2.8mug/g creat, for benzene, t,t-MA, and S-PMA, respectively) if compared with the ACGIH limits. Cigarette smoking was confirmed to be a strong confounding factor for the urinary excretion of both metabolites: statistically significant increases of t,t-MA and S-PMA levels were recorded in smokers when compared to non-smokers (p<0.0001). The best correlation found was that between exposure to benzene and S-PMA levels, particularly in non-smokers. This was partly due to the hydrolysis of the S-PMA precursor N-acetyl-S-(1,2-dihydro-2-hydroxyphenyl)-l-cysteine, a crucial step of the new analytical method used, which indeed reduced the variability of the results by means of an improved standardization of this critical preanalytical factor. A weaker correlation was found between exposure to benzene and t,t-MA, possibly explained by the fact that the latter is also a metabolite of sorbic acid, a common diet component. In summary, even at such low levels of exposure, urinary metabolites proved to be a useful tool for assessing individual occupational exposure to benzene, S-PMA appearing to be a more specific biomarker than t,t-MA, particularly in non-smokers., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to assess gasoline filling-station attendants' exposure to benzene and to determine which biological exposure index (BEI), trans,trans-muconic acid (t,t-MA) or S-phenylmercapturic acid (S-PMA), shows better correlation with environmental exposure. Exposure to benzene was measured using passive samplers (Radiello) attached to the collar of the overalls of subjects (n=33) just before the work-shift (approximately 8h); analysis was performed by GC-FID. S-PMA and t,t-MA were determined, respectively, by an immunochemiluminescent assay based on specific monoclonal antibodies and by HPLC-UV at 264 nm. Both methods of biological monitoring were performed on beginning and end-shift urine samples, and expected t,t-MA and S-PMA values were calculated. Smoking habits and life-style were ascertained by means of a questionnaire. Both environmental and biological monitoring data showed that benzene exposure for gasoline filling-station attendants was low when compared with the respective ACGIH limit values (means-benzene: 0.044 mg/m(3); t,t-MA: 171 microg/g creatinine; S-PMA: 2.7 microg/g creatinine). No significant correlation was found between exposure to benzene and t,t-MA or S-PMA excretion data. The use of expected values was also experimented for S-PMA and t,t-MA. This consists of calculating, on the basis of the known half-life of the benzene metabolite, the concentration of that metabolite that a worker should present at the end of the work-shift, the difference between this value and the value actually found is a measure of benzene exposure during work. The use of expected values in biological monitoring did not improve correlations. At these low benzene levels, environmental monitoring seems to be the best method of evaluating individual exposure. However, biological monitoring remains useful, as a mean of assessing group exposure.