Biomedical subjects

S Fustinoni

Publications and source records attributed to S Fustinoni.

At least 19 recordsLinked to original sources

PubMed2004

Biological monitoring in occupational exposure to low levels of 1,3-butadiene.

Exposure to 1,3-butadiene (BD), a probable carcinogen to humans, was investigated in two groups of subjects working in a petrochemical plant where BD is produced and used to prepare polymers: 42 occupationally exposed workers and 43 internal non-occupationally exposed controls. BD personal exposure was very low but significantly different in the two groups (median airborne BD 1.5 and 0.4 microg/m(3) in exposed and controls, respectively). Similarly, BD in blood and urine, but not in exhaled air, was higher in the exposed workers than in controls (blood BD 3.7 ng/l versus <1.8 ng/l, urinary BD 2.4 ng/l versus <1.0 ng/l). These three biomarkers correlated significantly with personal exposure ( 0.283 < or = Pearson's r < or = 0.383) and between them (0.780 < or = r < or = 0.896). Excretion of urinary mercapturic acids N-acetyl-S-(3,4-hydroxybutyl)-l-cysteine (MI), N-acetyl-S-(1-hydroxymethyl-2-propenyl)-l-cysteine and N-acetyl-S-(2-hydroxy-3-butenyl)-l-cysteine (MII), chromosomal aberrations (CA), and sister chromatid exchanges (SCE) in peripheral blood lymphocytes were not influenced by occupational exposure. Our results show that unmetabolised BD in biological fluids, and particularly urinary BD, represents the biomarker of choice for assessing occupational exposure to low airborne concentrations of BD.

Acetylcysteine↗

PubMed2002

Ethylenethiourea in urine as an indicator of exposure to mancozeb in vineyard workers.

In the present study, the personal exposure to mancozeb and/or ethilenethiourea (ETU) in 13 Italian vineyard workers and in 13 subjects without occupational exposure to pesticides was investigated. With this aim, the level of ETU in urine and the dermal exposure to mancozeb were determined. Baseline urinary ETU results were lower than the analytical limit of detection for all controls (<0.5 microg/g creatinine) and for ten workers (median <0.5, range <0.5-3.4 microg/g creatinine). In workers, urinary ETU was significantly increased at the end of shift (2.5, <0.5-95.2 microg/g creatinine) compared with baseline levels. End-shift urinary ETU was higher in operators using open tractors (n=7) than in those using closed tractors (n=5) (16.2 vs. 2.4 microg/g creatinine), but the difference was not significant (P=0.073). End-shift urinary ETU was positively correlated with dermal exposure to mancozeb determined both over the clothes and on the skin (Spearman's rho=0.770 and 0.702, P=0.009 and 0.024, respectively). Wine consumption positively influenced the excretion of ETU.

Adult↗

PubMed2001

Hemoglobin adducts as biomarkers of 1,3-butadiene in occupationally low exposed Italian workers and a few diesel-exposed miners.

Hemoglobin adducts were determined as biomarkers of 1,3-butadiene (BD) in 30 workers and 10 controls from an Italian BD plant and in 14 diesel-exposed miners. N-(2,3,4-trihydroxybutyl)valine (THBVal), an N-terminal valine globin adduct of reactive butadiene metabolites, was analyzed by gas chromatography/high resolution mass spectrometry after a modified Edman degradation and further acetylation. The BD exposure for the plant workers was 31 microg/m(3) (personal sampling). Whereas there was no detectable difference in hemoglobin adduct levels (range 17.7-61.4 pmol/g globin) between the total group of exposed and controls, slight but significant differences could be found between two subgroups of workers from different production units as well as one subgroup and controls (P<0.05), between smoking (n=13) and non-smoking exposed workers (n=17; P=0.066) as well as between smoking exposed workers and controls (P=0.055). Adduct levels of the miners (all non-smokers) were in the same range as those of the Italian BD-workers and controls. The internal exposure and strain measured by THBVal levels resulting from a very low occupational BD exposure was in the range of the contribution of moderate smoking.

Biomarkers↗

PubMed2001

Determination of monobromobimane derivatives of phenylmercapturic and benzylmercapturic acids in urine by high-performance liquid chromatography and fluorimetry.

A method was developed for the determination in human urine of S-phenylmercapturic (PMA) and S-benzylmercapturic (BMA) acids, metabolites respectively of benzene and toluene. PMA and BMA were determined, after alkaline hydrolysis, to give respectively thiophenol and benzylmercaptan, and coupling of the thiol-containing compounds with monobromobimane (MB), by reversed-phase HPLC on a diphenyl-silica bonded cartridge (100 x 4.6 mm I.D., 5 microm particle size) with fluorimetric detection. Wavelengths for excitation and emission were 375 and 480 nm, respectively. The recovery of PMA and BMA from spiked urines was >90% in the 10-500 microg/l range; the quantification limits were respectively 1 and 0.5 microg/l; day-to-day precision at 42 microg/l was C.V. <7%. The suitability of the proposed procedure for the biological monitoring of exposure to low-level airborne concentrations of benzene and toluene, was evaluated by analyzing the urinary excretion of PMA and BMA in subjects exposed to different sources of aromatic hydrocarbons, namely occupationally-unexposed referents (non-smokers, n=15; moderate smokers, n=8; mean number of cigarettes smoked per-day=17 cig/day) and non-smoker workers occupationally exposed to toluene in maintenance operations of rotogravure machines (non-smokers, n=17). Among referents, non-smokers showed values of PMA ranging from <1 to 4.6 microg/l and BMA from 1.0 to 10.4 microg/l; in smokers, PMA values ranging from 1.2 to 6.7 microg/l and BMA from 9.3 to 39.9 microg/l, were observed. In occupationally exposed non-smoker subjects, BMA median excretion value (23.6 microg/l) was higher than in non-smoker referents (3.5 microg/l) (P<0.001) and individual BMA values (y, microg/l) were associated and increased with airborne toluene concentration (x, mg/m3) according to the equation y=6.5+0.65x (r=0.69, P<0.01, n=17). The proposed analytical method appears to be a sensitive and specific tool for biological monitoring of low-level exposure to benzene and toluene mixtures in occupational and environmental toxicology laboratory.

Acetylcysteine↗

PubMed2001

Urinary benzene as a biomarker of exposure among occupationally exposed and unexposed subjects.

Urinary benzene (UB) was investigated as a biomarker of exposure among benzene-exposed workers and unexposed subjects in Shanghai, China. Measurements were performed via headspace solid phase microextraction of 0.5 ml of urine specimens followed by gas chromatography-mass spectrometry. This assay is simple and more sensitive than other methods (detection limit 0.016 microg benzene/l urine). The median daily benzene exposure was 31 p.p.m. (range 1.65-329 p.p.m.). When subjects were divided into controls (n = 41), those exposed to < or =31 p.p.m. benzene (n = 22) and >31 p.p.m. benzene (n = 20), the median UB levels were 0.069, 4.95 and 46.1 microg/l, respectively (Spearman r = 0.879, P < 0.0001). A linear relationship was observed between the logarithm of UB and the logarithm of benzene exposure in exposed subjects according to the following equation: ln(UB, microg/l) = 0.196 + 0.709 ln (exposure, p.p.m.) (r = 0.717, P < 0.0001). Considering all subjects, linear relationships were also observed between the logarithm of UB and the corresponding logarithms of four urinary metabolites of benzene, namely t,t-muconic acid (r = 0.938, P < 0.0001), phenol (r = 0.826, P < 0.0001), catechol (r = 0.812, P < 0.0001) and hydroquinone (r = 0.898, P: < 0.0001). Ratios of individual metabolite levels to total metabolites versus UB provide evidence of competitive inhibition of CYP450 enzymes leading to increased production of phenol and catechol at the expense of hydroquinone and muconic acid. Among control subjects UB was readily detected with a mean level of 0.145 microg/l (range 0.027-2.06 microg/l), compared with 5.63 microg/l (range 0.837-26.38 microg/l) in workers exposed to benzene below 10 p.p.m. (P < 0.0001). This suggests that UB is a good biomarker for exposure to low levels of benzene.

Benzene↗

PubMed2000

Comparison between blood and urinary toluene as biomarkers of exposure to toluene.

OBJECTIVES: To compare blood toluene (TOL-B) and urinary toluene (TOL-U) as biomarkers of occupational exposure to toluene, and to set a suitable procedure for collection and handling of specimens. METHOD: An assay based on headspace solid-phase microextraction (SPME) was used both for the determination of toluene urine/air partition coefficient (lambdaurine/air) and for the biological monitoring of exposure to toluene in 31 workers (group A) and in 116 non-occupationally exposed subjects (group B). Environmental toluene (TOL-A) was sampled during the work shift (group A) or during the 24 h before specimen collection (group B). Blood and urine specimens were collected at the end of the shift (group A) or in the morning (group B) and toluene was measured. RESULTS: Toluene lambdaurine/air was 3.3 +/- 0.9. Based on the specimen/air partition coefficient, it was calculated that the vial in which the sample is collected had to be filled up to 85% of its volume with urine and 50% with blood in order to limit the loss of toluene in the air above the specimen to less than 5%. Environmental and biological monitoring of workers showed that the median personal exposure to toluene (TOL-A) during the work-shift was 80 mg/m3, the corresponding TOL-B was 82 microg/l and TOL-U was 13 microg/l. Personal exposure to toluene in environmentally exposed subjects was 0.05 mg/m3, TOL-B was 0.36 microg/l and TOL-U was 0.20 microg/l. A significant correlation (P < 0.05) was observed between TOL-B or TOL-U and TOL-A (Pearson's r = 0.782 and 0.754) in workers, but not in controls. A significant correlation was found between TOL-U and TOL-B both in workers and in controls (r = 0.845 and 0.681). CONCLUSION: The comparative evaluation of TOL-B and TOL-U showed that they can be considered to be equivalent biomarkers as regards their capacity to distinguish workers and controls and to correlate with exposure. However, considering that TOL-U does not require an invasive specimen collection, it appears to be a more convenient tool for the biological monitoring of exposure to toluene.

Adult↗

PubMed2000

Assessment through environmental and biological measurements of total daily exposure to volatile organic compounds of office workers in Milan, Italy.

Personal exposure to total volatile organic compounds (TVOCs), benzene and toluene of 100 Milan office workers was assessed through personal air monitoring at home, in the office, and during commuting. Biological monitoring was performed by measuring blood benzene and toluene concentrations together with urinary trans-trans-muconic acid (t,t-MA) and cotinine at the end of the monitoring period. The geometric means of the total 24-h personal exposure were 514 micrograms/m3 for TVOCs, 21.2 micrograms/m3 for benzene and 35.2 micrograms/m3 for toluene. Daily exposure to the volatile organic compounds was almost totally determined by indoor exposure at home and in the office, with a minor contribution in the transport means. An important factor determining exposure to benzene was found to be tobacco smoke, both for active smokers and for non-smokers exposed to environmental tobacco smoke (ETS). All the mean levels of the biological indicators were significantly higher in active smokers than in non-smoking subjects non-exposed to ETS; urine cotinine and t,t-MA levels were also significantly higher in non-smokers exposed to ETS than in non-smokers non-exposed to ETS.

Adult↗

PubMed1999

Matrix interferences in the analysis of benzene in urine.

The analysis of benzene in urine of the general population or of exposed workers can be performed with different methods using the 'purge and trap' or 'solid-phase microextraction' techniques in combination with gas chromatographic analysis and photoionisation or mass spectrometric detection. The published results, however, are deeply conflicting. Differences in sample preparation by different research groups and our own preliminary observations prompted us to investigate pre-analytical and analytical factors potentially capable of modifying the urinary benzene quantification results. Benzene concentrations were measured in 20 urine samples in relation to different conditioning conditions (at 24, 40 and 80 degrees C) and at basic or acid pH. Urinary protein concentrations were measured in the same samples. Urine heating at 80 degrees C yields benzene concentrations on average five times higher than at 24 degrees C. On acidification of urine, the benzene released increases up to 28-fold in comparison to that obtained at uncorrected 'physiological' pH. Despite a widely scattered data distribution, a statistically significant linear correlation was found between 'heat-released' and 'acid-labile' benzene values. There was no correlation between total urinary proteins present in 'physiological' concentrations (between 12 and 110 mg/l) and the different kinds of benzene in urine. Our results could perhaps be explained if it is supposed that part of the benzene in urine is absorbed onto sediment, or bound to specific proteins, or derived from parent molecules and is released with pH modification or heat administration. Our observations may also help to explain why the urinary benzene concentrations reported by different investigators vary considerably even when environmental levels are comparable.

Artifacts↗

PubMed1999

Gas chromatography-electron-capture detection of urinary methylhippuric acid isomers as biomarkers of environmental exposure to xylene.

Methylhippuric acid isomers (MHAs), urinary metabolites of xylenes, were determined, after clean-up by C18-SPE and esterification with hexafluoroisopropanol and diisopropylcarbodiimide, by GC with ECD detection, on an SPB-35 capillary column (30 m, 0.32 mm I.D., 0.25 microm film thickness, beta = 320). S-benzyl-mercapturic acid was used for internal standardization. Chromatographic conditions were: oven temperature 162 degrees C, for 14.2 min; ramp by 30 degrees C/min to 190 degrees C, for 3.5 min; ramp by 30 degrees C/min to 250 degrees C, for 4 min; helium flow rate: 1.7 ml/min; detector and injector temperature: 300 degrees C. The sample (1 microl) was injected with a split injection technique (split ratio 5:1). MHA recovery was >95% in the 0.5-20 micromol/l range; the limit of detection was <0.25 micromol/l; day-to-day precision, at 2 micromol/l, was Cv<10%. Urinary MHAs were determined in subjects exposed to different low-level sources of xylenes: (a) tobacco smoking habit and (b) BTX urban air pollution (airborne xylene ranging from 0.1 to 3.7 micromol/m3). Study (a) showed a significant difference between urinary MHA median excretion values of nonsmokers and smokers (4.6 micromol/l vs. 8.1 micromol/l, p<0.001). Study (b) revealed a significant difference between indoor workers and outdoor workers (4.3 micromol/l vs. 6.9 micromol/l, p<0.001), and evidenced a relationship between MHAs (y, micromol/mmol creatinine) and airborne xylene (x, micromol/m3) (y = 0.085+0.34x; r = 0.82, p<0.001, n = 56). Proposed biomarkers could represent reliable tools to study very low-level exposure to aromatic hydrocarbons such as those observed in the urban pollution due to vehicular traffic or in indoor air quality evaluation.

Air Pollution↗

PubMed1999

Headspace solid-phase microextraction for the determination of benzene, toluene, ethylbenzene and xylenes in urine.

A method for the determination of benzene, toluene, ethylbenzene and xylenes (BTEX) in urine of people exposed to these airborne pollutants present in the living environment, has been described. Solid-phase microextraction has been used for sampling BTEX from the headspace of urine and gas chromatography-mass spectrometry has been applied for the selective analysis of chemicals. The method has the following features: small volume of urine (2 ml) needed, linearity in the range of interest (from the limit of detection up to 5000 ng/l) with coefficient of correlation > or =0.998, limit of detection in the range 12-34 ng/l, good repeatability (coefficient of variation 2-7%), high specificity. The stability of the urine sample during storage (-20 degrees C) was evaluated: BTEX remained stable for up to 2 months. The assay has been successfully applied to the biological monitoring of two subjects environmentally exposed to airborne BTEX in an urban area.

Benzene↗

PubMed1998

Albumin and hemoglobin adducts as biomarkers of exposure to styrene in fiberglass-reinforced-plastics workers.

OBJECTIVE: The purpose of this work was to compare levels of styrene-7,8-oxide (SO) adducts of albumin (Alb) and hemoglobin (Hb) with those of two urinary metabolites of styrene, mandelic acid (MA) and phenylglyoxylic acid (PGA), among workers exposed to styrene in the reinforced-plastics industry and in unexposed subjects. We also wished to determine whether cigarette smoking influenced adduct levels among these subjects. METHODS: A group of 22 male workers was selected on basis of an expectedly high level of exposure to styrene, and a group of 15 controls was selected from hospital blood donors and hospital staff. In the exposed group, MA and PGA were quantified by high-performance liquid chromatography (HPLC) analysis of urine samples collected prior to the work shift. The SO adducts were cleaved from cysteine residues by reaction with Raney nickel to give 1-phenylethanol (1-PE) and 2-phenylethanol (2-PE), which, after derivatization, were measured using gas chromatography-mass spectrometry (GC-MS) in the negative-chemical-ionization (NCI) mode. RESULTS: The estimated mean levels of MA and MA + PGA were 74 and 159 mg/g creatinine, respectively. Using the levels of urinary metabolites, an average styrene concentration of about 100 mg/m3 in the workplace air was estimated. The mean levels of 2-PE and 1-PE adducts in exposed workers were 2.84 and 0.60 nmol/g Alb and 5.44 and 0.43 nmol/g Hb, respectively. When subjects were stratified by level of urinary metabolites [zero (controls), low-level exposure (MA + PGA < or = 159 mg/g creatinine), and high-level exposure (MA + PGA > 159 mg/g creatinine)] and smoking status (smokers versus nonsmokers), a difference in Alb adduct levels was found among the groups (2-PE P = 0.002, I-PE P = 0.052). The difference in 2-PE-Alb levels was related to exposure category, to smoking status, and to their interaction. Correlations at or near a 0.05 level of significance were observed among the workers (n = 22) between individual levels of SO-protein adducts and MA + PGA (2-PE Alb, r = 0.54, 2-PE Hb, r = 0.40). CONCLUSION: Our data suggest that only exposure to relatively high levels of styrene allows a clear relationship to be detected between styrene exposure and SO adducts, due in part to the effects of cigarette consumption and to the high background levels of these adducts observed in unexposed subjects.

Adult↗

PubMed1996

Fast liquid chromatographic determination of urinary trans,trans-muconic acid.

trans, trans-Muconic acid (1,3-butadiene-1, 4-dicarboxylic acid, MA), a minor urinary metabolite of benzene exposure, was determined, after clean-up by solid-phase anion-exchange chromatography, by reversed-phase HPLC on a C18 column (5 x 0.46 cm I.D., 3 microns particle size), using formic acid-tetrahydrofuran-water (14:17:969) as mobile phase and UV detection at 263 nm. The recovery of MA from spiked urine was > 95% in the 50-500 microgram/l range; the quantification limit was 6 micrograms/l; day-to-day precision, at 300 micrograms/l, was C.V. = 9.2%; the run time was less than 10 min. Urinary MA excretion was measured in two spot urine samples of 131 benzene environmentally exposed subjects: midday values obtained in non-smokers (mean +/- S.D. = 77 +/- 54 micrograms/l, n = 82) were statistically different from those of smokers (169 +/- 85 micrograms/l, n = 30) (P < 0.0001); each group showed a statistically significant increase between MA excretion in midday over morning samples. Moreover, in subjects grouped according to tobacco-smoke exposure level, median values of MA were positively associated with and increased with daily smoking habits.

Air Pollutants↗

PubMed1995

Biological and environmental monitoring of exposure to airborne benzene and other aromatic hydrocarbons in Milan traffic wardens.

Environmental and biological monitoring of airborne aromatic hydrocarbons has been performed in 20 policemen working as traffic wardens exposed to motor vehicle exhausts and in 19 peers employed as clerks. Airborne benzene, toluene, ethylbenzene and xylene concentrations, measured during the workshift, resulted in significantly higher outdoor than indoor concentrations (benzene and related aromatic hydrocarbons mean values, respectively of 53 and 350 micrograms/m3 vs. 29 and 180 micrograms/m3). Blood benzene, toluene, ethylbenzene and xylene concentrations did not differ significantly between indoor and outdoor workers; no differences were found between values obtained at the beginning (07:30 h) and the end of shift (00:30) in either group. Blood hydrocarbon concentrations seem to reflect airborne pollution, whilst the blood benzene concentration determined after the workshift poorly reflects airborne benzene morning peaks. Endshift blood benzene mean concentration in smokers (462 ng/l, n = 9) differs significantly from non-smokers (292 ng/l, n = 39).

Adult↗

PubMed1993

Cinnamamide analogs as inhibitors of protein tyrosine kinases.

Protein tyrosine kinases (PTK) are important signal transducing enzymes involved in the modulation of normal cellular growth and differentiation and have been associated with the etiology of various human cancers. The development of properly designed inhibitors, which block their function by interfering with the substrate binding, may therefore offer an unique target for selective anticancer chemotherapy. Here we describe synthesis and biochemical testing of a novel series of non-peptide PTK inhibitors which have as characteristic active pharmacophore the cinnamamide moiety. For testing we used an exogenous substrate kinase assay based on the phosphorylation of (Val5)-angiotensin II with radiolabelled ATP by the catalytic domain of the PTK encoded by the v-abl oncogene (p45 v-abl). The most potent compounds were found in the class of 3-arylidene-2-oxindoles (II) with IC50 values in the 1 microM range. Among these the 2-tetralylmethylene-, 4-quinolylmethylene-, 5-quinolylmethylene- and 3-indolylmethylene-2-oxindole compounds of formulae 16, 20, 21 and 24 respectively were selected for further investigation.

Acetonitriles↗

PubMedDate not supplied

[European multicenter cross-sectional study on exposure to low doses of benzene].

A cross-sectional multicenter european study has been carried out to evacuate the relations between exposure to low level of benzene and biological markers of internal dose (t,t-MA, S-PMA) and early biological effect (DNA-SSB). The research has shown significantly increased levels (adjusted for smoking habits) of the urinary excretion of t,t-MA, S-PMA and DNA-SSB in petrochemical workers (mean benzene level = 5,694 micrograms/m3) but not in filling station attendants, traffic police officers, and bus drivers compared to referent workers. Dose-response relations were detected between benzene air levels, t,t-MA, S-PMA and DNA-SSB in petrochemical workers, with significantly increased levels of DNA-SSB detected for benzene exposure levels in the range 391-1,800 micrograms/m3 (0.12-0.58 ppm).

Benzene↗

PubMedDate not supplied

[Assessment of exposure to polycyclic aromatic hydrocarbons during road paving].

Asphalt is a mixture of bitumen, (its fumes contain about 1% of polycyclic aromatic hydrocarbons, PAH), and mineral matter. 18 Workers were investigated during road paving to assess PAH exposure by environmental air-monitoring (the 16 most relevant, according to the American Environmental Protection Agency, EPA) and biological monitoring (urinary 1-hydroxypyrene excretion). Our results show that PAH exposure in these workers is not higher than that observed in traffic policemen working in urban areas.

Adult↗

PubMedDate not supplied

[Occupational exposure to fungicides in floriculture in Ecuador].

Floriculture represents one of the major sources of income in the Ecuadorian Andean Region that can be carried out either in open fields as in greenhouses by using chemical compounds, growing hormones and xenobiotics. Among pesticides, ethylenbisdithiocarbamate (EBDTCs) fungicides represent the most extensively used. The aim of the study was the assessment of exposure to EBDTCs in Ecuadorian floricultural workers by the determination of the urinary excretion of the main metabolite of these compounds, ethylenethiourea (ETU). For this purpose, thirty-six floriculture workers and 7 unexposed healthy subjects were recruited for the study. Median level of ETU excretion in agricultural workers before the work shift was 3.2 micrograms/g creatinine, ranging from 0.4 to 34.5 micrograms/g creatinine. After pesticide application, urinary ETU increased to 6.2 micrograms/g creatinine (1.5-26.5) microgram/g creatinine. Urinary ETU resulted significantly higher in overall workers, taken as pre- and post-shift samples, when compared to controls (0.7, 0.4-2.1 micrograms/g creatinine, p < 0.01). According to jobs, applicators showed the highest levels of ETU excretion whereas growing, post-harvesting and maintenance workers showed similar levels of exposure. Higher level ETU excretion was observed in greenhouse compared to open field workers.

Agriculture↗

PubMedDate not supplied

[Lombardy regional project: prevention of occupational tumors].

In Lombardy, the regional project "Prevention of occupational cancers" is ongoing. The main objectives of this project are to identify work environments in which there might be a possible exposure to carcinogenic substances and to elaborate preventive measures. A casual sample of 250 working settings representing the different economic activities has been selected and evaluated. The 10% of the examined workplaces showed a possible exposure to chemical carcinogens. The most common carcinogens were trichloroethylene, preparation of plastics materials containing acrylonitrile-butadiene-stirene, formaldehyde, wood dust, hexavalent chromium, silica and polycyclic aromatic hydrocarbons. Galvanic industries, Bitumen production and placing companies and Plastics processing plants will be studied for environmental and biological monitoring and for the development of preventive measures.

Humans↗