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Biomedical subjects

M Imbriani

Publications and source records attributed to M Imbriani.

At least 19 recordsLinked to original sources
PubMed2004

Gases and organic solvents in urine as biomarkers of occupational exposure: a review.

A brief review of urine analysis in studies of occupational exposure to volatile organic compounds and gases is provided. Analysis of exhaled breath for volatile compounds does not have a long history in occupational medicine. A number of studies has been undertaken since the 1980s, and the methods are well enough accepted to be put forward as biological equivalents of threshold limit values (TLVs) for some volatile organic compounds (VOCs) such as acetone; methanol; methyl ethyl ketone (MEK); methyl isobutyl ketone (MIBK); tetrahydrofurane; dichloromethane. In the last 20 years many scientific articles have shown that the urinary concentrations of unchanged solvents are correlated with environmental exposure and could be used for biological monitoring. The use of urine analysis of unchanged solvents in occupational applications is not yet widespread. Nonetheless, in the short time since its application, a number of important discoveries has been made, and the future appears bright for this branch of analysis. In this paper, the basic concepts and methodology of urine analysis are briefly presented with a critical revision of the literature on this matter. The excretion mechanisms of organic solvents in urine are discussed, with regard to biological variability, and the future directions of research are described.

Biomarkers↗
PubMed2002

Urinary determination of N-acetyl- S-( N-methylcarbamoyl)cysteine and N-methylformamide in workers exposed to N, N-dimethylformamide.

OBJECTIVES: We conducted this biomonitoring study with the aim of evaluating the correlation between the excretion of N-methylformamide (NMF) (mainly from N-hydroxy- N-methylformamide) and N-acetyl- S-( N-methylcarbamoyl)cysteine (AMCC), and levels of exposure to N, N-dimethylformamide (DMF) among occupationally exposed subjects. METHODS: Exposure levels were determined by personal sampling: breathing zone air samples were collected by means of passive samplers. DMF collected by the charcoal in personal samplers was analysed after extraction with methanol by a gas chromatograph. For the purpose of biological monitoring the levels of NMF and AMCC were measured in pre-shift and post-shift samples. Determinations were carried out by, respectively, gas chromatography and high performance liquid chromatography (HPLC). RESULTS AND CONCLUSIONS: The mean time-weighted average (TWA) exposure was approximately half (13.5 mg/m(3)) of the current threshold limit value, the range of the values was from 0.4 to 75.2 mg/m(3). Environmental DMF concentrations exhibited a significant correlation with the specific mercapturic acid (AMCC) collected at the end of the working week (AMCC Friday morning mg/l=1.384xDMF (mg/m(3))+8.708; r(2)=0.47; P<0.008]; hence urinary AMCC represents an index of the average exposure during several preceding working days, making it possible to calculate the approximate relationship between DMF uptake and excretion of this metabolite. A significant correlation was found also between the daily excretion of NMF and the corresponding levels of DMF in air. The equation of the regression line was: NMF (mg/g creatinine)=0.936xDMF (mg/m(3))+7.306; r(2)=0.522 ( P<0.0001).

Acetylcysteine↗
PubMed2001

Metabolic polymorphisms and urinary biomarkers in subjects with low benzene exposure.

The effect of some common metabolic polymorphisms on the rate of trans,trans-muconic acid (TMA) and S-phenylmercapturic acid (SPMA) excretion was investigated in 169 policemen exposed to low benzene levels (<10 microg/m3) during the work shift. End-shift urinary concentrations of TMA and SPMA, normalized to unmetabolized blood benzene concentration, were used as indicators of individual metabolic capacity. CYP2E1, NQO1, GSTM1, and CSTT1 polymorphisms were analyzed in all subjects by polymerase chain reaction (PCR) restriction fragment length (RFL). The results obtained show significantly elevated levels of TMA and SPMA in urine of smokers compared to nonsmokers, whereas no correlation with environmental benzene was observed. TMA/blood benzene ratio was partially modulated by glutathione S-transferase (GST) genotypes, with significantly higher values in null individuals (GSTM1 and GSTT1 combined). However, a greater fraction of total variance of TMA/blood benzene in the study population was explained by other independent variables, that is, season of sampling, smoking habits, and gender. Variance in SPMA/blood benzene ratio was only associated with smoking and occupation, whereas no significant role was observed for the metabolic polymorphisms considered. These results suggest that in a population exposed to very low benzene concentrations, urinary TMA and SPMA levels are affected to a limited extent by metabolic polymorphisms, whereas other factors, such as gender, lifestyle, or other confounders, may account for a larger fraction of the interindividual variability of these biomarkers.

Acetylcysteine↗
PubMed2001

Environmental and biological monitoring of traffic wardens from the city of Rome.

A molecular epidemiological study on Roman policemen is ongoing. The results of a first assessment of the occupational exposure to aromatic compounds of 66 subjects engaged in traffic control and of 33 office workers are presented in this paper. Passive personal samplers and urinary biomarkers were used to assess exposure to benzene and polycyclic hydrocarbons during work shifts. The results obtained indicate that benzene exposure in outdoor workers is about twice as high as in office workers (geometric mean 7.5 and 3.4 micrograms/m3, respectively). The distribution of individual exposure values was asymmetrical and skewed toward higher values, especially among traffic wardens. Environmental benzene levels recorded by municipal monitoring stations during work shifts (geometric mean 11.2 micrograms/m3) were in the first instance comparable to or greater than individual exposure values. However, several outlier values were observed among personal data that greatly exceeded average environmental benzene concentrations. Among the exposure biomarkers investigated, only blood benzene correlated to some extent with previous exposure to benzene, while a seasonal variation in the excretion of 1-hydroxypyrene and trans-muconic acid was observed in both study groups. In conclusion, these results suggest that outdoor work gives a greater contribution than indoor activities to benzene exposure of Roman citizens. Moreover, relatively high-level exposures can be experienced by outdoor workers, even in the absence of large-scale pollution episodes.

Adult↗
PubMed2001

Exposure to benzene in urban workers: environmental and biological monitoring of traffic police in Rome.

OBJECTIVES: To evaluate the contribution of traffic fumes to exposure to benzene in urban workers, an investigation on personal exposure to benzene in traffic police from the city of Rome was carried out. METHODS: The study was performed from December 1998 to June 1999. Diffusive Radiello personal samplers were used to measure external exposures to benzene and alkyl benzenes during the workshift in 139 policemen who controlled medium to high traffic areas and in 63 office police. Moreover, as biomarkers of internal exposure to benzene, blood benzene, and urinary trans, trans-muconic and S-phenyl mercapturic acids were measured at the beginning and at the end of the workshift in 124 traffic police and 58 office police. RESULTS: Time weighted average (TWA) exposure to benzene was consistently higher among traffic police than among indoor workers (geometric mean 6.8 and 3.5 microg/m(3), respectively). Among the traffic police, the distribution of individual exposures was highly asymmetric, skewed toward higher values. Mean ambient benzene concentrations measured by municipal air monitoring stations during workshifts of traffic police were generally higher (geometric mean 12.6 microg/m(3)) and did not correlat with personal exposure values. In particular, no association was found between highest personal exposure scores and environmental benzene concentrations. Among the exposure biomarkers investigated, only blood benzene correlated slightly with on-shift exposure to benzene, but significant increases in both urinary trans, trans-muconic and S-phenylmercapturic acids were found in active smokers compared with non-smokers, irrespective of their job. CONCLUSION: The exposure to traffic fumes during working activities in medium to high traffic areas in Rome may give a relatively greater contribution to personal exposure to benzene than indoor sources present in confined environments. Smoking significantly contributed to internal exposure to benzene in both indoor and outdoor workers.

Adult↗
PubMed2001

Trichloroethylene in urine as biological exposure index.

Occupational exposure to trichloroethylene (TRI) was studied by analysis of environmental air and urine from 49 workers operating in a special printing house on glass. For the measurement of environmental concentration of TRI (Cenv), the ambient air was sampled using personal passive dosimeters. The activated charcoal was desorbed with carbon disulfide and injected into a gas-cromatograph - mass spectrometer (GC-MSD). The biological monitoring of exposed workers was conducted by determining the concentration of TRI in urine (Curine) Urine concentration of TRI was determined by headspace analysis using GC-MSD. Significant correlation was found between the environmental TRI concentration and urinary TRI concentration. The use of a regression equation between Curine (microg/l) and Cenv (mg/m3) (Curine = 0.081 x Cenv + 4.27) resulted in a value of Curine corresponding to Threshold Limit Value-Time Weighted Average (TLV-TWA) exposure value (269 mg/m3) of 26.0 microg/L.

Adult↗
PubMed2000

Evaluation of half-mask respirator protection in styrene-exposed workers.

OBJECTIVE: The protection afforded by respirators to styrene (St)-exposed workers varies considerably. Our objective was to study the effective 'in the field' reduction in St exposure obtained by negative-pressure half-mask respirators worn by a group of fiberglass-reinforced plastics (FRP) workers. Protection was evaluated by measuring the reduction in urinary St (StU) excretion. METHODS: Seven FRP workers not using respiratory protection devices were studied for a week. External exposure to St was evaluated by personal passive sampling, and the internal dose by StU measurement. Then workers were asked to use a half-mask respirator for a week for the entire morning half-shift, and St exposure and internal dose were re-assessed. RESULTS: Mean environmental levels of St during the morning half-shift were 230-280 mg/m3, i.e., about three times the current limit proposed by ACGIH; the difference among days was not significant. Using respirators was accompanied by a large inter-individual and also intra-individual variability: the estimated reduction of StU values ranged from 30% to 90% (mean 60%). Mean StU values increased by 50% from Monday to Friday, while environmental St concentrations remained steady. Furthermore, the proportion of workers exceeding the biological equivalent exposure limit (BEEL) was 14% on Monday, double (33%) on Thursday, and triple (43%) on Friday. These data suggest a decrease of protection during the week. CONCLUSIONS: The protection afforded by negative-pressure half-mask respirators varies widely, which stresses the need to assess the effective reduction of exposure whenever these devices are introduced for St-exposed workers. If respirators are to be re-used for several days, their performance must be evaluated during the last shift of use. Measurement of urinary excretion of unmodified St proved a useful tool for the evaluation of respirator effectiveness in exposed workers.

Air Pollutants, Occupational↗
PubMed1999

Determination of S-phenylmercapturic acid in urine as an indicator of exposure to benzene.

S-phenylmercapturic acid (S-PMA) was measured in urine from 145 subjects exposed to low benzene concentrations in the air (C(I), benzene). The 8-h, time-weighted exposure intensity of individual workers was monitored by means of charcoal tubes and subsequent gas-chromatographic analysis after desorption with CS2. S-PMA excretion level in urine was determined by high-performance liquid chromatography with fluorescence detection. The following linear correlation was found between S-PMA concentrations in urine and benzene concentrations in the breathing zone: log(S-PMA, microg/g creatinine) = 0.712 log (C(I)-benzene, ppm) + 1.644 (n = 145, r = 0.74, P < 0.001). The geometric mean (GSD) of S-PMA concentrations in urine from 45 subjects occupationally not exposed to benzene but smoking more than 20 cigarettes/day was 7.8 microg/g creatinine (2.11), the corresponding value among non-smokers being 1.0 microg/g creatinine (2.18). It is concluded that the urinary level of S-PMA can be regarded as a useful indicator of exposure to benzene.

Acetylcysteine↗
PubMed1998

Biological monitoring of workers exposed to carbon disulfide (CS2) in a viscose rayon fibers factory.

The exposure-excretion relationship to carbon disulfide (CS2) vapor in 407 exposed workers was studied during the second half of the working week. Carbon disulfide concentrations were also determined in 50 nonexposed subjects. The geometric mean value for CS2 in urine samples from the latter was: 0.23 microgram/l (95% upper limit = 0.52 microgram/l) when log-normal distribution was assumed. Among the exposed workers, the CS2 level in urine samples collected after the first half shift exceeded the 95% upper limit of nonexposed subjects in every case. The time-weighted average intensity of exposure to CS2 vapor was measured using personal diffusive samplers (in which carbon cloth served as an adsorbent). CS2 concentrations in urine were determined in samples collected at the end of the first half shift from the 407 exposed cases as well as from 50 nonexposed controls. There was a significant correlation (p < 0.0001) between the exposure to CS2 vapor at concentrations of up to 64 mg/m3 and the levels of CS2 measured in the urine samples after four hours of exposure. The correlation indicated that a mean level of 15.5 micrograms CS2/l urine (95% confidence range, 13.8-17.1 micrograms/l) was excreted following an exposure to CS2 at 31 mg/m3 (the current occupational exposure limit).

Adult↗
PubMed1997

The urinary excretion of solvents and gases for the biological monitoring of occupational exposure: a review.

'In the field' application of the measurement of urinary excretion of unmodified solvent for the biological monitoring of exposed workers has been investigated in many recent papers. The results obtained for several solvents are reviewed. The values of correlation coefficients (r) and regression lines obtained for benzene, toluene, xylene, styrene, n-hexane, cyclohexane, 2- and 3-methylpentane, methyl chloride, tetrachloroethylene, carbon tetrachloride, methyl chloroform, p-dichlorobenzene, nitrous oxide, halothane, isoflurane, enflurane, acetone, methyl ethyl ketone and methyl isobutyl ketone are presented. The correlations observed were generally good: r values range from 0.50-0.97, and the majority are between 0.84 and 0.90. The regression lines reported for the same solvent in different studies present some variability: this is possibly due to an inadequate control of factors influencing the relationship between external dose and absorption, such as differences in body burden, work load, individual characteristics, etc. These factors are discussed. As a whole, results reported in the literature show that measuring of urinary excretion of unmodified solvents provides a highly sensitive and specific exposure index, and can also be applied for the biological monitoring of occupational exposure to low levels of solvents or to solvent mixtures. Nevertheless, for an adequate assessment of biological limit values, further studies evaluating the reproducibility of regression lines are needed, given that the aspects influencing the correlation between external dose and urinary excretion are fully controlled. Another crucial aspect is the correlation with early effects: even though this has yet to be evaluated for several solvents, for others such as styrene and perchloroethylene a good correlation was obtained, further supporting the usefulness of the measurement of urinary excretion of solvent for the biological monitoring of occupational exposure.

Absorption↗
PubMed1997

Excretion of N-acetyl-S-(1-phenyl-2-hydroxyethyl)-cysteine and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-cysteine in workers exposed to styrene.

Styrene (S) has been shown to be responsible for neurotoxic effects, including behavioural changes and neuroendocrine disturbances. The initial step of S metabolism is conversion to styrene 7,8-epoxide (SO), which is present in two enantiomeric forms [(R)(+)-SO and (S)(-)-SO]; this electrophilic intermediate is considered to be directly responsible for most toxic effects of S. The major urinary metabolites derived from the biotransformation of SO in man are mandelic acid (MA) and phenylglyoxylic acid (PGA). In rats an alternative pathway has been demonstrated, which involves the conjugation of SO to glutathione (GSH), leading to the excretion of two specific mercapturic acids, N-acetyl-S-(-(1-phenyl-2-hydroxyethyl)-cysteine [M1] and N-acetyl-S-(2-phenyl-2-hydroxy-ethyl)-cysteine [M2]; a close relationship has been found between exposure to S and urinary excretion of M1 and M2 in rats. As a consequence of the chiral nature of SO, both M1 and M2 consist of two diastereoisomers (M1-'R', M1-'S', M2-'R' and M2-'S'). Early reports have shown that the conversion of S to mercapturic acids is much lower in man (below 1% of the absorbed dose) than in rats (about 10%). We propose an analytical method for the determination of urinary M1 and M2 in man, which involves a urine clean-up by a chromatographic technique with a short reversed-phase pre-column; purified samples are then deacetylated with porcine acylase and deproteinized by centrifugal ultrafiltration. A derivatization is then performed with o-phthaldialdehyde and 2-mercaptoethanol and the fluorescent derivatives are separated on a reversed-phase analytical column. The mobile phase consists of acetate buffer and methanol mixed at variable proportions, the fluorescence detector is set at 330 nm (exc.) and 440 nm (em.). M1-'S' and M1-'R' are separated (retention times = 52.8 and 73.7 min, respectively) while the diastereoisomers of M2 coelute as a single peak at 70.5 min. The detection limit is about 7 micrograms/l, the coefficients of variation are below 7% and the error percentages are less than 6%. The method was applied to 25 urine samples from workers exposed to S: significant correlations were found between mercapturic acids and MA and PGA, the best correlation being between M2 and PGA (r = 0.79). Urine samples form unexposed subjects showed no detectable amounts of the analytes. A high stereoselectivity is shown by the enzymes involved in the metabolism of S to mercapturic acids: M1-'S', which derives from (S)-SO, is excreted in much higher amounts than M1-'R', which derives from (R)-SO.

Acetylcysteine↗
PubMed1997

Urinary excretion of specific mercapturic acids in workers exposed to styrene.

Styrene is an important chemical of wide industrial use, particularly in the manufacture of polymers and reinforced plastics. Environmental and occupational exposures to styrene occur predominantly via inhalation. Styrene undergoes biotransformation mainly by side chain oxidation catalyzed by cytochrome P-450 enzymes to its reactive metabolite, styrene oxide. The (R)- and (S)-enantiomers of styrene oxide can be conjugated with glutathione to both (R)- and (S)-diastereoisomers of specific mercapturic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). We conducted this biomonitoring study with the aim of evaluating the association between excretion of specific mercapturic acids (M1 and M2) and level of exposure to styrene among occupationally exposed people. The mean time-weighted average (TWA) exposure was about one-half the current threshold limit value, the range of the values varied from 44 to 228 mg/m3. Geometric mean (GM) concentrations of 650, 1,084, and 31.8 micrograms/g creatinine were measured, respectively, for M1-S, M2, and M1-R. The environmental styrene concentration exhibited a significant correlation with total specific mercapturic acid (Mtot = sum of M1-R, M1-S, and M2), making it possible for the first time to calculate the approximate relationship between styrene uptake and excretion of these substances. The M2 mercapturic acid had a better correlation (r = 0.56) with respect to M1-R and M1-S. Significant correlations were found also between the excretion of specific mercapturic acids and biological exposure indices (i.e., mandelic and phenylglyoxylic acids and urinary styrene).

Acetylcysteine↗
PubMed1997

Determination of specific mercapturic acids as an index of exposure to environmental benzene, toluene, and styrene.

Methods were developed for the determination of urinary phenylmercapturic acid (PMA), a metabolite specific for benzene, benzylmercapturic acid (BMA), a metabolite of toluene and phenylhydroxyethylmercapturic acids (PHEMAs), specific for styrene, in human beings. Methods involved sample clean up followed by deacetylation and derivatization of the compounds with o-phthaldialdehyde and 2-mercaptoethanol. The fluorescent derivatives were separated on reversed-phase columns with gradient runs and detected by a fluorescence detector. The detection limits were 0.5 microgram/l for PMA and BMA, and 7 micrograms/l for PHEMAs. The background levels of PMA were higher in smokers than in nonsmokers, while no difference was found in the levels of BMA and PHEMAs. Coexposure to ethanol enanched the excretion of BMA in subjects experimentally exposed to toluene. Correlations were found between environmental benzene (r = 0.74, log transformed data), toluene (r = 0.74) or styrene (r = 0.56) and specific mercapturic acids in workers. The usefulness of PMA, BMA and PHEMAs as biomarkers is critically evaluated.

Acetylcysteine↗
PubMed1996

Determination of urinary mercapturic acids of styrene in man by high-performance liquid chromatography with fluorescence detection.

A method for the determination of urinary N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2) in man was developed. Clean-up of urine samples was obtained by a chromatographic technique, using a short reversed-phase precolumn; purified samples were then deacetylated with porcine acylase I for 16 h at 37 degrees C and deproteinized by centrifugal ultrafiltration. Derivatization was performed with o-phthaldialdehyde and 2-mercaptoethanol and the fluorescent derivatives were separated on a reversed-phase analytical column with a gradient mobile phase consisting of 50 mM acetate buffer (pH 6.5) and methanol. The retention times of the diastereoisomers of M1 (M1-"S" and M1-"R") were 52.8 and 73.7 min, respectively: M2 diastereoisomers eluted as a single peak at 70.5 min. The fluorescence detector was set at 330 nm (excitation) and 440 nm (emission). The detection limit (at a signal-to-noise ratio of three) was about 7 micrograms/1. The method was applied to 25 urine samples from workers exposed to styrene. A relationship was found between urinary mandelic and phenylglyoxylic acids and mercapturic acids specific for styrene. Urine samples from ten non-exposed subjects showed no detectable amounts of analytes.

Acetylcysteine↗
PubMed1996

Acetone in urine as biological index of occupational exposure to isopropyl alcohol.

In order to investigate a role of acetone in urine (AcU, mg/l) as an indicator of occupational exposure to isopropyl alcohol (IPA, ppm), AcU was measured in 80 male workers exposed to this substance in a plastic factory. The exposure concentration of solvent was also monitored personal diffusive sampling in the individuals during morning 4-hr shift. Urine samples were collected near the end of the shift and were analyzed for acetone by head-space gas chromatography. The correlation between airbornre concentration of IPA and its urinary metabolite acetone was significant: AcU (mg/l) = 0.031 x IPA (ppm) + 0.608, r = 0.75, n = 80, P < 0.001. We established 44 ppm as the lowest airborne concentration of IPA that caused excessive urinary excretion of acetone which could be discriminated from the endogenous production of acetone in non-exposed people. This concentration was as low as one ninth to one tenth of the current exposure limit of 400 ppm. At higher concentrations than 44 ppm, AcU was found to be a useful index for monitoring occupational exposure to IPA.

1-Propanol↗
PubMed1996

Prognostic value of some laboratory parameters in a group of intravenous drug users in the early stages of HIV infection.

During a 5 year follow-up we found significantly reduced survival for non-accidental deaths in 37 intravenous drug users (IVUDs) in the early stages of HIV infection when compared with 32 HIV-negative IVUDs (p = 0.017). Moreover, in HIV-positive subjects, survival was significantly reduced for those groups which at the beginning of the follow-up showed the following values: circulating CD4+ lymphocytes <250/mmc (p = 0.007), CD4+/CD8+ ratio < 0.5 (p = 0.027), serum albumin < 4.13 g/dl (p = 0.045), IgA > or = 2.5 g/l (p = 0.043), IgM < 1.8 g/L (p = 0.041) and platelet count < 130 x 1,000/mmc (p = 0.038). In HIV positive patients, the value of 250 units/mmc for the circulating CD4+ lymphocytes still remained the most predictive parameter of increased mortality for disease at 5 years, even following investigations conducted with other cut-offs. Relationships existing at the beginning of the follow-up between circulating CD4+ lymphocytes and other prognostic parameters suggest that IgA (r = -0.34; p = 0.04), serum albumin (r = 0.33; p = 0.05), and CD4+/CD8+ ratio (r = 0.72; p = 0.0001), but not IgM (r = 0.25; N.S.) and platelets (r = 0.07; N.S.), are dependent variables of shortened survival.

CD4 Lymphocyte Count↗