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Biomedical subjects

M Imbriani

Publications and source records attributed to M Imbriani.

At least 91 records · Page 5Linked to original sources

[Significance of urinary concentrations of S-benzyl-N-acetylcysteine (S-BMA) in subjects exposed to toluene].

Toluene is a widely diffuse solvent for oils, resins, rubber and paints, either alone or as a major component in a mixture; in the industrial environment it is currently present at concentrations of ppm. Toluene can be absorbed via the lungs or via the skin. The absorption of toluene via inhalation is related to the exposure level as well as the activities level of workers. Once absorbed into the body, toluene is metabolized in man to benzoic acid, followed by hepatic cytochrome P450 catalyzed glycine conjugation to form hippuric acid. Relatively small amounts appear in urine as o-cresol and p-cresol where they occur as glucoronide and sulfate derivate. Only a minor fraction of inhaled solvent is conjugated with glutathione with the production of S-benzyl-N-acetylcysteine (S-BMA). Several biological indicators have been proposed for evaluating toluene exposure in the workplace. These include urinary hippuric acid, toluene in blood, toluene in breath, o-cresol in urine and toluene in urine. We examined a group of 18 workers occupationally exposed to toluene, determining the concentrations of toluene in ambient air and S-BMA in urine. All urine samples were collected at the end of work shift. The renal excretion of S-BMA showed highly significant correlations with environmental data and with the other established parameters of biological monitoring of toluene. The median ambient air concentration was 15.7 ppm ranging from 2.9 to 70.3 ppm, the median concentration of S-BMA was 16.0 micrograms/g creatinine. S-BMA was detectable in urine samples of a control group of 87 subjects non occupationally exposed to toluene. Most of unexposed subjects showed S-BMA values lower than 10 micrograms/g creatinine both in smokers and in nonsmokers and no significant difference was found in samples (20) collected at three intervals during one day. Our finding further indicates that the metabolite S-BMA could be a marker of occupational toluene exposure.

Acetylcysteine↗

[Mercapturates and biologic monitoring: styrene].

The biological monitoring of styrene exposure is currently performed by the measurement of the urinary excretion of mandelic acid (MA) and phenylglyoxylic acid (PGA), which originate from the conversion of styrene 7,8-epoxide (SO), an electrophilic compound considered responsible for most toxic effects of styrene. In rats, an alternative pathway in the detoxification processes of SO has been shown, which involves its conjugation with glutathione (GSH), leading to the excretion of N-acetyl-S-(1-phenyl-2-hydroxyethyl)-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-cysteine (M2). Giving the chiral nature of SO, which is present in two enantiomeric forms (R and S), both M1 and M2 consist of two diastereoisomers: thus, four specific mercapturic acids are excreted in styrene-exposed rats, namely M1-R, M1-S, M2-R and M2-S. Until now, the excretion of these compounds in man has not been confirmed directly, giving the analytical difficulties in measuring the low levels of urinary mercapturic acids which are expected following styrene exposure in the working environment. In the present study we applied an analytical method, based on HPLC with fluorometric detection, to measure the excretion of M1-R, M1-S, and M2 in post-shift urines from 22 workers exposed to styrene and in 10 unexposed subjects. The results clearly demonstrated that the GSH pathway is involved in the detoxification processes of styrene, even if to a low extent (the biotransformation rates of styrene to mercapturic acids varied from 0.021 to 0.325%) and that M1 and M2 are specific for styrene exposure, in fact unexposed subjects showed no detectable amounts of these metabolites. In spite of the marked interindividual variability, significative correlations were found between mercapturic acids excretion and environmental styrene concentration or urinary levels of MA and PGA. The urinary levels of M1-S and M1-R were significantly different, thus indicating a stereoselectivity of the enzymes involved in the biotransformation of styrene to mercapturic acids.

Acetylcysteine↗

[Biologic monitoring of carbon disulfide: role of glutathione].

Work goal is a critical analysis of the possibility of using TTCA as a future marker for next environmental limit values which will be probably fixed to much lower levels. Four metabolites have been identified in the urines of CS2 exposed subjects, exactly: thiocarbamide, 2-mercaptothiazolinone, 2-thiothiazolidine-4-carboxylic acid (TTCA), 2-oxothiazolidine-4-carboxylic acid. TTCA represents about the 6% of absorbed CS2 during occupational exposure. TTCA discovery in the urines of CS2 exposed workers (an heterocyclic compound which develops in vivo through direct reaction between CS2 and Glutatione) allowed a more specific approach to exposure assessment. The end-shift urine TTCA concentration seems to be in strict relationship with CS2 absorbed amount. In 1998 ACGIH maintained the 1997 limit value (TLV-TWA 10 ppm). In the 1997 DFG cut down the limit value in half (MAK 5 ppm), while, until 1996, it accepted the ACGIH value.

Carbon Disulfide↗

[The use of Internet in occupational medicine and industrial hygiene].

The internet as we know is today includes an array of tools that make information exchange easier than ever before. The best known Internet tools are the World Wide Web and the electronic mail. In the present job we identify those that are the home pages that better can help Industrial Hygienists and Doctors to acquire useful information for the profession. From the detailed examination of the possibilities offered from Internet (web documents acquisition, reading on line of scientific papers, use of mailing lists and e-mail) we can wait in future that the this new instrument will play an important role by offering extensive knowledge and information in the field of occupational and environmental health.

Databases, Bibliographic↗

[Measurement of N-methylformamide in occupational exposure to N,N-dimethylformamide].

N,N-dimethylformamide (DMF) is a solvent that is widely used in industry. The major occupational sources of exposure results from production of synthetic leather. The main metabolite formed in both man and animals is N-hydroxymethyl-N-methylformamide. Demethylation leads to N-methylformamide (NMF) and formamide and also to a small extent to hydroxy-methylformamide. All the metabolites are excreted in urine, as are very small amounts of the unchanged substance. N-acetyl-S-(N-methyl-carbamoyl)-cysteine can be determined in urine as a further metabolite. We conducted this biomonitoring study with the aim of evaluating the correlation between the excretion of N-methylformamide (mainly from N-hydroxymethylformamide) and levels of exposure to N,N-dimethylformamide among occupationally exposed people. The mean time-weighted average (TWA) exposure was about half (13.5 mg/m3) of the current threshold limit value, the range of the values varying from 0.4 to 75.2 mg/m3. A linear equation existed between urinary NMF concentration and DMF concentration in the environment. The findings show that the urinary NMF concentration can be used as an appropriate biological exposure index. The authors suggest for occupationally exposed subjects, a urinary NMF concentration corresponding to the time-weighted average of the threshold limit value of 39.9 mg/l (37.2 mg/g creatinine) and a 95% lower confidence limit (biological threshold) of 23.4 mg/l (22.2 mg/g creatinine).

Adult↗

[Biological monitoring of occupational exposure to sevoflurane].

Sevoflurane has been used in the last few years in brief surgical operations, either alone or in combination with nitrous oxide. Occupationally exposed groups include anesthesiologists, surgeons and operating room nurses. In 1977 the National Institute for Occupational Safety and Health (NIOSH) recommended that occupational exposure to halogenated anesthetic agents (halothane, enflurane, and isoflurane), when used as the sole anesthetic, should be controlled so that no worker would be exposed to time-weighted average concentrations greater than 2 ppm during anesthetic administration. When halogenated anesthetics are associated with nitrous oxide, NIOSH recommends that the limit value should not exceed 0.5 ppm. We think these recommendations can be extended to sevoflurane. Metabolism of sevoflurane is catalyzed by cytochrome P-450; this involves oxidation of the fluoromethyl side chain of the molecule, followed by glucuronidation. Two urinary metabolites of sevoflurane have been identified: inorganic fluoride (which, however, is not specific) and a non-volatile compound that yields hexafluoroisopropanol (HFIP) when digested with the enzyme beta-glucuronidase. In order to investigate the role of urinary HFIP as an indicator of occupational exposure to sevoflurane (CI, ppm), CI was measured in 145 members of 18 operating room staffs. The measurements of the time-weighted average of CI in the breathing zone were made by means of diffusive personal samplers. Each sampler was exposed during the whole working period. Sevoflurane was desorbed with CS2 from charcoal and the concentrations were measured on a gas chromatograph (GC) equipped with a mass selective detector (MSD). The GC was equipped with a 25 meter cross-linked phenylmethylsilicon column (internal diameter 0.2 mm). GC conditions were as follows: injector column temperature = 200 degrees C; column temperature = 30 degrees C; carrier gas = helium; injection technique of samples = splitless. The analytical conditions for the MSD were the following: ion mass monitored = 131 m/e; dwell time = 50 msec; selected ion monitoring window time = 0.1 amu; electromultiplier = 400 V. Urine samples were collected near the end of the shift and were analyzed for HFIP by head-space gas chromatography after glucuronide hydrolysis. 0.5 ml of urine and 1.5 ml of 10 M sulfuric acid were added to 21.8 ml headspace vials. The vials were immediately capped, vortexed, and loaded into the headspace autosampler. Samples were maintained at 100 degrees C for 30 min, after which glucuronide hydrolysis was 99% complete. Analyses were performed on a GC equipped with a MSD. The analytical conditions for urine analysis were as follows: cross-linked 5% phenylmethylsilicon column (internal diameter 0.2 mm, length 25 m); column temperature = 35 degrees C; carrier gas = helium. The analytical conditions for the MSD were: monitored ions = 51.05 and 99; dwell time = 100 ms; selected ion monitoring window time = 0.1 amu; electromultiplier voltage = 2000 Volt. With our analytical procedure, the detection limit of HFIP in urine was 20 micrograms/L. The variation coefficient (CV) for HFIP measurement in urine was 8.7% (on 10 determinations; mean value = 1000 micrograms/L). The median value of CI was 0.77 ppm (Geometric Standard Deviation = 4.08; range = 0.05-27.9 ppm). The correlation between CI and HFIP (Cu, microgram/L) was: Log Cu (microgram/L) = 0.813 x Log CI (ppm) + 2.517 (r = 0.79, n = 145, p < 0.0001). On the basis of the equation it was possible to establish tentatively the biological limit values corresponding to the respective occupational exposure limit values proposed for sevoflurane. According to our experimental results, HFIP values of 488 micrograms/L and 160 micrograms/L correspond to airborne sevoflurane concentrations of 2 and 0.5 ppm respectively.

Anesthesiology↗

[High-pressure liquid chromatography (HPLC) with UV developer for the analysis of N-acetyl-S-(N-methylcarbomoyl)cysteine (AMCC)].

N,N-dimethylformamide (DMF) is a solvent widely used to prepare synthetic fibers. Biomonitoring of DMF is usually performed by measuring urinary N-methylformamide, which allows us to estimate exposure during the working day. An alternative biomarker is the mercapturic acid N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) whose excretion accounts for about 13% of the absorbed DMF dose. Owing to its slow excretion (mean half-life = 23 hours) the urinary levels of AMCC at the end of a workweek reflect the cumulative dose of DMF during the whole week. Methods given in literature for measuring AMCC need the derivatization of the molecule before analysis. The paper describes a method for the determination of urinary AMCC by high-performance liquid chromatography (HPLC) with direct UV detection. Samples were purified by solid phase extraction with C18 and ENV+ cartridges, then 10 microliters were directly injected onto an Aminex HPX-87H Ion Exclusion column maintained at a temperature of 37 degrees C. Analyses were performed by isocratic run with 1 mM sulphuric acid delivered at 0.85 mL/min. The detector was set at 196 nm. Under these conditions, AMCC eluted at 11.1 min., and the detection and quantification limits were 1.32 mg/L and 3.96 mg/L, respectively. The performance of the method was evaluated on samples containing 25 mg/L and 400 mg/L of AMCC: each sample was analysed three times. The mean recovery of the extraction procedure was 88.3%. The precision (CV%) and the accuracy (Error%) ranged from 0.8% to 2.9%, and from -1.2% to +3.2%. The calibration curve was linear up to a concentration of 1000 mg/L, the coefficient of correlation was r = 0.9997. AMCC was measured in urine samples from 30 exposed and 20 unexposed (smokers and nonsmokers) subjects. Measurable amounts of AMCC were found in all of the samples from workers exposed to DMF; on the contrary, none of the samples from unexposed subjects contained this metabolite. The proposed method is sufficiently sensitive and specific for the evaluation of occupational exposure to DMF, thus it could be useful for the biological monitoring of workers exposed to this solvent.

Acetylcysteine↗

[The Italian version of "OREGE" (Outil de Repérage et d'Evaluation des Gestes) of the INRS (Institut national de recherche et de sécurité) for the assessment of musculoskeletal disorders of the upper limb].

The upper extremity work-related musculoskeletal disorders (UEWMSDs) are a heterogeneous group of disorders not yet standardised mainly epidemiological criteria for case definition. They are multifactorial, often they are work related even if sometimes they show an individual origin. In recent years they show a rapid increase but it's worth noting that this trend is also affected by a more widespread and easy recognition as work related diseases. There are many ergonomic analysis tools, currently available, that claim to accurately measure variables associated with UEWMSDs. They are essentially based on biomechanical, epidemiological and physiological approaches and identify work activities at risk of developing: OSHA's checklist, Strain Index, OCRA Index, ACGIH (Hand Activity Level). A method for the study of musculoskeletal disorders of the upper limb has been proposed by French INRS (National de Recherche et de Sécurité). It is defined as a project based on ergonomics applied to occupational medicine and it includes: (1) OSHA's checklist as a screening tool; (2) MSDs questionnaire for standardised record of symptoms and of worker's opinions (3) OREGE, (Outil de Repérage et d'Evaluation des Gestes) a exhaustive evaluation tool to be used by ergonomics-trained personnel, aimed to identify risk factors to be considered for preventive and corrective actions. OREGE includes: force evaluation through Latko's scale (which take into account: weight of objects and tools, kind of hold, pressure, vibration, temperature, use of gloves), articular position analysis, repetition analysis, synthesis of the different biomechanical risk factors, calculation of an index of risk. The authors have considered of interest to provide occupational physicians and ergonomic professionals with an Italian version of OREGE. The expected results are: a critical review of the method, a comparison with the other most known evaluation methods and the selection of the best method for specific work activity.

Arm↗

[Biological monitoring of occupational exposure to desflurane].

In these last years Desflurane (D) has become used, alone or in combination with nitrous oxide, in surgical procedures. Occupational exposed groups include anesthesiologists, other physicians, (e.g. surgeons) and operating room nurses. Desflurane is a halogenated methylethylether which is administered by inhalation. Desflurane is halogenated exclusively with fluorine. The blood/gas partition coefficient of Desflurane is 0.42. Changes in the clinical effects of Desflurane rapidly follow changes in the inspired concentration. Studies in man indicate that Desflurane washes into the body rapidly. It also washes out of the body rapidly, allowing flexibility in adjustment of the depth of anaesthesia. Desflurane is eliminated via the lungs, undergoing only minimal metabolism (0.02%). In order to investigate the role of urinary D as an indicator of occupational exposure to Desflurane (CI, ppm), CI was measured in 21 members of operating room staffs. For the measurement of environmental concentration of Desflurane (CI), the ambient air was sampled using personal passive dosimeters. The analyte was desorbed by a water-methanol mixture and was analysed by means a gas chromatograph--mass spectrometer (GC-MSD) and headspace technique. The biological monitoring of exposed workers was conducted by determining the concentration of Desflurane in urine (Cu, microgram/L). Urine concentrations of Desflurane were determined by headspace analysis using GC-MSD. Significant correlations were found between the environmental Desflurane concentration and the urinary concentrations. The correlation between CI (ppm) and Cu (microgram/L) was: Log D (Cu, microgram/L) = .191 + .922 * LogCI; r = .916 On the basis of the equation it was possible to establish tentatively the biological limit values corresponding to the respective occupational exposure limit values proposed for Desflurane.

Air Pollutants, Occupational↗

[Proposal of environmental and biological monitoring and health surveillance of the exposed to inhalation anesthetics. Consensus. A Study Group on Occupational Exposure to Inhalation Anesthetics].

The Study Group on Occupational Exposure to Inhalation Anaesthetics of the Lombardy Association of Occupational Health and Industrial Hygiene prepared a document that was discussed during the Congress "Occupational Risks due to Inhalation Anaesthetics", held in Brescia, Italy, on May 12, 1992. The same document was then approved by the Directory Council of the Lombardy Association of Occupational Health and Industrial Hygiene. Data on environmental concentrations of Nitrous Oxide collected from 1989 to 1991 in 269 operating rooms of 47 hospitals in Lombardy are reported. The measured levels are considerably lower than those collected from the same Study Group from 1985 to 1987 in 111 operating rooms. The methodologies for exposure control are discussed, regarding both environmental and biological monitoring. These two techniques are complementary and can be used with standardized methods. The review of the literature on the early effects showed, even with some uncertainty at the current exposure levels, effects on liver and Central Nervous System. Still controversial are the data regarding the reproductive toxicity. Health surveillance programs have been organized in the last 5 years in 18 Lombardy hospitals and they indicate no cases of pathologies due to inhalation anesthetics on 1498 subjects. Operative proposals are suggested on the methodology and the frequency of environmental/biological monitoring and health surveillance. The "technical limit values" reported in the document from the Italian Ministry of Health are also discussed. Finally, research topics are suggested in order to assess the early effects of exposure.

Anesthesia, Inhalation↗

[Measurements and environmental and biological monitoring of occupational exposure to inhalation anesthetics].

This paper reports the data of nitrous oxide (N2O) environmental pollution in 269 operating rooms of 47 hospitals in Italy in 1989-91. In 40% of the operating rooms the N2O concentrations are lower than 50 ppm, limit value proposed by Health Council for new operating rooms. In 65.4% of the operating room studied, N2O mean environmental concentrations are lower than 100 ppm, value proposed by the above-mentioned Health Council as limit value for the already existing operating rooms. Concerning the biological monitoring, the authors report several N2O data in urine (2193), whose levels confirm the data obtained with environmental monitoring. The authors believe that they presently have reliable methods to perform biological and environmental monitoring: the two techniques are complementary in the assessment of the exposure. The method of measuring N2O concentrations as exposure index, both for the environmental and biological monitoring, is considered very useful to simplify the performance of the analyses. In order to assess exposure more precisely, it is however necessary also to determine the environmental and/or biological measure of the other different anaesthetics used.

Air Pollutants, Occupational↗

[Evaluation of several neuropsychological parameters in subjects occupationally exposed to anesthetics].

51 workers, occupationally exposed to anaesthetic gases and vapours (nitrous oxide, halothane, and isoflurane), were studied monitoring their environmental and biological exposure. Moreover, they were tested for visual reaction times and neurobehavioural batteries. There was no evidence of important neurotoxic effects nor of neurobehavioural problems with low concentrations of anaesthetics.

Adult↗

[Occupational exposure to endocrine disruptors: state of the art].

Research into how exposure to "endocrine disrupters chemicals" affects human health is attracting increasing attention among European and international scientists since these contaminants are so widespread in the home and work environment and can have far-reaching effects on mental and physical health. Here we draw a general picture of studies to date on specific occupational exposures to single chemicals such as bisphenol A, styrene, etc., or homogeneous groups such as pesticides, metals, dioxins, phthalates and others. Although the exposure occurs in different ways, the toxic mechanisms of action vary widely, and it is hard to establish precisely the conditions of occupational exposure, significant correlations are nevertheless evident between the potential dose and its effects and further studies are certainly needed. There is still much debate on the epidemiological methods employed, which may overestimate exposure. The "measure" or at least an accurate description of exposure conditions is critical to the whole question and attempts to ensure this involve standardized procedures and statistical tests as the basis for a protocol for assessing the risk of occupational exposure. Investigations to date have focused on the effects on the reproductive system, in males in particular. However, considering the broad range of equilibria and systems on which endocrine destructive compounds can act, the international scientific community needs to persist in its efforts to develop methods for checking the effects on other endocrine organs--particularly the thyroid gland--and on the immune and neurological systems.

Adult↗

[Excretion kinetics of phenylhydroxyethyl mercapturic acids (PHEMAs), ethanol consumption, and chronic exposure to styrene: preliminary data on humans].

Styrene (S) is a widely used aromatic hydrocarbon, responsible for several adverse effects. In humans, the metabolism of S is well characterized: besides the major metabolites (mandelic and phenylglyoxylic acid), a minor metabolic pathway leads to phenylhydroxyethyl mercapturic acids (PHEMAs) [N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2)], that are potentially useful for biomonitoring purposes. A pilot study on a volunteer exposed under controlled conditions to S, with or without ethanol administration, allowed us to characterize the excretion profile of PHEMAs and the ethanol-induced interference on PHEMAs metabolic pathway. We further considered a group of 9 workers exposed to S during the working week to determine the confounding role of chronic exposure. Our results confirm the wide interindividual variability of both the biotransformation rate of S into PHEMAs and of the excretion rate of these metabolites. Moreover, both the above parameters changed during the working week, suggesting the existence of a large intraindividual variability as a consequence of the exposure to S and to other solvents. As a practical rule, the data indicate that it is necessary to collect samples at the beginning of the working week when studies on the correlation between genotype and phenotype are carried out. Finally, the results emphasise the importance of excluding an even extemporary ethanol assumption when practicing a biological monitoring programme based on the determination of urinary PHEMAs.

Acetylcysteine↗

[New biomarkers of exposure].

In this paper we have defined the new biomarkers of exposure (NBE) as those biomarkers discovered in the last five years and, among previously validated biomarkers, also those applied in different ranges of doses or those determined in biological matrices which differ from matrices originally considered. We examined the results from the surveys carried out by the main Italian research units involved in biological monitoring, i.e. those from the Universities of Brescia, Milan, Naples, Padua, Parma, Pavia, Turin and Verona. The data were collected using a standardized model and included the following: type of element or organic compound, type of biomarker, analytical technique and method, their relationship with environmental monitoring data, their relationship with effect indicators or effects in general, improvement with respect to old biomarkers, reference values. Twenty two NBEs were identified: 14 elements and chemical compounds as such or as metabolites, 4 examples of mixtures, 3 of new matrices, one of speciation. Among the others, aspects such as interest in requiring NBE, quality assurance, availability, cost-benefit ratio were discussed. We conclude that development of this specific field of research appears to be a crucial point for future improvement in risk assessment and health surveillance procedures.

Animals↗