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Biomedical subjects

E Capodaglio

Publications and source records attributed to E Capodaglio.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

Anesthetic in urine as biological index of exposure in operating-room personnel.

The aim of this study was to determine if a relationship existed between some inhalation anesthetics airborne exposure levels (Cl) and the concentration of anesthetics in samples of urine produced throughout the exposure time (Cu). The concentrations of nitrous oxide (N2O), halothane (fluothane), enflurane (ethrane), and isoflurane (forane) in the ambient atmosphere were determined in 190 operating theaters of 41 hospitals in Italy. Nitrous oxide, halothane, enflurane and isoflurane were detected in the urine of 1521 exposed subjects (anesthetists, surgeons, and nurses). The environmental measurements were performed using personal passive samplers, and the biological measurements were performed using the head space method. Significant correlations were found between the anesthetics concentration in urine produced during the shift collected after a 4-h exposure (Cu, microgram/L) and anesthetics environmental concentration (Cl, ppm). The results show that the urinary anesthetic concentration can be used as an appropriate biological exposure index. The biological values (urinary concentration values) proposed are the following: nitrous oxide, 25 micrograms/L, for an environmental value of 50 ppm; halothane, 97 micrograms/L, corresponding to 50 ppm of environmental exposure; 6.2 micrograms/L, corresponding to 2 ppm of environmental exposure; enflurane, 145 micrograms/L for an environmental exposure of 75 ppm and 5.6 micrograms/L for an environmental exposure of 2 ppm; isoflurane, 5.3 micrograms/L for an environmental exposure of 2 ppm. The values proposed are the respectively 95% lower confidence limit and therefore should be considered as a protection for the individual, especially if each biological value is corrected according to analytical variability of the measurements. In our opinion, the method of choice in the assessment of occupational exposure to inhalation anesthetics is the measurement of the urinary anesthetic concentration.

Adult↗

Determination of 2,5-hexandione by high-performance liquid chromatography after derivatization with dansylhydrazine.

A sensitive method for the determination of free and total urinary 2,5-hexandione (2,5-HD) using high-performance liquid chromatography with fluorescence detection was developed. After purification of urine with a disposable C18 cartridge, 2,5-HD was derivatized with dansylhydrazine; 1,3-diacetyl benzene (1,3-DAB) was added to the samples, as internal standard, prior to extraction. The resulting fluorescent adducts were separated on a reversed-phase column with a gradient mobile phase of 25 mM phosphate buffer (pH 6.4) and acetonitrile. The retention times of the 2,5-HD and 1,3-DAB derivatives were 9.4 and 13.7 min, respectively. The derivatives were detected by a fluorescence detector (excitation 340 nm, emission 525 nm). The mean recoveries of 2,5-HD and 1,3-DAB were 92.0 and 94.0%, respectively; the detection limit of 2,5-HD (signal-to-noise ratio of 3) was 5 micrograms/l in urine without hydrolysis and ca. 12 micrograms/l in hydrolyzed samples. The method was applied to 39 urine samples from workers exposed to n-hexane; the mean values were 2.597 mg/l (S.D. = +/- 0.758) for total 2,5-HD and 0.179 mg/l (S.D. = +/- 0.086) for free 2,5-HD. Urine samples of 22 non-exposed subjects showed a mean concentration of 0.437 mg/l (S.D. = +/- 0.109) and 0.022 mg/l (S.D. = +/- 0.011) for total and free 2,5-HD, respectively.

Acetonitriles↗

1,2-Dichloropropane hepatotoxicity in rats after inhalation exposure.

The hepatic effects of 1,2-dichloropropane (DCP) were investigated in male Wistar rats exposed to 15, 50, 100, 250, 450, 1000, 1300, 1800 or 4900 mg DCP m-3. At the end of a 4-h period of exposure, average blood DCP levels were 0.025 and 5.38 micrograms ml-1 in animals treated with 15 and 1300 mg m-3, respectively. Blood DCP concentrations were correlated with the air DCP concentrations in the inhalation chamber. At DCP concentrations of 100 mg m-3 or higher, the liver non-protein thiol (NPT) content was significantly reduced. Assays performed 20 h after 4-h DCP exposure showed that exposure to 100-1000 mg DCP m-3 had no effect on hepatic NPT levels. The NPT content increased only in the liver of rats exposed to higher (1300-4900 mg m-3) DCP concentrations. Treatment with DCP did not cause hepatic lipid peroxidation and did not modify total protein content. The observed changes in liver cell thiol homeostasis are likely to reflect the action of reactive intermediates formed during DCP metabolism. These changes can occur in rats following exposure to considerably low levels of DCP vapour.

Administration, Inhalation↗

Trace element reference values in tissues from inhabitants of the European community. I. A study of 46 elements in urine, blood and serum of Italian subjects.

Neutron activation analysis-electrothermal atomic absorption spectroscopy (ETA-AAS) and inductively coupled plasma atomic emission spectrometry (ICP-AES) have been used for the determination of 46 elements in urine, 35 in blood and 26 in serum of unexposed Italian subjects living in the same region (Lombardy). The results allowed the proposal of reference values for various elements determined in more than 350 healthy subjects, these being Ag, Al, As, Be, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Se, Tl, V, Zn, in urine; Ag, As, Bi, Cd, Cr, Co, Cu, Hg, Pb, Se, Tl, Zn in blood; and Ag, Al, Be, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V, Zn in serum (or plasma). For all other elements indicative values are suggested. In addition to the mean value and the "reference range", a "range of uncertainty" and an upper limit above which metabolic abnormalities could be expected have also been defined on the basis of simple statistical considerations.

Humans↗

Methyl ethyl ketone (MEK) in urine as biological index of exposure.

Fifteen human volunteers were exposed to methyl ethyl ketone (MEK) vapor at 11.9-621.8 mg/m3 for a period of 2 to 4 hours at rest (ten cases) and during light physical exercise (five cases). Subsequently 78 workers occupationally exposed to MEK in a manufacture of leather suitcases (median value: 75.5 mg/m3; geometrical standard deviation: 3.12 mg/m3; range: 6-790) were studied. The analyses were performed by means of a Gas Chromatograph (GC) Hewlett-Packard 5880 A connected with a Mass Selective Detector (MSD). The relative uptake (R) of MEK was about 0.54 (standard deviation: 0.05) and it keeps practically constant either at rest or during light effort (V < 30 L/min). A linear relationship existed in the experimentally exposed subjects between urinary concentration (Cu) and amount of MEK absorbed (U) (Cu = 3.05 x U-162.1; r = 0.95; n = 15) (Cu = micrograms/L; U = mg). Both in the experimentally exposed subjects and in the occupationally exposed workers, the urinary concentration of MEK shoved a linear relationship to the corresponding environmental time-weighted average concentration (CI). The correlation coefficients (r) were 0.93 in occupationally exposed subjects (regression equation: Cu = 0.004 x CI + 0.118; n = 78); Cu = mg/L; CI = mg/m3) and more than 0.93 in experimentally exposed groups. The findings indicate that the urinary concentration of MEK can be used as an appropriate biological exposure indicator.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Urinary chromium levels in subjects living in two north Italy regions.

The concentration of total urinary chromium (Cr-U) in two different groups of healthy occupationally non-exposed subjects living in the Italian regions of Lombardia and Veneto has been determined using an ETA-AAS direct method. The age, sex, residence and smoking habits were correlated with CrU excretion. The mean CrU value found in subjects living in Lombardia (n = 310, males 170 and females 140) was 0.59 + 0.26 microgram/l (range 0.08 - 2.10); in Veneto subjects (n = 238, males 187 and females 51) the mean value was 0.52 +/- 0.31 microgram/l (range 0.05 - 1.90). A significative difference between male and female values and a decrease of CrU levels with age increasing have been evidenced in both groups. Smoking habits seem to influence metal urinary levels while, on the other hand, no influence of living sites was observed. Some analytical problems of ETA-AAS Cr determination systems are discussed and "normal" CrU values measured in this study are compared with data reported in the literature.

Adult↗

1,1,1-Trichloroethane (methyl chloroform) in urine as biological index of exposure.

Fifteen human volunteers were exposed to 1,1,1-trichloroethane (methyl chloroform) vapor at 72-495 mg/m3 for a period of 2 to 4 hours at rest (ten cases) and during light physical exercise (five cases). Subsequently 60 workers occupationally exposed to 1,1,1-trichloroethane in a refrigerator manufacturing plant were studied (median value: 178 mg/m3; geometrical standard deviation: 2.19 mg/m3). As expected, the relative uptake (R) of 1,1,1-trichloroethane decreased in the course of exposure at rest (R = 0.44 after 20 minutes of exposure; R = 0.26 after 240 minutes of exposure). Both in the experimentally exposed subjects and in the occupationally exposed workers, the urinary concentration of 1,1,1-trichloroethane showed a linear relationship to the corresponding environmental time-weighted average concentration. The correlation coefficients (r) were 0.95 in occupationally exposed subjects and more than 0.90 in experimentally exposed groups. A linear equation also existed between urinary concentration and amount of 1,1,1-trichloroethane absorbed (r = 0.88). The findings indicate that the urinary concentration of 1,1,1-trichloroethane can be used as an appropriate biological exposure indicator. In occupationally exposed subjects performing moderate work, the urinary 1,1,1-trichloroethane concentration corresponding to the time-weighted average of the threshold limit value was found to be 860 micrograms/L and its 95% lower confidence limit (biological threshold) 805 micrograms/L.

Adult↗

Effects of silver in isolated rat hepatocytes.

Addition of silver nitrate or silver lactate to freshly isolated hepatocytes caused dose-dependent loss of cell viability, measured by trypan blue exclusion, at concentrations within 30-70 microM. Silver cytotoxicity was accompanied by a decrease in hepatic thiol concentration and an increase in lipid peroxidation. Treatment of hepatocytes with the reduced glutathione (GSH)-depleting agent diethylmaleate markedly increased their vulnerability to silver toxicity whereas protective effects were produced by the thiol-reducing agent, dithiothreitol. Both alpha-tocopherol, which protected from the onset of silver-associated lipid peroxidation, and the iron chelator agent, deferoxamine failed to prevent loss of cell viability. These data suggest that perturbation of intracellular thiol homeostasis may play a critical role in the mechanism underlying silver-induced lethal damage to isolated rat hepatocytes.

Animals↗

Evaluation of exposure to isoflurane (Forane): environmental and biological measurements in operating room personnel.

The concentration of isoflurane (Forane) in the ambient atmosphere was determined in 11 operating theaters of 5 hospitals in Italy. The concentration of isoflurane in the ambient air exceeds the recommended time-weighted average exposure levels (median value: 113 mumol/m3). Isoflurane was detected in the urine of 45 exposed subjects (anesthetists, surgeons, and nurses). A significant correlation was found between the isoflurane concentration in urine produced during the shift (Cu' nmol/l) and isoflurane environmental concentration (Cl' mumol/m3) (Cu = 0.243 X Cl + 3.712) (r = .90). The results show that the urinary isoflurane concentration can be used as an appropriate biological exposure index. The authors suggest a biological exposure index of 18 nmol/l (3.4 micrograms/l). This is the biological value obtained after 4 h of an average environmental exposure to 81 mumol/m3 (2 ppm).

Adult↗

Urinary concentration, environmental concentration, and respiratory uptake of some solvents: effect of the work load.

The physical demands of the workplace differ depending on specific jobs. This implies that workers exposed to the same environmental level of an airborne contaminant can absorb different amounts of it depending on their pulmonary ventilation. Starting from the relationship between the uptake (U) and the urinary concentration of six solvents (Cu) (acetone, styrene, toluene, xylenes, methylchloroform, tetrachloroethylene) and from the equation expressing their lung uptake (U = K.V.CI.R.T) the expected values of a biological index after a given time of exposure can be derived. Such values are a function not only of the environmental level of exposure (CI) but also of the pulmonary ventilation (V - dependent solvent) and of the retention index (R) (V - R dependent solvent).

Air Pollutants, Occupational↗

[Toxicological and analytical lists: chromium and its compounds].

The main aspects of occupational exposure to chromium and chromium compounds are surveyed. Special attention is paid to the toxic action of this metal at the different target organs. The nutritional aspect of CrIII is examined preliminarily, and data detailing the metal contents in water and food are provided. As far the different working processes that entail occupational exposure to chromium are concerned, hygienic and environmental problems are discussed while identifying the average environment exposure to the different chemical forms of chromium (CrIII, CrIV, soluble and not soluble), as a function of the worker's tasks, and the relevant human response (total human Cr). Different hygienic and environmental standards in force in various countries and applicable to chromium compounds are compared. Additional information is given on the main aspects of chromium metabolism (absorption, distribution, excretion), and on the prevailing toxic actions, with specific reference to cancerogenesis. As far as biologic monitoring of the exposed people is concerned, the significance of Cr-U as dose-exposure indicator is discussed, also in the light of a critical review of the reference values. The report describes a series of analytical methods for the identification of chromium in aqueous and biologic matrices. The problems connected with health monitoring and fitness for work are eventually covered.

Chromium↗

The urinary concentration of solvents as a biological indicator of exposure: proposal for the biological equivalent exposure limit for nine solvents.

Organic solvents are generally volatile substances that are absorbed mainly through the lungs; they are eliminated chiefly through the lungs and kidneys. In urine they are present as metabolites and, in very little part, as parent compound. The urinary concentration of solvent (Cu) can be used for the biological monitoring of exposed subjects to evaluate their exposure and correlate with the Threshold Limit Value (TLV) during the working day. The authors report some results obtained with workers occupationally exposed to solvents. The results concern the correlation between urinary concentration (Cu, micrograms/L) vs. average environmental concentration (Ci, mg/m3) measured in the breathing zone. For each solvent studied (acetone, 2-cyclohexane, 1,2-dichloropropane, n-hexane, methyl ethyl ketone, perchloroethylene, styrene, toluene, 1,1,1-trichloroethane) the authors propose a Biological Equivalent Exposure Limit (BEEL) corresponding to the environmental TLV.

Air Pollutants, Occupational↗

Urinary elimination of acetone in experimental and occupational exposure.

Fifteen volunteers were exposed to an acetone vapor concentration of 964-8, 610 mumol/m3 (56-500 mg/m3) for 2-4 h in an exposure chamber. Ten subjects were at rest during the exposure, and five were exposed at alternate rest and light physical exercise. Subsequently 104 workers occupationally exposed to acetone were studied. The relative uptake averaged about 53%, and the ratio of the alveolar concentration to the environmental concentration averaged about 0.28. Both for the experimentally exposed subjects and the occupationally exposed workers the urinary acetone concentration showed a linear relationship to the corresponding environmental time-weighted average concentration. A linear equation also existed between urinary concentrations and the amounts of acetone absorbed. The findings enable a consideration of the urinary concentration of the unaltered acetone as an appropriate exposure indicator and the proposal of a "biological equivalent threshold" to be used in the field of biological monitoring.

Acetone↗

Urinary elimination of styrene in experimental and occupational exposure.

Twenty human volunteers were exposed to styrene vapor at 273-1 654 mumol/m3 (28.4-172.3 mg/m3) for a period of 1 to 3 h at rest (15 cases) and during light physical exercise (5 cases). Subsequently 51 workers occupationally exposed to styrene were studied during a workweek (median value 1 138 mumol/m3, geometric standard deviation 2.23). As expected, the relative uptake averaged about 65%, and the ratio of the alveolar concentration to the time-weighted average of the environmental concentration averaged about 0.15. Both in the experimentally exposed subjects and in the occupationally exposed workers the urinary styrene concentration showed a linear relationship to the corresponding environmental time-weighted average concentration. The correlation coefficients of the regression lines ranged between 0.88 (occupationally exposed group) and more than 0.93 (experimentally exposed groups). The regression coefficients were closely linked to the amount of styrene taken up and to the exposure times. The findings show that the urinary styrene concentration can be used as an appropriate biological exposure indicator whose meaning differs from that of other suggested indices. As an example, in occupationally exposed subjects performing moderate work the urinary styrene concentration corresponding to the time-weighted average of the threshold limit value is 815 nmol/l, and the 95% lower confidence limit (biological threshold) is 740 nmol/l.

Adult↗