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Biomedical subjects

L Perbellini

Publications and source records attributed to L Perbellini.

At least 55 records · Page 3Linked to original sources

Environmental and occupational exposure to benzene by analysis of breath and blood.

Benzene exposure of chemical workers was studied, during the entire workshift, by continuous monitoring of workplace benzene concentration, and 16 hours after the end of the workshift by the measurement of alveolar and blood benzene concentrations and excretion of urinary phenol. Exposure of hospital staff was studied by measuring benzene concentrations in the alveolar and blood samples collected during the hospital workshift. Instantaneous environmental air samples were also collected, at the moment of the biological sampling, for all the subjects tested. A group of 34 chemical workers showed an eight hour exposure to benzene, as a geometric mean, of 1.12 micrograms/l which corresponded, 16 hours after the end of the workshift, to a geometric mean benzene concentration of 70 ng/l in the alveolar air and 597 ng/l in the blood. Another group of 27 chemical workers (group A) turned out to be exposed to an indeterminable eight hour exposure to benzene that corresponded, the morning after, to a geometric mean benzene concentration of 28 ng/l in the alveolar air and 256 ng/l in the blood. The group of hospital staff (group B) had a benzene concentration of 14 ng/l in the alveolar air and 269 ng/l in the blood. Instantaneous environmental samples showed that in the infirmaries the geometric mean benzene concentration was 58 ng/l during the examination of the 34 chemical workers, 36 ng/l during the examination of the 27 chemical workers (group A), and 5 ng/l during the examination of the 19 subjects of the hospital staff (group B). Statistical analysis showed that the alveolar and blood benzene concentrations in the 34 workers exposed to 1.12 microgram/l of benzene differed significantly from those in groups A and B. It was found, moreover, that the alveolar and blood benzene concentrations were higher in the smokers in groups A and B but not in the smokers in the group of 34 chemical workers. The slope of the linear correlation between the alveolar and the instantaneous environmental benzene concentrations suggested a benzene alveolar retention of about 55%. Blood and alveolar benzene concentrations showed a highly significant correlation and the blood/air partition coefficient, obtained from the slope of the regression line, was 7.4. In the group of the 34 chemical workers no correlation was found between the TWA benzene exposure and the urinary phenol excretion.

Benzene↗

Hippuric acid and ortho-cresol as biological indicators of occupational exposure to toluene.

Industrial exposure to toluene was studied in a group of 18 subjects working in a printing plant, exposed only to this solvent. Environmental monitoring was carried out using personal samplers for the whole work-shift. Urine samples were collected for the determination of hippuric acid and ortho(o)-cresol before toluene exposure, at the end of the work-shift, and 5, 9, and 17 h after the end of the work-shift. The values of two metabolites in all the urinary samples were corrected for g creatinine and specific gravity (1.024). Toluene time weighted average (TWA) concentrations ranged from 51 to 221 mg/m3 (7-h samples; two samplings lasting 3.5 h each). Urinary hippuric acid and o-cresol values at the end of the work-shift were significantly higher than the prework-shift values. Both hippuricuria and o-cresoluria end-of-work-shift values, corrected for creatinine and specific gravity, were significantly related to the mean daily environmental concentration of toluene, the correlation being weaker for o-cresol. Correlation coefficients were 0.88 and 0.84 for hippuric acid and 0.63 and 0.62 for o-cresol after correction for creatinine and specific gravity, respectively. No significant relationship was observed between environmental exposure and the values of the two urinary metabolites 5, 9, and 17 h after the end of the work-shift. Extrapolated values from the linear regression analysis at 375 mg/m3 were in good agreement with the biological exposure index (BEI) suggested by ACGIH for hippuric acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Cresols↗

Identification of the n-heptane metabolites in rat and human urine.

Numerous n-heptane metabolites have been identified and quantified by gas chromatography and mass spectrometry in some tissues and in the urine of Sprague Dawley rats exposed for 6 h to 1800 ppm n-heptane. 2-Heptanol and 3-heptanol were the main biotransformation products of the solvent. 2-Heptanone, 3-heptanone, 4-heptanol, 2,5-heptanedione, gamma-valerolactone, 2-ethyl-5-methyl-2,3-dihydrofuran and 2,6-dimethyl-2,5-dihydropyran were also found as metabolites of n-heptane. In five shoe factory workers and in three rubber factory workers the mean exposure to technical heptane was measured (n-heptane ranged between 5 and 196 mg/m3). In the urine collected at the end of their work shift some n-heptane biotransformation products were found: 2-heptanol, 3-heptanol, 2-heptanone, 4-heptanone and 2,5-heptanedione. 2-Heptanol was the main n-heptane metabolite and its urinary concentrations ranged between 0.1 and 1.9 mg/l. Urinary 2,5-heptanedione was detectable only in some samples and at very low concentration (0.1-0.4 mg/l). These data suggest that n-heptane can be considered as a neurotoxic product, since it gives rise to 2,5-heptanedione, but the small amount of the urinary metabolite is very unlikely to cause clinical damage to the peripheral nervous system.

Animals↗

Ethylene oxide exposure. Biological monitoring by analysis of alveolar air and blood.

Occupational exposure to ethylene oxide (ETO) was studied in ten workers employed in a hospital sterilizer unit by testing environmental air, alveolar air and blood during and at the end of the workshift. Alveolar (Ca) and blood (Cb) ETO concentrations were correlated with each other (r = 0.744, n = 36, P less than 0.001) and both with the environmental (Ci) concentrations (r = 0.947, n = 144, P less than 0.001; r = 0.827, n = 36, P less than 0.001). The alveolar retention of ETO (1-Ca/Ci) was equal to 75-80% of the inhaled ETO. In comparison with a blood/air partition coefficient equal in vitro to 90 (SD = 20), the mean Cb/Ca ratio found in the exposed workers was equal to 12-17. During work the blood ETO concentration was, on average, three times the environmental ETO concentration.

Air↗

Toluene concentrations in the blood and alveolar air of workers during the workshift and the morning after.

Occupational toluene exposure was studied during the workshift and the morning after by the analysis of environmental air, alveolar air, and blood. Environmental toluene exposure was measured by both continuous and instantaneous sampling. Instantaneous environmental toluene concentrations correlated better with alveolar toluene concentrations (r = 0.94; n = 155) than with blood toluene concentrations (r = 0.71; n = 52). Continuous environmental toluene concentrations correlated better with blood toluene concentrations (r = 0.84; n = 65) than with alveolar toluene concentrations (r = 0.52; n = 46). During the workshift and the morning after, blood and alveolar toluene concentrations correlated significantly with each other (r = 0.75; n = 66 and r = 0.67; n = 52). In a group of workers who were exposed to a mean environmental toluene concentration of 146 micromilligrams the concentrations of toluene in the alveolar air and blood the morning after were 3.2 micromilligrams (SD = 1.7) and 27.5 micromilligrams (SD = 12.7) respectively. With regard to the morning after toluene determinations, blood concentrations correlated (r = 0.52; n = 52; p less than 0.001) better than the alveolar concentrations with the corresponding afternoon values (r = 0.36; n = 52; p less than 0.01). The decline of the toluene concentrations from the end of one workshift to the start of the next exposure indicated a mean toluene half life of 3.8 hours in the alveolar air and of 4.5 hours in blood and therefore the 17 hour interval between two consecutive workshifts was insufficient for the complete elimination of absorbed toluene.

Air Pollutants, Occupational↗

Physiologicomathematical model for studying human exposure to organic solvents: kinetics of blood/tissue n-hexane concentrations and of 2,5-hexanedione in urine.

The physiologicomathematical model with eight compartments described allows the simulation of the absorbtion, distribution, biotransformation, excretion of an organic solvent, and the kinetics of its metabolites. The usual compartments of the human organism (vessel rich group, muscle group, and fat group) are integrated with the lungs, the metabolising tissues, and three other compartments dealing with the metabolic kinetics (biotransformation, water, and urinary compartments). The findings obtained by mathematical simulation of exposure to n-hexane were compared with data previously reported. The concentrations of n-hexane in alveolar air and in venous blood described both in experimental and occupational exposures provided a substantial validation for the data obtained by mathematical simulation. The results of the urinary excretion of 2,5-hexanedione given by the model were in good agreement with data already reported. The simulation of an exposure to n-hexane repeated five days a week suggested that the solvent accumulates in the fat tissue. The half life of n-hexane in fat tissue equalled 64 hours. The kinetics of 2,5-hexanedione resulting from the model suggest that occupational exposure results in the presence of large amounts of 2,5-hexanedione in the body for the whole working week.

Adipose Tissue↗

Acetone-induced changes in the toxicokinetics of 2,5-hexanedione in rabbits.

Male rabbits were intravenously injected with 2,5-hexanedione or 2,5-hexanedione plus acetone. A toxicokinetic analysis showed that a two-compartment model satisfactorily described the kinetics of 2,5-hexanedione in rabbits. Simultaneous dosing with acetone altered the toxicokinetic model which best described the plasma concentration versus time data. The model-independent parameter body clearance, calculated according to the trapezoidal rule, showed a decrease in the body clearance of 2,5-hexanedione in rabbits simultaneously injected with acetone. The results suggest that toxicokinetic interference may partly explain the neurotoxic potentiation of that which occurs in 2,5-hexanedione-induced axonopathy as a response to simultaneous exposure to acetone.

Acetone↗

Concentration of ethylene oxide in the alveolar air of occupationally exposed workers.

Ethylene oxide was tested in environmental air and in the alveolar air of 10 workers employed in a hospital sterilizer unit at hourly intervals during the work shift. Alveolar ethylene oxide concentrations (Ca) were correlated with environmental concentration (Ci) in all the workers studied (r = 0.89-0.99). The ratio between alveolar and environmental concentration (Ca/Ci) given by the slope of the regression line obtained for all the data collected was 0.24. This means that the alveolar retention of ethylene oxide, expressed as 1 - (Ca/Ci), corresponded, on average, to about 75% of the environmental concentration.

Ethylene Oxide↗

The validity of urinary metabolites as indicators of low exposures to toluene.

Exposure to toluene was studied in a group of 14 subjects working in a printing industry, who were exposed to this solvent only. Environmental monitoring was carried out using personal samplers for the whole workshift over three consecutive days. Toluene TWA concentrations ranged from 37 to 229 mg/m3. At the end of the workshift on each day of investigation, urine samples were collected for the determination of hippuric acid and ortho-cresol. Hippuric acid was also determined for urine before the workshift and on the Saturday and Monday mornings after the end of exposure; hippuric acid was also determined in 16 controls over the same five-day period. At the end of the workshift, hippuricuria levels in exposed workers always turned out to be statistically different from pre-workshift levels and those of the controls. The end-of-workshift hippuricuria levels of exposed workers were significantly correlated with the mean daily environmental concentration (TWA): in the three days of comparative study, we found r = 0.63 (P less than 0.05) on Day 1, r = 0.90 (P less than 0.001) on Day 2, and r = 0.87 (P less than 0.001) on Day 3. Ortho-cresol turned out to be correlated with daily exposure less significantly than hippuric acid: r = 0.49 (n.s.) on Day 1; r = 0.78 (P less than 0.001) on Day 2, and r = 0.65 (P less than 0.05) on Day 3. Using all available data (41 observations), a very significant correlation (P less than 0.001) was found between the TWA and both metabolites (r = 0.80 for hippuric acid; r = 0.68 for o-cresol). The values of the two metabolites in the end-of-workshift urine samples (41 observations) also turned out to be well correlated (r = 0.70; P less than 0.001). The authors conclude that hippuric acid is a valid test for evaluating even low exposures to toluene.

Air Pollutants, Occupational↗

Partition coefficients of some industrial aliphatic hydrocarbons (C5-C7) in blood and human tissues.

Saline/air, blood/air, olive oil/air, and tissue/air (lung, kidney, liver, brain, muscle, heart, and fat) partition coefficients were determined for nine aliphatic hydrocarbons: n-pentane, 2,2-dimethylbutane, 3-methylpentane, 2-methylpentane, methylcyclopentane, n-hexane, cyclohexane, 3-methylhexane, and n-heptane. Blood/air partition coefficients were found to range between 0.38 (n-pentane) and 1.9 (n-heptane) and the value of the tissue/air partition coefficients rose from n-pentane to n-heptane. The tissue/air partition coefficients were significantly correlated with the blood/air partition coefficients (r = 0.92-0.98). According to the slope of the regression lines, the mean solubility of the nine aliphatic hydrocarbons in the different tissues was higher than in blood by the factors: lung 1.4 (range 1.2-2.1) heart 3.9 (range 0.5-4.5), liver 5.6 (range 5.5-13.5), kidney 5.2 (range 1.6-5.8), brain 6.5 (range 5.8-10.7), muscle 7.6 (range 1.8-8.8), and fat 205 (range 104-254). The blood/air and olive oil/air partition coefficients were significantly correlated with the boiling points and the molecular weights of the aliphatic hydrocarbons studied.

Adipose Tissue↗

Methyl ethyl ketone exposure in industrial workers. Uptake and kinetics.

Exposure to methyl ethyl ketone (MEK) was studied in workers occupationally exposed in industrial workplaces. Alveolar concentrations of MEK were compared with environmental exposure and with blood MEK concentrations. Urinary excretion of MEK and its metabolite, acetylmethylcarbinol , were compared with environmental exposure. The solubility of MEK was also studied in human body tissues which allowed us to estimate the distribution and kinetics of MEK by means of data computing on a multicompartimental mathematic model. The alveolar MEK concentration was correlated with the environmental MEK concentration and corresponded to 30% of it. Blood MEK concentration was correlated with alveolar MEK concentration and corresponded to 104-116 times the alveolar concentration and 31-35 times the environmental concentration. Urinary MEK excretion was correlated with environmental MEK exposure and the urinary excretion of acetylmethylcarbinol . The mean urinary MEK concentration was 4.8 times the mean environmental MEK concentration. The MEK solubility in the human tissues (brain, kidney, lung, fat, heart, muscles and liver) turned out to be similar to that found in blood (blood/air = 183). The amount of MEK and its metabolite, acetylmethylcarbinol , eliminated by the kidney corresponded together to 0.1% of the alveolar MEK uptake.

Acetoin↗

Occupational styrene exposure: environmental and biological monitoring.

Occupational exposure to styrene was studied by environmental and biological monitoring in 22 workers employed in a fiberglass reinforced plastic factory. The mean environmental styrene concentration in individual workplaces ranged from 120 to 684 microliter/l. Blood styrene, which was tested at the end of the work shift, ranged from 450 to 3700 micrograms/l. Urinary mandelic and phenylglyoxylic acid, which were determined at the end of the work shift, ranged from 133 to 2100 and from 107 to 685 mg/l, respectively. Environmental styrene exposure was better correlated with styrenemia than with mandelicuria and phenylglyoxylicuria considered either individually or together. The ratio between environmental and blood styrene showed that styrenemia was, on average, 3.3-4.9 times higher than environmental styrene concentration.

Air↗

Decline of blood and alveolar toluene concentration following two accidental human poisonings.

In two workers admitted to hospital because of a coma due to an accidental occupational exposure to a mixture of solvents, the level of toluene was respectively 823-1122 micrograms/l in the blood and 53-38 micrograms/l in the alveolar air on the second day of admission (36 h after the accidental exposure). On the fifth day, 112 h after exposure, the toluene level was 120-45 micrograms/l in the blood and 3-1 micrograms/l in the alveolar air. The urinary excretion of o-cresol, calculated as a toluene equivalent, was 0.8-0.9 mg on the second day and 1.7-1.6 mg on the third day. Urinary hippuric acid, as a toluene equivalent, was 1.7-1.4 g on the second day and 1.3-0.7 g on the third day. A half-life of between 19 and 21 h was calculated for toluene both in the blood and in the alveolar air.

Accidents, Occupational↗

Isopropanol exposure: environmental and biological monitoring in a printing works.

Occupational exposure to isopropanol was studied in 12 workers by testing environmental air, alveolar air, venous blood, and urine during their work shift. Isopropanol, which ranged in environmental air between 7 and 645 mg/m3, was detected in alveolar air, where it ranged between 4 and 437 mg/m3, but not in blood or in urine. Alveolar isopropanol concentration (Ca) was significantly correlated with environmental isopropanol concentration (Ci) at any time of exposure. The value of the arithmetical Ca/ci ratio was 0.418 (SD 0.101). Acetone, which is a metabolite of isopropanol, was found in alveolar air, blood, and urine in concentrations that were higher during exposure than before. Alveolar and blood acetone concentrations were highly correlated with alveolar isopropanol concentrations at any time during exposure. Acetone ranged between 0.76 and 15.6 mg/l in blood, between 4 and 93 micrograms/l in alveolar air, and between 0.85 and 53.7 mg/l in urine. Alveolar (Ca) and blood (Cb) acetone concentrations were highly correlated (r = 0.67), with a Cb/Ca ratio of 101. Alveolar isopropanol uptake ranged between 0.03 and 6.8 mg/min and was highly correlated with environmental isopropanol concentration (r = 0.92). During exposure, acetone eliminated by the lungs ranged between 20 and 273 mg in seven hours and in urine between 0.3 and 9.6 mg in seven hours. Acetonuria was higher the next morning than at the end of exposure.

1-Propanol↗