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Biomedical subjects

F Brugnone

Publications and source records attributed to F Brugnone.

At least 19 recordsLinked to original sources

Reference values for blood benzene in the occupationally unexposed general population.

Blood benzene was determined by gas chromatography-mass spectrometry in 431 "normal" subjects, subdivided into 155 rural subjects and 276 urban subjects. Blood benzene (mean value 262 ng/l) was significantly lower in rural (200 ng/l) than in urban (296 ng/l) workers, as well as differing significantly between 293 non-smokers and 138 smokers (205 ng/l and 381 ng/l, respectively). Among non-smokers, values were significantly higher (307 ng/l) in 76 chemical workers. In the total study population, in 95% of cases blood benzene was less than 718 ng/l, the 95th percentile being 514 ng/l in non-smokers vs 901 ng/l in smokers and 576 ng/l in rural vs 822 ng/l in urban subjects. Within each population subgroup, the difference between non-smokers and smokers was statistically significant, except among office workers (non-smokers 234 ng/l, smokers 304 ng/l). Blood benzene (y) was directly proportional to the number of cigarettes smoked (x) (y = 201 + 12x; r = 0.44; n = 431), and inversely proportional to the interval between the last cigarette and the time at which the blood samples was taken (z) (log y = 6.167-0.0015z; r = -0.461; n = 135). The blood half-life of benzene was about 8h. The multiple correlation between blood benzene (Cb), number of cigarettes per day (x) and time since the last cigarette (z) is: Cb = 417 + 7.2x - 0.41z (n = 135; R = 0.20; P less than 0.00001).

Adult

Blood concentration of carbon disulphide in "normal" subjects and in alcoholic subjects treated with disulfiram.

Assay of free and acid labile carbon disulphide (free and total CS2 respectively) in human blood was performed by gas chromatography/spectrometry. The method used a large dynamic head space volume and a "cryogenic trap". Blood CS2 concentration was measured in 42 subjects not occupationally exposed to CS2 (group A) and in 11 alcoholic subjects (group B) treated with disulfiram. Free CS2 concentration showed a mean value of 261 ng/l in the 42 subjects in group A and 9482 ng/l in eight subjects of group B. Total CS2 concentration was 897 ng/l and 40,084 ng/l in groups A and B respectively. Differences between the groups were highly significant for concentrations of both free and total CS2. Total CS2 concentration was about four times as high as free CS2 concentration in both groups. A significant correlation was found between free and total CS2 concentration both in group A and in group B. In the alcoholic subjects (group B), blood concentrations of both free and total CS2 were related to time of sampling after treatment with disulfiram.

Alcoholism

Ubiquitous pollution by n-hexane and reference biological levels in the general population.

n-Hexane levels were determined by gas chromatography and mass spectrometry in environmental air and in the alveolar air, blood and urine of a group of subjects aged on average of 38 years who had not been occupationally exposed to this hydrocarbon. n-Hexane was found in all environmental air samples examined (n = 49), with the mean concentration being 104 ng/l (limit values, 1-279 ng/l). It was also found in all 49 samples of alveolar air, with the mean concentration being 50 ng/l (variation limit, 1-304 ng/l). In 64 samples of urine, n-hexane was found in only 50 samples, with the mean concentration being 1,417 ng/l (limit values, 34-8,820 ng/l). In 77 of the 90 blood samples taken, a mean concentration of 608 ng/l was detected (variation limit, 15-7,684 ng/l). Particularly the haematic and urinary concentration showed significant differences among the nine groups of individuals classified according to their work activity. The lowest levels were found in the blood and urine of farmers: 270 and 298 ng/l, respectively. The highest values were found for chemical workers (1,377 and 411 ng/l), respectively printers (585 and 2,691 ng/l respectively), and traffic wardens (740 and 8,820 ng/l, respectively). In all, 95% of the determinations of n-hexane yielded values of less than 255 ng/l in environmental samples, less than 105 ng/l in alveolar air, less than 1,475 ng/l in blood and less than 5,875 ng/l in urine. A comparison of these data revealed a significant correlation between environmental levels and alveolar (r/s = 0.769; P less than 0.00001), haematic (r/s = 0.624; P less than 0.0002), and urinary (r/s = 0.597; P less than 0.0005) values for n-hexane.

Adult

"Dynamic" biological exposure indexes for n-hexane and 2,5-hexanedione, suggested by a physiologically based pharmacokinetic model.

Biological exposure index (BEI) of n-hexane was studied for accuracy using a physiologically based pharmacokinetic (PB-PK) model. The kinetics of n-hexane in alveolar air, blood, urine, and other tissues were simulated for different values of alveolar ventilations and also for constant and variable exposures. The kinetics of 2,5-hexanedione, the toxic n-hexane metabolite, were also simulated. The ranges of n-hexane concentrations in biological media and the urinary concentrations of 2,5-hexanedione are discussed in connection with a mean n-hexane exposure of 180 mg/m3 (50 ppm) (threshold limit value [TLV] suggested by American Conference of Governmental Industrial Hygienists [ACGIH] for 1988-89). The experimental and field data as well as those predicted by simulation with the PB-PK model were comparable. The physiological-pharmacokinetic simulations are used to propose the "dynamic" BEIs of n-hexane and 2,5-hexanedione. The use of simulation with PB-PK models enables a better understanding of the limits, advantages, and issues associated with biological monitoring of exposures to industrial solvents.

Hexanes

An improved method of analysing 2,5-hexanedione in urine.

A short gas-chromatographic method for analysing urinary concentrations of 2,5-hexanedione is based on acid hydrolysis of urine at pH below 0.1 and "purification" of the urine samples by microcolumns containing an octadecyl-silane phase. A 5% acetonitrile solution allows a fairly selective elution of 2,5-hexanedione from the microcolumns. Recovery of 2,5-hexanedione from urine is as great as 79.9%. The variation coefficient of the measurements is 2.8%. The results obtained from different working conditions and using packed or wide bore or capillary gas-chromatographic columns are reported.

Calibration

Benzene in the blood and breath of normal people and occupationally exposed workers.

Benzene was measured in blood and alveolar air of 168 men, aged 20-58 years, subdivided into four groups: blood donors, hospital staff, chemical workers occupationally exposed to benzene, and chemical workers not occupationally exposed to benzene. The group of exposed workers was employed in work places with a mean environmental exposure to benzene of 1.62 mg/M3 (8 hr TWA). Non-exposed workers were employed elsewhere in the same plant, with an environmental exposure to benzene lower than 0.1 mg/M3. Blood and alveolar air samples were collected in the morning, before the start of the work shift for the chemical workers. The group of exposed workers was found to be significantly different from the other three groups, both for blood and alveolar benzene concentrations. The mean blood benzene concentration was 789 ng/l in the exposed workers, 307 ng/l in the non-exposed workers, 332 ng/l in the hospital staff, and 196 ng/l in the blood donors. Apart from the exposed workers, blood benzene concentration was significantly higher in smokers than in non-smokers. The mean alveolar benzene concentration was 92 ng/l in the exposed workers, 42 ng/l in the non-exposed workers, 22 ng/l in the hospital staff, and 11 ng/l in the blood donors. Alveolar benzene concentration was significantly higher in smokers than in non-smokers in the groups of the hospital staff and non-exposed workers, but not in the blood donors and exposed workers. In the three groups without occupational exposure considered altogether, the alveolar benzene concentration correlated significantly with environmental benzene concentration measured at the moment of the individual examinations, both in the smokers (r = .636; p less than .001) and non-smokers (r = .628; p less than .001). In the same three groups and in the exposed workers, alveolar benzene concentration showed a significant correlation with the blood benzene concentration.

Adult

Breath and blood levels of benzene, toluene, cumene and styrene in non-occupational exposure.

Benzene, toluene, cumene and styrene were measured in the breath and blood of two groups of individuals. The first group included individuals belonging to a hospital staff, the second group included chemical workers who were not exposed to the abovementioned chemicals. The chemical workers were examined in plant infirmaries on the morning before the start of the workshift, and the hospital staff in the hospital infirmaries. One environmental air sample was taken in the infirmaries for each individual at the moment of the biological samplings. The environmental concentrations of benzene and styrene were significantly higher in the infirmaries of the chemical plant than in the infirmaries of the hospital. On the other hand, the environmental concentrations of toluene and cumene were not significantly different in the plant infirmaries and in the hospital infirmaries. In the hospital staff the alveolar concentrations of benzene, toluene and styrene were significantly lower than those in the chemical workers. In the hospital staff the blood concentrations of benzene, toluene and styrene were not significantly different from those in the chemical workers. Only the blood cumene concentration was significantly higher in the chemical workers. In hospital staff, smokers showed alveolar and blood concentrations of benzene and toluene that were significantly higher than those measured in the non smoker hospital staff. With reference to chemical workers, only alveolar benzene concentration was significantly higher in smokers than in non smokers.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzene

Biological exposure index of styrene suggested by a physiologico-mathematical model.

We used a physiologico-mathematical model to study the biological exposure index of styrene correlated to the Threshold Limit Value (TLV) suggested by the ACGIH for 1986-87. This model allows the solvent concentrations in blood, alveolar air, fat tissue, and in other biological media to be estimated and simultaneously the kinetics of its metabolites to be followed when a specific exposure is settled. The comparison between the results obtained from the mathematical model and the numerous research projects documented in the literature suggests a reciprocal validation. Moreover, some biological parameters (particularly the alveolar ventilation) can explain the variability of results obtained from studies concerning the solvent pollution of the factories, which used biological monitoring. The ranges of styrene concentrations in blood and alveolar air and the urinary concentrations of its metabolites (mandelic and phenylglioxylic acids) are discussed in connection with the exposure at 215 mg/m3. Important differences correlated to the definition of set-levels of TLV and Biological Exposure Index (BEI) have been found: particularly the TLVs lead to different solvent uptakes according to some biological parameters; the BEI can better explain the individual solvent uptake and body burden.

Environmental Exposure

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

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