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Biomedical subjects

L Perbellini

Publications and source records attributed to L Perbellini.

At least 37 records · Page 2Linked to original sources

Effects of acute n-hexane and 2,5-hexanedione treatment on the striatal dopaminergic system in mice.

In order to investigate the effect of n-hexane and its metabolites on the Central Nervous System (CNS), we treated mice with n-hexane and 2,5-hexanedione (2,5-HD) by intraperitoneal (i.p.) administration. Gascromatographic mass spectrometric (GCMS) analyses of striatum and cerebellum revealed a consistent increase of 2,5-HD concentration at 0.5 and 2 hours after treatment and a decline to baseline levels at 24 hours. Traces of 2,5-HD were detected in the brain of control animals. Biochemical analyses revealed a precocious, short lasting, significant increase of striatal dopamine (DA) and homovanillic acid (HVA) levels. A significant increase of striatal synaptosomal DA uptake, suggesting a DA releasing effect on the dopaminergic terminals, was also observed. These results support the hypothesis of a possible role of n-hexane and its metabolites in inducing parkinsonism in humans and animals.

3,4-Dihydroxyphenylacetic Acid↗

Blood acetone concentration in "normal people" and in exposed workers 16 h after the end of the workshift.

Acetone levels were measured by gas chromatography mass spectrometry (GC-MS) in environmental and alveolar air, blood and urine of 89 non-occupationally exposed subjects and in three groups of workers exposed to acetone or isopropanol. Acetone was detected in all samples from non-exposed subjects, with mean values of 840 micrograms/l in blood (Cb), 842 micrograms/l in urine (Cu), 715 mg/l in alveolar air (Ca) and 154 ng/l in environmental air (Ci). The ninety-fifty percentiles were 2069 micrograms/l in Cb, 2206 micrograms/l in Cu and 1675 ng/l in Ca. The blood/air partition coefficient of acetone was 597. Correlations were found in Cb, Cu and Ca. In specimens sampled at the end of the workshift from subjects occupationally exposed to acetone, a correlation was found in the blood, urine, alveolar and environmental air concentrations. The blood/air partition coefficient of acetone was 146. On average, the blood acetone levels of workers were 56 times higher than the environmental exposure level, and the concentration of acetone in alveolar air was 27% more than that found in inspiratory air. The half-life for acetone in blood was 5.8 h in the interval of 16 h between the end of the workshift and the morning after. The morning after a workshift with a mean acetone exposure of 336 micrograms/l, blood and urinary levels were 3.5 mg/l and 13 mg/l, respectively, which were still higher than those found in "normal" subjects. It can be concluded that endogenous production of acetone and environmental exposure to acetone or isopropanol do not affect the reliability of biological monitoring of exposed workers, even 16 h after low exposure.

Acetone↗

Reference values for blood toluene in the occupationally nonexposed general population.

Blood toluene was measured by gas chromatography--mass spectrometry in 232 occupationally nonexposed subjects, consisting of 126 rural and 106 urban workers, and 37 chemical workers. Mean blood toluene was significantly lower in rural (698 ng/l) and urban workers (984 ng/l) than in chemical workers (2789 ng/l). Blood toluene was not significantly different between the rural and urban workers or among the urban workers with different jobs. Smokers had significantly higher levels (median 606 ng/l) than nonsmokers (median 424 ng/l). Subjects who had smoked at least one cigarette in the last 2 h before blood sampling had significantly higher blood toluene (median 1170 ng/l) than those who had not smoked during this time (median 693 ng/l), for whom the level was not significantly different from that in nonsmokers. Blood toluene in the total population was less than 2863 ng/l in 95% cases.

Adult↗

Blood styrene concentrations in a "normal" population and in exposed workers 16 hours after the end of the workshift.

Blood styrene was measured by a gas chromatography-mass spectrometry method in 81 "normal people" and in 76 workers exposed to styrene. In the normal subjects, styrene was also tested in alveolar and environmental air. Styrene was found in nearly all (95%) blood samples. Average styrene levels in the normal subjects were 221 ng/l in blood (Cb), 3 ng/l in alveolar air (Ca) and 6 ng/l in environmental air (Ci). Styrene levels did not differ significantly between smokers and nonsmokers, 95% of values being below 512 ng/l in Cb, 7 ng/l in Ca and 15 ng/l in Ci. In workers with an average exposure to styrene of 204 micrograms/l, at the end of the workshift, mean blood styrene concentration was 1211 micrograms/l. In blood samples collected at the end of the Thursday shift, styrene levels were significantly higher (1590 micrograms/l) than those found at the end of the Monday shift (1068 micrograms/l). A similar difference was found in samples taken the morning after exposure (60 and 119 micrograms/l, respectively). Significant correlations between blood and environmental styrene were found both at the end of the shift and the morning after exposure (r = 0.61 and 0.41, respectively). In workers occupationally exposed to styrene, 16 h after the end of the workshift, blood styrene (94 micrograms/l) was significantly higher than that found in the normal subjects (0.22 microgram/l). The half-life of blood styrene was 3.9 h.

Adult↗

Biochemical and physiological aspects of 2,5-hexanedione: endogenous or exogenous product?

This article reports results regarding two different physiological aspects of 2,5-hexanedione (2,5-HD). The first is the relationship between "free" 2,5-HD (the fraction of "real" 2,5-HD) and "total" 2,5-HD (2,5-HD obtained from acid hydrolysis) in urine and blood of workers exposed to n-hexane. The second part of the study is an attempt to clarify "physiological" excretion of 2,5-HD in subjects not occupationally exposed to n-hexane. The concentration of free 2,5-HD in urine of workers exposed to n-hexane is about 8% of total urinary 2,5-HD. In blood, free 2,5-HD is about 50% of the total. The serum concentration range of total and free 2,5-HD in workers from whom blood was taken was 33-418 micrograms/l and 14-283 micrograms/l respectively. In subjects not exposed to n-hexane, urinary concentration of 2,5-HD ranged between 0.17 and 0.98 mg/l, the urinary excretion rate between 0.23 and 0.57 microgram/min, and renal clearance between 14 and 66 ml/min. The blood concentration of 2,5-HD in nonexposed subjects was 6-30 micrograms/l. Fluctuations typical of a circadian rhythm were not observed for 2,5-HD in blood or urine. We think that 2,5-HD is mainly a product of intermediate metabolism in the human body. Only a minimal part could derive from n-hexane as a ubiquitous micropollutant.

Circadian Rhythm↗

Biological monitoring of occupational exposure to n-hexane by measurement of urinary 2,5-hexanedione.

Occupational exposure to n-hexane in shoe factory workers was monitored by measuring urinary 2,5-hexanedione, the major metabolite of this solvent and the probable cause of peripheral neuropathy in exposed workers. Solvent pollution was monitored in the work environments of 189 employees, of whom 123 (65%) worked in Alicante, Spain, and 66 (35%) in Veneto, Italy. 2,5-Hexanedione was measured in spot urine samples collected from workers at the end of the shift. Information on working conditions was obtained from a previous study. A significant linear correlation was found between mean environmental concentration of n-hexane and urinary concentration of 2,5-hexanedione. The variability in the correlation may have been due to the variable use of protective clothing (gloves), and to variations in exposure during the working week. In numerous workers, percutaneous absorption of n-hexane represented as much as 50% of the total absorbed dose. Urinary concentrations of 2,5-hexanedione tended to increase during the working week. Simultaneous exposure to n-hexane and toluene tended to reduce urinary excretion of 2,5-hexanedione, whereas exposure to n-hexane and methyl ethyl ketone tended to increase excretion of the metabolite.

Adolescent↗

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↗

Acute trichloroethylene poisoning by ingestion: clinical and pharmacokinetic aspects.

Five hours after ingestion of an unknown amount of trichloroethylene (TCE) a 32-year-old woman was admitted to hospital in deep coma. The neurological condition remained unchanged for 3 days, after which there was an improvement of the central nervous system function. The concentrations of TCE in the blood, which were measured during 7 days after the solvent ingestion, gave us the opportunity to study some toxicokinetic parameters of TCE. Using a physiologically based pharmacokinetic model, the toxicokinetic parameters and blood concentrations of TCE are discussed in relation to the neurological conditions. Moreover the same model has suggested that the alveolar hyperventilation during the first 12 h following the TCE poisoning is the only treatment which may shorten the duration of the poisoning.

Adult↗

Efficacy of ketanserin in the therapy of Raynaud's phenomenon: thermometric data.

After a two-week washout (WO) period with placebo 1 capsule/bid, 12 patients suffering from stable Raynaud's phenomenon were treated with ketanserin (K) 40 mg/bid for fifteen days. Blood pressure, heart rate, and laboratory parameters were evaluated at the end of each period. Patients used diary cards to record the number, duration, and intensity of attacks. Computerized thermometry of the fingers was evaluated at basal temperature after acclimatization, 23 degrees C for thirty minutes; after cold test, 10 degrees C for five minutes; and after thermal recovery, 23 degrees C for eighteen minutes. Results were analyzed statistically by use of Student's t-test for paired data (p less than 0.05). No marked changes were observed in the symptoms of the attacks, but K proved effective in significantly reducing the number and duration of daily attacks and in promoting their spontaneous regression. Thermometry revealed a parallel increase in temperatures, particularly basal and recovery values. The data suggest increased flow and decreased vasospasm following 5-HT2 receptor blockade.

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↗

Controlled comparison of ketanserin and nifedipine in Raynaud's phenomenon.

Twenty-eight patients suffering from either primary or secondary Raynaud's phenomenon were treated with nifedipine and ketanserin. Each patient was treated with one of the two drugs administered after an adequate washout period. Furthermore each patient was submitted before and after treatment with each drug to computerized digital thermometry to evaluate the therapeutic response. The data obtained during the intake of the two drugs at zero, five, and twenty-three minutes were compared with thermometry-relevant baseline data at the same periods. Ketanserin proved to be useful in the treatment of Raynaud's phenomenon and statistically significantly superior (alpha less than 0.05) with respect to nifedipine in the thermometric controls and also in the subjective evaluation of the patients (p less than 0.02). In this study nifedipine did not show particular efficacy. Furthermore only 2 patients had to discontinue treatment with ketanserin, whereas 8 had to discontinue treatment with nifedipine (p less than 0.001).

Adult↗

Use of computerized digital thermometry for diagnosis of Raynaud's phenomenon.

The authors have used computerized digital thermometry for the instrumental diagnosis of Raynaud's phenomenon; such a technique enables them to evaluate the temperature of the ten fingers of the hands separately in baseline conditions, during and after the "cold test." In baseline conditions the mean digital skin temperature was 31.2 degrees C (SD 1.67) in control subjects and 26.8 degrees C (SD 2.84) in patients suffering from Raynaud's phenomenon (p less than 0.001). During the cold test the mean skin temperature decreased to 12.7 degrees C (SD 1.94) in control subjects and to 13.0 degrees C (SD 1.67) in patients (p = n.s.). The mean final skin temperature, at the end of the recovery period after the cold test, was 31.1 degrees C (SD 1.76) in controls and 21.9 degrees C (SD 2.78) in patients (p less than 0.001). The sensitivity of the computerized digital thermometry was high (63.6% and 92.7% for basal and final temperature, respectively), while the specificity was 100% for both values. In conclusion, computerized digital thermometry is a useful technique for the diagnosing and quantifying the extent of Raynaud's phenomenon.

Adult↗

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↗