Urinary excretion of O-cresol and hippuric acid after toluene exposure in rotogravure printing

Summary In 62 male rotogravure printers, the time-weighted average (TWA) toluene exposure during one workweek ranged from 8 to 496 mg/m³ (median 96). Post-shift urinary excretion of hippuric acid showed a poor correlation with the air toluene concentration. Level of o-cresol excretion ranged from 0.08 to 2.37 mmol/mol creatinine and was associated with the exposure (r _s = 0.57, P<0.0001), although the variation was considerable. However, this metabolite was significantly influenced by smoking habits, both in the workers (0.34 vs 0.10 mmol/mol creatinine after adjustment to zero exposure for the smokers and non-smokers, respectively; P = 0.03) and in 21 unexposed controls (0.18 vs 0.06 mmol/mot creatinine; P = 0.002). The excretion of these metabolites was followed during vacation, when the workers were unexposed. The shared one-compartment half-time was 44h (± SE 30, 82). After 2–4 weeks of vacation, the concentration of o-cresol was significantly higher for the smokers than the non-smokers (0.14 vs 0.06 mmol/mol creatinine; P = 0.02).No smoking-associated difference was found for the urinary hippuric acid concentration. However, there was an association between alcohol consumption and hippuric acid excretion (P = 0.03); no such difference was shown for o-cresol. These results demonstrate that hippuric acid excretion is unsuitable for biological monitoring of toluene exposure when the exposure level is below 200 mg/m³. Also, in spite of the favourable excretion kinetics, the impact of smoking and the large interindividual variation warrant the same conclusion for o-cresol as a means of monitoring low level exposure in an individual worker.     

Comparative evaluation of biomarkers of occupational exposure to toluene

Objectives This study was initiated to make comparative evaluation of five proposed urinary markers of occupational exposure to toluene, i.e., benzyl alcohol, benzylmercapturic acid, o-cresol, hippuric acid and un-metabolized toluene. Methods In practice, six plants in Japan were surveyed, and 122 Japanese workers (mostly printers; all men) together with 12 occupationally nonexposed control subjects (to be called controls; all men) agreed to participate in the study. Surveys were conducted in the second half of working weeks. Time-weighted average exposure (about 8 h) to toluene and other solvents were monitored by diffusive sampling. End-of-shift urine samples were collected and analyzed for the five markers by the methods previously described; simultaneous determination of o-cresol was possible by the method originally developed for benzyl alcohol analysis. Results The toluene concentration in the six plants was such that the grand geometric mean (GM) for the 122 cases was 10.4 ppm with the maximum of 121 ppm. Other solvents coexposed included ethyl acetate (26 ppm as GM), methyl ethyl ketone (26 ppm), butyl acetate (1 ppm) and xylenes (1 ppm). By simple regression analysis, hippuric acid correlated most closely with toluene in air (r = 0.85 for non-corrected observed values) followed by un-metabolized toluene (r = 0.83) and o-cresol (r = 0.81). In a plant where toluene in air was low (i.e., 2 ppm as GM), however, un-metabolized toluene and benzylmercapturic acid in urine showed better correlation with air-borne toluene (r = 0.79 and 0.61, respectively) than hippuric acid (r = 0.12) or o-cresol (r = 0.17). Benzyl alcohol tended to increase only when toluene exposure was intense. Correction for creatinine concentration or specific gravity of urine did not improve the correlation in any case. Multiple regression analysis showed that solvents other than toluene did not affect the levels of o-cresol, hippuric acid or un-metabolized toluene. Levels of benzylmercapturic acid and un-metabolized toluene were below the limits of detection [limit of detections (LODs); 0.2 and 2 μg/l, respectively] in the urine from the control subjects. Conclusions In over-all evaluation, hippuric acid, followed by un-metabolized toluene and o-cresol, is the marker of choice for occupational toluene exposure. When toluene exposure level is low (e.g., 2 ppm), un-metabolized toluene and benzylmercapturic acid in urine may be better indicators. Detection of un-metabolized toluene or benzylmercapturic acid in urine at the levels in excess of the LODs may be taken as a positive evidence of toluene exposure, because their levels in urine from the controls are below the LODs. The value of benzyl alcohol as an exposure marker should be limited.     

Toluene itself as the best urinary marker of toluene exposure

Head-space gas chromatography (GC) and high-performance liquid chromatography (HPLC) (with fluorescence detectors) methods were developed for toluene (TOL-U) and o-cresol (CR-U) in urine, respectively. In order to identify the most sensitive urinary indicator of occupational exposure to toluene vapor (TOL-A) among TOL-U, CR-U, and hippuric acid in urine (HA-U), the two methods together with an HPLC (with untraviolet detectors) method for determination of HA-U were applied in the analysis of end-of-shift urine samples from 115 solvent-exposed workers (exposed to toluene at 4 ppm as geometric mean). Regression analysis showed that TOL-U correlated with TOL-A with a significantly higher correlation coefficient than did HA-U or CR-U. With regard to the TOL-A concentrations at which the exposed subjects could be separated from the nonexposed by the analyte, TOL-U achieved separation at < 10 ppm TOL-A, whereas both HA-U and CR-U did so only when TOL-A was 30 ppm or even higher. The ratio of the analyte concentrations at 50 ppm TOL-A to those at 0 ppm TOL-A was also highest for TOL-U. Overall, the results suggest that TOL-U is a better marker of exposure to toluene vapor than HA-U or CR-U.     

Biological monitoring of exposure to solvents using the chemical itself in urine: application to toluene

Objective Biomonitoring of solvents using the unchanged substance in urine as exposure indicator is still relatively scarce due to some discrepancies between the results reported in the literature. Based on the assessment of toluene exposure, the aim of this work was to evaluate the effects of some steps likely to bias the results and to measure urinary toluene both in volunteers experimentally exposed and in workers of rotogravure factories. Methods Static headspace was used for toluene analysis. o-Cresol was also measured for comparison. Urine collection, storage and conservation conditions were studied to evaluate possible loss or contamination of toluene in controlled situations applied to six volunteers in an exposure chamber according to four scenarios with exposure at stable levels from 10 to 50 ppm. Kinetics of elimination of toluene were determined over 24 h. A field study was then carried out in a total of 29 workers from two rotogravure printing facilities. Results Potential contamination during urine collection in the field is confirmed to be a real problem but technical precautions for sampling, storage and analysis can be easily followed to control the situation. In the volunteers at rest, urinary toluene showed a rapid increase after 2 h with a steady level after about 3 h. At 47.1 ppm the mean cumulated excretion was about 0.005% of the amount of the toluene ventilated. Correlation between the toluene levels in air and in end of exposure urinary sample was excellent (r = 0.965). In the field study, the median personal exposure to toluene was 32 ppm (range 3.6–148). According to the correlations between environmental and biological monitoring data, the post-shift urinary toluene (r = 0.921) and o-cresol (r = 0.873) concentrations were, respectively, 75.6 μg/l and 0.76 mg/g creatinine for 50 ppm toluene personal exposure. The corresponding urinary toluene concentration before the next shift was 11 μg/l (r = 0.883). Conclusion Urinary toluene was shown once more time a very interesting surrogate to o-cresol and could be recommended as a biomarker of choice for solvent exposure.     

Evaluation of biomarkers of occupational exposure to toluene at low levels

Objectives The purpose of the present study was to compare validity of various biomarkers of occupational exposure to toluene (Tol) at low levels. The focus was placed on the comparison of un-metabolized toluene in urine (Tol-U) and peripheral blood (Tol-B) with hippuric acid in urine (HA-U). Methods Surveys were conducted in 16 workplaces on the second half of working weeks, with participation of male solvent workers. Urine and peripheral blood samples were collected at the end of the shifts. After exclusion of cases with dense or diluted urine samples, 473 valid sets of samples were obtained for statistical evaluation. Time-weighted average exposure (for about 8-h) were monitored by diffusive sampling for toluene and other four solvents. Blood samples were subjected to the analyses for Tol-B, whereas urine samples were analyzed for HA-U and Tol-U. Results The solvent exposures were low, i.e., a grand geometric mean (GM) Tol concentration was 1.6 ppm, and the GM for the SUM in the additiveness equation was 0.12. The correlation analyses of the biomarkers in urine and blood with Tol exposure showed that Tol-U and Tol-B were more closely [correlation coefficients (r) being 0.67 and 0.60, respectively] related than HA-U (r = 0.27). Results of receiver operator characteristic analyses were in agreement with the correlation analysis results. Conclusions Taking the non-invasive nature of sampling together, Tol in the end-of-shift spot urine sample appears to be the marker of choice for biological monitoring of occupational exposure to Tol at low levels such as <2 ppm as a geometric mean.     

Comparison between blood and urinary toluene as biomarkers of exposure to toluene

Objectives: To compare blood toluene (TOL-B) and urinary toluene (TOL-U) as biomarkers of occupational exposure to toluene, and to set a suitable procedure for collection and handling of specimens. Method: An assay based on headspace solid-phase microextraction (SPME) was used both for the determination of toluene urine/air partition coefficient (λ_urine/air) and for the biological monitoring of exposure to toluene in 31 workers (group A) and in 116 non-occupationally exposed subjects (group B). Environmental toluene (TOL-A) was sampled during the work shift (group A) or during the 24 h before specimen collection (group B). Blood and urine specimens were collected at the end of the shift (group A) or in the morning (group B) and toluene was measured. Results: Toluene λ_urine/air was 3.3 ± 0.9. Based on the specimen/air partition coefficient, it was calculated that the vial in which the sample is collected had to be filled up to 85% of its volume with urine and 50% with blood in order to limit the loss of toluene in the air above the specimen to less than 5%. Environmental and biological monitoring of workers showed that the median personal exposure to toluene (TOL-A) during the work-shift was 80 mg/m³, the corresponding TOL-B was 82 μg/l and TOL-U was 13 μg/l. Personal exposure to toluene in environmentally exposed subjects was 0.05 mg/m³, TOL-B was 0.36 μg/l and TOL-U was 0.20 μg/l. A significant correlation (P < 0.05) was observed between TOL-B or TOL-U and TOL-A (Pearson's r=0.782 and 0.754) in workers, but not in controls. A significant correlation was found between TOL-U and TOL-B both in workers and in controls (r=0.845 and 0.681). Conclusion: The comparative evaluation of TOL-B and TOL-U showed that they can be considered to be equivalent biomarkers as regards their capacity to distinguish workers and controls and to correlate with exposure. However, considering that TOL-U does not require an invasive specimen collection, it appears to be a more convenient tool for the biological monitoring of exposure to toluene. Received: 20 October 1999 / Accepted: 4 March 2000     

Self-collected urine sampling to study the kinetics of urinary toluene (and <Emphasis Type="Italic">o</Emphasis>-cresol) and define the best sampling time for biomonitoring

Purpose  To study the excretion kinetics of urinary toluene, TOL-U, and o-cresol, o-C, following occupational exposure to toluene in order to define the best time for sample collection, to apply a non-invasive approach based on self-collected urine sampling. Methods  Five rotogravure printing workers exposed to uncontrolled levels of toluene collected spot urine samples over three consecutive working days and the following day of rest. In each sample TOL-U and o-C were measured and kinetics of excretion evaluated. Results  Toluene exposure ranged from 48.3 to 75.3 mg/m³; TOL-U and o-C ranged from 1.4 to 34.6 μg/L and from 0.013 to 1.012 mg/L. A time course trend was obtained: TOL-U and o-C increased during the shift and peaked at the end of exposure and up to 2 h later, respectively; afterwards they rapidly decreased following apparent first order kinetics. Considering TOL-U, the elimination half-life for the first fast phase was 79 (±35 standard error) min, and for the second slow phase was 1,320 (±1,162) min. For o-C the elimination half-life for the first fast phase was 231 (±48) min. Considering a toluene uptake of 86%, TOL-U and o-C excreted in urine were about 0.0067 and 0.18% of the up taken. Conclusion  Our results support the use of end shift TOL-U as a short term biomarker of occupational exposure to toluene and show the feasibility of self-collected urine sampling to investigate the elimination kinetics of industrial toxics in humans.     

Chronic occupational exposure to toluene

Summary Chronic occupational exposure to toluene was studied in a factory preparing tarpaulins. Seventy-eight workers were studied; 46 were exposed to various concentrations of toluene in air (20–200 ppm), 32 were unexposed workers in the same factory. In many cases the exposure had lasted for 10–20 years. The urinary hippuric acid excretion at the end of work shift showed good correlations to toluene concentrations in air, and it seems to be a good measure of exposure. The hippuric acid in urine samples collected overnight showed that elimination of toluene still occurs several hours after exposure. Most of the biological parameters measured showed no correlation to toluene exposure. The blood leukocyte count did show slight positive correlations to toluene exposure, but even this parameter stayed inside the range of normal values. The occurrence of chronic diseases, drug using habits, and drinking and smoking habits did not show any correlations to toluene exposure.This study has been supported by the grant of Y. Jahnsson Foundation in Finland     

High-pressure liquid chromatographic determination of toluenein urine as a marker of occupational exposure to toluene

Objective: To establish a convenient method by high-pressure liquid chromatography (HPLC) to measure toluene in urine as a marker of occupational exposure to toluene. Methods: As soon after sampling as possible, 1 ml of urine was mixed with an equal volume of acetonitrile in a 2.2-ml HPLC glass bottle, and the bottle was tightly sealed and stored at 4 °C. Immediately before HPLC determination, 100 μl methanol was added to the mixture to prevent confounding effects of glycosuria, and the bottle was spun to remove any suspended matter. An aliquot of the supernate was introduced into the HPLC system and analyzed on a PRODIGY column, with an acetonitrile – perchloric acid – phosphoric acid – water mixture serving as the mobile phase. The effluent was monitored at 191 nm. Results: The method can measure toluene in urine every 20 min; the detection limit was 2 μg/l, the coefficient of variation was less than 5%, and the recovery rate was 100%. No significant reduction in toluene concentration was observed for 1 week after storage at 4 °C. When the method was applied to end-of-shift urine samples from 13 male workers exposed to toluene at 18–140 ppm and also to urine samples from 10 nonexposed male controls, toluene in urine was linearly related to toluene exposure concentration, with a regression line passing close to the origin. The correlation coefficient was as high as 0.97 (n = 23). No toluene was detected in control urine samples. Calculations suggest that urinary toluene accounts for as little as less than 0.01% of the toluene absorbed via inhalation and that the absorbed toluene is converted almost quantitatively to hippuric acid and, by less than 0.1%, to o-cresol. Received: 25 August 1997 / Accepted: 13 February 1998     

Epidemiological study on the hepatotoxicity of occupational toluene exposure

Summary In a cross-sectional study of 181 male workers of a rotogravure printing plant, most of whom were exposed to toluene levels well above the GDR threshold limit values, 55 subjects revealed pathological liver screening values (activities of serum aspartate aminotransferase, alanine amino-transferase, gamma glutamyltransferase; liver size). The differential diagnostic examination showed in 51 out of these 55 subjects an association with competing factors such as alcohol abuse (78%) and overweight (40%), to a slight extent disorders of fat and carbohydrate metabolism and of the gallbladder. Drug intake did not play any role. The variance and regression analyses of the biochemical data have shown that alcohol significantly and considerably increases the activities of all three enzymes tested. Bodyweight had a similar, but less pronounced, significant effect. On the other hand, in subjects with a higher alcohol intake the activities of liver enzymes in highly toluene exposed subgroups were significantly and clearly lower than among slightly toluene exposed workers.     

Biological monitoring of occupational exposure to toluene diisocyanate

Summary The study validated the use of urinary toluene diamine (TDA) in postshift samples as an indicator of preceding 8-h exposure to toluene diisocyanate (TDI). Nine workers exposed in TDI-based polyurethane foam production were studied. Their exposure levels varied in 8-h time-averaged samples from 9.5 to 94 g/m³. The urinary TDA concentrations varied from 6.5 to 31.7g/g creatinine and they were linearly related to the atmospheric TDI levels. Approximately 20% of TDI is metabolized to diamines but their specificity is remarkable to the extent that by analysis for the 2,4- and 2,6-diamino isomers an idea of the percutaneous absorption may be had.     

Metabolic interaction between n-hexane and toluene in vivo and in vitro

Summary Metabolic interference between n-hexane and toluene was studied both in vivo and in vitro. In in vivo experiments the urinary excretion of n-hexane and toluene metabolites was tested in rats treated with the two solvents separately or in combination. The same experimental program was repeated in rats pretreated with phenobarbital (PB). The urinary excretion of n-hexane metabolites in rats treated with the two solvents showed a significantly decreased excretion of all n-hexane metabolites in comparison with those treated with n-hexane alone. In rats pretreated with PB the excretion of n-hexane metabolites was significantly higher compared with that of unpretreated rats; the combined administration of the two solvents showed in this case, too, that n-hexane metabolite excretion was less than that found in rats treated with n-hexane alone. The biotransformation of toluene to o-cresol and hippuric acid studied in the urine of rats treated with or without n-hexane and pretreated or not with PB did not show any difference. The in vitro metabolic interference was studied by measuring the disappearance of solvents from rat's incubated liver microsomes. The maximum velocity (Vmax) of n-hexane was 2.8 nmol/g/min when incubated alone, 1.9 and 0.9 nmol/g/min when incubated with 5 and 20 M of toluene respectively. The Vmax of toluene was 14.9 nmol/g/min when incubated alone and 13.1 and 10.5 nmol/g/min when incubated with 10.4 and 20.9 M of n-hexane respectively. The inhibition constant (Ki) of toluene on n-hexane biotransformation was 7.5 M and that of n-hexane on toluene was 30 M. The data show that a mutual non-competitive interference exists in vitro betweeen n-hexane and toluene. The interference of toluene on n-hexane biotransformation was detectable also in vivo experiments, while n-hexane did not modify the biotransformation of toluene.     

Saliva as an analytical tool to measure occupational exposure to toluene

OBJECTIVE: To describe a sensitive and rapid method for the determination of toluene in saliva. Biomonitoring of toluene exposure is commonly performed by determination of urinary hippuric acid, o-cresol or toluene itself. The analysis of blood toluene has been verified as another method for biomonitoring. However, drawing blood is invasive and can often not be performed at the workplace for hygienic reasons. Sampling of saliva may be non-invasive, easy to perform and a viable alternative for biomonitoring in the workplace. METHODS: We measured the solvent concentration in saliva specimens of 5 healthy volunteers studied in the laboratory and a group of 36 workers exposed to toluene in the synthetic leather industry. Saliva was collected into Salivette (Sarstedt, Germany) devices by sterile cotton rolls placed in the mouth and then squeezed into pre-weighted vials. Environmental toluene was collected for the duration of a work-shift by Radiello (FSM, Italy) passive samplers. Toluene in urine and saliva (head space analysis) and in environmental samples was measured by GC-MS. RESULTS: Environmental toluene levels ranged from 0.22 to 57.20 mg/m(3), while the concentrations of the solvent in saliva and urine ranged from 0.12 to 18.30 mug/L, and from 0.47 to 26.64 mug/L, respectively. The correlation coefficients (r) between biological and environmental levels of toluene were 0.77 and 0.93, respectively, for saliva and urine samples. CONCLUSION: This preliminary study suggests that saliva may offer many advantages over 'classical' biological fluids such as blood as it is readily accessible and collectible: therefore saliva toluene may be considered as a possible biomarker of exposure to toluene.     

尿邻甲酚作为接触甲苯生物监测指标的探讨

目的探讨尿邻甲酚作为接触甲苯生物监测指标的可能性。方法建立柱前衍生高效液相色谱法测定人体尿中邻甲酚,且使用该方法测定非职业及职业接触甲苯人群尿中邻甲酚水平,并进行接触评定。结果甲苯接触者尿邻甲酚水平为(2.61±1.94)mg/L,明显高于对照组[(0.32±0.23)mg/L],差异有显著性(P<0.001),且接触甲苯工人班后尿邻甲酚水平比班前明显升高,最高可达29倍。接触甲苯者尿邻甲酚水平与个体接触甲苯浓度明显相关(r=0.6295,P<0.01)。结论尿邻甲酚可以作为接触甲苯的生物监测指标。     

Ethylene oxide exposure

Summary 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, na = 36, P < 0.001) and both with the environmental (Ci) concentrations (r = 0.947, n = 144, P < 0.001; r = 0.827, n = 36, P < 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.     

Measurements of alveolar concentrations of toluene

Summary The use of a photoionisationdetector (PID) for measurement of alveolar concentrations of gases and vapours was evaluated during a human exposure experiment with toluene. Two other methods, the standard gas-pipette method and the gasbag/charcoal method, was tested for comparison. The best method appeared to be the PID-method. The major disadvantage in using this instrument was the missing selectivity towards individual compounds in a mixed atmosphere. In all other respects, the method is just as good as or better than the standard gaspipette method and the gasbag method. Results from 40 measurements with the three methods on 16 persons were examined statistically, and the average toluene absorption at 100 ppm exposure levels was estimated to be 1.6 mg/min.     

Biological monitoring of occupational exposure to methyl ethyl ketone

Summary This study was conducted to evaluate the usefulness of three commonly used methods of biological monitoring for worker exposed to methyl ethyl ketone (MEK) under field conditions using blood, breath and urine. Environmental MEK exposures were measured by personal sampling with carbon-felt dosimeters. The correlation coefficient (r) between the time-weighted average (TWA) MEK concentration in air and the MEK concentration in blood collected at the end of the work shift was 0.85. The correlation coefficient between the TWA MEK level in air and the concentration exhaled in the breath of workers at the end of the work shift was 0.71. The end-of-shift urinary MEK excretion correlated best with the environmental concentration (r = 0.89). Correlations became lower after urine samples had been corrected for urinary creatinine (r = 0.83) or specific gravity (r = 0.73). After 8 h exposure to 200 ppm MEK, the corresponding end-of-shift urinary excretion was 5.11ol/l or 4.11 mg/g creatinine. This value is higher than that previously found in some studies, the difference probably being due to the physical acitivites of the present workers and their extensive skin contact with the solvent. The kinetics of inhaled MEK was also studied in eight subjects. Breath and urine samples were collected during the 8-h work shift on 2 consecutive Mondays. The results showed that urinary MEK excretion rose steadily until the end of exposure, whereas the MEK concentration in exhaled air varied markedly throughout the day. These findings suggest that the determination of MEK levels in end-of-shift urine samples appears to be the most reliable biological indicator of occupational exposure.     

Comparative evaluation of urinalysis and blood analysis as means of detecting exposure to organic solvents at low concentrations

Summary One hundred and forty-three workers exposed to one or more of toluene, xylene, ethylbenzene, styrene, n-hexane, and methanol at sub-occupational exposure limits were examined for the time-weighted average intensity of exposure by diffusive sampling, and for biological exposure indicators by means of analysis of shift-end blood for the solvent and analysis of shift-end urine for the corresponding metabolite(s). Urinalysis was also performed in 20 nonexposed control men to establish the background level. Both solvent concentrations in blood and metabolite concentrations in urine correlated significantly with solvent concentrations in air. Comparison of blood analysis and urinalysis as regards sensitivity in identifying low solvent exposure showed that blood analysis is generally superior to urinalysis. It was also noted that estimation of exposure intensity on an individual basis is scarcely possible even with blood analysis. Solvent concentration in whole blood was the same as that in serum in the case of the aromatics, except for styrene. It was higher in blood than in serum in the case of n-hexane, and lower in the cases of styrene and methanol.     

Cumulative effects of daily toluene exposure

Summary To study the elimination of toluene under irregular long-term exposure conditions, we investigated eight workmen who were exposed to concentrations of toluene between 184 ppm and 332 ppm in a plastic processing factory during 2 consecutive weeks. Besides the daily toluene concentrations in ambient air, the toluene concentrations in blood before and after the shifts were determined three times a week.The average concentrations in blood before the shift during the 2 weeks increased 10-fold and in some cases to 20 times the initial value. At average concentrations in the ambient air about the MAC-value the increase was found to be nearly the same. The relevance of these findings concerning the accumulation in other organs of the human body is discussed.     

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

Summary 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. A significant blood benzene difference was found between the non smoker hospital staff and the non smoker chemical workers. A correlation between alveolar and environmental concentrations was found for benzene, toluene and cumene, but not for styrene. In the two groups of individuals, correlations between blood and alveolar concentrations of the four compounds were also studied.