Effects of ethanol on the kinetics of methyl ethyl ketone in man.

The kinetics of inhaled methyl ethyl ketone (MEK) at a concentration of 200 ppm for four hours were studied in volunteers after swallowing ethanol at a dose of 0.8 g/kg. Ethanol was given either before or at the end of the exposure to MEK. The blood concentrations of MEK, 2-butanol, and 2,3-butanediol were monitored during and after the exposure. MEK concentrations in exhaled air and MEK and 2,3-butanediol concentrations in urine were also measured. Ethanol inhibited the primary oxidative metabolism of MEK and caused an increase in the blood concentrations of MEK and 2-butanol after ingestion. Ethanol ingestion, through higher blood MEK concentrations, also increased the elimination of MEK in the urine and exhaled air. Ethanol taken before exposure to MEK reduced the serum concentration of 2,3-butanediol initially but there was an increase about eight hours after the exposure. Urinary excretion of 2,3-butanediol followed the same pattern. Prior ingestion of ethanol thus seemed to interfere with the metabolism of 2,3-butanediol during and after exposure to MEK.     

Effects of ethanol on the kinetics of methyl ethyl ketone in man

The kinetics of inhaled methyl ethyl ketone (MEK) at a concentration of 200 ppm for four hours were studied in volunteers after swallowing ethanol at a dose of 0.8 g/kg. Ethanol was given either before or at the end of the exposure to MEK. The blood concentrations of MEK, 2-butanol, and 2,3-butanediol were monitored during and after the exposure. MEK concentrations in exhaled air and MEK and 2,3-butanediol concentrations in urine were also measured. Ethanol inhibited the primary oxidative metabolism of MEK and caused an increase in the blood concentrations of MEK and 2-butanol after ingestion. Ethanol ingestion, through higher blood MEK concentrations, also increased the elimination of MEK in the urine and exhaled air. Ethanol taken before exposure to MEK reduced the serum concentration of 2,3-butanediol initially but there was an increase about eight hours after the exposure. Urinary excretion of 2,3-butanediol followed the same pattern. Prior ingestion of ethanol thus seemed to interfere with the metabolism of 2,3-butanediol during and after exposure to MEK.     

Kinetics of methyl ethyl ketone in man: absorption,distribution and elimination in inhalation exposure

Summary The kinetics of inhaled methyl ethyl ketone (MEK) in human volunteers was studied in an exposure chamber. Relative pulmonary uptake was about 53% throughout a 4-h exposure period at 200 ppm. Blood MEK concentration rose steadily until the end of exposure. Repeated bicycle exercise increased the overall blood MEK level markedly in comparison to sedentary activity, with transient peaks in association with cycling; thus blood MEK concentration depended both on the rate of uptake and the amount taken up. Only 3% of the absorbed dose was excreted unchanged by exhalation. A well-known metabolite of MEK, 2,3-butanediol, was detected in the urine with maximum rates of excretion at about 6 to 12 h from the beginning of exposure. About 2% of the MEK dose taken up by the lungs was excreted in the urine as 2,3-butanediol. The main part of inhaled MEK is supposedly metabolized in the intermediary metabolism. Elimination of MEK in blood appeared to exhibit two phases: the initial alpha-phase (T_1/2 = 30min; k_{el alpha} = 0.023) over the first post-exposure hour, followed by the terminal beta-phase (T_1/2 = 81 min; k_{el beta} = 0.009).     

Biological monitoring of occupational exposure to methyl ethyl ketone in Japanese workers

The relationship between occupational exposure to methyl ethyl ketone (MEK) and its concentration in urine and blood was studied in a group of 72 workers in a printing factory. Personal exposure monitoring was carried out with passive samplers during the workshifts. The time weighted average (TWA) concentration of MEK ranged from 1.3 to 223.7 ppm, with a mean concentration of 47.6 ppm. In addition to MEK, toleuene, xylene, isopropyl alcohol, and ethyl acetate were detected as the main contaminants in all samples.At the end of the workshift, urine samples were collected to determine the urinary MEK, hippuric acid (HA), and creatinine, and blood samples were also collected at the same time for determination of MEK. The concentrations of urinary MEK ranged from 0.20 to 8.08 mg/L with a mean of 1.19 mg/L and significantly correlated with TWA concentrations of MEK in the air with a correlation coefficient of 0.889 for uncorrected urine samples. The concentration of MEK in the blood was also significantly correlated with the TWA concentration of MEK with a correlation coefficient of 0.820.From these relationships, MEK concentrations in urine and blood corresponding to the threshold limit value-TWA (200 ppm; ACGIH 1992) were calculated to be 5.1 mg/L and 3.8 mg/L as a biological exposure index (BEI), respectively. Although the BEI for urinary MEK obtained from the present study was higher than that of previous reports and ACGIH's recommendation (2.0 mg/L), the BEI agreed well with a previous study in Japan. On the other hand, the relationship between toluene exposure and urinary HA level, an index of toluene exposure, was also studied at the same time. The urinary concentration of HA corresponding to TWA at 100 ppm was 2.6 g/g creatinine as BEI. This value agreed well with both ACGIH's recommendation (2.5 g/g creatinine) and the values reported by Japanese researchers who have studied Japanese workers. Ethnic differences of MEK metabolism may affect the relationship between exposure and BEI.     

Ethanol induced modification of m-xylene toxicokinetics in humans.

This study was undertaken to determine whether previous subacute treatment with ethanol could modify the kinetics of m-xylene in humans. A group of six volunteers was exposed twice to either 100 or 400 ppm of m-xylene during two hours (between 0800 and 1000). Ethanol was given orally in the early evening on each of two consecutive days before exposures (total ethanol intake of 137 g). Such ethanol pretreatment affected the kinetics of m-xylene but only at the high exposure (400 ppm). The modifications were: (1) decreased concentration of m-xylene in blood and alveolar air during and after exposure; (2) increased urinary excretion of m-methylhippuric acid at the end of exposure. Ethanol treatment also enhanced the elimination of antipyrine in saliva. Overall, this study showed that the effect of enzyme induction on the metabolism of m-xylene, after ethanol ingestion, depends on the exposure concentration and is not likely to occur as long as the exposure concentrations remain under the current maximum allowable concentration (100 ppm) in the workplace.     

Correlation of xylene exposure and methyl hippuric acid excretion in urine among paint industry workers

Different calculations of methyl hippuric acid excretion in urine were correlated to the time-weighted average (TWA) of the xylene exposure of a complete workday for 40 paint industry workers exposed to 12 different solvents. The 8-h TWA xylene exposure varied between 0 and 865 (median 69) mg/m3. The amount of methyl hippuric acid excreted in about 24 h showed only a slightly higher linear correlation to the xylene exposure than the amount of methyl hippuric acid excreted per hour during the latter part of the workshift among the 37 subjects exposed to TWA xylene air concentrations of 0-200 mg/m3. It was concluded that the methyl hippuric acid excretion rate during the latter part of the workshift can be used for crude xylene exposure categorizations.     

Occupational exposure to solvent mixtures: effects on health and metabolism.

Exposure monitoring by personal diffusive samplers, biological monitoring of toluene exposure by urinary hippuric acid determination, haematology, serum biochemistry for liver function, and a subjective symptom survey by questionnaire were conducted on 303 male solvent workers. They were exposed to a mixture of solvents including toluene (geometric mean 18 ppm), methyl ethyl ketone (MEK; 16 ppm), isopropyl alcohol (IPA; 7 ppm), and ethyl acetate (9 ppm). The intensity was mostly below unity using the additiveness formula based on current Japanese occupational exposure limits, but more than eight times unity at the maximum. The results were compared with the findings in 135 non-exposed male workers of similar ages. Haematology and liver function tests did not show any exposure related abnormality, and subjective symptoms were mostly related to central nervous system depression and local irritation. Further analysis suggested that the irritation effects were not related to exposure to MEK. Analysis of the relation between toluene exposure and hippuric acid excretion in urine showed that there was no metabolic interaction between MEK and toluene, or between IPA and toluene. Overall, therefore, it is concluded that there was no sign or symptom detected to suggest anything other than toluene toxicity, that there was no evidence to indicate any modification of toluene toxicity or metabolism due to coexposure, and that the additiveness assumption is reasonable for risk assessment for the combination of solvents under these exposure conditions.     

Percutaneous absorption of m-xylene in man

Summary Percutaneous absorption of m-xylene was studied in volunteer experiments by means of monitoring xylene concentrations in blood and in exhaled air, and urinary methylhippuric acid excretion. Compared to normal working practices a rather extreme skin exposure, i.e. immersion of both hands in liquid xylene resulted in an estimated absorption of 35 mg xylene in 15 min which equals an estimated pulmonary retention within the same time period at TLV air.level of 100 ppm. The observed absorption rate for m-xylene was approximately 2 g/cm²/min. The penetration of xylene was fairly rapid, peak concentrations appearing in the draining venous blood 4–6 min after exposure. Further absorption took place for five hours, however, after the termination of exposure and the removal of the contaminant by alcohol and water rinsing. It was found, as expected, that venous blood from a contaminated area exhibits a much higher concentration of the contaminant than mixed venous blood. To exclude this error in biological monitoring of xylene (and other skin penetrating solvents) exposure, exhaled air determinations are recommended. As a sporadic finding in the investigation, a symptom-free subject with previous history of atopic dermatitis developed toxic eczema of the hands after xylene exposure and exhibited a three times greater absorption of the compound than the average for the rest of the group.     

Effect of simultaneous exposure to toluene and xylene on their respective biological exposure indices in humans

Summary Studies that specifically address the influence of controlled human exposure to a combination of solvents on the biological monitoring of exposure are limited in number. The present study was undertaken to investigate whether simultaneous exposure of human volunteers to toluene and xylene could modify the respective metabolic disposition of these solvents. Five adult Caucasian men were exposed for 7 consecutive h/day over 3 consecutive days to 50 ppm toluene and 40 ppm xylene either separately or in combination in a dynamic, controlled exposure chamber (low-level exposure). The experiment was repeated three times at intervals of 2 weeks. In another experiment, three subjects were exposed to 95 ppm toluene and 80 ppm xylene or a combination of both for 4h (high-level exposure). The concentration of unchanged solvents in blood (B) and in end-exhaled air (EA) as well as the urinary excretion of hippuric acid (HA) and methylhippuric acids (MHAs) were determined. Simultaneous exposure to the lowest level of solvents did not alter the concentration of unchanged solvents in blood or in exhaled air (average of 3-weekly means; single vs mixed exposure at 6.5 h exposure): B-toluene, 77.1 vs 78.1 g/100 ml; B-xylene, 67.6 vs 77.8 g/100 ml; EA-toluene, 9.9 vs 9.5 ppm; EA-xylene, 5.3 vs 4.8 ppm. Similarly, mixed exposure did not modify the excretion of urinary metabolites during the 3- to 7-h exposure period: HA, 1.11 vs 1.11 g/g creatinine; MHAs, 0.9 vs 0.87 g/g creatinine. However, simultaneous exposure to higher levels did affect the concentration of unchanged solvents in blood and in exhaled air as measured at 3.5 h exposure (mean value for three subjects ± SD): B-toluene, 135.7 ± 26.7 vs 215.7 ± 34.9 g/100 ml; B-xylene, 114 ± 19 vs 127.6 ± 22.1 g/100 ml; EA-toluene, 16.6 ± 0.4 vs 20.5 ± 2.8 ppm; EA-xylene, 9.9 ± 0.6 vs 12.3 ± 1.2 ppm. Such effects were accompanied by a significant delay in the urinary excretion of HA but not of MHAs. These data suggest that there is a threshold level below which metabolic interaction between toluene and xylene is not likely to occur in humans.     

Measurement by gas chromatography of urinary hippuric acid and methylhippuric acid as indices of toluene and xylene exposure.

A gas chromatographic method was applied to the determination of the urinary glycine conjugates, hippuric, o-, m- and p-methylhippuric acids. These were extracted with ethyl acetate from urine after acidification with hydrochloric acid. The internal standard solution (heptadecanoic acid methanol solution) was added before extraction and a diazomethane-ether-ethanol solution was subsequently added to the dried extracts. The methylated residues were dissolved in methanol and injected into a gas chromatograph as described by Buchet and Lauwerys (1973). By the combined use of gas chromatography and mass spectrometry the methyl esters of hippuric acid and m-methylhippuric acid were identified in the urine of a volunteer who had been exposed to toluene and m-xylene vapours. When the urine specimen contained salicyluric acid (a urinary metabolite of salicylic acid) two sharp peaks were observed. The faster peak coincided with m- or p-methylhippuric acid. The upper limit of urinary hippuric acid concentration in healthy subjects with no occupational exposure was calculated by this method to be 1.026 microgram/ml (fiducial limit 5%) after correction to 1.024 for variation in urinary density.     

Measurement of toluene and xylene metabolites by gas chromatography

Summary A new method for analyzing urinary hippuric and methyl hippuric acids by gas chromatography was developed. As well the direct analysis of hippuric acids as the determination of their alkaline hydrolytic products, benzoic and toluic acids, are described. Results of the two different methods are compared and discussed. The method was applied to workers occupationally exposed to paints containing mainly toluene and xylene. The urinary hippuric acid concentrations were related to the level of toluene and xylene in blood.     

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.     

Experimental human exposure to toluene

Summary The relationship between the individual toluene uptake and the urinary hippuric acid excretion was studied under experimental conditions. Six healthy male subjects were exposed to various concentrations in inspired air (50, 100, 125, 150, and 200 ppm) at rest or under different levels of physical effort.The hippuric acid excretion near the end of the exposure appeared under all circumstances directly proportional to the time-weighted uptake rate of toluene. The correlation between respiratory uptake rate and the rate of metabolite excretion near the end of the exposure period proved not to be systematically influenced by personal factors such as body weight, amount of body fat, urine flow rate and urinary pH. The relatively pronounced differences in background excretion of hippuric acid and, perhaps, distribution phenomena of toluene between different tissues under heavy workload conditions, can partly explain the greater variability in metabolite excretions as compared to the individual uptake rates.The correlation between the individual uptake rate of toluene and the hippuric acid excretion proved substantially better when using the end exposure excretion rate as exposure parameter as compared with the end exposure hippuric acid concentration, even after correcting the latter for urine density.Reasonable biological limit values complying to an acceptable time-weighted toluene dose were found to be 3000–3500 mg/l and 2.0–2.5 mg/min, resp. for average hippuric acid concentrations and excretion rates in spot samples during the second half of a complete work shift.     

Delayed and Competitively Inhibited Excretion of Urinary Hippuric Acid in Field Workers Coexposed to Toluene,Ethyl Benzene,and Xylene

The purpose of this study was to investigate whether the metabolic suppression of hippuric acid (HA) occurs in field workers coexposed to toluene, xylene and ethyl benzene. Eleven male spray painters were recruited into this study and monitored for 2 weeks using a repeated-measures study design. The sampling was conducted for 3 consecutive working days each week. Toluene, ethyl benzene, and xylene in the air were collected using 3M 3500 organic vapor monitors. Urine samples were collected before and after work shift, and urinary HA, methyl hippuric acid, mandelic acid, and phenylgloxylic acid concentrations were determined. In the first week, toluene concentrations were 2.66 ± 0.95 (mean ± SE) ppm, whereas ethyl benzene and xylene concentrations were 27.84 ± 3.61 and 72.63 ± 13.37 ppm, respectively, for all subjects. Pre–work shift HA concentrations were 230.23 ± 37.31 mg/g creatinine, whereas pre–work shift HA concentrations were 137.81 ± 14.15 mg/g creatinine. Mean urinary HA concentration was significantly greater in the pre–work shift samples than in the pre–work shift samples (p = 0.043). In the second week, toluene concentrations were much lower (0.28 ppm), whereas ethyl benzene and xylene were 47.12 ± 8.98 and 23.88 ± 4.09 ppm, respectively, for all subjects. Pre–work shift HA concentrations were 351.98 ± 116.23 mg/g creatinine, whereas pre–work shift HA concentrations were 951.82 ± 116.23 mg/g creatinine. Mean urinary HA concentration was significantly greater in the pre–work shift samples than in the pre–work shift samples (p <0.01); a significant correlation (r = 0.565; p = 0.002) was found between pre–work shift urinary HA levels and ethyl benzene exposure. This study showed that urinary HA peak was delayed to next morning for workers coexposed to toluene, ethyl benzene, and xylene; xylene and ethyl benzene probably played competitive inhibitors for metabolism of toluene. The study also presumed that urinary HA became the major metabolite of ethyl benzene at the end of work shift, when the exposure concentrations of ethyl benzene were 2.0 times those of xylene.     

Occupational chronic exposure to organic solvents XVI. Ambient and biological monitoring of workers exposed to toluene

Object Ambient air and biological monitoring of an occupational toluene exposure was carried out on a group of 33 workers. Method The biological monitoring of the workers was based on determination of the concentration of toluene in blood and on quantification of the urinary metabolites o-cresol and hippuric acid. All blood and urine samples were collected post-shift. Results The average toluene concentration in the workplace air was 65?ppm, ranging from 13 to 151?ppm. An average concentration of toluene in blood of 911?μg/l was found, corresponding to an average urinary concentration of 2.9?mg/l (2.3?mg/g creatinine) o-cresol and 2.4?g/l (1.9?g/g creatinine) hippuric acid. Both urinary metabolites can be correlated with the concentration of toluene in ambient air and blood, respectively. Conclusions The results of our study indicate that the determination of the urinary o-cresol excretion represents a diagnostically specific and sensitive parameter for the estimation of an individual toluene uptake. In contrast, monitoring of the concentration of hippuric acid in urine cannot be recommended for assessment of individual exposure. To set up a biological tolerance value (BAT) for o-cresol, a urinary concentration of 3?mg/l o-cresol should be in accordance with the current MAK value of 50?ppm toluene.     

Effect of various exposure scenarios on the biological monitoring of organic solvents in alveolar air

Summary The present study was undertaken to investigate the influence of different exposure scenarios on the elimination of toluene and m-xylene in alveolar air and other biological fluids in human volunteers. The study was also aimed at establishing the effectiveness of physiologically based toxicokinetic models in predicting the value of biological monitoring data after exposure to toluene and m-xylene. Two adult male and two adult female white volunteers were exposed by inhalation, in a dynamic, controlled-environment exposure chamber, to various concentrations of toluene (21–66 ppm) or mxylene (25–50 ppm) in order to establish the influence of exposure concentration, duration of exposure, variation of concentration within day, and work load on respective biological exposure indices. The concentrations of unchanged solvents in end-exhaled air and in blood as well as the urinary excretion of hippuric acid and m-methylhippuric acid were determined. The results show that doubling the exposure concentration for both solvents led to a proportional increase in the concentrations of unchanged solvents in alveolar air and blood at the end of a 7-h exposure period. Cumulative urinary excretion of the respective metabolites exhibited a nearly proportional increase. Adjustment of exposure concentration to account for a prolongation of the duration of exposure resulted in essentially identical cumulative urinary excretion of the metabolites. Induced within-day variations in the exposure concentration led to corresponding but not proportional changes in alveolar concentration for both solvents, depending on whether or not sampling preceded or followed peak exposure to solvent. At the end of repeated 10-min periods of physical exercise at 50 W, alveolar air concentrations of both solvents were increased by 40%. Experimental data collected during the present study were adequately simulated by physiologically based toxicokinetic modeling. These results suggest that alveolar air solvent concentration is a reliable index of exposure to both toluene and m-xylene under various experimental exposure scenarios. For clinical situations likely to be encountered in the workplace, physiologically based toxicokinetic modeling appears to be a useful tool both for developing strategies of biological monitoring of exposure to volatile organic solvents and for predicting alveolar air concentrations under a given set of exposure conditions.     

Effects of ethanol and phenobarbital treatments on the pharmacokinetics of toluene in rats.

Rats were exposed to toluene at a wide range of concentrations from 50 to 4000 ppm for six hours, and the effects of ethanol and phenobarbital (PB) treatments on the pharmacokinetics of toluene metabolism were investigated. Ethanol treatment influenced toluene metabolism mainly at low exposure concentrations. Thus ethanol accelerated the clearance of toluene from blood only when the blood concentration of toluene was not high (less than 360 microM), and ethanol increased hippuric acid (HA) excretion in urine more significantly at low (less than 250 ppm) than at high atmospheric toluene concentrations. Ethanol also expressed a similar effect on p-cresol excretion as on HA, but had little effect on o-cresol. Phenobarbital treatment promoted the urinary excretion of all of the metabolites of toluene, especially after exposure to high toluene concentration. As well as HA, benzoylglucuronide (BG) and free benzoic acid were found in urine. These are the products of the side chain metabolism of toluene. Amounts of BG could be detected when the urinary excretion of free benzoic acid exceeded 5 mumol/kg/6 h, indicating that a great deal of benzoic acid is required for the formation of BG. The Michaelis constant (Km) and the maximum rate of metabolic excretion in urine during six hours exposure (Vmax) of isozymes involved in the excretion of toluene metabolites were calculated, and correlated with the subtypes of cytochrome P-450. The significance of the result was suggested in the biological monitoring of exposure to toluene.     

Effects of ethanol and phenobarbital treatments on the pharmacokinetics of toluene in rats.

Rats were exposed to toluene at a wide range of concentrations from 50 to 4000 ppm for six hours, and the effects of ethanol and phenobarbital (PB) treatments on the pharmacokinetics of toluene metabolism were investigated. Ethanol treatment influenced toluene metabolism mainly at low exposure concentrations. Thus ethanol accelerated the clearance of toluene from blood only when the blood concentration of toluene was not high (less than 360 microM), and ethanol increased hippuric acid (HA) excretion in urine more significantly at low (less than 250 ppm) than at high atmospheric toluene concentrations. Ethanol also expressed a similar effect on p-cresol excretion as on HA, but had little effect on o-cresol. Phenobarbital treatment promoted the urinary excretion of all of the metabolites of toluene, especially after exposure to high toluene concentration. As well as HA, benzoylglucuronide (BG) and free benzoic acid were found in urine. These are the products of the side chain metabolism of toluene. Amounts of BG could be detected when the urinary excretion of free benzoic acid exceeded 5 mumol/kg/6 h, indicating that a great deal of benzoic acid is required for the formation of BG. The Michaelis constant (Km) and the maximum rate of metabolic excretion in urine during six hours exposure (Vmax) of isozymes involved in the excretion of toluene metabolites were calculated, and correlated with the subtypes of cytochrome P-450. The significance of the result was suggested in the biological monitoring of exposure to toluene.     

Urinary hippuric acid concentration after occupational exposure to toluene.

The results of industrial investigations have shown a correlation between the rate of hippuric acid excretion in a single urine sample collected after daily occupational exposure and the amount of toluene absorbed. The rate of hippuric acid excretion and the average concentration of toluene vapour during exposure time were also related. The quantitative range of the test has been limited to amounts exceeding 425 mg of toluene and concentrations exceeding 69 ppm of toluene in the air because of the physiological presence of hippuric acid in urine. The rate of hippuric acid excretion in urine depends on diuresis and is constant for urinary fractions with diuresis of 30 ml/h. The physiological excretion rate was 20 mg/h with a standard deviation +/- 4.3 mg/h, maximal physiological level 33 mg/h.     

Methyl ethyl ketone exposure in industrial workers uptake and kinetics

Summary 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.Presented in part at the IV Congr. sulla Patologia da tossici ambientali ed occupazionali Cagliari 26/28 May, 1983