Eight male subjects were experimentally exposed to toluene, p-xylene, and a combination of toluene and p-xylene in order to study the influence of coexposure and exposure to different levels of each solvent on their uptake and elimination. The exposures were performed for four hours at exposure levels equivalent to or lower than the Swedish threshold limit value for toluene, 300 mg/m3 (3.2 mmollm3). During and after the exposure, solvent concentrations were measured in blood and in expired air. In addition, the pulmonary ventilation rate was measured during the exposure. Decreases in the blood/end exhaled air concentration ratio were found for both toluene and p-xylene when given in combination compared with separate exposure. The total solvent uptake relative to the exposure level was decreased after exposure to the higher solvent concentrations, and the apparent clearance was also decreased after exposure to the higher concentrations of solvent. Finally, the blood solvent concentrations were lower at the end of the exposure compared with the maximal concentration during each exposure condition. In the kinetics of toluene and p-xylene the total amount of toluene or p-xylene, or both, seems to be of major importance. possible to replicate in man or in rats exposed to low doses of m-xylene.9 With this information to hand there seemed to be a need to study the effects on the uptake and elimination of commonly used organic solvents by simultaneous exposure to more than one solvent at a total level of exposure not exceeding the threshold limit value. In the present investigation subjects were exposed to toluene and p-xylene, both of which frequently occur in the industrial environment either singly or in combination as, for example, while working with thinners used for paints or in the printing trade. Furthermore, some metabolic interaction or dose dependent kinetics, or both, would be expected, especially at higher doses, since the main metabolic pathway is the same for toluene and xylenenamely, microsomal hydroxylation by cytochrome P-450 and further oxidation through alcohol and aldehyde dehydrogenases to the corresponding acid."0-'3 This metabolic pathway, like all enzymatically mediated processes, is limited by capacity. The main purpose of the present investigation was to study how the uptake and elimination of toluene and p-xylene in man were influenced by coexposure and by exposure to different levels of each solvent. 111
To study the influence of cigarette smoking on the toxicokinetics of toluene, 10 habitual smokers who intended to stop smoking were exposed to toluene vapor (3.2 mmol/m3, 4 h) at three different exposure occasions: (I) while the smoking habit was still ongoing, and (II and III) 1 and 3-4 wk, respectively, after the day at which the smoking habit was discontinued. Solvent concentrations in the exhaled air and in the blood as well as hippuric acid concentrations in the urine were measured during the exposure period and for 3 h after the exposure period. The apparent clearance of toluene decreased significantly (p less than 0.05) 3-4 wk after the smoking habit was discontinued. This decrease was not a consequence of the increased body weight noticed in the subjects. No statistically significant differences between the three exposure occasions in the elimination rate of hippuric acid could be demonstrated. Thus, cigarette smoking seems to enhance the elimination rate of toluene from the body, since the apparent clearance was decreased after smoking was stopped.
To study the influence of paracetamol and acetylsalicylic acid on the toxicokinetics of toluene, 2 groups of 10 male volunteers were exposed to toluene vapor (3.25 mmol/m3, 4 hr) at two different exposure occasions: toluene alone and toluene + analgesics. Solvent concentrations in blood and hippuric acid concentrations in urine were measured during the exposure period and 3 hr after exposure. The concentration of toluene in blood increased after ingestion of paracetamol or acetylsalicylic acid, as compared to the control exposure. The ingestion of paracetamol significantly increased the area under the blood concentration versus time curve (P less than 0.05) and the apparent blood clearance was significantly reduced (P less than 0.05) after ingestion of paracetamol but not after ingestion of acetylsalicylic acid. No statistically significant differences in the urinary excretion of hippuric acid were found.
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