WIGAEUS E, HOLM S, ASTRAND 1. Exposure to acetone: Uptake and elimination in man. Scand j work environ health 7 (1981) 84-94. Eight male subjects were exposed to ·a<:'etone vapor on two occasions for 2:h d.n lIhe laboratory. On the jjirst iOccasion t'hey wer,e ,exposed Ito about 1,300 mg/m 3 dumng r,est a'nd on the second occals'ion to about 700 mg/m 3 during rest (30 min) and eX8l'cise at dJifferent work ]oads on a bicycle ergometer (90 min). The total uptake of acetone was 0.6-1.2 g, 'and the r,elative uptake was ,about 45 0/0. The concentration of acetone in alveol,ar air was 30-40 % of tihat in ,the 'inspiratory air, and rl.t was not affected by exposure time or work 1oad. The concentration of acetone in blood increased continuously wli.t'h inc,reased uptake during exposure, and ,there was no 'tendency towarolS equili'briurn. 'I'he half-time of acetone in alveolar air as about 4 h, and in venous and arterial blood it was about 6 and 4 h, respectively. The 'h~ighest conceIllwatiions of acetone in urine were measur,ed 3-3.5 h after exposure. The ,e)jminat~on of acetone v,ia the lungs corresponded to about 20 % of the Itotal uptake. Only about 1 % of 'the uplta'ke was excreted via ur.ine.

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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

Single doses of 2,4,5,2',5-pentachlorobiphenyl uniformly labeled with 14-C have been administered intravenously and orally to mice. Whole-body autoradiograms and scintillation counting of tissue samples have shown that most radioactivity leaves the circulation for the tissues within one hour. Peak concentrations varied, being highest in brown fat, which after 24 hours comprised the major reservoir of the unchanged compound in the body. Radioactivity disappeared rather rapidly drom most other tissues, although the longest retention occurred in bronchial epithelium and some parts of the renal tubules. The excretion of radioactivity was mainly through the bile, into feces, with a half-time of six days. There was little unchanged compound in the feces, the major metabolite was a hydroxylated derivative, both free and conjugated.

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