JOHANSON G, KRONBORG H, NAsLUND PH , BYFALT NORDQVIST M. Toxicokin etics of inhaled 2-butoxyethanol (ethylene glycol monobutyl ether) in man . Scand J Work Environ Health 12 (1986) 594-602. Seven male volunteers were exposed to 2-butoxyethanol at the Swedish occupational exposure limit (20 ppm or 0.85 mrnol /rnt) during light physical exercise (50 W) on a bicycle ergometer. The exposure took place in an exposure chamber and lasted 2 h. Expired air was collected at regular time intervals for estimation of the respiratory uptake of the solvent. Arterialized capillary blood and urine were sampled during and after the exposure period and analyzed for 2-butoxyethanol and its metabolite butoxyacetic acid. A new sensitive method for analyzing 2-butoxyethanol in biological specimens is described . 2-Butoxyethanol was derivatized with pentafluorobenzoyl chloride and analyzed by gas chromatography with electron capture detection. The respiratory uptake of 2-butoxyethanol averaged 10.1 /lmollmin or 57 010 of the inspired amount. The concentration in blood reached a plateau level of 7.4 /lmolli. The apparent values of elimination half-t ime, mean residence time, total blood clearance, and steady-state volume of distribution were 40 min , 42 min , 1.2 l1min and 541, respecti vely. The amount of 2-butoxyethanol excreted in urine was less than 0.03 010 of the total uptake, while that of butoxyacetic acid ranged from 17 to 55 010.

WIGAEUS E, LOF A, BJURSTROM R, BYFALT NORDQVIST M. Exposure to styrene: Uptake, distribution, metabolism and elimination in man. Scand j work environ health 9 (1983) 479-488. Eight male subjects were exposed for 2 h to about 2.88 mmol/m3 (300 mg/m3) of styrene vapor during light physical exercise. The uptake of styrene averaged 4.4 mmol, or 68 % of the amount supplied. The arterial blood concentration of styrene reached a relatively stable level of about 20 pmol/l after 75 min of exposure. The calculated value of blood clearance was 1.7 (SD 0.3) l/min, and the extraction ratio about 0.2. The half-time for the elimination phase was 41 (SD 7) min, and the calculated volume of distribution 99 (SD 13) 1. The concentration of styrene in the subcutaneous adipose tissue was about 50 pmol/kg 30-90 min after exposure. The concentration of nonconjugated styrene glycol in blood increased linearly during exposure and was about 15 % of the styrene concentration in blood at the end of exposure. It was eliminated with a halftime of 72 (SD 13) min. Within 28 h after exposure 58 % of the total uptake of styrene was recovered in the urine as mandelic and phenylglyoxylic acid. Their excretion halftimes (0-20 h) were 3.6 (SD 0.4) and 8.8 (SD 1.3) h, respectively. Styrene-7,8-oxide was detected and quantified in blood in a complementary study.

Six male subjects were exposed for two hours during light physical exercise to 2-81 mmol/m3 (293 mg/r3) of styrene on one occasion and to a mixture of 2-89 mmolm3 (301 mg/m3) of styrene and 21-3 mmollm3 (1240 mg/m3) of acetone on another (combination study). About 68% of the dose (somewhat more than 4 mmol) of styrene was taken up. The arterial blood concentration of styrene reached a relatively stable level after about 75 minutes of exposure of about 18 and 20 ,umoiIl after the single and combined exposure, respectively. Calculated values of mean blood clearance were 1-9 /min in the styrene study and 1-6 /min in the combination study; the half life of styrene in blood was about 40 minutes in both studies. The concentration of non-conjugated styrene glycol increased linearly during exposure and reached about 3 umol/l at the end of exposure and was eliminated with a half life of about 70 minutes. Styrene-7,8-oxide was detected and quantified in the blood in a complementary study. The half lives for the excretion of mandelic and phenylglyoxylic acid in the urine were about four and nine hours, respectively, in both studies.Styrene is one of the most widely used raw materials in the modem polymer industry and the most extensive and intensive exposure occurs in the reinforced plastics industry.' Laminaters are also often exposed to acetone used as a cleaning agent. The mechanism of potentiation of hepatotoxicity has been postulated to be either non-specific membrane changes which render the cell more susceptible to toxic injury4 or increased bioactivation of the toxicants to reactive intermediates,4671113-'7 or both. Other effects on cellular function or metabolism, however, cannot be excluded.671'

No abstract

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