Kinetics of styrene in workers from a plastics industry after controlled exposure: a comparison with subjects not previously exposed.

Eight male workers from a glass reinforced plastics industry were experimentally exposed for 2 hours to 2.84 mmol/m3 (296 mg/m3) styrene during light physical exercise (50 W). About 63% of the amount supplied (4.6 mmol styrene) was taken up in the body. The arterial blood concentration of styrene reached a relatively stable level of 15 mumol/l at the end of exposure which was about 70% of the blood concentration in a group of volunteers with no previous exposure to solvents. The apparent blood clearance was significantly higher in the occupationally exposed subjects 2.01/h X kg compared with 1.51/h X kg. Contrary to the relatively stable level of styrene at the end of exposure the concentration of non-conjugated styrene glycol increased throughout the exposure and reached about 3 mumol/l in both groups. Like styrene, the non-conjugated styrene glycol seemed to be eliminated faster from the occupationally exposed workers. The blood concentration of styrene-7,8-oxide was low and seldom exceeded the detection limit of 0.02 mumol/l. The results show that long term exposure in a glass reinforced plastics industry may facilitate the metabolism of styrene.

Biological monitoring of styrene metabolites in blood.

Ten men occupationally exposed to styrene in two glass-fiber reinforced plastics factories were studied during three consecutive workdays. The mean external exposure level was 99 mg/m3. The total pulmonary uptake of styrene was estimated from measurements of the styrene concentration in inspired air, the pulmonary ventilation, and the relative uptake. A gas chromatographic method based on electron capture detection was used to quantify styrene glycol, as well as styrene-7,8-oxide, in blood. The concentration of styrene glycol appeared to be linearly related to the preceding uptake of styrene. When the uptake during 5 h immediately before the blood sampling was considered, the correlation coefficient (r) obtained the value of 0.90. The concentration of styrene-7,8-oxide was at the detection limit of 0.02 mumol/l in most samples. A weaker correlation between the concentration of styrene in blood and the uptake during the hour immediately preceding the blood sampling was obtained (r = 0.71).

Coexposure to toluene and p-xylene in man: uptake and elimination.

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 mmol/m3). 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. The change in blood/end exhaled air concentration ratio may indicate an effect of coexposure.

The effects of ethanol on the kinetics of toluene in man.

Eleven men were exposed in an exposure chamber to toluene vapor (3.2 mmol/m3, 4.5 hr) with and without a simultaneous po intake of ethanol (15 mmol/kg body wt). The ethanol was administered 70 to 85 min after the onset of the toluene exposure to achieve maximum concentrations of toluene and ethanol in blood at the same time. During the exposure period the solvent concentrations in inspired and expired air as well as the pulmonary ventilation were determined. The solvent concentrations in blood were measured during and for 3 hr after the exposure period. No effect of ethanol on the pulmonary ventilation could be seen during the exposure period. Ethanol decreased the total uptake as well as the relative uptake of toluene. The maximum toluene concentration in the blood increased from 7.4 to 12.5 mumol/liter in the presence of ethanol and apparent clearance of toluene decreased significantly. Toluene exerted no effect on the uptake and elimination of ethanol in blood. The results indicate an influence of a moderate dose of ethanol on the kinetics of toluene. The distribution and/or elimination of toluene from the blood was inhibited resulting in increased tissue exposure.

Uptake, distribution, metabolism, and elimination of styrene in man. A comparison between single exposure and co-exposure with acetone.

Six male subjects were exposed for two hours during light physical exercise to 2.81 mmol/m3 (293 mg/m3) of styrene on one occasion and to a mixture of 2.89 mmol/m3 (301 mg/m3) of styrene and 21.3 mmol/m3 (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 mumol/l after the single and combined exposure, respectively. Calculated values of mean blood clearance were 1.9 l/min in the styrene study and 1.6 l/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 mumol/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.

Occurrence of styrene-7,8-oxide and styrene glycol in mouse after the administration of styrene.

Styrene-7,8-oxide and its hydrated product styrene glycol were determined in mouse tissues at different times (0.5-5 h) after the intraperitoneal administration of 7-[14C]-styrene (3.8 mmol/kg). In a study of the influence of dose on the metabolite pattern of styrene, mice were killed 2 h after a dose of 1.1, 2.3, 3.4, and 5.1 mmol/kg, respectively. The mouse tissues studied (blood, liver, kidney, lung, brain, subcutaneous adipose tissue) were isolated and extracted first with hexane to remove styrene and styrene-7,8-oxide and then with ethyl acetate to remove styrene glycol. beta-Glucuronidase was used to liberate conjugated styrene glycol. A gas-liquid chromatographic method based on the use of an electron capture detector (GLC-EC) was used to quantify styrene glycol, as well as styrene-7,8-oxide, after hydrolysis. In addition all homogenates and extracts were assayed by radioactivity counting. Styrene-7,8-oxide and styrene glycol reached maximum concentrations within 2 h. The highest levels of styrene-7,8-oxide were detected in the kidneys and subcutaneous adipose tissue, while the lungs showed the lowest levels. Styrene glycol was found in the highest concentrations in the kidneys, liver, blood, and lungs. The concentration of unmetabolized styrene increased exponentially at higher doses. There seemed to be a linear increase with the dose of styrene-7,8-oxide and styrene glycol in all the tissues studied. The more polar metabolites occurred at relatively lower levels in the liver and kidneys at higher doses. In a complementary study the epoxide hydratase inhibitor trichloropropene oxide was added to the removed tissues, and the hexane extracts were analyzed for styrene-7,8-oxide both by GLC-EC and mass spectrometry (GLC-MS).

Exposure to styrene. Uptake, distribution, metabolism and elimination in man.

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 mumol/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) l. The concentration of styrene in the subcutaneous adipose tissue was about 50 mumol/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 half-time 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 half-times (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.

Urinary excretion of hippuric acid and o-cresol after laboratory exposure of humans to toluene.

The urinary excretion of hippuric acid and o-cresol was studied after respiratory exposure of human volunteers to approximately 80 ppm (306 mg/m3 +/- SD 13) of toluene for 2 h under different work loads (0, 50, 100, 150 W, respectively, during 30-min periods). The diet before and after exposure varied. An isotachophoresis method for the determination of hippuric acid is described. The correlation between the total urinary excretion, excretion rate and concentration of hippuric acid, and the respiratory uptake of toluene was poor or non-existing. The same was true for the excretion of o-cresol, which 4 h after exposure was concluded amounted to 0.03-0.26% of the toluene uptake. Thus, after a short-time exposure neither metabolite proved to be a reliable measure of individual toluene uptake at varying workloads or food intake in combination with low exposure levels.