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

Abstract

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'

Coexposure of man to m-xylene and methyl ethyl ketone. Kinetics and metabolism.

“…In a Swedish study on combined inhalation exposure involving human volunteers, acetone (about 500 ppm) did not affect the metabolism of styrene (about 70 ppm, 2 h) (25). Large intraperitoneal doses of acetone did not affect the excretion of styrene metabolites in rats either (12).…”

Urinary elimination of styrene in experimental and occupational exposure.

“…The small slope difference of the regression lines corresponding to 2 and 3 h of exposure (figure 5) should mean that an increment in the blood concentration is still occurring throughout the third hour of exposure or that a stable level of urinary concentration is not rapidly reached, a phenomenon similar to what happens to the alveolar (constant) and arterial concentration (increasing up to over 75 min of exposure) (37,38).…”

“…This occurrence was probably due to a continuous increase in styrene concentration in arterial blood from the beginning of exposure up to I h or more later (6,10,37,38).…”

“…Finally it is to be pointed out that the unchanged styrene urinary concentration should not be affected either by other solvents interfering with each other in the biotransformation rat e or by the presence of common metabolites (38). Last, the method is simple, quickly performed, and noninvasive .…”

“…Therefore the styrene arterial concentration (CJ (at equilibrium) is likely to be about C A • A, ie, in this case, 5 350 nmol/I. [No direct measurement of the styrene concentration in arterial blood was made because the introduction of a catheter into an artery was not included in the acceptance protocol of the volunteers and because reference data are already available (1,12,37,38). ]…”