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Description of key information

Short description of key information on bioaccumulation potential result: 
The toxicokinetics of alpha-methylstyrene were extensively investigated in rats with oral, intravenous and inhalative exposure:
i.v.: 10 mg/kg
oral: 1000 mg/kg
inhalation: 300 or 900 ppm over 6 hrs (nose-only).
Alpha-methylstyrene was readily metabolized to form products that were chiefly excreted in the urine. There was little accumulation of radiolabeled equivalents in the tissues, so that a bioaccumulation potential can be excluded.

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Additional information

Male F344/N rats were exposed to alpha-methylstyrene via intravenous or nose-only inhalation exposure. In both studies, the substance was eliminated primarily in the urine (approximately 90 %) within 72 hours, with volatile breath and faeces accounting for only a small amount (1 - 3 %) of elimination. In the inhalation study, the elimination half-life was calculated at 3 to 5 hours, with the highest concentrations of alpha-methylstyrene-derived radioactivity retained in the adipose tissue, urinary bladder, liver, kidney, and skin. Following intravenous dosing, the kidney, heart, lung, liver, urinary bladder, and spleen retained the highest concentrations of radioactivity. In both the intravenous study and the inhalation study, the major urinary metabolites of alpha-methylstyrene were the glucuronide conjugate of 2-phenyl-1,2-propanediol and atrolactic acid. In the inhalation study, the major metabolites in the blood were 2-phenyl-1,2-propanediol and 2-phenylpropionic acid.

The proposed metabolic pathway for alpha-methylstyrene involves an initial non-stereoselective epoxidation followed by hydrolysis to form 2-phenyl-1,2-propanediol followed by either oxidation to atrolactic acid or formation of the glucuronide conjugate, conjugation with glutathione and subsequent cleavage to the mercapturate, or rearrangement to form an aldehyde that is oxidized to yield 2-phenylpropionic acid. The dose-dependent pharmacokinetic parameters coupled with decreased excretion of 2-phenyl-1,2-propanediol glucuronide at 900 ppm indicate that glucuronide formation was saturated at this dose.