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Metabolism and Pharmacokinetics

The metabolism and pharmacokinetics of the subject chemical have been determined in rats following intravenous, oral, dermal and inhalation exposures to 14C-labeled material. Regardless of route of administration, radioactivity was eliminated rapidly, with the majority within 12 hours. Oral administration in rats at 15 or 150 mg/kg bw resulted in 97% and 96%, respectively, overall elimination by 72 hours. Of this, 75% and 81%, respectively, were recovered in the urine. The half-life for elimination following oral administration was 0.13 hour. This half-life increased to 0.20 hour at the 150 mg/kg bw dose level suggesting saturation of the metabolism or excretion process. Following intravenous administration, the half-life for elimination of the parent material was 0.12 hours. Inhalation exposures of rats at concentrations of 25 ppm or 175 ppm of labeled material resulted in similar paterns of elimination with 80% appearing in urine at 25 ppm and 79% in urine at the 175 ppm concentration. Following dermal administration at 475.5 mg/kg bw of the labeled material, less than 27% was absorbed following a 6 -hour exposure period, with the majority of applied dose (74%) recovered as unabsorbed liquid or in washings of the application site.

The primary metabolite resulting from exposure to the subject chemical was 2 -propoxyacetic acid. This acid was the principle urinary metabolite regardless of route of administration and representing 42 to 61% of urinary radioactivity in 12 -hour urine samples. The glycine conjugate of 2 -propoxyacetic acid accounted for an additional 24% to 38% of radioactivity present in urine samples. Minor urinary components included ethylene glycol (up to 14%) and the glucuronide conjugate of the parent material, at levels of 2% to 6%.

Dermal Absorption

The subject chemical is absorbed moderately rapidly through both human and rat skin. The in vitro dermal absorption of the subject chemical was determined with both human statum corneum and full thickness rat skin using Franz-type glass diffusion cells. Absorption rates obtained were 0.58 mg/cm2/hour and 2.30 mg/cm2/hour, respectively, for human and rat skin samples. The corresponding permeability coefficients calculated were 6.43 x 10 -4 cm/hour and 2.52 x 10 -3, respectively.