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The toxicokinetic profiles of phthalic acid (PA), were studied in rats after orally administering doses 20, 100, or 500 mg/kg. Concentrations of PA were determined in serum or urine by high-performance liquid chromatography (HPLC). The plasma concentrations of PA showed a biexponential increase following oral administration of doses ranging from 20 to 500 mg/kg. The terminal elimination half-lives (t1/2) of PA at dosages of 20, 100, or 500 mg/kg were 6.46+1.13, 5.19+3.56, and 5.10+1.10 h respectively, total clearances (CL/F) of PA at 20, 100, or 500 mg/kg were 97.43+4.20, 215.01+55.42, and 721.07+51.81 ml/h, and apparent distribution volumes of PA in the steady state (Vz/F) at 20, 100, or 500 mg/kg were 903.28+125.28, 1419.87+527.53, and 5264.86+993.65 ml, respectively. PA was absorbed rapidly after an oral dose of 500 mg/kg with peak concentration (Cmax) in blood (3.5+0.33 µg/ml) at 30 min post administration. After oral administration, the dose-normalized area under the curve (AUC) (146.90+9.33 µg/h/ml) for 500 mg/kg was significantly greater than at 20 mg/kg (44.69+2.56 µg/h/ml). Urine analysis indicated that 13+0.45% of the administered PA dose (at 500 mg/kg, p. o.) was recovered unchanged in urine within 24 h (Lim, 2007).

In a toxicokinetic study following a single oral dose of carbonyl labeled phthalic acid to rats 95% of the radioactivity was recovered as phthalic acid in the feces and urine. The distribution between the feces and the urine was relatively independent of the dose level with 70-80% of the radioactivity in the feces and 20 -25% in the urine. No metabolites of phthalic acid could be detected in the feces or the urine but a small amount of the phthalic acid was converted to carbon dioxide (0.11 – 0.15%). Four hours after dosing approximately 2% of the radioactivity was distributed throughout the organs and tissues with most of this radioactivity detected in the liver, kidney, spleen and testes. No radioactivity could be detected in these organs twenty-four hours after dosing. (Williams, 1974).

These results indicate that phthalic acid administered orally to the rat is rapidly absorbed by the gastrointestinal tract with peak plasma concentrations after 30 minutes and a short terminal half-life of 5-6 h. PA is not retained in the organs or tissues and is almost quantitatively excreted in feces and urine as unchanged PA. The main excretion route was the feces followed by urine.

No experimental data on PA is available for some toxicological endpoints. For these endpoints read across with phthalic anhydride is proposed due to the rapid hydrolysis of phthalic anhydride to the phthalic acid. In an in vitro hydrolysis test the rate of hydrolysis of phthalic anhydride was determined at different pHs at 25°C in water/buffer containing a small amount of acetonitrile. Phthalic anhydride hydrolyses rapidly in the presence of water forming phthalic acid. Half-life for phthalic anhydride was 30.5 seconds at pH 7.24. At pH 6.8 the half-life of phthalic anhydride in water was prolonged to 61 seconds (Andrés, 2001).