Toxicokinetics of phthalic acid: The common final metabolite of phthalic acid esters in rats

The toxicokinetic profiles of phthalic acid (PA), which is the common final metabolite of phthalic acid esters (PAE), 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 ug/ml) at 30 min postadministration. 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. Data concerning the toxicokinetic profiles of PA improve our understanding of the toxicological potential of PAE and may prove useful for risk assessments of multiple phthalates exposure.