A toxicokinetic study to elucidate 3‐hydroxybenzo(a)pyrene atypical urinary excretion profile following intravenous injection of benzo(a)pyrene in rats

The toxicokinetics of benzo(a)pyrene (BaP) and 3‐hydroxybenzo(a)pyrene (3‐OHBaP) were assessed in 36 male Sprague–Dawley rats injected intravenously with 40 µmol kg¹ of BaP to explain the reported atypical urinary excretion profile of 3‐OHBaP. Blood, liver, kidney, lung, adipose tissue, skin, urine and feces were collected at t = 2, 4, 8, 16, 24, 33, 48, 72 h post‐dosing. BaP and 3‐OHBaP were measured by high‐performance liquid chromatography/fluorescence. A biexponential elimination of BaP was observed in blood, liver, skin and kidney (t_½ of 4.2–6.1 h and 12.3–14.9 h for initial and terminal phases, respectively), while a monoexponential elimination was found in adipose tissue and lung (t_½ of 31.2 and 31.5 h, respectively). A biexponential elimination of 3‐OHBaP was apparent in blood, liver and skin (t_½ of 7.3–11.7 h and 15.6–17.8 h for initial and terminal phases, respectively), contrary to adipose tissue, lung and kidney. In adipose tissue and lung, a monophasic elimination of 3‐OHBaP was observed (t_½ of 27.0 h and 24.1 h, respectively). In kidney, 3‐OHBaP kinetics showed a distinct pattern with an initial buildup during the first 8 h post‐dosing followed by a gradual elimination (t_½ of 15.6 h). In the 72‐h post‐treatment, 0.21 ± 0.09% (mean ± SD) of dose was excreted as 3‐OHBaP in urine and 12.9 ± 1.0% in feces while total BaP in feces represented 0.40 ± 0.16% of dose. This study allowed the identification of the kidney as a retention compartment governing 3‐OHBaP atypical urinary excretion. Copyright © 2010 John Wiley & Sons, Ltd.