Metabolism, bioavailability, and toxicokinetics of Benzo(alpha)pyrene in F-344 rats following oral administration

The objective of this study was to evaluate the bioavailability of Benzo(a) pyrene [B(a)p], subsequent to oral exposure. Eight-week-old F-344 rats were dosed orally with 100 mg/kg body weight B(a)p and sacrificed at 0, 0.5, 1. 0, 2.0, 4.0, 8.0, 24, 48 and 72 hours post exposure. Blood, liver, reproduc tive tissues, urine and fecal samples were collected at necropsy and were a nalyzed for parent B(a)p and metabolites by HPLC with fluorescence detectio n, Peak levels of B(a)p in plasma occurred 8 hours after exposure (67%) fol lowed by a gradual decrease. Liver retained 10% of the administered B(a)p u p to 24 hours following, which the levels dropped during the remaining time periods studied. Twenty-four hours after administration, 45% of the dose w as excreted in feces and urine. Metabolite levels in plasma peaked at 24 ho urs (10%) and decreased to I% at 72 hours. In the liver, metabolite levels were higher at 8 hours (10%) but were only 3% at 72 hours. Benzo(a)pyrene l evels increased after 24 hours in the reproductive organs and constituted 1 0% of the administered dose at 72 hours. Blood showed high levels of 7,8-di ol than 9,10 and 4,5-diols which were high in liver and reproductive organs . Compared to diols, the hydroxy metabolites were detected at high levels i n urine and fecal samples. Among the aqueous phase metabolites, glucuronide s were at higher levels compared to glutathiones and sulfates. The slow rel ease of unmetabolized B(a)p from reproductive organs and the presence of re active metabolites in these organs is a matter of concern as they could int erfere with gonadal steroid synthesis and release and its regulatory role i n gamete production, maturation and function of male animals in a continuou s exposure paradigm.