Comparison of oral bioavailability of benzo[a]pyrene in soils using rat and swine and the implications for human health risk assessment.

BACKGROUND There are many uncertainties concerning variations in benzo[a]pyrene (B[a]P) soil guidelines protecting human health based on carcinogenic data obtained in animal studies. Although swine is recognised as being much more representative of the human child in terms of body size, gut physiology and genetic profile the rat/mice model is commonly used in practice. OBJECTIVES We compare B[a]P bioavailability using a rat model to that estimated in a swine model, to investigate the correlation between these two animal models. This may help reduce uncertainty in applying bioavailability to human health risk assessment. METHODS Twelve spiked soil samples and a spiked silica sand (reference material) were dosed to rats in parallel with a swine study. B[a]P bioavailability was estimated by the area under the plasma B[a]P concentration-time curve (AUC) and faecal excretion as well in the rats. Direct comparison between the two animal models was made for: firstly, relative bioavailability (RB) using AUC assay; and secondly, the two assays in the rat model. RESULTS Both AUC and faecal excretion assays showed linear dose-response for the reference material. However, absolute bioavailability was significantly higher when using faecal excretion assay (p<0.001). In aged soils faecal excretion estimated based on solvent extraction was not accurate due to the form of non-extractable fraction through ageing. A significant correlation existed between the two models using RB for soil samples (RBrat=0.26RBswine+17.3, R(2)=0.70, p<0.001), despite the regression slope coefficient revealing that the rat model would underestimate RB by about one quarter compared to using swine. CONCLUSIONS In the comparison employed in this study, an interspecies difference of four in RB using AUC assay was identified between the rat and swine models regarding pharmacokinetic differences, which supported the body weight scaling method recommended by US EPA. Future research should focus on the carcinogenic competency (pharmacodynamics) used in experiment animals and humans.