Estimation of a possible tumorigenic risk of styrene from daily intake via food and ambient air

Concerns of a tumorigenic risk of styrene (ST) originate from the findings that styrene (ST) is metabolized to the genotoxic intermediate styrene-7,8-oxide (SO). Therefore, it was hypothesized that results of animal long-term studies with ST and SO together with the SO tissue burden are sufficient for conducting a ‘worst case’ estimate of the tumorigenic risk of ST. On this basis we predicted the excess human lifetime risk for lung tumors ( p EXL) and the highest possible risk for other systemic tumors ( p HPS) resulting from daily intake of ST via food and ambient air. As measures for p EXL the mean lifetime concentration of SO in the transitional zone of the lung and for p HPS the mean lifetime concentration of SO in blood were calculated using a physiological toxicokinetic model. For a daily oral intake of 12 μg ST, p EXL was obtained to be between 5×10 −9 and 2×10 −8 and p HPS to be between 7×10 −9 and 2×10 −8. Lifetime risks calculated for continuous exposure to 3 μg/m 3 ST in ambient air were between 8×10 −7 and 3×10 −6 ( p EXL) and between 2×10 −8 and 4×10 −8 ( p HPS). Although these values indicate very low risks, the actual risks are expected to be even by far smaller. This is discussed in detail for lung tumorigenesis.