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 microST, p(EXL) was obtained to be between 5x10(-9) and 2x10(-8) and p(HPS) to be between 7x10(-9) and 2x10(-8). Lifetime risks calculated for continuous exposure to 3 microg/m(3) ST in ambient air were between 8x10(-7) and 3x10(-6) (p(EXL)) and between 2x10(-8) and 4x10(-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.