Risk Assessment for Human Lung Cancer due to Diesel Exhaust Particles
I. Estimation from Animal Experimental Data
1992 Volume 27 Issue 6 Pages 289-295
Details
1992 Volume 27 Issue 6 Pages 289-295
Extrapolation of animal data of high-dose inhalation of diesel exhaust particles (DEP) into a human risk in low-dose exposure was carried out on the data, which were obtained at the 5 institutions in the world (Table 1).
The incidence rate of lung tumors was extrapolated, at first, from a high-dose to low-dose risk in rats by computer calculation using mathematic models. Among the five models used, the multistage model revealed the narrowest range of the estimated VSD values from 10 0 to 10-2 (Table 2), which indicates that it is the most applicable model for cancer risk assessment. According to this multistage model, life time risk for life time inhalation of 1 μg/m3 (unit risk) of DEP in rats was calculated to be 2.1-8.4×10-5.
How to extrapolate an animal risk into a human risk is an unsolved problem. EPA prefers an extrapolation by using a ratio in energy consumption corrected by body surface area between the two species. Unit risk in human for lung cancer by low-dose DEP exposure was calculated in this study to be 5.2-21.1×10-5, when the ratio of 2.5 was adopted.
Lung cancer incidence in rats correlated better to the lung burden of DEP than to the accumulated inhalation dose. Then, an estimation of lung cancer risk was made both from the amount of deposited carboneous dust in the lungs of Tokyo inhabitants and from the risk of lung cancer due to the deposited DEP in the rats. The risk of lung cancer for 1 mg DEP/gr rat lung was calculated to be 4.4×10-2 by using the multistage model, and the presumed average amount of DEP deposition in the lungs of Tokyo inhabitants was estimated as 0.19mg/gr lung, accordingly, their lung cancer risk was estimated as 82.7×10-4.
Then, the rate of deposited amount of particles in the lung due to the lfe time inhalation dose in both species was calculated, and the ratio of the rate in the two species was shown to be approximately 3.5 (Table 3). This was used as another extrapolation coefficient, and by using the two coefficients, 2.5 and 3.5, a unit risk range for human lung cancer due to DEP was estimated, finally, to be 5.2-29.5×10-5 with the geometric mean value of 12.3×10-5.
