Application of human volunteer studies in setting exposure limits

Human volunteer studies can provide many of the quantitative data on human radionuclide biokinetics needed to relate organ doses to intakes. They are best suited to characterising parameters that apply to a wide range of compounds, e.g. particle deposition in the respiratory tract, and the retention and excretion of elements after injection into the blood. Their application to quantifying particle clearance from the respiratory tract is discussed, with particular reference to recent findings and the NRPB's programme of volunteer investigations. Evidence to support the view that particle clearance rates are similar for different materials is summarised. Rates of particle clearance from the human lung to the GI tract are calculated from the results of two recent studies. The fraction of the remaining lung content cleared per day is estimated to decrease from ∼ 3 x 10-3 d-1 at 25 days to ∼ 5 x 10-4 d-1 at 350 days. There is a large degree of inter-subject variation, with most results conforming to a log-normal distribution with σg of 1.6. There remains considerable uncertainty about subsequent clearance, and about sites of long-term lung retention. (author)