POSSIBLE RANGE OF DIOXIN CONCENTRATION IN HUMAN TISSUES: SIMULATION WITH A PHYSIOLOGICALLY BASED MODEL

Abstract

In risk evaluation of dioxins, monitoring chemical concentrations in human tissues is an important step, and these concentration data can be utilized along with animal toxicity data for extrapolation of human manifestation. However large differences in dioxin concentrations usually exist even among individuals who have never been accidentally exposed to high quantities of dioxin, and this may cause problems in risk analysis. Body size, age, and history of food consumption are factors responsible for these interindividual differences in addition to exposure levels. Using a physiologically based pharmacokinetic (PBPK) model, the influence of differences in body weight, gastrointestinal absorption, and half-life and intake of dioxin were examined on tissue chemical concentration. Dioxin concentrations over a 40-yr time course in human liver, kidneys, fat, blood, muscle and richly perfused tissue were simulated for polychlorinated dibenzo- p -dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (CoPCBs). Model parameters such as tissue-blood partition coefficients for CoPCBs were prepared, and sensitivity analysis was also performed on these parameters. The range of tissue concentrations was approximately 0.17 to 4.1 times the standard concentration, which was calculated using standard model parameters. The simulated ranges included more than 80% of the individual anatomical data for 2,3,7,8-tetrachlorodibenzo- p -dioxin, 1,2,3,7,-pentachlorodibenzo- p -dioxin, and 3,3',4,4',5-pentachlorobiphenyl in liver, fat, and blood. These results suggest that differences in body weight, gastrointestinal absorption, and food intake behavior may partially explain variation in tissue concentrations among individuals, and the possible interindividual uncertainty, which is approximately 24 for the general Japanese population.