A MODEL TO EVALUATE PAST EXPOSURE TO 2,3,7,8-TCDD

Data from several studies suggest that concentrations of dioxins rose in the environment from the 1930s to about the 1960s/70s and have been declining over the last decade or two. The most direct evidence of th is trend comes from lake core sediments, which can be used to estimate past atmospheric depositions of dioxins. The primary source of human exposure to dioxins is through the food supply. The pathway relating a tmospheric depositions to concentrations in food is quite complex, and accordingly, it is not known to what extent the trend in human exposu re mirrors the trend in atmospheric depositions. This paper describes an attempt to statistically reconstruct the pattern of past human expo sure to the most toxic dioxin congener, 2,3,7,8-TCDD (abbreviated TCDD ), through use of a simple pharmacokinetic (PK) model which included a time-varying TCDD exposure dose. This PK model was fit to TCDD body b urden data (i.e., TCDD concentrations in lipid) from five U.S. studies dating from 1972 to 1987 and covering a wide age range. A Bayesian st atistical approach was used to fit TCDD exposure; model parameters oth er than exposure were all previously known or estimated from other dat a sources. The primary results of the analysis are as follows: (1) use of a time-varying exposure dose provided afar better fit to the TCDD body burden data than did using a dose that was constant over time; th is is strong evidence that exposure to TCDD has, in fact, varied durin g the 20th century (2) the year of peak TCDD exposure was estimated to be in the late 1960s, which coincides with peaks found in sediment co re studies, (3) modeled average exposure doses during these peak years was estimated at 1.4-1.9 pg TCDD/kg-day, and (4) modeled exposure dos es of TCDD for the late 1980s of less than 0.10 pg TCDD/kg-day con-ela ted well with recent estimates of exposure doses around 0.17 pg TCDD/k g-day (recent estimates are based on food concentrations combined with food ingestion rates; food is thought to explain over 90% of total di oxin exposure). This paper describes these and other results, the good ness-of-fit between predicted and observed lipid TCDD concentrations, the modeled impact of breastfeeding on lipid concentrations in young i ndividuals, and sensitivity and uncertainty analyses.