Technical uncertainty in the back-calculation of occupational exposure to dioxins

Members of a cohort of workers in chemical industry (the so-called Boehringer cohort) exposed to 2, 3, 7, 8-tetrachlorodibenzo-para-dioxin (TCDD) from 1950 to 1984 were subject in the years 1985-1986 and 1992-1994 to an extensive biomonitoring programme on the TCDD levels of the individual workers. For establishing a dose-response relationship between TCDD-exposure and potentially carcinogenic response, the individual TCDD concentration-time courses had to be back-calculated over a period of up to more than four decades. Two back-calculations were attempted for this sophisticated modelling and estimation task, both based on the same toxicokinetic model but yielding different results. We demonstrate here by means of a computer simulation study that these differences could be plausibly explained by the so-called technical uncertainty caused by the employment of differently statistical estimation techniques. We show that the estimation techniques perform particularly differently in the presence of workplace misclassification and TCDD measurement error, two complications of exposure assessment that are with high probability affecting concurrently that cohort's data. We conclude that technical uncertainty sensibly enlarges the pool of possible explanations for contradictory empirical results of complex modelling and estimation approaches and should be considered as an obligatory uncertainty analysis step after the primary risk analysis evaluation in epidemiological and environmental studies.