ALTERNATIVE MODELS FOR LOW DOSE-RESPONSE ANALYSIS OF BIOCHEMICAL AND IMMUNOLOGICAL END-POINTS FOR TETRACHLORODIBENZO-P-DIOXIN

As part of the current reassessment of dioxin, the empirical relations hips between administered tetrachlorodibenzo-p-dioxin and selected imm une and biochemical endpoints were investigated. A dose-response analy sis from the published literature was performed using Linear, Sigmoid- E(max) and Power Law functions. The results of this analysis indicate that the use of a wide dose range may bias the interpretation of low-d ose phenomenon. The Power Law function was applied exclusively to low- dose subsets enabling estimation of dose response in the low-dose rang e. Subsequently, high-dose data were fit using Power Law subset analys is. This approach resulted in a change in slope value from low- to hig h-dose subsets for thymic atrophy, immune suppression, benzo(a)pyrene hydroxylase activity, and ethoxyresorufin-o-deethylase activity. This change suggests that there is a high probability that there is a tissu e concentration along the dose-response continuum which results in bio logical activity from low to high dose. This analysis also demonstrate s that, the Power Law functional fit to the low-dose data differs quan titatively from the fit to the high-dose data for several noncancer en dpoints. Therefore, by using the Power Law function a more accurate an d biologically relevant assessment of risk can be produced for noncanc er endpoints. (C) 1995 Academic Press, Inc.