Quantitative aspects of enhanced liver tumour formation in CF-1 mice by dieldrin

Abstract

The dose-response characteristics of dieldrin-mediated enhancement of liver tumour formation in CF-1 mice were analysed, using existing tumour data from chronic feeding studies at six levels of continuous exposure, involving a total of greater than 1500 animals. The dose-response relationship can be expressed as: Dx X Tx = D0 X T0 = constant, where T0 = the median liver tumour induction period in control CF-1 mice, Tx = the median liver tumour induction period in dieldrin-treated mice at a dose level Dx, D0 = the background dose equivalent for the induction of 'spontaneous' liver tumours, Dx = the sum of background dose (D0) and actual dieldrin dose (delta x). The relationship, which is a Druckrey equation (D X Tn = constant) where n = 1, indicates that: (i) the velocity of liver tumour development is proportional to the daily dose level (Dx), (ii) the total tumourigenic dose is constant across all doses, (iii) the effects of dieldrin on the neoplastic process in mouse liver are essentially irreversible and cumulative, and (iv) there is no evidence for a threshold level. However, when delta x much less than D0, the actual contribution of dieldrin to tumour formation is expected to be negligible.