Analysis of bioassays with time-varying concentrations

In the analysis of eco toxicological bioassays the concentration of the tes t compounds is assumed to be constant. In many situations this assumption i s questionable, as various processes may cause a substantial decline in the concentration during exposure. This leads to difficulties in the estimatio n of parameters that characterise the toxicity of the test compound. As a s olution to this problem, time-varying concentrations are often replaced by their mean values for the estimation of toxicity parameters. However. Monte -Carlo simulations show that this approach results in biased estimates of t he toxicity parameters. As an alternative approach, we propose models to es timate one important toxicity parameter, the no effect concentration, in si tuations where the concentration of the compound varies in time. These mode ls are extensions of the DEBtox model (Kooijman and Bedaux, 1996) which is based on biological assumptions about toxicokinetics and toxic effects. We also propose a new approach for the estimation of toxicity parameters for s trongly accumulating non-metabolisable compounds. This approach does not re quire any kinetics assumption. Computer simulation and experimental data co nfirm the relevance of the different proposals. (C) 2001 Elsevier Science L td, All rights reserved.