Modeling receptor kinetics in the analysis of survival data for organophosphorus pesticides
Jager, T. and Kooijman, S. A. L. M. 2005.
Modeling receptor kinetics in the analysis of survival data for organophosphorus pesticides.
Environmental Science \& Technology, 39: 8307 - 8314
Abstract
Acute ecotoxicological tests usually focus on survival at a
standardized exposure time. However, LC50s decrease in time in a
manner that depends both on the chemical and on the organism. DEBtox
is an existing approach to analyze toxicity data in time, based on
hazard modeling (the internal concentration increases the probability
to die). However, certain chemicals elicit their response through
(irreversible) interaction with a specific receptor, such as
inhibition of acetylcholinesterase (AChE). Effects therefore do not
solely depend on the actual internal concentration, but also on its
(recent) past. In this paper, the DEBtox method is extended with a
simple mechanistic model to deal with receptor interactions. We
analyzed data from the literature for organophosphorus pesticides in
guppies, fathead minnows, and springtails. Overall, the observed
survival patterns do not clearly differ from those of chemicals with a
less-specific mode of action. However, using the receptor model,
resulting parameter estimates are easier to interpret in terms of
underlying mechanisms and reveal similarities between the various
pesticides. We observed that the no-effect concentration estimated
from the receptor model is basically identical to the value from
standard DEBtox, illustrating the robustness of this summary
statistic.