title: Modeling receptor kinetics in the analysis of survival data for organophosphorus pesticides.
abstract: Acute ecotoxicological tests usually focus on survival at a standardized exposure time. However, LC50's 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 thatthe no-effect concentration estimated from the receptor model is basically identical to the value from standard DEBtox, illustrating the robustness of this summary statistic.
authors.affiliation: Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam, The Netherlands. tjalling@bio.vu.nl
authors.forename: Tjalling
authors.initials: T
authors.lastname: Jager
authors.forename: Sebastiaan A L M
authors.initials: SA
authors.lastname: Kooijman
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000187:drug effects; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D003530:Cyprinidae; D007700:Kinetics; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology; D010575:Pesticides / Q000737:chemistry* / Q000494:pharmacology; D011036:Poecilia
chemical_list: D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D010575:Pesticides; D000110:Acetylcholinesterase