title: A simple mechanistic model to interpret the effects of narcotics.
abstract: In this research we will show the advantages of using a time-independent dose metric in a mechanistic model to evaluate toxic effects for different narcotic compounds on different species. We will show how different already existing QSARs can be combined within a mechanistic framework to 1) make predictions of lethal thresholds; 2) show some limitations in the use of existing QSARs; 3) show how a mechanistic framework solves some conceptual problems in current approaches and 4) show how such a framework can be used to be of aid in an experimental setup in predicting the outcome of a survival experiment. The approach we chose is based on the simplest mechanistic model available, a scaled one-compartment model to describe uptake and elimination and hazard model to link the exposure to effects on survival. Within this theoretical framework a prediction for an internal threshold for effects on survival of 3 mmol/kg bw can be made, which should be similar for different species and independent of the partitioning characteristics of the toxicant. To demonstrate this, a threshold for 51 different species was derived, which indeed appeared to lie in a relatively small range, typically between 1 and 10 mmol/kg bw.
authors.affiliation: a Centre for Ecology and Hydrology , Wallingford , UK.
authors.forename: J
authors.initials: J
authors.lastname: Baas
authors.forename: D
authors.initials: D
authors.lastname: Spurgeon
authors.forename: M
authors.initials: M
authors.lastname: Broerse
mesh_terms: D000818:Animals; D007448:Invertebrates / Q000187:drug effects*; D007700:Kinetics; D008954:Models, Biological; D009294:Narcotics / Q000493:pharmacokinetics / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment; D014714:Vertebrates / Q000378:metabolism*
chemical_list: D009294:Narcotics
keywords: QSAR; critical body residue; mechanistic modelling; narcotics; no effect concentration; time