Analysis of the Time-Dependent Acute Aquatic Toxicity of Organophosphorus Pesticides:  The Critical Target Occupation Model

Abstract

A model is presented for the acute toxicity of organophosphorus (OP) pesticides belonging to the class of phosphorothionates. The acute toxicity of these pesticides is governed by the irreversible inhibition of the enzyme acetylcholinesterase (AChE), after their metabolic activation to oxon analogues. The model is based on the idea that, for chemicals exhibiting an irreversible receptor interaction, mortality is associated with a critical amount of “covalently occupied” target sites, i.e., the “critical target occupation” (CTO). For a given compound and species, this CTO is associated with a critical time-integrated concentration of the oxon analogue in the target tissue, which can be modeled by the critical area under the curve (CAUC) that describes the time−concentration course of the phosphorothionate in the aqueous phase or in the entire aquatic organism. In contrast to the classical critical body residue (CBR) model, the CTO model successfully describes the 1−14-d LC50(t) data of several phosphorothionates in the pond snail and guppy. Furthermore, the time dependency of lethal body burdens (LBBs) of phosphorothionates is explained by the model. Although the CTO model is specifically derived for OP pesticides, it can be applied to analyze the acute toxicity and to estimate incipient LC50 values of organic chemicals that exert an irreversible receptor interaction in general.

Dimethoate 40% organosphosphorous pesticide toxicity in Prochilodus lineatus (Prochilodontidae, Characiformes) eggs and larvae

“…Modeling the acute toxicity of these compounds based on simple structure prediction is rather difficult because of the high specific activity of AChE and the specificity of the metabolic processes of each species (De Bruijin & Hermens, 1993;Legierse et al, 1999).…”

Advantages of toxicokinetic and toxicodynamic modelling in aquatic ecotoxicology and risk assessment

“…45,46 The TD model structure and method of parameter estimation can differ widely, depending on the endpoint that the model predicts (e.g. survival 31,36,38,46,61 or sublethal endpoints 51,62,63 ), the model assumptions about the reversibility of effects 47 and the question addressed (e.g. 46,50,51,59,64,65 ).…”

Critical Body Residues Linked to Octanol−Water Partitioning, Organism Composition, and LC50QSARs: Meta-analysis and Model

“…Deviations of more than a factor of 10 are noted for dioxin and insecticides, in particular for methoxychlor (crustaceans), pyrethroids (fish, rat), and miscellaneous neurotoxic B and C compounds (8)(9)(10)(11) in Figure 6c-f). The patterns noted in all fish data also apply to P. promelas, the species for which most QSARs were derived (Figure 6e).…”