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

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.