Common Mechanism of Toxicity: A Case Study of Organophosphorus Pesticides

Abstract

The Food Quality Protection Act of 1996 (FQPA) requires the EPA to consider "available information concerning the cumulative effects of such residues and other substances that have a common mechanism of toxicity ... in establishing, modifying, leaving in effect, or revoking a tolerance for a pesticide chemical residue." This directive raises a number of scientific questions to be answered before the FQPA can be implemented. Among these questions is: What constitutes a common mechanism of toxicity? The ILSI Risk Science Institute (RSI) convened a group of experts to examine this and other scientific questions using the organophosphorus (OP) pesticides as the case study. OP pesticides share some characteristics attributed to compounds that act by a common mechanism, but produce a variety of clinical signs of toxicity not identical for all OP pesticides. The Working Group generated a testable hypothesis, anticholinesterase OP pesticides act by a common mechanism of toxicity, and generated alternative hypotheses that, if true, would cause rejection of the initial hypothesis and provide criteria for subgrouping OP compounds. Some of the alternative hypotheses were rejected outright and the rest were not supported by adequate data. The Working Group concluded that OP pesticides act by a common mechanism of toxicity if they inhibit acetylcholinesterase by phosphorylation and elicit any spectrum of cholinergic effects. An approach similar to that developed for OP pesticides could be used to determine if other classes or groups of pesticides that share structural and toxicological characteristics act by a common mechanism of toxicity or by distinct mechanisms.

Analytical Applications of Enzymatic Growth of Quantum Dots

“…[17] Inhibitors of AChE, such as nerve gases and pesticides, are able to block enzymatic decomposition of acetylcholine, causing fatal consequences. [18] AChE can also hydrolyze the alternative artificial substrate acetylthiocholine (ATCh) and yield the thiol-containing compound thiocholine and acetic acid. Our method consists of the synthesis of CdS QDs in the presence of thiosulfate, cadmium sulfate and thiocholine.…”

Electrochemical biosensing strategy for highly sensitive pesticide assay based on mercury ion-mediated DNA conformational switch coupled with signal amplification by hybridization chain reaction

“…However, irrational use of carbamates and organophosphates results in excessive pesticide residues and metabolites that are hazardous to the environment and human health [3]. The high toxicity of carbamates and organophosphates is ascribed to their capability of irreversibly inhibiting the activity of acetylcholinesterase (AChE) in the central and peripheral nervous system, resulting in the accumulation of the neurotransmitter acetylcholine throughout the body, thus affecting the physiology of the nervous system with serious or even fatal consequences [4]. These environmental and health problems caused by carbamate and organophosphate pesticide residues have attracted great interest in the past decades to develop sensitive and reliable methods for efficient detection of pesticides in agricultural products, waters, and soils.…”

Use of NMR techniques for toxic organophosphorus compound profiling

“…The inhibition is caused by formation of a stoichiometric (1:1) covalent conjugate with the active site serine. This causes excess of acetylcholine to accumulate in nerve synapses, leading to nerve overstimulation [27]. The symptoms, depending on the level of exposure, are hypersecretions, fasciculations, tremor, convulsions, coma and death [28].…”