Organophosphate biological effects

The primary biological effects of the organophosphates are well defined. They act generally by inhibition of... 

This chapter describes and compares the reported toxic effects of various types of organophosphate (OP) neurotoxicants on cell and tissue culture models (i.c., in vitro models), that represent the constituents of the central nervous system (CNS). Like several environmental neurotoxicants, OP compounds affect multiple cell types, employ various mechanisms of toxic action, produce sublethal functional impairment to cells at low concentrations, and are nonessential from a primary metabolic standpoint. Individual cells are the basic functional unit in which the toxic actions of chemicals can be deduced, and cell and tissue culture modcLs excel at providing controlled environments for exposing known cell types to toxicants and dircedy measuring their biological effects. 

Iron oxide surfaces do facilitate the hydrolysis of organophosphate esters. (The term catalysis is not appropriate because the phosphate product is adsorbed and the oxide surface altered.) Generally the organic residue is not strongly adsorbed and its chemical and biological effects are of interest. Dannen-berg and Pehkonen (1998) examined the hydrolysis of four pesticides on three iron oxides. Hazardous and persistent products can be formed and the distribution of products can depend on the reaction conditions. 

No common structural denominator is apparent between the organophosphates to which this biological effect may be attributed, although the inclusion of a 2-chloroethyl group has been considered to lead to neurotoxicity whereas diethylphosphate compounds are devoid of this effect [107]. 

The pharmacology of the organophosphorus cholinesterase inhibitors has many facets. Much has been discovered concerning their mode of action and the therapeutic measures to be adopted in the event of intoxication by these compounds. Accepting the specificity of the antidotes used in these therapies, laboratory studies with them may indicate the principal locus of the toxic effects of the organophosphates. Because of the multiplicity of the biological effects of the organophosphorus pesticides, whether these effects... 

Enzyme Inhibition. Some materials produce toxic effects by inhibition of biologically vital enzyme systems, leading to an impairment of normal biochemical pathways. The toxic organophosphates, for example, inhibit the cholinesterase group of enzymes. An important factor in thek acute toxicity is the inhibition of acetylocholinesterase at neuromuscular junctions, resulting in an accumulation of the neurotransmitter material acetylcholine and causing muscle paralysis (29) (see Neuroregulators). 

Organophosphate insecticides also inhibit RBC-ACHE and PCHE. Inhibition of ACHE in erythrocytes is assumed to mirror inhibition of ACHE in the nervous system, which is the receptor of the toxic action, to some extent. Therefore, measurements of RBC-ACHE and PCHE are used for biological monitoring of exposure to OP insecticides (Maroni, 1986). Inhibitions of RBC-ACHE and PCHE activities are correlated with intensity and duration of exposure, although at different levels for each OP compound. Blood ACHE, being the same molecular target as that responsible for acute toxicity in the nervous system, is a true indicator of effect, while PCHE can only be used as an indicator of exposure. 

Noncarcinogenic toxicities are detrimental effects caused by chemicals that do not induce cancer. The most common effects are due to interactions between the chemical and the biological molecules in the receptor, especially enzymes. Toxic chemicals can bind to an important enzyme and reduce or eliminate its function. Some of the most important noncarcinogenic interactions between toxic chemicals and biological molecules include the inhibition of acetylcholinesterase by organophosphate ester and carbamate insecticides, the binding of carbon... 

Ibrahim NA and El-Gamal BA (2003) Effect of diazinon, an organophosphate insecticide, on plasma lipid constituents in experimental animals. Journal of Biochemistry, Molecular Biology and Biophysics 36(5) 499-504. 

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