Organophosphates effects

Menking, D.E., Thompson, R.G., Wolff, V.L., Valdes, J.J. (1990). Irreversible organophosphate effects on nicotinic acetylcholine receptor/ion channel complex. Def. Techn. Inf. Cent. Rep. 

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). 

In 1916, calcium arsenate [7778-44-1] dusted by airplane was used to control the boU weevil however, throughout many developments in effective insecticides, such as organophosphates, the boU weevils became resistant to poisons that were formerly effective (see Insectcontroltechnology). 

Developmental Effects. Adverse effects of methyl parathion on hirman fetal development have not been reported. Based on studies in animals, such effects appear to be possible if pregnant women were exposed during the first trimester to high concentrations of methyl parathion that resulted in significant depression of cholinesterase levels, particularly if concomitant signs and symptoms of organophosphate intoxication occur. Such an exposure scenario may occur with occupational exposure, exposure in homes or offices illegally sprayed with methyl parathion, or accidental exposure to methyl parathion, but is less likely as a result of low-level exposure. 

In addition to effects mediated through glucocorticoid secretion (stress-related), a hypothetical mechanism for direct immunotoxicity of organophosphates is the inhibition of esterases and stabilization of the lysosomal membrane of lymphocytes, thus blocking release of lymphokines (Sharma and Reddy 1987). 

Following exposure of humans to organophosphates, but not specifically methyl parathion, restoration of plasma cholinesterase occurs more rapidly than does restoration of erythrocyte cholinesterase (Grob et al. 1950 Midtling et al. 1985). These findings are supported by studies of methyl parathion in animals. Erythrocyte cholinesterase levels are representative of acetylcholinesterase levels in the nervous system, and, therefore, may be a more accurate biomarker of the neurological effects of chronic low level exposure of humans to methyl parathion (Midtling et al. 1985 NIOSH 1976). 

Individuals with hereditary low plasma cholinesterase levels (Kalow 1956 Lehman and Ryan 1956) and those with paroxysmal nocturnal hemoglobinuria, which is related to abnormally low levels of erythrocyte acetylcholinesterase (Auditore and Hartmann 1959), would have increased susceptibility to the effects of anticholinesterase agents such as methyl parathion. Repeated measurements of plasma cholinesterase activity (in the absence of organophosphate exposure) can be used to identify individuals with genetically determined low plasma cholinesterase. 

A recent method, still in development, for determining total 4-nitrophenol in the urine of persons exposed to methyl parathion is based on solid phase microextraction (SPME) and GC/MS previously, the method has been used in the analysis of food and environmental samples (Guidotti et al. 1999). The method uses a solid phase microextraction fiber, is inserted into the urine sample that has been hydrolyzed with HCl at 50° C prior to mixing with distilled water and NaCl and then stirred (1,000 rpm). The fiber is left in the liquid for 30 minutes until a partitioning equilibrium is achieved, and then placed into the GC injector port to desorb. The method shows promise for use in determining exposures at low doses, as it is very sensitive. There is a need for additional development of this method, as the measurement of acetylcholinesterase, the enzyme inhibited by exposure to organophosphates such as methyl parathion, is not an effective indicator of low-dose exposures. 

Boyes WK, Tandon P, Barone S, et al. 1994. Effects of organophosphates on the visual system of rats. J Appl Toxicol 14 135-143. 

Degraeve N, Moutschen J, Moutschen-Dahmen M, et al. 1979. Genetic effects of organophosphate insecticides in mouse [Abstract]. Mutat Res 64 131. 

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