Methyl parathion inhibition

Male rats exposed to 264 mg/m of methyl parathion by inhalation had 59% (range 53-61%) inhibition of blood (a combination of erythrocyte and plasma) cholinesterase 1 hour after exposure (EPA 1978e). These animals had typical cholinergic signs of toxicity salivation, exophthalmos, laerimation, spontaneous defecation and urination, and muscle fasciculation. Values for controls were not provided. Death was not correlated to the degree of eholinesterase inhibition in whole blood. 

Neurologic signs did not occur over a 30-day period in male prisoner volunteers in California who ingested daily doses of methyl parathion ranging from 1.0 to 19 mg. There were no uniform changes in plasma or erythrocyte cholinesterase levels at any of these doses (Rider et al. 1969). By increasing concentrations of methyl parathion administered to the same experimental population and using the same protocol, a dose that inhibited cholinesterase values was established. These additional studies were published nearly 20 years ago in abstract form only therefore, they are not discussed in this section. 

When methyl parathion was given orally to rats at doses of 1.5 mg/kg and to guinea pigs at 50 mg/kg, plasma, erythrocyte, and brain cholinesterase activity was maximally inhibited within 30 minutes after administration. In rodents of both species that died after acute intoxication, brain cholinesterase levels decreased to 20% of control values and often to 5-7% (Miyamoto et al. 1963b). The species difference in susceptibility to orally administered methyl parathion is noted in Section 3.2.2.1. 

Mice that were exposed dermally to residues of methyl parathion in emulsifiable concentrate on foliage, and were muzzled to prevent oral intake, developed inhibition of plasma cholinesterase and erythrocyte cholinesterase after two 10-hour exposures (Skinner and Kilgore 1982b). For the organophosphate pesticides tested in this study, cholinergic signs generally were seen in mice with cholinesterase inhibition >50% results for this end point were not broken down by pesticide. 

Based on the rapid appearance of clinical signs and cholinesterase inhibition, methyl parathion appears to be readily absorbed by humans and animals following inhalation, oral, and dermal exposure. Following oral administration of methyl parathion to animals, the extent of absorption was at least 77-80% (Braeckman et al. 1983 Hollingworth et al. 1967). No studies were located regarding the extent of absorption following inhalation and dermal exposure, or the mechanism of absorption. 

Exposure of two species of freshwater fish to 0.106 ppb of a commercial formulation containing 50% methyl parathion increased serum levels of T3 and reduced T4 (Bhattacharya 1993). This effect was attributed to inhibition of acetylcholinesterase activity in the fish brain, but no direct evidence was presented. Similar treatment of freshwater perch for 35 days resulted in decreased release of progesterone from the ovaries (Bhattacharya and Mondal 1997). Also, treatment of freshwater perch for up to 90 days with methyl parathion induced a decrease in the gonadosomatic index (not defined) after day 15 of... 

Diagnosis of organophosphate poisoning (including methyl parathion) can be confirmed by evaluation of serum (plasma) cholinesterase and erythrocyte cholinesterase. However, cholinesterase inhibition is not specific for organophosphates. For example, carbamate insecticides also result in cholinesterase inhibition, which is usually transitory. Erythrocyte cholinesterase measurement is a specific test for... 

Compounds that affect activities of hepatic microsomal enzymes can antagonize the effects of methyl parathion, presumably by decreasing metabolism of methyl parathion to methyl paraoxon or enhancing degradation to relatively nontoxic metabolites. For example, pretreatment with phenobarbital protected rats from methyl parathion s cholinergic effects (Murphy 1980) and reduced inhibition of acetylcholinesterase activity in the rat brain (Tvede et al. 1989). Phenobarbital pretreatment prevented lethality from methyl parathion in mice compared to saline-pretreated controls (Sultatos 1987). Pretreatment of rats with two other pesticides, chlordecone or mirex, also reduced inhibition of brain acetylcholinesterase activity in rats dosed with methyl parathion (2.5 mg/kg intraperitoneally), while pretreatment with the herbicide linuron decreased acetylcholine brain levels below those found with methyl parathion treatment alone (Tvede et al. 1989). 

Cimetidine, an H2 antagonist used therapeutically in patients with ulcers, inhibits activity of hepatic microsomal enzymes. When rats or mice were pretreated with cimetidine, dose-related lethality of methyl parathion was reduced, and cholinergic signs of toxicity were delayed. Simultaneous administration with methyl parathion did not reduce toxicity (Joshi and Thornburg 1986). 

Piperonyl butoxide, a common potentiator of insecticide effects that inhibits microsomal enzymes, antagonized the toxic effects of methyl parathion in mice (Mirer et al. 1977). 

Permethrin, a pyrethrin pesticide, decreased the inhibition of brain cholinesterase activity by methyl parathion, but methyl parathion decreased the LD50 of permethrin when the two pesticides were simultaneously administered to rats (Ortiz et al. 1995). The potentiation of permethrin lethality may be due to the inhibition by methyl parathion of carboxylesterase, which metabolizes permethrin. 

Following inhibition by methyl parathion, acetylcholinesterase activity recovers as a result of the synthesis of new enzyme, generally at a rate of approximately 1% per day. However, the symptoms of methyl parathion poisoning usually resolve much more rapidly. Therefore, even though they are symptom-free, persons poisoned by methyl parathion may be hypersusceptible to its effects and should avoid reexposure for several weeks (Aaron and Howland 1998 Proctor et al. 1988). 

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. 

Organophosphates, such as methyl parathion, are known to inhibit cholinesterase activity. A method has been developed to measure the extent of this inhibition and relate it to organophosphate exposure (EPA 1980d Nabb and Whitfield 1967). In this EPA-recommended method, blood is separated into plasma and red blood cell fractions. The fractions are treated with saline solution, brought to pH 8 with sodium hydroxide, and dosed with acetylcholine perchlorate. The ensuing acetic acid releasing enzyme reaction... 

Blasiak J. 1995. Inhibition of erythrocyte membrane (Ca + Mg )-ATPase by the organophosphoms insecticides parathion and methyl parathion. Comp Biochem Physiol 1 IOC 119-125. 

Dhondup P, Kaliwal BB. 1997. Inhibition of ovarian compensatory hypertrophy by the administration of methyl parathion in hemicastrated albino rats. Reprod Toxicol 11 77-84. 

Hahn T, Ruhnke M, Luppa H. 1991. Inhibition of acetylcholinesterase and butyrylcholinesterase by the organophosphorus insecticide methyl parathion in the central nervous system of the golden hamster i Mesocricetus aumtus). Acta Histochem (Jena) 91 13-19. 

Izmirova H, Shalash S, Kaloianova F. 1984. [Dynamics of inhibition of cholinesterase activity in methyl parathion intoxication]. Probl Khig 9 42-49. (Russian)... 

Tripathy G, Shukla SP. 1988. Inhibition of liver and skeletal enzymes by methyl parathion. Biochem Arch 4 55-62. 

Udaya Bhaskar S, Nanda Kumar NV. 1981. Thin layer chromatographic determination of methyl parathion as paraoxon by cholinesterase inhibition. J AOAC 64 1312-1314. 

Other additional studies or pertinent information that lend sunnort to this MRL Methyl parathion affects the nervous system by inhibiting acetylcholinesterase activity. Cholinesterase inhibition and neurological effects have been observed in humans and animals, for all exposure routes and durations (for example. Dean et al. 1984 Desi et al. 1998 EPA 1978e Gupta et al. 1985 Nemec et al. 1968 Suba 1984). 

FIGURE 2.5 (a) Amperometric response of CNT modified screen-printed biosensor for methyl parathion in 0.1 M PBS containing 0.1 M NaCl (pH 7.4) at applied potential of 0.50 V and (b) die relative inhibition of CNT AChE/CHO biosensor as a function of methyl parathion concentration (adapted from [40]). 

MWNTs favored the detection of insecticide from 1.5 to 80 nM with a detection limit of InM at an inhibition of 10% (Fig. 2.7). Bucur et al. [58] employed two kinds of AChE, wild type Drosophila melanogaster and a mutant E69W, for the pesticide detection using flow injection analysis. Mutant AChE showed lower detection limit (1 X 10-7 M) than the wild type (1 X 10 6 M) for omethoate. An amperometric FIA biosensor was reported by immobilizing OPH on aminopropyl control pore glass beads [27], The amperometric response of the biosensor was linear up to 120 and 140 pM for paraoxon and methyl-parathion, respectively, with a detection limit of 20 nM (for both the pesticides). Neufeld et al. [59] reported a sensitive, rapid, small, and inexpensive amperometric microflow injection electrochemical biosensor for the identification and quantification of dimethyl 2,2 -dichlorovinyl phosphate (DDVP) on the spot. The electrochemical cell was made up of a screen-printed electrode covered with an enzymatic membrane and combined with a flow cell and computer-controlled potentiostat. Potassium hexacyanoferrate (III) was used as mediator to generate very sharp, rapid, and reproducible electric signals. Other reports on pesticide biosensors could be found in review [17],... 

Most insecticides, especially the organophosphate group, cause neurotoxicity as their major mode of action. Assessment of the neurotoxicity includes neurochemical endpoints such as cholinesterase (including acetylcholinesterase, which is the major neurotransmitter in vertebrates such as fish, and other enzymes such as butyrylcholinesterase) inhibition and behavioral endpoints such as swimming speed [79]. Studies done in rats show the neurotoxic action of insecticides such as dimethoate, methyl parathion, dichlorvos, ethyl parathion or propoxur after a prolonged exposure [80,81]. 

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