Parathion liver

Methyl parathion can enter your body if you eat food or drink water containing it if you swim, bathe, or shower in contaminated water if you touch recently sprayed plants or soil if you touch contaminated soil near hazardous waste sites or if you breathe air that contains methyl parathion, such as near factories or recently sprayed farm fields (or in recent accounts of the illegal use of methyl parathion, if you breathe air or touch contaminated surfaces inside homes where methyl parathion has been used to kill insects). By any means of exposure, methyl parathion goes into your body quickly and gets into your blood. From your bloodstream, methyl parathion goes to your liver, brain, and other organs. Your liver changes some of methyl parathion to a more harmful chemical called methyl paraoxon. Both methyl parathion and methyl paraoxon can bind to enzymes of your nerves within minutes or hours. Your liver breaks down methyl parathion and methyl paraoxon into less harmful substances. These less harmful substances leave your body in urine within hours or days. For more information, see Chapter 3. 

Hepatic Effects. Liver lesions have been reported in humans acutely intoxicated by methyl parathion formulation (Wolfatox) (Fazekas 1971 Fazekas and Rengei 1964). These studies are discussed in detail in Section 3.2.2.1. Liver lesions were hepatocellular swelling, degeneration, and fatty change. 

Intoxicated patients surviving for 28 hours to 9 days had hepatocytes free in central or hepatic veins this finding was described as mobilization of liver cells. The role of methyl parathion in the induction of all of these lesions is unclear. 

Following single dermal applications of 10 mg/kg of radiolabeled methyl parathion to pregnant rats, methyl parathion was found to be widely distributed to all major tissues and organs. Concentrations were highest in plasma and kidney, maximum levels measured 2 hours postapplication. Peak levels in liver, brain, fetus, and placenta, were measured 2 to 10 hours later, at which times the highest concentration of methyl parathion was in the fetus (Abu-Quare et al. 2000). 

Data from a single study in dogs suggest that hepatic first-pass metabolism may limit systemic availability of the parent compound following oral exposure (Braeckman et al. 1983). Placental transfer of methyl parathion was demonstrated in pregnant rats 1-3 days before parturition. Thirty minutes after administration, both methyl parathion and methyl paraoxon were found in fetal brain, liver, and muscle methyl parathion, but not methyl paraoxon, was detected in placenta and maternal liver (Ackermann and Engst 1970). Methyl parathion binds reversibly to serum albumin, but is readily distributed to the tissues (Braeckman et al. 1980, 1983). 

These results are supported by studies in animals in which methyl parathion was detected 30-155 minutes after exposure (oral, dermal, inhalation, or intravenous routes) in plasma and liver (Abu-Qare et al. 2000 EPA 1978e). Due to extensive and rapid metabolism of methyl parathion (see Section 3.3), measurable levels are not expected to persist in tissue or serum for prolonged periods after exposure. 

Huang YS, Sultatos LG. 1993. Glutathione-dependent biotransformation of methyl parathion by mouse liver in vitro. Toxicol Lett 68 275-284. 

Radulovic LL, Kulkami AP, Dauterman WC. 1987. Biotransformation of methyl parathion by human foetal liver glutathione S-transferases An in vitro study. Xenobiotic 17 105-114. 

Sultatos LG. 1987. The role of the liver in mediating the acute toxicity of the pesticide methyl parathion in the mouse. Drug Metab Disp 15 613-617. 

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

Zhang HX, Sultatos EG. 1991. Biotransformation of the organophosphorus insecticides parathion and methyl parathion in male and female rat livers perfused in situ. Drug Metab Dispos 19 473-477. 

Fate. Preliminary investigations directed at adapting the method of Averell and Norris (2) to the analysis of animal tissues indicated that if precautions were taken to avoid emulsions the method could be used satisfactorily. Tissue samples of about 5 grams were most convenient, and the usual reagent and tissue blanks were run simultaneously. Following the administration of an acutely lethal intravenous dose to a dog it was found that parathion could be recovered from the urine, liver, bile, kidney, spleen, and lung. 

Following oral administration of a lethal dose to a dog (25 mg. per kg. wettable powder) tissues taken immediately after death analyzed as follows no parathion recovered from bladder bile, liver, kidney, abdominal fat, saliva, or intestine small quantities (2 to 7 p.p.m.) of parathion recovered from oxalated blood, spleen, lung, brain, and spinal cord. The urinary bladder was strongly contracted and no urine could be collected. The results of these two experiments indicate a universal distribution of parathion following acutely lethal doses. 

Male and female rats fed on 10, 50, and 100 p.p.m. food for several months showed no storage of parathion in the abdominal fat, nor was any recovered from the lung, liver, spleen, brain, whole blood, or kidney. 

A. M. Butler, M. Murray, Biotransformation of Parathion in Human Liver Participation of CYP3A4 and Its Inactivation During Microsomal Parathion Oxidation , J. Pharmacol. Exp. Ther. 1997, 280, 966 - 973. 

ENRICHMENT IN PARAOXON FOLLOWING INCUBATION OF PARATHION WITH RABBIT LIVER MICROSOMES ... 

Results similar to those described above for parathion were obtained by McBain (7, 8) in oxygen-18 studies of the metabolism of the phosphonothionate, Dyfonate (0-ethyl S-phenyl ethylphosphonodithioate), using rat liver microsomes. 

PARATHION METABOLISM BY A RECONSTITUTED MONOOXYGENASE SYSTEM FROM RABBIT LIVER ... 

We have also examined the metabolism of parathion by purified reconstituted monooxygenase systems isolated from the livers of... 

We have examined whether the sulfur that was bound to the proteins of a reconstituted system from the liver of phenobarbital-treated rats was bound to both the reductase and cytochrome P-450. I this experiment, the reconstitued system was incubated with [ s] parathion. The reaction mixture was dialyzed and applied to a Sephadex G-25 column to remove the last traces of unreacted parathion and its noncovalently bound metabolites. The protein fraction from the Sephadex column was reduced in volume and subjected to SDS-polyacrylamide gel electrophoresis in the absence of either dithiothreitol or mercaptoethanol. The results are shown in Figure 5. There was considerable protein and radioactivity at the origin. This material at the origin represents an aggregate of reductase... 

Figure 4. Linearity of the metabolism of parathion and benzphetamine by a reconstituted monooxygenase oxidase enzyme system from rabbit liver. The 0.5-mL reaction mixture contained 50 fig of sodium deoxycholate, 15 iig of dilauroyl l-5-phosphatidylcholine, 1.5 units of NADPH-Cytochrome c reductase, 0.5 nmol of Cytochrome P-450, 0.05M Hepes buffer (pH 7.8), 0.015M MgCh, O.lmU EDTA, and 5 X lO M [ethyl- C] parathion or / X 10 M benzphetamine.

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