Parathion metabolites

Nitrophenol and 4-nitrophenol glucuronide are excreted in urine. The studies of urinary excretion of methyl parathion metabolites, including those reported in this section, generally hydrolyze the glucuronide prior to analysis and report the resulting total 4-nitrophenol values. 

The available evidence suggests that excretion of methyl parathion metabolites in humans and animals following acute oral exposure is essentially the same and occurs rapidly. Excretion occurs primarily via the urine. Methyl parathion can also be excreted in breast milk, although it has been detected only in a limited number of samples from women of central Asia, for which exposure data were not available (Lederman 1996) (see also Section 3.4.2.2). A study in rats also reported excretion of methyl parathion in the milk (Golubchikov 1991 Goncharuk et al. 1990). 

Analytical Methods for Determining Methyl Parathion and Metabolites in... 

The LD50 values for methyl parathion were compared to those for methyl paraoxon, the active metabolite of methyl parathion, in rats, guinea pigs, and mice by Miyamoto et al. (1963b). Methyl paraoxon was 5.4 times more potent than methyl parathion in male rats, 5 times more potent in male guinea pigs, and 1.6 times more potent in mice. 

Urinary excretion of metabolites of methyl parathion is rapid and efiicient in animals (Braeckman et al. 1983 Hollingworth et al. 1967). In mice, 70-80% of the activity was excreted in the urine within... 

Only two studies were available that reported detection of a metabolite of methyl parathion in the urine of persons dermally exposed to methyl parathion (Ware et al. 1974, 1975). Four subjects were exposed for 5 hours to a methyl parathion formulation in a field that had been sprayed 24 hours prior to exposure (Ware et al. 1974). At 48 hours, an average of 0.5 mg 4-nitrophenol was found in the urine, but... 

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). 

No studies were located regarding excretion of methyl parathion in humans following inhalation exposure. The limited information available from human case studies indicates that the chemical s metabolites are rapidly excreted primarily in the urine in humans following oral (Morgan et al. 1977) or dermal (Ware et al. 1974, 1975) exposure and in animals following oral (Hollingworth et al. 1973) or dermal (Abu-Qare et al. 2000) exposure. 

Practically all toxicokinetic properties reported are based on the results from acute exposure studies. Generally, no information was available regarding intermediate or chronic exposure to methyl parathion. Because methyl parathion is an enzyme inhibitor, the kinetics of metabolism during chronic exposure could differ from those seen during acute exposure. Similarly, excretion kinetics may differ with time. Thus, additional studies on the distribution, metabolism, and excretion of methyl parathion and its toxic metabolite, methyl paraoxon, during intermediate and chronic exposure are needed to assess the potential for toxicity following longer-duration exposures. 

Exposure Levels in Humans. Methyl parathion has been detected in serum and tissue shortly after acute exposure (EPA 1978e Ware et al. 1975). It is rapidly metabolized and does not persist in serum and tissues for long (Braeckman et al. 1983). Two metabolites of methyl parathion, 4-nitrophenol and dimethyl phosphate, can be detected in urine and tissues for up to 2 days following exposure (Morgan et al. 1977). These compounds are specific for methyl parathion when there is a history of exposure. 

The purpose of this chapter is to describe the analytical methods that are available for detecting, measuring, and/or monitoring methyl parathion, its metabolites, and other biomarkers of exposure and effect to methyl parathion. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is to identify well-established methods that are used as the standard methods of analysis. Many of the analytical methods used for environmental samples are the methods approved by federal agencies and organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other methods presented in this chapter are those that are approved by groups such as the Association of Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). Additionally, analytical methods are included that modify previously used methods to obtain lower detection limits and/or to improve accuracy and precision. 

The primary method for detecting methyl parathion and metabolites in biological tissues is gas chromatography (GC) coupled with electron capture (BCD), flame photometric (FPD), or flame ionization detection (FID). Sample preparation for methyl parathion analysis routinely involves extraction with an organic solvent (e g., acetone or benzene), centrifugation, concentration, and re suspension in a suitable solvent prior to GC analysis. For low concentrations of methyl parathion, further cleanup procedures, such as column chromatography on silica gel or Florisil are required. 

Table 7-1 summarizes the analytical methods used to detect methyl parathion and its metabolites in biological tissues and fluids. 

Abe T, Fujimoto Y, Tatsuno T, et al. 1979. Separation of methyl parathion and fenitrothion metabolites by liquid chromatography. Bull Environ Contam Toxicol 22 791-795. 

Jaglan PS, Gunther FA. 1969. Column esterification in the gas chromatography of the desalkyl metabolites of methyl parathion and methyl paraoxon. Anal Chem 41 1671-1673. 

Jaglan PS, Gunther FA. 1970. Single column gas liquid chromatography of methyl parathion and metabolites using temperature programming. Bull Environ Contam Toxicol 5 111-114. 

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