Human parathion

Eyer F, Meischner V, Kiderlen D, et al. (2003) Human parathion poisoning. A toxicokinetic analysis. Toxicological Reviews 22(3) 143-163. 

In the context of the treatment of acute OP pe.sticide poisoning, the acute toxicity is the only consideration of importance. The acute toxicity of PAM salts and of obidoxime is of the same order of magnitude. Impaired liver function has been observed after treatment of human parathion poisoning with obidoxime (Barckow etal., 1969 Wirth, 1968), and reversible fatty change has been reported in the liver of rats treated with that oxime BLsa ei al., 1964). However, Boelcke and Gaaz (1970) did not find evidence of hepatotoxicity in mice in terms of en ,yme elevation, and bilirubin clearance and bromsulfthalcin retention were unaffected in the rat (Boelcke and Kamphenkel, 1970). Therefore, some or all of the hepatotoxicity of obidoxime may be attributable to other factors, such as the OP or solvents. 

The hazards of human poisoning by the parathions have stimulated the development of safer analogues. Two chlorinated derivatives have gready reduced mammalian toxicides. Dicapthon [2463-84-5], 0,0-dimethyl 0-(2-chloro-4-nitrophenyl) phosphorothioate (63) (mp 53°C), has rat LD qS of 400, 330 (oral) and 790, 1250 (dermal) mg/kg. Chlorthion [500-20-8], 0,0-dimethyl 0-(3-chloro-4-nitrophenyl) phosphorothioate (64) (mp 21°C, <71.437), has rat LD qS of 890, 980 (oral) and 4500, 4100 (dermal) mg/kg. These compounds have been used as household insecticides. 

These experts collectively have knowledge of methyl parathion s physical and chemical properties, toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer review specified in Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as amended. 

Children are affected by methyl parathion in the same manner as adults. Exposure to high levels of methyl parathion, even for short periods, may result in changes in the nervous system, leading to headaches, dizziness, confusion, blurred vision, difficulty breathing, vomiting, diarrhea, loss of consciousness, and death (see also Section 1.5 for a more complete description of how methyl parathion affects human health). It is not known whether children are more sensitive to the effects of methyl parathion than adults. There is some indication that young rats may be more sensitive than adults to nervous system effects. 

There is no evidence in humans that methyl parathion causes birth defects. Birth defects have not been seen when methyl parathion was given to animals by mouth, but minor birth defects did occur in one study in which high doses were injected into pregnant animals. It is not known whether these effects occur in people. It is unlikely that people would be exposed by breathing, touching, or eating as much methyl parathion as was injected in the animal studies. 

Hematological Effects. No information was found regarding hematological effects in humans following exposure to methyl parathion. Repeated oral exposure to methyl parathion resulted in decreased mean corpuseular volume in one study and decreased hematocrit and erythrocyte count in another study in rats. Chronic ingestion of methyl parathion induced reduction of mean hemoglobin, hematocrit, and erythrocyte eounts in rats. 

Although a number of studies have reported the effects of inhalation exposure to methyl parathion in humans, no inhalation MRLs were derived based on human data because of the lack of adequate quantitative exposure information. Animal data were also insufficient to support the derivation of an acute-, intermediate-, or chronic-duration inhalation MRL. 

An intermediate-duration oral MRL of 0.0007 mg/kg/day was derived for methyl parathion based on the observation of electrophysiological effects in the central and peripheral nervous systems of male rats exposed to methyl parathion through gavage administration of 0.22 mg/kg/day to the dams on days 5-15 of gestation and days 2-28 of lactation, followed by direct administration of the same dose to the male pups for 8 weeks. More marked effects occurred at the two higher doses, 0.44 and 0.88 mg/kg/day. The effects were dose-related, and were statistically significant at all three dose levels. The MRL was derived by dividing the LOAEL from this study (0.22 mg/kg/day) by an uncertainty factor of 300 (3 for a minimal LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability). 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for methyl parathion. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

No studies were located regarding gastrointestinal, hematological, musculoskeletal, or dermal effects in humans or animals after inhalation exposure to methyl parathion. Dean et al. (1984) reported that seven children exposed to methyl parathion by many routes exhibited pinpoint pupils, abdominal pain, and diarrhea. The respiratory, cardiovascular, hepatic, and renal effects reported by Fazekas (1971) that were found in humans acutely exposed to methyl parathion intoxication resulted from exposure by all three routes however, the results did not distinguish between the routes. 

Respiratory Effects. Pulmonary edema was reported in humans dying from acute methyl parathion (Wofatox) intoxication (Fazekas 1971). Edema was found in a man who died 2 hours after intoxication, and, in other cases, edema was found in others who died as long as 9 days after exposure. Broncho-constriction and hypersecretion of bronchial glands (bronchorrhea) are primary muscarinic effects of methyl parathion. The broncoconstriction, bronchorrhea, and bradycardia caused by methyl parathion are strongly conducive to pulmonary edema. 

Cardiovascular Effects. Eesions in the heart and blood vessels have been reported in humans acutely intoxicated with methyl parathion (Wofatox) (Fazekas 1971) and are discussed in Section 3.2.2.2. However, many of these lesions may be secondary to the effects of methyl parathion on the conduction system of the heart, to other components ingested, or to therapeutic regimens that some of these patients received. 

Hepatic Effects. Eiver lesions were reported in humans dying of acute methyl parathion (Wofatox)... 

No studies were located regarding immunological effects in humans or animals after inhalation exposure to methyl parathion. 

There have been a number of cases of human intoxication and death from oral exposure to methyl parathion. 

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. 

Renal Effects. Acute nephrosis has been reported in humans after acute, lethal intoxication (Fazekas 1971) by methyl parathion (Wofatox). This may be a secondary effect of hypoxia related to the neurologic effects of methyl parathion on vascular smooth muscle and on the electrical conduction system of the heart. It could also be related to therapeutic efforts. 

A single case report of skin allergy to methyl parathion has been reported in humans (Lisi et al. 1987). Also see Section 3.2.3.2. 

Results of methyl parathion assays involving effects on chromosomes have also been contradictory. For sister chromatid exchange, Waters et al. (1982) reported a positive response in Chinese hamster ovary cells only in the presence of metabolic activation system, while methyl parathion tested positive without a metabolic activation system in Chinese hamster V79 cells (Chen et al. 1981), cultured normal human lymphoid cells (Chen et al. 1981 Gomez-Arroyo et al. 1987 Sobti et al. 1982), and Burkitt s l5miphoma cells (Chen et al. 1981). Chen et al. (1981) found a significant dose-related increase in sister chromatid exchange in both hamster and human cultured cells, but dose-related cell cycle delays were less pronounced in human cell lines than in V79 cells. Negative results were obtained for chromosomal aberrations in human lymphocytes without a metabolic activation system (Kumar et al. 1993). 

---