Toxicity parathion

The only other information regarding the potential for age-related differences in susceptibility to methyl parathion came from a study by Garcia-Lopez and Monteoliva (1988). The investigators showed increasing mean erythrocyte acetylcholinesterase activity levels with increasing age range, starting at birth (in 10-year increments and >60 years of age) in both males and females. However, it is not known whether increased erythrocyte acetylcholinesterase activity indicates a decreased susceptibility to methyl parathion toxicity. 

Evans and Wroe 1980 Evans et al. 1988 Howard et al. 1978 Sanz et al. 1991 Venkataraman et al. 1990) and significantly increased erythrocyte acetylcholinesterase levels (De Peyster et al. 1994 Sanz et al. 1991 Venkataraman et al. 1990) during pregnancy. It is not known whether these differences might make pregnant women more susceptible to methyl parathion toxicity. 

Several studies in animals suggest that age may affect susceptibility to methyl parathion toxicity, and that children may be more susceptible than adults, but the data are limited. (See Section 3.7 for more information on Children s susceptibility.) A study in humans showed that mean erythrocyte acetylcholinesterase activity levels increase with increasing age from birth through old age in both sexes (Garcia-Lopez ad Monteoliva 1988), but it is not known whether increased erythrocyte acetylcholinesterase activity indicates decreased susceptibility to methyl parathion. 

Fazekas 1971) exposed by various routes. Because of a lack of toxicokinetic data, it cannot be assumed that the end points of methyl parathion toxicity would be quantitatively similar across all routes of exposure. The acute effects of dermal exposures to methyl parathion are not well characterized in humans or animals. Therefore, additional dermal studies are needed. 

Dorough HW Jr. 1970. Effect of Temik on methyl parathion toxicity to mice. Texas Agricultural Experiment Station Progress Report. Texas A M University, College Station, TX. Report No. PR-2771. 

Finlayson BJ, Harrington JA, Fujimura R, et al. 1993. Identification of methyl parathion toxicity in Colusa basin drain water. Environ Toxicol Chem 12 291-303. 

Mirer FE, Levinl BS, Murphy SD. 1977. Parathion and methyl parathion toxicity and metabolism in piperonyl butoxide and diethyl maleate pretreated mice. Chem Biol Interactions 17 99-112. 

Tvede KG, Loft S, Poulsen HE, et al. 1989. Methyl parathion toxicity in rats is changed by pretreatment with the pesticides chlordecone, mirex and linuron. Arch Toxicol Suppl 13 446-447. 

To test for tissue storage of parathion, female rats on 50 and 100 p.p.m. diet, and appropriate control rats, were allowed water while food was withdrawn. During the withdrawal period the behavior of the treated and control rats was typical of starvation with no evidence of parathion toxicity. Death was neither hastened nor delayed. 

The understandable correlation among careless technique, absenteeism, cholinesterase inhibition, and elevated average urinary PNP levels suggested that the latter was a highly reliable biological index of chronic parathion exposure and one that could ultimately predict chronic parathion toxicity. 

Levine, S.L. and J.T. Oris. Enhancement of acute parathion toxicity to fathead minnows following preexposure to propiconazole. Pestic. Biochem. Physiol. 65 102-109, 1999. 

Moorthy, K.S., Kasi Reddy, B., Swami, K.S., Chetty, C.S., 1984. Changes in respiration and ionic content in tissues of freshwater mussel exposed to methyl parathion toxicity. Toxicol. Lett. 21, 287-292. 

Moradeshaghi, M.J., Brindley, W.A. and Youssef, N.N. (1974). Chlorcyclizine and SKF 525A effects on parathion toxicity and midgut tissue structure in alkali bees, Nomia melanderi. Environ. Entomol. 3, 455-463. 

Spade, A. (1976). Acute and Chronic Parathion Toxicity to Fish and Invertebrates. U.S. Environ. Prot. Agency, Washington, D.C., PB 257 800, Natl. Tech. Inf. Serv., Springfield, Virginia. 

The rat LD qS are 13, 3.6 (oral) and 21, 6.8 (dermal) mg/kg. Parathion is resistant to aqueous hydrolysis, but is hydroly2ed by alkah to form the noninsecticidal diethjlphosphorothioic acid and -nitrophenol. The time required for 50% hydrolysis is 120 d ia a saturated aqueous solution, or 8 h ia a solution of lime water. At temperatures above 130°C, parathion slowly isomerizes to 0,%diethyl 0-(4-nitrophenyl) phosphorothioate [597-88-6] which is much less stable and less effective as an insecticide. Parathion is readily reduced, eg, by bacillus subtilis ia polluted water and ia the mammalian mmen to nontoxic 0,0-diethyl 0-(4-aminophenyl) phosphorothioate, and is oxidized with difficulty to the highly toxic paraoxon [511-45-5] diethyl 4-nitrophenyl phosphate d 1.268, soluble ia water to 2.4 mg/L), rat oral LD q 1.2 mg/kg. 

The development of malathion in 1950 was an important milestone in the emergence of selective insecticides. Malathion is from one-half to one-twentieth as toxic to insects as parathion but is only about one two-hundredths as toxic to mammals. Its worldwide usage in quantities of thousands of metric tons in the home, garden, field, orchard, woodland, on animals, and in pubHc health programs has demonstrated substantial safety coupled with pest control effectiveness. The biochemical basis for the selectivity of malathion is its rapid detoxication in the mammalian Hver, but not in the insect, through the attack of carboxyesterase enzymes on the aUphatic ester moieties of the molecule. 

Encapsulated fonofos, a soil insecticide, was developed to coat seeds before they were planted (72). Encapsulation reduces oral toxicity 100-fold and dermal toxicity 10-fold while extending activity of the fonofos. Other encapsulated pesticides available include permethrin and parathion (69). Significantly, all commercial encapsulated pesticides are prepared by interfacial polymeri2ation. 

Moreover organophosphoric acid esters have found application as insecticides (e.g. Parathion). Some derivatives are highly toxic to man (e.g. Sarin, Soman). The organophosphonates act as inhibitors of the enzyme cholinesterase by phosphorylating it. This enzyme is involved in the proper function of the parasympathetic nervous system. A concentration of 5 x 10 g/L in the air can already cause strong toxic effects to man. 

No acute oral MRL was derived for methyl parathion because data regarding the most sensitive effect that was observed after acute oral exposure are conflicting. Increased pup mortality and altered behavior occurred in offspring of rats exposed to 1 mg/kg/day methyl parathion during, but no effects on pup survival or on sensitive electrophysiological indices of neurotoxicity were seen at virtually the same dose, 0.88 mg/kg/day, in a similar developmental toxicity study. 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective on the toxicology of methyl parathion. It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

The LC50 values of methyl parathion have been established in rats. A 1-hour LC50 of 200 mg/m and a 4-hour LC50 of 120 mg/m for males were determined by Kimmerle and Lorke (1968). One-hour LC50 values of 257 mg/m for male rats and 287 mg/m for female rats were determined for 70-80% pure methyl parathion by EPA (1978e) the rats were exposed to aerosols of respirable size. Survivors of toxic doses recovered clinically by 10-14 days postexposure. Sex-related differences in acute mortality of rodents have also been observed after exposure to methyl parathion by other routes (Murphy and Dubois 1958). 

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. 

No studies were located regarding developmental toxicity in humans after oral exposure to methyl parathion. 

Similar results for rats were reported by Crowder et al. (1980). Oral administration of 1 mg/kg/day of methyl parathion (99.9% purity) in com oil on days 7-15 of gestation resulted in increased mortality in pups, relative to controls. Significant difference from controls in a maze transfer test was observed in pups from the treated group. However, use of a single-dose level precluded the assessment of dose-response, and several other behavioral end points were not affected. Furthermore, no information was presented regarding body weights or signs of toxicity in the treated dams. 

No dose-response relationship can be established for the developmental toxicity of methyl parathion from the available database. All reliable LOAEL values in rats for developmental effects for the acute- and intermediate-duration categories are recorded in Table 3-3 and plotted in Figure 3-2. 

Erythrocyte cholinesterase levels were monitored in two men exposed dermally to methyl parathion after entering a cotton field that had been sprayed with this pesticide (Nemec et al. 1968). The field was entered on two separate occasions twice within 2 hours after an ultra-low-volume spraying and a third time within 24 hours after spraying. Dermal methyl parathion residues 2 hours after spraying were 2-10 mg on the arms dermal residues 24 hours after spraying were 0.16-0.35 mg on the arms. The exposed individuals did not have signs of cholinergic toxicity, but erythrocyte cholinesterase levels after the third exposure were 60-65% of preexposure levels. 

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