Biomonitoring Summary

Methyl Parathion

CAS No. 298-00-0

Ethyl Parathion

CAS No. 56-38-2

General Information

Para-nitrophenol is a metabolite of the insecticides methyl parathion, ethyl parathion, O-ethyl-O-(4-nitrophenyl) phenylphosphonothioate, and of the chemical nitrobenzene. Methyl parathion use is highly restricted, with limited applications in agriculture. Many previous registered agricultural uses of methyl parathion have been cancelled (U.S.EPA, 2003). It had been applied to cotton, and to a lesser extent, on cereal grains. In the 1990s, peak domestic use was as high as 5-6 million pounds per year. Methyl parathion is not registered for residential use in the United States. Ethyl parathion, first registered in 1948, was once a restricted-use insecticide with limited applications on certain agricultural crops, but by 2003, all registered uses were voluntarily cancelled (U.S.EPA, 2000). Methyl parathion has low water solubility, binds tightly to soils resulting in low leachability, and has a short half-life in soils and on plants. Ethyl and methyl parathion are infrequently detected in groundwater sampling (USGS, 2007). Both are toxic to birds, fish, and aquatic invertebrates.

Given its limited use, the potential for human exposure to either ethyl or methyl parathion through the diet or drinking water is low. Estimated intakes from diet and drinking water have been below recommended limits. Increased risk of exposure via dermal, pulmonary, and oral routes can occur in pesticide and agricultural workers (Muttray et al., 2006). In animal studies, methyl parathion was rapidly absorbed after ingestion, more slowly absorbed through the skin, and eliminated rapidly from the body after absorption (Kramer et al., 2002; Morgan et al., 1977). Once absorbed, phosphorothioates such as methyl and ethyl parathion are metabolically activated to the "oxon" forms which have greater toxicity than the parent insecticides. Metabolism of ethyl or methyl parathion leads to the formation of para-nitrophenol, dialkyl phosphate metabolites, and other metabolites. In addition to being a metabolite of methyl and ethyl parathion, para-nitrophenol also can occur in the environment from the breakdown of the parent these organophosphorus pesticides and from nitrobenzene. Thus, the detection of para-nitrophenol in a person's urine may also reflect exposure to the environmental degradate.

Human health effects from parathion or ethyl parathion at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Parathion and methyl parathion have high acute toxicity in animal testing. In large doses, methyl parathion, ethyl parathion, and other organophosphorus insecticides share a common mechanism of toxicity: inhibition of the activity of acetylcholinesterase enzymes in the nervous system, resulting in excess acetylcholine at nerve terminals, and producing acute symptoms such as nausea, vomiting, cholinergic effects, weakness, paralysis, and seizures. The metabolite, para-nitrophenol, does not inhibit acetylcholinesterase enzymes. At high animal doses of methyl parathion, retinal atrophy and sciatic nerve degeneration have also been observed (IPCS, 1995; WHO, 2004). Recent in vitro and in vivo animal studies suggest that parathion may have additional neuronal and glial cell effects at lower doses (Guizzetti et al., 2005; Karanth and Pope et al., 2003; Slotkin et al., 2006; Zurich et al., 2004). Overt cholinergic toxicity and death from methyl and ethyl parathion have been described following suicidal ingestion, accidental exposure, and unintentional acute or chronic high-level occupational exposure (Hill et al., 1990; Jaga and Dharmani, 2006; Lores et al., 1978; Orsorio et al, 1991). Methyl parathion is not considered genotoxic, teratogenic, or generally to have reproductive toxicity at doses below those causing acetylcholinesterase inhibition in most animal studies (IPCS, 1995). IARC does not consider ethyl parathion and methyl parathion classifiable as human carcinogens. U.S.EPA considers methyl parathion unlikely to be carcinogenic to humans, but lists ethyl parathion as a possible human carcinogen. Additional information about external exposure (i.e., environmental levels) and health effects is available from ATSDR athttps://www.atsdr.cdc.gov/toxprofiles/index.asp and from U.S. EPA at https://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of para-nitrophenol reflect recent exposure. Levels of para-nitrophenol in the NHANES 1999-2000 and 2001-2002 subsamples were similar or slightly lower than those in a nonrandom subsample of NHANES III (1988-1994) participants (CDC, 2009; Hill et al., 1995), and levels were similar or slightly lower that those in a small convenience sample of the U.S. population (Olsson et al., 2003) and in 482 pregnant females from an agricultural region of California (Eskenazi et al., 2004). A study of 13 children from an agricultural region of Washington State reported median levels that were more than three times higher than median levels in the NHANES 1999-2000 subsample (Kissel et al., 2005). Children and adults living in residences where methyl parathion was applied indoors had urinary levels of para-nitrophenol which were several hundred times higher than those in the NHANES 1999-2000 subsample, and many residents were symptomatic (Barr et al., 2002; CDC, 2009; McCann et al., 2002; Rubin et al., 2002).

Pesticide workers may have much higher levels following pesticide applications. ACGIH recommends a BEI of 0.5 mg (500 µg)/g creatinine for workers at the end of shift. In a study of workers who handle parathion, end-of-shift urinary para-nitrophenol levels ranged from 190 to 410 µg/gram of creatinine (Leng and Lewalter, 1999), a range of values several hundred times higher than levels found in the U.S. general population (CDC, 2009).

Finding a measurable amount of para-nitrophenol in urine does not imply that the level of para-nitrophenol causes an adverse health effect. Biomonitoring studies of para-nitrophenol can provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of parathion than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

References

Barr DB, Turner WE, DiPietro E, McClure PC, Baker SE, Barr JR, et al. Measurement of p-nitrophenol in the urine of residents whose homes were contaminated with methyl parathion. Environ Health Perspect 2002;110 Suppl 6:1085-1091.

Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. 2009. [online] Available at URL: https://www.cdc.gov/exposurereport/. 1/24/13

Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr DB, et al. Association of in utero organophosphate pesticide exposure and fetal growth and length of gestation in an agricultural population. Environ Health Perspect 2004;112(10):1116-1124.

Guizzetti M, Pathak S, Giordano G, Costa LG. Effect of organophosphorus insecticides and their metabolites on astroglial cell proliferation. Toxicology 2005;215(3):182-190.

Hill RH Jr, Alley CC, Ashley DL, Cline RE, Head SL, Needham LL, et al. Laboratory investigation of a poisoning epidemic in Sierra Leone. J Anal Toxicol 1990;14(4):213-216.

Hill RH Jr, Head SL, Baker S, Gregg M, Shealy DB, Bailey SL, et al. Pesticide residues in urine of adults living in the United States: reference range concentrations. Environ Res 1995;71:99-108.

International Programme on Chemical Safety-INCHEM (IPCS). Parathion-Methyl (addendum). 1995. Available at URL: http://www.inchem.org/documents/jmpr/jmpmono/v95pr14.htm. 1/24/13

Jaga K, Dharmani C. Methyl parathion: an organophosphate insecticide not quite forgotten. Rev Environ Health 2006;21(1):57-67.

Karanth S, Pope C. Age-related effects of chlorpyrifos and parathion on acetylcholine synthesis in rat striatum. Neurotoxicol Teratol 2003;25(5):599-606.

Kissel JC, Curl CL, Kedan G, Lu C, Griffith W, Barr DB, et al. Comparison of organophosphorus pesticide metabolite levels in single and multiple daily urine samples collected from preschool children in Washington State. J Expo Anal Environ Epidemiol 2005;15(2):164-171.

Kramer RE, Wellman SE, Rockhold RW, Baker RC. Pharmacokinetics of methyl parathion: a comparison following single intravenous, oral or dermal administration. J Biomed Sci 2002;9:311-320.

Leng G, Lewalter J. Role of individual susceptibility in risk assessment of pesticides. Occup Environ Med 1999;56(7):449-553.

Lores EM, Bradway DE, Moseman RF. Organophosphorus pesticide poisonings in humans: determination of residues and metabolites in tissues and urine. Arch Environ Health 1978;33(5):270-276.

McCann KG, Moomey CM, Runkle KD, Hryhorczuk DO, Clark JM, Barr DB. Chicago area methyl parathion response. Environ Health Perspect 2002;110 Suppl 6:1075-1078.

Morgan DP, Hetzler HL, Slach EF, Lin LI. Urinary excretion of paranitrophenol and alkyl phosphates following ingestion of methyl or ethyl parathion by human subjects. Arch Environ Contam Toxicol 1977;6(2-3):159-173.

Muttray A, Backer G, Jung D, Hill G, Letzel S. External and internal exposure of wine growers spraying methyl parathion. Toxicol Lett 2006;162(2-3):219-224.

Olsson AO, Nguyen JV, Sadowski MA, Barr DB. A liquid chromatography/electrospray ionization tandem mass spectrometry method for quantification of specific organophosphorus pesticide biomarkers in human urine. Anal Bioanal Chem 2003;376(6):808-815.

Osorio AM, Ames RG, Rosenberg J, Mengle DC. Investigation of a fatality among parathion applicators in California. Am J Ind Med 1991;20(4):533-546.

Rubin C, Esteban E, Kieszak S, Hill RH Jr, Dunlop B, Yacovac R, et al. Assessment of human exposure and human health effects after indoor application of methyl parathion in Lorain County, Ohio, 1995-1996. Environ Health Perspect 2002;110 Suppl 6:1047-1051.

Slotkin TA, Tate CA, Ryde IT, Levin ED, Seidler FJ. Organophosphate insecticides target the serotonergic system in developing rat brain regions: disparate effects of diazinon and parathion at doses spanning the threshold for cholinesterase inhibition. Environ Health Perspect 2006;114(10):1542-1546.

U.S. Environmental Protection Agency (U.S. EPA). R.E.D. Facts. Ethyl parathion. September 2000. EPA-738-FOO-009. Available at URL: https://www.epa.gov/oppsrrd1/REDs/factsheets/0155fct.pdf. 1/24/13

U.S. Environmental Protection Agency (U.S. EPA). Interim reregistration eligibility decision (IRED) for Methyl Parathion. Case No. 0153. May 2003. Available at URL: https://www.epa.gov/oppsrrd1/REDs/methylparathion_ired.pdf. 1/24/13

U.S. Geological Survey (USGS). The Quality of Our Nation's Waters. Pesticides in the Nation's Streams and Ground Water, 1992-2001. March 2006, revised February 15, 2007 [online]. Available at URL: https://pubs.usgs.gov/circ/2005/1291/. 1/24/13

World Health Organization (WHO). Methyl parathion in drinking-water. WHO/SDE/WSH/03.04/106. 2004. Available at URL: http://www.who.int/water_sanitation_health/dwq/chemicals/methylparathion.pdf. 1/24/13

Zurich MG, Honegger P, Schilter B, Costa LG, Monnet-Tschudi F. Involvement of glial cells in the neurotoxicity of parathion and chlorpyrifos. Toxicol Appl Pharmacol 2004;201(2):97-104.