Organophosphate exposures

Mental disturbances have been reported after organophosphate exposure. Neuropsychiatric symptoms occurred in two aerial applicators, one of whom used methyl parathion as well as other insecticides. One of these pilots had high levels of exposure to a mixture containing methyl parathion, toxaphene, and Dipterex when his clothing became saturated when the tank of his aircraft accidentally overflowed. Several months after the accident, the subject complained of anxiety, dizziness, emotional lability, and frequent and severe disagreements with family members and associates. Similar observations had been... 

Functional neurological changes due to acute organophosphate exposure generally correlate with acetylcholinesterase inhibition in erythrocytes (Wills 1972). 

Individuals with hereditary low plasma cholinesterase levels (Kalow 1956 Lehman and Ryan 1956) and those with paroxysmal nocturnal hemoglobinuria, which is related to abnormally low levels of erythrocyte acetylcholinesterase (Auditore and Hartmann 1959), would have increased susceptibility to the effects of anticholinesterase agents such as methyl parathion. Repeated measurements of plasma cholinesterase activity (in the absence of organophosphate exposure) can be used to identify individuals with genetically determined low plasma cholinesterase. 

Organophosphates, such as methyl parathion, are known to inhibit cholinesterase activity. A method has been developed to measure the extent of this inhibition and relate it to organophosphate exposure (EPA 1980d Nabb and Whitfield 1967). In this EPA-recommended method, blood is separated into plasma and red blood cell fractions. The fractions are treated with saline solution, brought to pH 8 with sodium hydroxide, and dosed with acetylcholine perchlorate. The ensuing acetic acid releasing enzyme reaction... 

Pope CN, Chakraborti TK. 1992. Dose-related inhibition of brain and plasma cholinesterase in neonatal and adult rats following sublethal organophosphate exposures. Toxicology 73 35-43. 

Hooper, M.J. et al. (1989). Organophosphate exposure in hawks inhabiting orchards during winter dormant spraying. Bulletin of Environmental Contamination and Toxicology 42, 651-660. 

Mandel JS, Berlinger NT, KayN. 1989. Organophosphate exposure inhibits Non-Specific esterase staining in human blood monocytes. Amer J Industrial Med 15 207-212. 

A combination of neurological signs is usually a biomarker of organophosphate exposure. Neurological signs such as pupil miosis, muscular tremors, and increased salivation have been observed in humans accidentally exposed to disulfoton (Yashiki et al. 1990) and in animals given disulfoton (Schwab et al. 1981). 

Inhibition of erythrocyte acetylcholinesterase activity or serum cholinesterase activity with or without concomitant neurological signs is usually a good indicator of organophosphate exposure. In addition, T-lymphocyte acetylcholinesterase activity was found to be rapidly and greatly depressed in rats during a 14-day daily exposure to disulfoton, but rapidly recovered after exposure (Fitzgerald... 

Fitzgerald BB, Costa LG. 1992. Modulation of Ml and M2 muscarinic receptor subtypes following repeated organophosphate exposure in rats. Toxicol Appl Pharmacol ] 17 112-125. 

Astroff AB and Young AD. The relationship between maternal and fetal effects following maternal organophosphate exposure during gestation in the rat. Toxicol Ind Health 14(6) 869-89, 1998... 

The fact that the birds developed delayed neurotoxicity under laboratory conditions indicates that the lack of it in the field study was not due to an inability of this mutant to develop the neuropathy. "Early warning" tests for delayed neurotoxicity are lacking. The laboratory data suggest that serum enzymes like CK may be useful markers for organophosphate exposure. However the conditions of this test must be controlled. The increase of CK in all birds taken to Visalia, regardless of their exposure to DEP in the field, suggests that the rigor of the trip may have stressed the birds and increased CK levels. Plasma CK activity in humans is known to increase under stress, such as after heavy exercise (12). 

Baker, D.J., Sedgwick, E.M. (1996). Single fibre electromyographic changes in man after organophosphate exposure. Hum. Exp. Toxicol. 15 369-75. 

Winrow, C.J., Heimning, M.L., Allen, D.A. et al. (2003). Loss of neuropathy target esterase in mice links organophosphate exposure to h peractivity. Nat. Genet. 33 477-85. 

Prendergast, M.A., Terry A.V., Buccafusco, J.J. (1998). Effects of chronic, low-level organophosphate exposure on delayed recall, discrimination and spatial learning in monkeys and rats. Neurotoxicol. Teratol. 20 115-22. 

Behan, P.D. (1996). Chronic fatigue syndrome as a delayed reaction to low dose organophosphate exposure. J. Nutr. Environ. Med. 6 341-50. 

Curtis, B.F., Tetz, L.M., Compton, J.R., Doctor, B.P., Gordon, R.K., Namhiar, M.P. (2005). Histone acetylase inhihitor tri-chostatin A induces acetylcholinesterase expression and protects against organophosphate exposure. J. Cell. Biochem. 96 839-49. 

Sudakin, D.L., Power, L.E. (2007). Organophosphate exposures in the United States a longimdinal analysis of incidents reported to poison centers. J. Toxicol. Environ. Health A 70 141-7. 

Polhuijs, M., Langenberg, J.P., Benschop, H.P. (1997a). A new method to detect organophosphate exposure serum analysis of victims of Japanese terrorists. In m-CB Medical Treatment Symposium, May 26-30, 1997, Hradec Kralove, Abstracts, p. 25. 

Carbamates and OPs are chemicals that are often used as fungicides, insecticides, or pesticides and possess actions similar to nerve agents. These compounds are considered weapons of opportunity since their primary use is not by conventional militaries. In the USA, toxicity from these compounds is fairly rare. In 2006, there were approximately 1,200 cases of carbamate exposures and 1,500 organophosphate exposures documented for children 19 years old and younger (Bronstein et al, 2007). Although there were a few fatalities reported in 2006 from these substances, these fatalities occurred only in older individuals. 

Key findings that have been reported inclnde significant hypoxia, acidosis, and carbon dioxide retention (Sofer et al, 1989). Also hyperglycemia, hypokalemia, and lenkocytosis were observed in a case series of organophosphate exposures (Levy-Khademi et al, 2007). A prospective study done on 17 children with typical organophosphate or carbamate poisoning looked at laboratory abnormalities that are associated with acute pancreatitis. Five of the patients (30%) had laboratory values consistent with pancreatitis with elevated immunoreactive trypsin, amylase, and serum... 

Petroianu, G.A., Hasan, M.Y., Numlain, S.M., Arafat, K., Shafiullah, M., Naseer, O. (2005b). Protective agents in acute high-dose organophosphate exposure comparison of rantidine with pralidoxime in rats. J. Appl. Toxicol. 25 68-73. 

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