Abstract
Organophosphate (OP) pesticides are potent nerve agents. Improper use and poor monitoring lead to intentional and unintentional exposures. Most of the suicidal cases are due to intentional consumption of OP. Organophosphate is a vast family of chemicals that inhibit Acetylcholinesterase (AChE) in synaptic gap of the neurons thereby causing neurotoxicity. Oximes and atropines are conventional therapy given to poisoning patients; however, many OP inhibit AChE irreversibly and do not respond to oximes. There are several developments in the area of OP poisoning treatment. This review has covered the usage, consumption, pathophysiology of OP exposure, and recent advances in the prophylactic approach to combat human poisoning. The review has also discussed the limitation and major drawbacks in the treatment of OP poisoned cases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Adie PA (1956) The effect of the sarinase levels of liver on the survival of rabbits injected with sarin. Can J Biochem Physiol 34:654–659
Allon N, Raveh L, Gilat E, et al (1998) Prophylaxis against soman inhalation toxicity in guinea pigs by pretreatment alone with human serum butyrylcholinesterase. Toxicol Sci 43:121–128
Aprea C, Strambi M, Novelli MT, et al (2000) Biologic monitoring of exposure to organophosphorus pesticides in 195 Italian children. Environ Health Perspect 108:521
Barak D, Kronman C, Ordentlich A, et al (1994) Acetylcholinesterase peripheral anionic site degeneracy conferred by amino acid arrays sharing a common core. J Biol Chem 269:6296–6305
Barr DB, Bravo R, Weerasekera G, et al (2004) Concentrations of dialkyl phosphate metabolites of organophosphorus pesticides in the US population. Environ Health Perspect 112:186
Berger LR (1988) Suicides and pesticides in Sri Lanka. Am J Public Health 78:826–828
Bismuth C, Inns RH, Marrs TC (1992) Efficacy, toxicity and clinical use of oximes in anticholinesterase poisoning. BUTTERWORTH-HEINEMANN, STONEHAM, MA(USA) 1992
Bourne Y, Taylor P, Radić Z, Marchot P (2003) Structural insights into ligand interactions at the acetylcholinesterase peripheral anionic site. EMBO J 22:1–12
Brazzolotto X, Wandhammer M, Ronco C, et al (2012) Human butyrylcholinesterase produced in insect cells: huprine-based affinity purification and crystal structure. FEBS J 279:2905–2916
Broomfield CA (1992) A purified recombinant organophosphorus acid anhydrase protects mice against soman. Pharmacol Toxicol 70:65–66
Boublik Y, Saint-Aguet P, Lougarre A, et al (2002) Acetylcholinesterase engineering for detection of insecticide residues. Protein engineering 15(1):43–50
Changeux J-P (1966) Responses of acetylcholinesterase from Torpedo marmorata to salts and curarizing drugs. Mol Pharmacol 2:369–392
Chatterjee S, Verma VK, Hazra A, Pal J (2020) An observational study on acute poisoning in a tertiary care hospital in West Bengal, India. Perspect Clin Res 11:75
Costa LG (2006) Current issues in organophosphate toxicology. Clin Chim acta 366:1–13
Curl CL, Fenske RA, Elgethun K (2003) Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets. Environ Health Perspect 111:377
Colovic, M.B., Krstic, D.Z., Lazarevic-Pasti, T.D., Bondzic, A.M. and Vasic, V.M., 2013. Acetylcholinesterase inhibitors: pharmacology and toxicology. Current neuropharmacology, 11(3):315–335
Daisley H, Hutchinson G (1998) Paraquat poisoning. Lancet 352:1393–1394
De Jong WH, Borm PJA (2008) Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine 3:133
De Silva HJ, Wijewickrema R, Senanayake N (1992) Does pralidoxime affect outcome of management in acute organophosphorus poisoning? Lancet 339:1136–1138
Delfino RT, Ribeiro TS, Figueroa-Villar JD (2009) Organophosphorus compounds as chemical warfare agents: a review. J Braz Chem Soc 20:407–428
Dougherty DA, Stauffer DA (1990) Acetylcholine binding by a synthetic receptor: implications for biological recognition. Science (80- ) 250:1558–1560
Dvir H, Silman I, Harel M, et al (2010) Acetylcholinesterase: from 3D structure to function. Chem Biol Interact 187:10–22
Ecobichon DJ, Joy RM (1993) Pesticides and neurological diseases. CRC Press
Eddleston M (2000) Patterns and problems of deliberate self-poisoning in the developing world. Qjm 93:715–731
Eddleston M, Eyer P, Worek F, et al (2005) Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet 366:1452–1459
Eddleston M, Szinicz L, Eyer P, Buckley N (2002) Oximes in acute organophosphorus pesticide poisoning: a systematic review of clinical trials. Qjm 95:275–283
Ekinci D, Beydemir Ş (2009) Evaluation of the impacts of antibiotic drugs on PON 1; a major bioscavenger against cardiovascular diseases. Eur J Pharmacol 617:84–89
Eyer P (2003) The role of oximes in the management of organophosphorus pesticide poisoning. Toxicol Rev 22:165–190
Eyer P, Buckley N (2006) Pralidoxime for organophosphate poisoning. Lancet 368:2110
Environmental Protection Agency (1979) National study of hospital admitted pesticide poisonings for 1974 to 1976. Washington DC, US Government Printing Office, 1979
Ferretti G, Bacchetti T, Marchionni C, et al (2001) Effect of glycation of high density lipoproteins on their physicochemical properties and on paraoxonase activity. Acta Diabetol 38:163–169
Gupta RC (2011) Toxicology of organophosphate and carbamate compounds. Academic Press
Haddad LM, Shannon MW, Winchester J (1998) Clinical Management of Poisoning and Drug Overdose. 3. Aufl, Saunders, Philadelphia
Iorizzo L, Bianchi A, Gamberini G, et al (1996) Assessment of human exposure to pesticides in greenhouses and effectiveness of personal protective devices. Arh Hig Rada Toksikol 47:25–32
Jeyaratnam J (1990) Acute pesticide poisoning: a major global health problem
Johnson MK, Jacobsen D, Meredith TJ, et al (2000) Evaluation of antidotes for poisoning by organophosphorus pesticides. Emerg Med 12:22–37
Johnson S, Peter J V, Thomas K, et al (1996) Evaluation of two treatment regimens of pralidoxime (1 gm single bolus dose vs 12 gm infusion) in the management of organophosphorus poisoning. J Assoc Physicians India 44:529–531
Jokanović M (2009) Medical treatment of acute poisoning with organophosphorus and carbamate pesticides. Toxicol Lett 190:107–115
Joseph A, Abraham S, Muliyil JP, et al (2003) Evaluation of suicide rates in rural India using verbal autopsies, 1994-9. Bmj 326:1121–1122
Kasilo OJ, Hobane T, Nhachi CFB (1991) Organophosphate poisoning in urban Zimbabwe. J Appl Toxicol 11:269–272
Kryger G, Harel M, Giles K, et al (2000) Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II. Acta Crystallogr Sect D Biol Crystallogr 56:1385–1394
Kumar SV, Fareedullah MD, Sudhakar Y, et al. (2010) Current review on organophosphorus poisoning. Archives of Applied Science Research 2(4):199–215
Lee EC (2003) Clinical manifestations of sarin nerve gas exposure. Jama 290:659–662
Lushchekina S V, Schopfer LM, Grigorenko BL, et al (2018) Optimization of cholinesterase-based catalytic bioscavengers against organophosphorus agents. Front Pharmacol 9:211
Lodge AM (2013) Kinetic evaluation of the inhibition and reactivation of human acetylcholinesterase. The University of Iowa, 2013
Main AR (1979) Mode of action of anticholinesterases. Pharmacol Ther 6:579–628
Masson P (2015) Catalytic bioscavengers: the new generation of bioscavenger-based medical countermeasures. In: Handbook of Toxicology of Chemical Warfare Agents (Second Edition). Elsevier, pp 1107–1123
Mumford H, Docx CJ, Price ME, et al (2013) Human plasma-derived BuChE as a stoichiometric bioscavenger for treatment of nerve agent poisoning. Chem Biol Interact 203:160–166
Nalin DR (1973) Epidemic of suicide by malathion poisoning in Guyana. Trop Geogr Med 25:8–14
Namba T, Hiraki K (1958) PAM (pyridine-2-aldoxime methiodide) therapy for alkylphosphate poisoning. J Am Med Assoc 166:1834–1839
Namba T, Nolte CT, Jackrel J, Grob D (1971) Poisoning due to organophosphate insecticides: acute and chronic manifestations. Am J Med 50:475–492
Ofek K, Soreq H (2013) Cholinergic involvement and manipulation approaches in multiple system disorders. Chem Biol Interact 203:113–119
Pang Z, Hu C-MJ, Fang RH, et al (2015) Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers. ACS Nano 9:6450–6458. https://doi.org/10.1021/acsnano.5b02132
Pashirova TN, Braïki A, Zueva I V, et al (2018a) Combination delivery of two oxime-loaded lipid nanoparticles: Time-dependent additive action for prolonged rat brain protection. J Control Release
Pashirova TN, Zueva I V, Petrov KA, et al (2018b) Mixed cationic liposomes for brain delivery of drugs by the intranasal route: the acetylcholinesterase reactivator 2-PAM as encapsulated drug model. Colloids Surfaces B Biointerfaces 171:358–367
Pawar KS, Bhoite RR, Pillay CP, et al (2006) Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet 368:2136–2141
Peter J V, Moran JL (2004) Role of oximes in human organophosphate poisoning—a critical look at the evidence. Crit Care Update 153–163
Peter P V, Cherian AM (2000) Organic insecticides. Anaesth Intensive Care 28:11
Phillips MR, Li X, Zhang Y (2002) Suicide rates in China, 1995–99. Lancet 359:835–840
Radić Z, Reiner E, Taylor P (1991) Role of the peripheral anionic site on acetylcholinesterase: inhibition by substrates and coumarin derivatives. Mol Pharmacol 39:98–104
Roberts DM, Fraser JF, Buckley NA, Venkatesh B (2005) Experiences of anticholinesterase pesticide poisonings in an Australian tertiary hospital. Anaesth Intensive Care 33:469
Rochu D, Chabriere E, Masson P (2007) Human paraoxonase: a promising approach for pre-treatment and therapy of organophosphorus poisoning. Toxicology 233:47–59
Saxena A, Fedorko JM, Vinayaka CR, et al (2003) Aromatic amino-acid residues at the active and peripheral anionic sites control the binding of E2020 (Aricept®) to cholinesterases. Eur J Biochem 270:4447–4458
Saxena A, Sun W, Luo C, et al (2006) Bioscavenger for protection from toxicity of organosphosphorus compounds. J Mol Neurosci 30:145–147
Schumacher M, Camp S, Maulet Y, et al (1986) Primary structure of Torpedo californica acetylcholinesterase deduced from its cDNA sequence. Nature 319:407
Shafferman A, Kronman C, Flashner Y, et al (1992) Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding. J Biol Chem 267:17640–17648
Silvers A, Florence BT, Rourke DL, Lorimor RJ (1994) How children spend their time: a sample survey for use in exposure and risk assessments. Risk Anal 14:931–944
Singh S, Batra YK, Singh SM, et al (1995) Is atropine alone sufficient in acute severe organophosphorus poisoning?: experience of a North West Indian Hospital. Int J Clin Pharmacol Ther 33:628–630
Somasundaram DJ, Rajadurai S (1995) War and suicide in northern Sri Lanka. Acta Psychiatr Scand 91:1–4
Stevens RC, Suzuki SM, Cole TB, et al (2008) Engineered recombinant human paraoxonase 1 (rHuPON1) purified from Escherichia coli protects against organophosphate poisoning. Proc Natl Acad Sci 105:12780–12784
Sussman JL, Harel M, Frolow F, et al (1991) Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science (80- ) 253:872–879
Thiermann H, Szinicz L, Eyer F, et al (1999) Modern strategies in therapy of organophosphate poisoning. Toxicol Lett 107:233–239
Valiyaveettil M, Alamneh Y, Rezk P, et al (2011) Protective efficacy of catalytic bioscavenger, paraoxonase 1 against sarin and soman exposure in guinea pigs. Biochem Pharmacol 81:800–809
Veltri JC, Litovitz TL (1984) 1983 annual report of the American Association of Poison Control Centers national data collection system. Am J Emerg Med 2:420–443
Vermeire T, MacPhail R, Waters M (2003) Integrated human and ecological risk assessment: A case study of organophosphorous pesticides in the environment. Hum Ecol Risk Assess 9:343–357
Wang W, Chen Q-F, Li Q-B, et al (2014) Efficiency of anisodamine for organophosphorus-poisoned patients when atropinization cannot be achieved with high doses of atropine. Environ Toxicol Pharmacol 37:477–481
WHO (2001) Organophosphorous pesticides in the environment- Integrated Risk Assessment, Geneva: WHO
WHO (1990) In collaboration with UNEP. Public Health Impact of Pesticides used in Agriculture. Updated June 2007, WHO, Geneva
WHO (2002) The World Health report 2002. Reducing risks, promoting healthy life. WHO, Geneva
Wolfe AD, Rush RS, Doctor BP, et al (1987) Acetylcholinesterase prophylaxis against organophosphate toxicity. Fundam Appl Toxicol 9:266–270
Worek F, Aurbek N, Thiermann H (2007) Reactivation of organophosphate-inhibited human AChE by combinations of obidoxime and HI 6 in vitro. J Appl Toxicol An Int J 27:582–588
Worek F, Seeger T, Reiter G, et al (2014) Post-exposure treatment of VX poisoned guinea pigs with the engineered phosphotriesterase mutant C23: a proof-of-concept study. Toxicol Lett 231:45–54
Worek F, Thiermann H (2013) The value of novel oximes for treatment of poisoning by organophosphorus compounds. Pharmacol Ther 139:249–259
Worek F, Thiermann H, Wille T (2016) Oximes in organophosphate poisoning: 60 years of hope and despair. Chem Biol Interact 259:93–98
Yeung DT, Lenz DE, Cerasoli DM (2008) Human paraoxonase I: A potential bioscavenger of organophosphorus nerve agents. In: The Paraoxonases: Their Role in Disease Development and Xenobiotic Metabolism. Springer, pp 151–170
Yusuf S (2002) Clinical research and trials in developing countries. Stat Med 21:2859–2867
Acknowledgments
The authors acknowledge the support of Dr. Ashok K. Chauhan, Founder President, Amity Universe, for his constant support and encouragement. The authors also thank Dr. Atul Chauhan, Chancellor, Amity University, Uttar Pradesh, for providing all the required facilities.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Ranjan, A., Chauhan, A., Jindal, T. (2022). Toxicology of Organophosphate and Recent Trends in Prophylactic Approaches. In: Jindal, T. (eds) New Frontiers in Environmental Toxicology. Springer, Cham. https://doi.org/10.1007/978-3-030-72173-2_8
Download citation
DOI: https://doi.org/10.1007/978-3-030-72173-2_8
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-72172-5
Online ISBN: 978-3-030-72173-2
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)