Organophosphate neurotoxicity and its relation to neurological changes and psychiatric disorders
DOI:
https://doi.org/10.33448/rsd-v14i1.48130Keywords:
Organophosphorus compounds; Neurotoxic syndromes; Herbicides; Autistic Spectrum Disorder.Abstract
Organophosphates are anticholinesterase agents suspected of interfering with the development, growth and functioning of different organ systems. Thus, the objective of this study was to develop a survey of data inherent to the neurotoxic effects of organophosphates and possible associated clinical conditions. A systematic review of the literature was developed, based on articles indexed in the main databases: Elsevier, Cochrane, PubMed and SciELO. Studies were selected using the search terms contained in Health Sciences Descriptors (Decs) and Medical Subject Headings (Mesh). The data obtained point to the neurotoxic effects of the use of organophosphates, from impairment in the development of the Nervous System to neurotoxic events, ranging from acute cholinergic crisis and intermediate syndrome to delayed polyneuropathy induced by organophosphate, clinical conditions due to axonal degeneration in different regions of the Central and Peripheral Nervous System, neurodegenerative and progressive diseases, in addition to cognitive and behavioral disorders, such as autism spectrum disorder. Thus, it is concluded that exposure to organophosphate compounds can trigger mild, moderate or severe clinical manifestations that reveal different neurotoxic syndromes, as well as psychiatric disorders, such as depression, repetitive behaviors, difficulty in social interaction and decreased intelligence quotient.
References
Agrotóxico. (2018). INCA - National Cancer Institute. https://www.inca.gov.br/en/node/1909
Aldridge, J. E., Seidler, F. J., & Slotkin, T. A. (2004). Developmental exposure to chlorpyrifos elicits sex-selective alterations of serotonergic synaptic function in adulthood: critical periods and regional selectivity for effects on the serotonin transporter, receptor subtypes, and cell signaling. Environmental Health Perspectives, 112(2), 148–155. https://doi.org/10.1289/ehp.6713
Aleyasin H. (2004) Nuclear Factor- B Modulates the p53 Response in Neurons Exposed to DNA Damage. Journal of Neuroscience, 24(12), 2963–73.
Aliomrani, M., Mesripour, A., & Sayahpour, Z. (2021). AChR is partly responsible in mice depressive-like behavior after Phosalone exposure. Neurotoxicology and Teratology, 84, 106957. https://doi.org/10.1016/j.ntt.2021.106957
Bouchard, M. F., Chevrier, J., Harley, K. G., Kogut, K., Vedar, M., Calderon, N., Trujillo, C., Johnson, C., Bradman, A., Barr, D. B., & Eskenazi, B. (2011). Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year-Old Children. Environmental Health Perspectives, 119(8), 1189–1195. https://doi.org/10.1289/ehp.1003185
Braquenier, J.-B., Quertemont, E., Tirelli, E., & Plumier, J.-C. (2010). Anxiety in adult female mice following perinatal exposure to chlorpyrifos. Neurotoxicology and Teratology, 32(2), 234–239. https://doi.org/10.1016/j.ntt.2009.08.008
Burke, R. D., Todd, S. W., Lumsden, E., Mullins, R. J., Mamczarz, J., Fawcett, W. P., Gullapalli, R. P., Randall, W. R., Pereira, E. F. R., & Albuquerque, E. X. (2017). Developmental neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical models and potential mechanisms. Journal of Neurochemistry, 142, 162–177. https://doi.org/10.1111/jnc.14077
Casarin, S. T. et al. (2020). Tipos de revisão de literatura: considerações das editoras do Journal of Nursing and Health. Journal of Nursing and Health. 10 (5). https://periodicos.ufpel.edu.br/index.php/enfermagem/article/view/19924.
Constantino, J. N. (2011). The Quantitative Nature of Autistic Social Impairment. Pediatric Research, 69(5 Part 2), 55R62R. https://doi.org/10.1203/pdr.0b013e318212ec6e
De Felice, A., Greco, A., Calamandrei, G., & Minghetti, L. (2016). Prenatal exposure to the organophosphate insecticide chlorpyrifos enhances brain oxidative stress and prostaglandin E2 synthesis in a mouse model of idiopathic autism. Journal of Neuroinflammation, 13(1). https://doi.org/10.1186/s12974-016-0617-4
De Felice, A., Scattoni, M. L., Ricceri, L., & Calamandrei, G. (2015). Prenatal Exposure to a Common Organophosphate Insecticide Delays Motor Development in a Mouse Model of Idiopathic Autism. PLOS ONE, 10(3), e0121663. https://doi.org/10.1371/journal.pone.0121663
Engel, S. M., Wetmur, J., Chen, J., Zhu, C., Barr, D. B., Canfield, R. L., & Wolff, M. S. (2011). Prenatal Exposure to Organophosphates, Paraoxonase 1, and Cognitive Development in Childhood. Environmental Health Perspectives, 119(8), 1182–1188. https://doi.org/10.1289/ehp.1003183
Eubig, P. A., Aguiar, A., & Schantz, S. L. (2010). Lead and PCBs as Risk Factors for Attention Deficit/Hyperactivity Disorder. Environmental Health Perspectives, 118(12), 1654–1667. https://doi.org/10.1289/ehp.0901852
Hallmayer, J. (2011). Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism. Archives of General Psychiatry, 68(11), 1095. https://doi.org/10.1001/archgenpsychiatry.2011.76
Hsieh B. H., Deng J. F., Ger J., & Tsai W. J. (2001). Acetylcholinesterase Inhibition and the Extrapyramidal Syndrome: A Review of the Neurotoxicity of Organophosphate. Neurotoxicology, 22(4), 423–7. https://doi.org/10.1016/S0161-813X(01)00044-4
Kane, M. J., & Engle, R. W. (2002). The role of prefrontal cortex in working-memory capacity, executive attention, and general fluid intelligence: An individual-differences perspective. Psychonomic Bulletin & Review, 9(4), 637–671. https://doi.org/10.3758/bf03196323
Karalliedde L., Baker D., & Marrs T. C. (2006). Organophosphate-Induced Intermediate Syndrome. Toxicological Reviews, 25(1), 1–14. https://doi.org/10.2165/00139709-200625010-00001
Kaya, Y., Bas, O., Hanci, H., Cankaya, S., Nalbant, I., Odaci, E., Avni Uydu, H., & Aslan, A. (2018). Acute renal involvement in organophosphate poisoning: histological and immunochemical investigations. Renal Failure, 40(1), 410–415. https://doi.org/10.1080/0886022x.2018.1489289
Langiano V. C (2006). Toxicidade do Roundup ® e seus efeitos para o peixe neotropical Prochilodus lineatus. http://www.uel.br/laboratorios/lefa/dissertacaovivian.pdf
Lee, J. E., Lim, M. S., Park, J. H., Park, C. H., & Koh, H. C. (2014). Nuclear NF-κB contributes to chlorpyrifos-induced apoptosis through p53 signaling in human neural precursor cells. NeuroToxicology, 42, 58–70. https://doi.org/10.1016/j.neuro.2014.04.001
Levin, E. D., Addy, N., Nakajima, A., Christopher, N. Channelle., Seidler, F. J., & Slotkin, T. A. (2001). Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats. Developmental Brain Research, 130(1), 83–89. https://doi.org/10.1016/s0165-3806(01)00215-2
Lorke, D. E., & Petroianu, G. A. (2019). Treatment of Organophosphate Poisoning with Experimental Oximes: A Review. Current Organic Chemistry, 23(5), 628–639. https://doi.org/10.2174/1385272823666190408114001
Lotti M., & Moretto A. (2005). Organophosphate-Induced Delayed Polyneuropathy. Toxicological Reviews, 24(1), 37–49. https://doi.org/10.2165/00139709-200524010-00003
Lovasi, G. S., Quinn, J. W., Rauh, V. A., Perera, F. P., Andrews, H. F., Garfinkel, R., Hoepner, L., Whyatt, R., & Rundle, A. (2011). Chlorpyrifos Exposure and Urban Residential Environment Characteristics as Determinants of Early Childhood Neurodevelopment. American Journal of Public Health, 101(1), 63–70. https://doi.org/10.2105/ajph.2009.168419
Marks, A. R., Harley, K., Bradman, A., Kogut, K., Barr, D. B., Johnson, C., Calderon, N., & Eskenazi, B. (2010). Organophosphate Pesticide Exposure and Attention in Young Mexican-American Children: The CHAMACOS Study. Environmental Health Perspectives, 118(12), 1768–1774. https://doi.org/10.1289/ehp.1002056
Mullen, B. R., Khialeeva, E., Hoffman, D. B., Ghiani, C. A., & Carpenter, E. M. (2012). Decreased Reelin Expression and Organophosphate Pesticide Exposure Alters Mouse Behaviour and Brain Morphology. ASN Neuro, 5(1), AN20120060. https://doi.org/10.1042/an20120060
Pereira A. S. et al. (2018). Metodologia da pesquisa científica. [free e-book]. Santa Maria/RS. Ed. UAB/NTE/UFSM.
Philippat, C., Barkoski, J., Tancredi, D. J., Elms, B., Barr, D. B., Ozonoff, S., Bennett, D. H., & Hertz-Picciotto, I. (2018). Prenatal exposure to organophosphate pesticides and risk of autism spectrum disorders and other non-typical development at 3 years in a high-risk cohort. International Journal of Hygiene and Environmental Health, 221(3), 548–555. https://doi.org/10.1016/j.ijheh.2018.02.004
Pope, C., Karanth, S., & Liu, J. (2005). Pharmacology and toxicology of cholinesterase inhibitors: uses and misuses of a common mechanism of action. Environmental Toxicology and Pharmacology, 19(3), 433–446. https://doi.org/10.1016/j.etap.2004.12.048
Premack, D., & Woodruff, G. (1978). Does the chimpanzee have a theory of mind? Behavioral and Brain Sciences, 1(4), 515–526. https://doi.org/10.1017/S0140525X00076512
Rauh, V. A., Garfinkel, R., Perera, F. P., Andrews, H. F., Hoepner, L., Barr, D. B., Whitehead, R., Tang, D., & Whyatt, R. W. (2006). Impact of Prenatal Chlorpyrifos Exposure on Neurodevelopment in the First 3 Years of Life Among Inner-City Children. PEDIATRICS, 118(6), e1845–e1859. https://doi.org/10.1542/peds.2006-0338
Rauh, V. A., Perera, F. P., Horton, M. K., Whyatt, R. M., Bansal, R., Hao, X., Liu, J., Barr, D. B., Slotkin, T. A., & Peterson, B. S. (2012). Brain anomalies in children exposed prenatally to a common organophosphate pesticide. Proceedings of the National Academy of Sciences, 109(20), 7871–7876. https://doi.org/10.1073/pnas.1203396109
Richardson R. J., Fink J. K., Glynn P., Hufnagel R. B., Makhaeva G. F., & Wijeyesakere S. J. (2020). Neuropathy target esterase (NTE/PNPLA6) and organophosphorus compound-induced delayed neurotoxicity (OPIDN). Advances in Neurotoxicology, 4, 1–78. https://doi.org/10.1016/bs.ant.2020.01.001
Richardson R. J., Hein N. D., Wijeyesakere S. J., Fink J. K., & Makhaeva G. F. (2013). Neuropathy target esterase (NTE): overview and future. Chemico-Biological Interactions, 203(1): 238–44.
Rother, E. T. (2007). Revisão sistemática x revisão narrativa. Acta Paul. Enferm. 20(2). https://doi.org/10.1590/S0103-21002007000200001.
Sagiv, S. K., Bruno, J. L., Baker, J. M., Palzes, V., Kogut, K., Rauch, S., Gunier, R., Mora, A. M., Reiss, A. L., & Eskenazi, B. (2019). Prenatal exposure to organophosphate pesticides and functional neuroimaging in adolescents living in proximity to pesticide application. Proceedings of the National Academy of Sciences, 116(37), 18347–18356. https://doi.org/10.1073/pnas.1903940116
Sagiv, S. K., Harris, M. H., Gunier, R. B., Kogut, K. R., Harley, K. G., Deardorff, J., Bradman, A., Holland, N., & Eskenazi, B. (2018). Prenatal Organophosphate Pesticide Exposure and Traits Related to Autism Spectrum Disorders in a Population Living in Proximity to Agriculture. Environmental Health Perspectives, 126(4), 047012. https://doi.org/10.1289/ehp2580
Van den Neucker K., Vanderstraeten G., De Muynck M., De Wilde V. (1991). The neurophysiologic examination in organophosphate ester poisoning. Case report and review of the literature. PubMed, 31(8), 507–511.
Velmurugan, G., Ramprasath, T., Swaminathan, K., Mithieux, G., Rajendhran, J., Dhivakar, M., Parthasarathy, A., Babu, D. D. V., Thumburaj, L. J., Freddy, A. J., Dinakaran, V., Puhari, S. S. M., Rekha, B., Christy, Y. J., Anusha, S., Divya, G., Suganya, K., Meganathan, B., Kalyanaraman, N., & Vasudevan, V. (2017). Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis. Genome Biology, 18(1). https://doi.org/10.1186/s13059-016-1134-6
Vommaro A., Alves M., Natália V., Oliveira S., Gomes R., & Sintia M. (2010). Praguicidas Organofosforados E Sua Toxicidade. http://www.pergamum.univale.br/pergamum/tcc/Praguicidasorganofosforadosesuatoxicidad
Yoshimasu K., Kiyohara C., Takemura S., & Nakai K. (2014). A meta-analysis of the evidence on the impact of prenatal and early infancy exposures to mercury on autism and attention deficit/hyperactivity disorder in the childhood. Neurotoxicology, 44, 121–31. https://doi.org/10.1016/j.neuro.2014.06.007
Zhang, J., Dai, H., Deng, Y., Tian, J., Zhang, C., Hu, Z., Bing, G., & Zhao, L. (2015). Neonatal chlorpyrifos exposure induces loss of dopaminergic neurons in young adult rats. Toxicology, 336, 17–25. https://doi.org/10.1016/j.tox.2015.07.014
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Larissa Dayelle Osternack; William Mattana dos Santos; Djanira Aparecida da Luz Veronez
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
