Toxicidade do imidacloprido sobre o desenvolvimento embriológico de roedores - Embryonic developmental toxicity of imidacloprid in rodents
Palavras-chave:
Neonicotinoides, Efeitos transgeracionais, Exposição ambiental, Alterações metabólicas, Alterações reprodutivas, MamíferosResumo
Objetivo: compreender como o uso do neonicotinoide imidacloprido promove efeitos transgeracionais em modelos animais. Método: trata-se de uma revisão narrativa da literatura, fundamentada na análise de estudos experimentais que investigaram a exposição ao imidacloprido, com ênfase em períodos críticos do desenvolvimento, especialmente a fase embrionária, e seus desfechos ao longo do ciclo vital e em gerações subsequentes. Resultados: embora o imidacloprido tenha sido desenvolvido e comercializado como seguro para humanos devido à sua maior afinidade por neurorreceptores nicotínicos de insetos, os estudos analisados evidenciam preocupações relevantes quanto à exposição e aos danos em organismos não alvo. Os dados indicam que a exposição embrionária ao imidacloprido pode induzir comprometimentos à saúde na idade adulta e efeitos transgeracionais, abrangendo alterações metabólicas, reprodutivas, imunológicas, comportamentais e teratogênicas, observadas tanto nas gerações parentais quanto nas descendentes. Considerações finais: a revisão evidencia riscos potenciais à saúde associados à exposição a neonicotinoides, especialmente durante janelas críticas do desenvolvimento, reforçando a necessidade de métodos de avaliação mais padronizados e de regulamentações de segurança mais rigorosas, com vistas à mitigação dos riscos para humanos e para espécies não alvo.
Referências
Abou-Donia MB, Goldstein LB, Bullman S, et al (2008) Imidacloprid induces neurobehavioral deficits and increases expression of glial fibrillary acidic protein in the motor cortex and hippocampus in offspring rats following in utero exposure. Jour of Toxi and Envi Heal - Part A: Curre Issu 71:119–130. https://doi.org/10.1080/15287390701613140
Akhtar T, Sheikh N, Abbasi MH (2014) Clinical and pathological features of Nerium oleander extract toxicosis in wistar rats. BMC Res Notes 7:1–6. https://doi.org/10.1186/1756-0500-7-947/figures/3
ANVISA (2023) Programa de Análise de Resíduos de Agrotóxicos em Alimentos – PARA: Relatório dos resultados das análises de amostras monitoradas nos ciclos 2018-2019 e 2022. Brasília. https://www.gov.br/anvisa/pt-br/assuntos/agrotoxicos/programa-de-analise-de-residuos-em-alimentos/relatorios-do-programa. Accessed 26 Aug 2024
ANVISA (2019) Programa de Análise de Resíduos de Agrotóxicos em Alimentos – PARA : Relatório das amostras analisadas no período de 2017-2018. Brasília. https://www.gov.br/anvisa/pt-br/assuntos/agrotoxicos/programa-de-analise-de-residuos-em-alimentos/relatorios-do-programa. Accessed 3 Jul 2023
Aria M, Cuccurullo C (2017) Bibliometrix: An R-tool for comprehensive science mapping analysis. J Info 11:959–975. https://doi.org/10.1016/j.joi.2017.08.007
Barker DJP (1998) In utero programming of chronic disease. Cli Sci 95:115–128. https://doi.org/10.1042/cs0950115
Beaupere C, Liboz A, Fève B, et al (2021) Molecular mechanisms of glucocorticoid-induced insulin resistance. Int J Mol Sci 22:1–30. https://doi.org/10.3390/ijms22020623
Bhaskar R, Mishra AK, Mohanty B (2017) Neonatal Exposure to Endocrine Disrupting Chemicals Impairs Learning Behaviour by Disrupting Hippocampal Organization in Male Swiss Albino Mice. Bas Cli Pha Tox 121:44–52. https://doi.org/10.1111/bcpt.12767
Bhaskar R, Mohanty B (2014) Pesticides in mixture disrupt metabolic regulation: In silico and in vivo analysis of cumulative toxicity of mancozeb and imidacloprid on body weight of mice. Gen Com End 205:226–234. https://doi.org/10.1016/j.ygcen.2014.02.007
Borsuah JF, Messer TL, Snow DD, et al (2020) Literature review: Global neonicotinoid insecticide occurrence in aquatic environments. Wat (Swi) 12:1–17. https://doi.org/10.3390/w12123388
Burke AP, Niibori Y, Terayama H, et al (2018) Mammalian Susceptibility to a Neonicotinoid Insecticide after Fetal and Early Postnatal Exposure. Sci Rep 8:1–13. https://doi.org/10.1038/s41598-018-35129-5
Calarco CA, Picciotto MR (2020) Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine’s Effects on Food Intake. Nic & Tob Res 22:152–163. https://doi.org/10.1093/NTR/NTZ010
Carroll MC (2004) The complement system in regulation of adaptive immunity. Nat Imm 2004 5:10 5:981–986. https://doi.org/10.1038/ni1113
Casida JE (2018) Neonicotinoids and Other Insect Nicotinic Receptor Competitive Modulators: Progress and Prospects. Ann Rev Ent 63:125–144. https://doi.org/10.1146/annurev-ento-020117-043042
Casida JE (2011) Neonicotinoid metabolism: Compounds, substituents, pathways, enzymes, organisms, and relevance. J Agr Foo Che 59:2923–2931. https://doi.org/10.1021/jf102438c
Casida JE, Durkin KA (2016) Pesticide chemical research in toxicology: Lessons from nature. Che Res Tox 30:94–104. https://doi.org/10.1021/acs.chemrestox.6b00303
Chen D, Liu Z, Barrett H, et al (2020) Nationwide Biomonitoring of Neonicotinoid Insecticides in Breast Milk and Health Risk Assessment to Nursing Infants in the Chinese Population. J Agr Foo Che 68:13906–13915. https://doi.org/10.1021/acs.jafc.0c05769
Craddock HA, Huang D, Turner PC, et al (2019) Trends in neonicotinoid pesticide residues in food and water in the United States, 1999-2015. Env Hea 18:1–16. https://doi.org/10.1186/s12940-018-0441-7
de Oliveira IM, Nunes BVF, Barbosa DR, et al (2010) Effects of the neonicotinoids thiametoxam and clothianidin on in vivo dopamine release in rat striatum. Tox Let 192:294–297. https://doi.org/10.1016/J.TOXLET.2009.11.005
DeSesso JM, Scialli AR (2018) Bone development in laboratory mammals used in developmental toxicity studies. Bir Def Res 110:1157–1187. https://doi.org/10.1002/BDR2.1350
Deus BCT de, Brandt EMF, Pereira R de O (2021) Priority pesticides not covered by GM Ordinance of the Ministry of Health No. 888, of 2021, on water potability standard in Brazil. Rev Bra de Ciê Amb 57:290–301. https://doi.org/10.5327/z2176-94781077
EFSA (2013a) Regulation (EU) 485/2013. Wiley-Blackwell Publishing Ltd. http://data.europa.eu/eli/reg_impl/2013/485/oj. Accessed 25 Aug 2024
EFSA (2018) Regulation (EU) 2018/783. http://data.europa.eu/eli/reg_impl/2018/783/oj. Accessed 10 Jun 2023
EFSA (2019) Review of the existing maximum residue levels for imidacloprid according to Article 12 of Regulation (EC) No 396/2005 - 2019. In: EFSA Journal. https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2019.5570. Accessed 25 Aug 2024
EFSA (2013b) Scientific Opinion on the developmental neurotoxicity potential of acetamiprid and imidacloprid. EFSA Journal 11:1–47. https://doi.org/10.2903/j.efsa.2013.3471
Elbert A, Becker B, Hartwig J, Erdelen C (1991) Imidacloprid - a new systemic insecticide. In: Pflanzenschutz-Nachrichten Bayer. https://agris.fao.org/agris-search/search.do?recordID=DE92U0152
EPA (2024) Regulatory Limits PESTICIDES/Pesticide MRLs. https://bcglobal.bryantchristie.com/db#/pesticides/query. Accessed 25 Aug 2024
Gawade L, Dadarkar SS, Husain R, Gatne M (2013) A detailed study of developmental immunotoxicity of imidacloprid in Wistar rats. Foo and Che Tox 51:61–70. https://doi.org/10.1016/j.fct.2012.09.009
Grilo LF, Tocantins C, Diniz MS, et al (2021) Metabolic Disease Programming: From Mitochondria to Epigenetics, Glucocorticoid Signalling and Beyond. Eur J Clin Inv 51:1–21. https://doi.org/10.1111/eci.13625
Haddad S, Chouit Z, Djellal D, et al (2023) Evaluation of mitochondrial and neurobehavioral disorders in brain regions of offspring (F1, F2) after gestating and lactating female rats exposure to low-dose of imidacloprid and cypermethrin. Jou of mic, bio and foo sci 12:e9541–e9541. https://doi.org/10.55251/JMBFS.9541
Han W, Tian Y, Shen X (2018) Human exposure to neonicotinoid insecticides and the evaluation of their potential toxicity: An overview. Chem 192:59–65. https://doi.org/10.1016/j.chemosphere.2017.10.149
Hassanen EI, Hussien AM, Mehanna S, et al (2022) Comparative assessment on the probable mechanisms underlying the hepatorenal toxicity of commercial imidacloprid and hexaflumuron formulations in rats. Env Sci and Poll Res 29:29091–29104. https://doi.org/10.1007/s11356-021-18486-z
Hladik ML, Main AR, Goulson D (2018) Environmental Risks and Challenges Associated with Neonicotinoid Insecticides. Env Sci Tec 52:3329–3335. https://doi.org/10.1021/acs.est.7b06388
Hofmann T, Buesen R, Schneider S, van Ravenzwaay B (2016) Postnatal fate of prenatal-induced fetal alterations in laboratory animals. Rep Tox 61:177–185. https://doi.org/10.1016/j.reprotox.2016.04.010
Javed S, Iqbal R, Ali R (2023) Teratogenic effect of imidacloprid and dimethoate on albino mice (Mus musculus). Pur and App Bio 12:11–20. https://doi.org/10.19045/bspab.2023.120002
Kapoor U, Srivastava MK, Srivastava AK, et al (2013) Analysis of imidacloprid residues in fruits, vegetables, cereals, fruit juices, and baby foods, and daily intake estimation in and around Lucknow, India. Env Tox Che 32:723–727. https://doi.org/10.1002/ETC.2104
Kapoor U, Srivastava MK, Srivastava LP (2011) Toxicological impact of technical imidacloprid on ovarian morphology, hormones and antioxidant enzymes in female rats. Foo and Che Tox 49:3086–3089. https://doi.org/10.1016/j.fct.2011.09.009
Kaur G, Farooq S, Malik YS, et al (2024) Assessment of Lung Damage via Mitochondrial ROS Production Upon Chronic Exposure to Fipronil and Imidacloprid. Agr Res. https://doi.org/10.1007/s40003-024-00738-2
Klarich KL, Pflug NC, DeWald EM, et al (2017) Occurrence of neonicotinoid insecticides in finished drinking water and fate during drinking water treatment. Env Sci Tec Let 4:168–173. https://doi.org/10.1021/acs.estlett.7b00081
Klarich Wong KL, Webb DT, Nagorzanski MR, et al (2019) Chlorinated Byproducts of Neonicotinoids and Their Metabolites: An Unrecognized Human Exposure Potential? Env Sci Tec Let 6:98–105. https://doi.org/10.1021/acs.estlett.8b00706
Lacagnina S (2020) The Developmental Origins of Health and Disease (DOHaD). Am J Lif Med 14:47–50. https://doi.org/10.1177/1559827619879694
Leslie M (2010) Beyond clotting: The powers of platelets. Science (1979) 328:562–564. https://doi.org/10.1126/science.328.5978.562
Lingappan K (2018) NF-κB in oxidative stress. Cur Opi Tox 7:81–86. https://doi.org/10.1016/j.cotox.2017.11.002
Loser D, Grillberger K, Hinojosa MG, et al (2021) Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling. Arc of Tox 2021 95:12 95:3695–3716. https://doi.org/10.1007/S00204-021-03168-Z
Mahai G, Wan Y, Xia W, et al (2022) Exposure assessment of neonicotinoid insecticides and their metabolites in Chinese women during pregnancy: A longitudinal study. Sci of the Tot Env 818:151806. https://doi.org/10.1016/j.scitotenv.2021.151806
Matsuda K, Ihara M, Sattelle DB (2020) Neonicotinoid insecticides: Molecular targets, resistance, and toxicity. Ann Rev Pha Tox 60:241–255. https://doi.org/10.1146/annurev-pharmtox-010818-021747
Matsuda K, Shimomura M, Ihara M, et al (2005) Neonicotinoids Show Selective and Diverse Actions on Their Nicotinic Receptor Targets: Electrophysiology, Molecular Biology, and Receptor Modeling Studies. Bio Bio Bio 69:1442–1452. https://doi.org/10.1271/bbb.69.1442
Mendy A, Pinney SM (2022) Exposure to neonicotinoids and serum testosterone in men, women, and children. Env Tox 37:1521–1528. https://doi.org/10.1002/tox.23503
Mörtl M, Vehovszky Á, Klátyik S, et al (2020) Neonicotinoids: Spreading, translocation and aquatic toxicity. Int J Env Res Pub Hea 17:1–14. https://doi.org/10.3390/ijerph17062006
Nabiuni M, Parivar K, Noorinejad R, et al (2015) The reproductive side effects of Imidacloprid in pregnant Wistar rat. International Journal of Cellular and Molecular Biotechnology 2015:10–18. https://doi.org/10.5899/2015/ijcmb-00017
Ndonwi EN, Atogho-Tiedeu B, Lontchi-Yimagou E, et al (2020) Metabolic effects of exposure to pesticides during gestation in female Wistar rats and their offspring: a risk factor for diabetes? Tox Res 36:249–256. https://doi.org/10.1007/s43188-019-00028-y
Ndonwi EN, Atogho-Tiedeu B, Lontchi-Yimagou E, et al (2019) Gestational exposure to pesticides induces oxidative stress and lipid peroxidation in offspring that persist at adult age in an animal model. Tox Res 35:241–248. https://doi.org/10.5487/TR.2019.35.3.241
Nedzvetsky VS, Masiuk DM, Gasso VY, et al (2021) Low doses of imidacloprid induce disruption of intercellular adhesion and initiate proinflammatory changes in Caco-2 cells. Reg Mec Bio 12:430–437. https://doi.org/10.15421/022159
Nimako C, Ikenaka Y, Akoto O, et al (2021) Simultaneous quantification of imidacloprid and its metabolites in tissues of mice upon chronic low-dose administration of imidacloprid. J Chr A 1652:462350. https://doi.org/10.1016/j.chroma.2021.462350
Nowell LH, Moran PW, Schmidt TS, et al (2018) Complex mixtures of dissolved pesticides show potential aquatic toxicity in a synoptic study of Midwestern U.S. streams. Sci of the Tot Env 613–614:1469–1488. https://doi.org/10.1016/j.scitotenv.2017.06.156
Ohno S, Ikenaka Y, Onaru K, et al (2020) Quantitative elucidation of maternal-to-fetal transfer of neonicotinoid pesticide clothianidin and its metabolites in mice. Tox Lett 322:32–38. https://doi.org/10.1016/j.toxlet.2020.01.003
Ottenbros I, Lebret E, Huber C, et al (2023) Assessment of exposure to pesticide mixtures in five European countries by a harmonized urinary suspect screening approach. Int J Hyg Env Hea 248:. https://doi.org/10.1016/j.ijheh.2022.114105
Passoni A, Mariani A, Comolli D, et al (2021) An integrated approach, based on mass spectrometry, for the assessment of imidacloprid metabolism and penetration into mouse brain and fetus after oral treatment. Tox 462:1–7. https://doi.org/10.1016/j.tox.2021.152935
Pedersen TL, Smilowitz JT, Winter CK, et al (2021) Quantification of Nonpersistent Pesticides in Small Volumes of Human Breast Milk with Ultrahigh Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry. J Agr Foo Che 69:6676–6689. https://doi.org/10.1021/acs.jafc.0c05950
R Core Team (2024) R: A Language and Environment for Statistical Computing
Rankin LC, Artis D (2018) Beyond Host Defense: Emerging Functions of the Immune System in Regulating Complex Tissue Physiology. Cell 173:554–567. https://doi.org/10.1016/J.CELL.2018.03.013
Saito H, Furukawa Y, Sasaki T, et al (2023) Behavioral effects of adult male mice induced by low-level acetamiprid, imidacloprid, and nicotine exposure in early-life. Fro Neu 17:1239808. https://doi.org/10.3389/FNINS.2023.1239808/BIBTEX
Schulz-Jander DA, Casida JE (2002) Imidacloprid insecticide metabolism: Human cytochrome P450 isozymes differ in selectivity for imidazolidine oxidation versus nitroimine reduction. Tox Lett 132:65–70. https://doi.org/10.1016/S0378-4274(02)00068-1
Sharma RK, Singh P, Setia A, Sharma AK (2020) Insecticides and ovarian functions. Env Mol Mut 61:369–392. https://doi.org/10.1002/em.22355
Shattuck A (2021) Generic, growing, green?: The changing political economy of the global pesticide complex. Jouof Pea Stu 48:231–253. https://doi.org/10.1080/03066150.2020.1839053
Sheets LP (2005) Imidacloprid. In: Wexler P (ed) Encyclopedia of Toxicology, 2nd edn. Elsevier, New York, pp 567–570
Shi L, Zou L, Gao J, et al (2016) Imidacloprid inhibits IgE-mediated RBL-2H3 cell degranulation and passive cutaneous anaphylaxis. Asia Pac All 6:236–244. https://doi.org/10.5415/apallergy.2016.6.4.236
Silvanima J, Woeber A, Sunderman-Barnes S, et al (2018) A synoptic survey of select wastewater-tracer compounds and the pesticide imidacloprid in Florida’s ambient freshwaters. Env Mon Ass 190:. https://doi.org/10.1007/s10661-018-6782-4
Stehle S, Ovcharova V, Wolfram J, et al (2023) Neonicotinoid insecticides in global agricultural surface waters – Exposure, risks and regulatory challenges. Sci of the Tot Env 867:161383. https://doi.org/10.1016/j.scitotenv.2022.161383
Stokes KY, Granger DN (2012) Platelets: a critical link between inflammation and microvascular dysfunction. J Phy 590:1023–1034. https://doi.org/10.1113/JPHYSIOL.2011.225417
Swenson TL, Casida JE (2013) Aldehyde oxidase importance in vivo in xenobiotic metabolism: Imidacloprid nitroreduction in mice. Tox Sci 133:22–28. https://doi.org/10.1093/toxsci/kft066
Tasman K, Hidalgo S, Zhu B, et al (2021) Neonicotinoids disrupt memory, circadian behaviour and sleep. Sci Rep 11. https://doi.org/10.1038/s41598-021-81548-2
Thompson DA, Lehmler HJ, Kolpin DW, et al (2020) A critical review on the potential impacts of neonicotinoid insecticide use: Current knowledge of environmental fate, toxicity, and implications for human health. Env Sci Pro Imp 22:1315–1346. https://doi.org/10.1039/c9em00586b
Tison L, Beaumelle L, Monceau K, Thiéry D (2024) Transfer and bioaccumulation of pesticides in terrestrial arthropods and food webs: State of knowledge and perspectives for research. Chem 357:142036. https://doi.org/10.1016/J.CHEMOSPHERE.2024.142036
Vohra P, Khera KS (2016) Effect of Imidacloprid on Reproduction of Female Albino Rats in Three Generation Study. J Vet Sci Tec 7. https://doi.org/10.4172/2157-7579.1000340
Vohra P, Khera KS (2015) A three generation study with effect of imidacloprid in rats: Biochemical and histopathological investigation. Tox Int 22:119–124. https://doi.org/10.4103/0971-6580.172270
Wittenberg RE, Wolfman SL, De Biasi M, Dani JA (2020) Nicotinic acetylcholine receptors and nicotine addiction: A brief introduction. Neur 177:108256. https://doi.org/10.1016/J.NEUROPHARM.2020.108256
Wood TJ, Goulson D (2017) The environmental risks of neonicotinoid pesticides: a review of the evidence post 2013. Env Sci and Pol Res 24:17285–17325. https://doi.org/10.1007/s11356-017-9240-x
Yan S, Meng Z, Tian S, et al (2020) Neonicotinoid insecticides exposure cause amino acid metabolism disorders, lipid accumulation and oxidative stress in ICR mice. Che 246:125661. https://doi.org/10.1016/J.CHEMOSPHERE.2019.125661
Zhang D, Lu S (2022) Human exposure to neonicotinoids and the associated health risks: A review. Env Int 163:107201. https://doi.org/10.1016/j.envint.2022.107201
Zhang H, Sulzer D (2004) Frequency-dependent modulation of dopamine release by nicotine. Nat Neu 2004 7:6 7:581–582. https://doi.org/10.1038/nn1243
Zhang Q, Li Z, Chang CH, et al (2018) Potential human exposures to neonicotinoid insecticides: A review. Env Pol 236:71–81. https://doi.org/10.1016/j.envpol.2017.12.101
Zhang Z, Shen L, Chen M, et al (2024) The alarming link between neonicotinoid insecticides and kidney injury. Eme Con 10:100376. https://doi.org/10.1016/J.EMCON.2024.100376
Statements & Declarations
Funding
This research was funded by the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES – Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) under grant number 88887.676039/2022-00.
Competing Interests
The authors declare no conflict of interest.
Author Contributions
Bárbara Zanardini de Andrade, Thaís Maylin Sobjak, Leanna Camila Macarini and Ana Tereza Bittencourt Guimarães contributed equally to this manuscript.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2026 Revista Educação, Meio Ambiente e Saúde

Este trabalho está licenciado sob uma licença Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
TERMO DE TRANSFERÊNCIA DE DIREITOS AUTORAIS
Transfiro os direitos autorais deste artigo para a REMAS, assim que ele for aceito para a devida publicação eletrônica. Os direitos de autor incluem o direito de reproduzir na íntegra ou em parte por qualquer meio, distribuir o referido artigo, incluindo figuras, fotografias, bem como as eventuais traduções. O autor pode ainda, imprimir e distribuir cópias do seu artigo, desde que mencione que os direitos pertencem à REMAS. Declaro que este manuscrito é original, não tendo sido submetido à publicação, na íntegra ou em partes para outros periódicos online ou não, assim como em Anais de eventos científicos ou capítulos de livros.

