Skip to main content Skip to journal navigation menu Skip to site footer
contact@ukscip.com
Review

Impact of Early‑Life Exposure to Environmental Neurotoxicants on Brain Development and Risk of Neurodevelopmental Disorders in Children

Laure Viviane Ndam Ngoungoure ORCID ,  Herman Philipe Nfombouot‑Njitoyap ORCID ,  Fils Armand Ella ,  Brice Vincent Ayissi Owona ,  Wilfred Angie Abia ORCID
    Received: 16 September 2025; Revised: 12 November 2025; Accepted: 8 December 2025; Published: 5 January 2026

    Abstract

    Environmental neurotoxicants pose significant risks to the developing brain, particularly during foetal and early postnatal periods when the blood-brain barrier is immature and highly permeable. Exposure during these critical windows of development can result in long-lasting structural and functional alterations to the nervous system, potentially leading to adverse neurodevelopmental and cognitive outcomes later in life. To synthesise current evidence on major environmental neurotoxicants, their mechanisms of action, neurodevelopmental effects, vulnerability factors, and implications for prevention and policy. A narrative review of published epidemiological, experimental, neuroimaging, and meta-analytic studies examining exposure to heavy metals, pesticides, industrial solvents, air pollutants, and endocrine-disrupting chemicals, with emphasis on developmental neurotoxicity and associated health outcomes. Environmental neurotoxicants disrupt neurodevelopment through oxidative stress, inflammation, excitotoxicity, apoptosis, epigenetic modifications, and neurotransmitter dysregulation. Prenatal and early-life exposures are associated with increased risks of autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disabilities, behavioural disorders, reduced intelligence quotient (IQ), and structural brain abnormalities. Susceptibility is influenced by genetic factors, socioeconomic conditions, nutritional status, and combined exposures to multiple toxicants. Environmental neurotoxicants remain a major threat to child neurodevelopment, while current regulatory frameworks are insufficient to adequately protect vulnerable populations. Strengthened preventive measures, child-specific regulations, coordinated international testing, and equitable public health interventions are urgently needed to reduce exposure and safeguard brain health.

    Keywords

    References

    1. 1. Vasung, L.; Abaci Turk, E.; Ferradal, S.L.; et al. Exploring early human brain development with structural and physiological neuroimaging. Neuroimage 2019, 187, 226–254.
    2. 2. Aragón-González, A.; Shaw, P.J.; Ferraiuolo, L. Blood–Brain Barrier Disruption and Its Involvement in Neurodevelopmental and Neurodegenerative Disorders. Int. J. Mol. Sci. 2022, 23, 15271.
    3. 3. Lautarescu, A.; Bonthrone, A.F.; Bos, B.; et al. Advances in fetal and neonatal neuroimaging and everyday exposures. Pediatr. Res. 2024, 96, 1404–1416.
    4. 4. Moretti, R.; Pansiot, J.; Bettati, D.; et al. Blood-brain barrier dysfunction in disorders of the developing brain. Front. Neurosci. 2015, 9, 40.
    5. 5. Ortega, R.; Carmona, A. Neurotoxicity of Environmental Metal Toxicants: Special Issue. Toxics 2022, 10, 382.
    6. 6. Zhou, F.; Xie, J.; Zhang, S.; et al. Lead, cadmium, arsenic, and mercury combined exposure disrupted synaptic homeostasis through activating the Snk-SPAR pathway. Ecotoxicol. Environ. Saf. 2018, 163, 674–684.
    7. 7. von Ehrenstein, O.S.; Ling, C.; Cui, X.; et al. Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study. BMJ 2019, 364, l962.
    8. 8. Capela, J.P.; Carmo, H.; Remião, F.; et al. Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: An overview. Mol. Neurobiol. 2009, 39, 210–271.
    9. 9. Franco, R.; Li, S.; Rodriguez-Rocha, H.; et al. Molecular mechanisms of pesticide-induced neurotoxicity: Relevance to Parkinson’s disease. Chem. Biol. Interact. 2010, 188, 289–300. DOI: https://doi.org/10.1016/j.cbi.2010.06.003
    10. 10. Gao, X.; Wang, X.; Zheng, X.; et al. Chemical Pollutant Exposure in Neurodevelopmental Disorders: Integrating Toxicogenomic and Transcriptomic Evidence to Elucidate Shared Biological Mechanisms and Developmental Signatures. Toxics 2025, 13, 282.
    11. 11. McCanlies, E.C.; Gu, J.K.; Kashon, M.; et al. Parental occupational exposure to solvents and autism spectrum disorder: An exploratory look at gene-environment interactions. Environ. Res. 2023, 228, 115769. DOI: https://doi.org/10.1016/j.envres.2023.115769
    12. 12. Farina, M.; Rocha, J.B.T.; Aschner, M. Mechanisms of methylmercury-induced neurotoxicity: Evidence from experimental studies. Life Sci. 2011, 89, 555–563.
    13. 13. Nabi, M.; Tabassum, N. Role of Environmental Toxicants on Neurodegenerative Disorders. Front. Toxicol. 2022, 4, 837579.
    14. 14. Newell, M.E.; Aravindan, A.; Babbrah, A.; et al. Epigenetic Biomarkers Driven by Environmental Toxins Associated with Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis in the United States: A Systematic Review. Toxics 2025, 13, 114.
    15. 15. Chin-Chan, M.; Navarro-Yepes, J.; Quintanilla-Vega, B. Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front. Cell. Neurosci. 2015, 9, 124.
    16. 16. Lopez-Suarez, L.; Awabdh, S. Al.; Coumoul, X.; et al. The SH-SY5Y human neuroblastoma cell line, a relevant in vitro cell model for investigating neurotoxicology in human: Focus on organic pollutants. Neurotoxicology 2022, 92, 131–155.
    17. 17. Rock, K.D.; Patisaul, H.B. Environmental Mechanisms of Neurodevelopmental Toxicity. Curr. Environ. Health Rep. 2018, 5, 145–157.
    18. 18. Schwartz, J.; Bellinger, D.; Glass, T. Exploring potential sources of differential vulnerability and susceptibility in risk from environmental hazards to expand the scope of risk assessment. Am. J. Public Health 2011, 101, S94–S101.
    19. 19. Segal, D.; Nachman, R.; Nweke, O.; et al. Identifying studies evaluating susceptibility factors for chemical health assessments: A case study focused on methylmercury developmental neurotoxicity. Environ. Int. 2025, 197, 109331. DOI: https://doi.org/10.1016/j.envint.2025.109331
    20. 20. Grineski, S.E.; Collins, T.W. Geographic and social disparities in exposure to air neurotoxicants at U.S. public schools. Environ. Res. 2018, 161, 580–587.
    21. 21. Payne-Sturges, D.C.; Cory-Slechta, D.A.; Puett, R.C.; et al. Defining and intervening on cumulative environmental neurodevelopmental risks: Introducing a complex systems approach. Environ. Health Perspect. 2021, 129, 35001.
    22. 22. Ames, J.L.; Sharma, V.; Lyall, K. Effects of Early-life PFAS Exposure on Child Neurodevelopment: A Review of the Evidence and Research Gaps. Curr. Environ. Health Rep. 2025, 12, 9.
    23. 23. Ngoungoure, L.V.N.; Abia, W.A.; Owona, B.V.A.; et al. Neurodevelopmental Outcomes of Mycotoxins Exposure and Effect on Brain Development in Infants and Young Children. Dev. Neurobiol. 2025, 85, e23000.
    24. 24. Petersen, I.; Evans-Lacko, S.; Semrau, M.; et al. Promotion, prevention and protection: Interventions at the population- and community-levels for mental, neurological and substance use disorders in low- and middle-income countries. Int. J. Ment. Health Syst. 2016, 10, 30. DOI: https://doi.org/10.1186/s13033-016-0060-z
    25. 25. Tran, N.Q.V.; Miyake, K. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism. Int. J. Genomics 2017, 2017, 7526592.
    26. 26. Stiles, J.; Jernigan, T.L. The basics of brain development. Neuropsychol. Rev. 2010, 20, 327–348.
    27. 27. Bellinger, D.C.; Matthews-Bellinger, J.A.; Kordas, K. A developmental perspective on early-life exposure to neurotoxicants. Environ. Int. 2016, 94, 103–112.
    28. 28. Rauh, V.A.; Margolis, A.E. Research Review: Environmental exposures, neurodevelopment, and child mental health—New paradigms for the study of brain and behavioral effects. J. Child Psychol. Psychiatry Allied Discip. 2016, 57, 775–793.
    29. 29. Ijomone, O.M.; Olung, N.F.; Akingbade, G.T.; et al. Environmental influence on neurodevelopmental disorders: Potential association of heavy metal exposure and autism. J. Trace Elem. Med. Biol. 2020, 62, 126638.
    30. 30. Bell, K.S.; O’Shaughnessy, K.L. The development and function of the brain barriers—An overlooked consideration for chemical toxicity. Front. Toxicol. 2022, 4, 1000212.
    31. 31. Ek, C.J.; Dziegielewska, K.M.; Habgood, M.D.; et al. Barriers in the developing brain and Neurotoxicology. Neurotoxicology 2012, 33, 586–604.
    32. 32. Bennett, D.H.; Busgang, S.A.; Kannan, K.; et al. Environmental exposures to pesticides, phthalates, phenols and trace elements are associated with neurodevelopment in the CHARGE study. Environ. Int. 2022, 161, 107075.
    33. 33. Davis, R.L.; Curtis, K.S. Estrogen disruptors and neuroimmune signaling in obesity: Focus on bisphenol A. Curr. Opin. Toxicol. 2020, 19, 15–20.
    34. 34. Aleya, L.; Uddin, M.S. Environmental pollutants and the risk of neurological disorders. Environ. Sci. Pollut. Res. 2020, 27, 44657–44658.
    35. 35. Kerna, N.A.; Ngwu, D.C.; Pruitt, K.D.; et al. The Morbid Impact of Environmental Toxins on the Human Nervous System: Peripheral Neuropathy Nexus with Organic Solvents, Pesticides, and Heavy Metals. Eur. J. Ecol. Biol. Agric. 2024, 1, 53–74.
    36. 36. Cardenas-Iniguez, C.; Burnor, E.; Herting, M.M. Neurotoxicants, the Developing Brain, and Mental Health. Biol. Psychiatry Glob. Open Sci. 2022, 2, 223–232.
    37. 37. Cecil, K.M. Pediatric Exposures to Neurotoxicants: A Review of Magnetic Resonance Imaging and Spectroscopy Findings. Diagnostics 2022, 12, 641.
    38. 38. Dórea, J.G. Exposure to environmental neurotoxic substances and neurodevelopment in children from Latin America and the Caribbean. Environ. Res. 2021, 192, 110199.
    39. 39. Grandjean, P.; Kishi, R.; Kogevinas, M. Prevention of Developmental Neurotoxicity. Epidemiology 2017, 28, 157–158.
    40. 40. Sachana, M.; Shafer, T.J.; Terron, A. Toward a better testing paradigm for developmental neurotoxicity: OECD efforts and regulatory considerations. Biology 2021, 10, 86.
    41. 41. Bennett, D.; Bellinger, D.C.; Birnbaum, L.S.; et al. Project TENDR: Targeting environmental neuro-developmental risks. The TENDR consensus statement. Environ. Health Perspect. 2016, 124, A118–A122.
    42. 42. Andersen, H.R.; David, A.; Freire, C.; et al. Pyrethroids and developmental neurotoxicity—A critical review of epidemiological studies and supporting mechanistic evidence. Environ. Res. 2022, 214, 113935.
    43. 43. Grandjean, P.; Landrigan, P.J. Neurobehavioural effects of developmental toxicity. Lancet Neurol. 2014, 13, 330–338.
    44. 44. Costa, L.G.; Cole, T.B.; Dao, K.; et al. Developmental impact of air pollution on brain function. Neurochem. Int. 2019, 131, 104580.
    45. 45. Modgil, S.; Lahiri, D.K.; Sharma, V.L.; et al. Role of early life exposure and environment on neurodegeneration: implications on brain disorders. Transl. Neurodegener. 2014, 3, 9.
    46. 46. Zhang, J.; Gao, S.; Du, Z.; et al. Contamination status and control of mycotoxins in grain and oil crops. J. Agro-Environ. Sci. 2022, 41, 2680–2687. (in Chinese)
    47. 47. Campbell, M.A.; Murphy, S.R.; Klasing, S.A.; et al. Life Course Considerations in Environmental Health: Developmental Neurotoxicity of Domoic Acid at Doses below Acute Effect Levels in Adult Humans. Birth Defects Res. 2024, 116, e2419. DOI: https://doi.org/10.1002/bdr2.2419
    48. 48. Yi, C.; Wang, Q.; Qu, Y.; et al. In-utero exposure to air pollution and early-life neural development and cognition. Ecotoxicol. Environ. Saf. 2022, 238, 113589.
    49. 49. Kanthasamy, A.; Jin, H.; Anantharam, V.; et al. Emerging neurotoxic mechanisms in environmental factors-induced neurodegeneration. Neurotoxicology 2012, 33, 833–837. DOI: https://doi.org/10.1016/j.neuro.2012.01.011
    50. 50. LoPachin, R.M.; DeCaprio, A.P. Protein adduct formation as a molecular mechanism in neurotoxicity. Toxicol. Sci. 2005, 86, 214–225. DOI: https://doi.org/10.1093/toxsci/kfi197
    51. 51. Kundakovic, M.; Jaric, I. The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders. Genes 2017, 8, 104.
    52. 52. Kebieche, N.; Yim, S.; Lambert, C.; et al. Epigenetic and Genotoxic Mechanisms of PFAS-Induced Neurotoxicity: A Molecular and Transgenerational Perspective. Toxics 2025, 13, 629.
    53. 53. Pozzi, E.; Ballarini, E.; Rodriguez-Menendez, V.; et al. Paclitaxel, But Not Cisplatin, Affects Satellite Glial Cells in Dorsal Root Ganglia of Rats with Chemotherapy-Induced Peripheral Neurotoxicity. Toxics 2023, 11, 93. DOI: https://doi.org/10.3390/toxics11020093
    54. 54. Jubair, H. Epigenetics and Environmental Exposures in Early Neurodevelopment: Implications for Pediatric Neurological Disorders. SAGE Open Pediatr. 2025, 12, 30502225251380331.
    55. 55. Doi, M.; Usui, N.; Shimada, S. Prenatal Environment and Neurodevelopmental Disorders. Front. Endocrinol. (Lausanne) 2022, 13, 860110.
    56. 56. Kaufman, J.A.; Wright, J.M.; Rice, G.; et al. Ambient ozone and fine particulate matter exposures and autism spectrum disorder in metropolitan Cincinnati, Ohio. Environ. Res. 2019, 171, 218–227.
    57. 57. Chen, G.; Jin, Z.; Li, S.; et al. Early life exposure to particulate matter air pollution (PM(1), PM(2.5) and PM(10)) and autism in Shanghai, China: A case-control study. Environ. Int. 2018, 121, 1121–1127.
    58. 58. Tolins, M.; Ruchirawat, M.; Landrigan, P. The developmental neurotoxicity of arsenic: Cognitive and behavioral consequences of early life exposure. Ann. Glob. Health 2014, 80, 303–314.
    59. 59. Islam, F.; Das Trisha, A.; Hafsa, J.M.; et al. Occurrence of aflatoxin M(1) in human breast milk in Bangladesh. Mycotoxin Res. 2021, 37, 241–248.
    60. 60. Sagiv, S.K.; Harris, M.H.; Gunier, R.B.; et al. Prenatal Organophosphate Pesticide Exposure and Traits Related to Autism Spectrum Disorders in a Population Living in Proximity to Agriculture. Environ. Health Perspect. 2018, 126, 47012.
    61. 61. Werder, E.J.; Lu, K.; Liu, C.W.; et al. Early life phthalate exposure impacts gray matter and white matter volume in infants and young children. Environ. Res. 2025, 279, 121826.
    62. 62. Payne-Sturges, D.C.; Taiwo, T.K.; Ellickson, K.; et al. Disparities in Toxic Chemical Exposures and Associated Neurodevelopmental Outcomes: A Scoping Review and Systematic Evidence Map of the Epidemiological Literature. Environ. Health Perspect. 2023, 131, 96001.
    63. 63. Cory-Slechta, D.A.; Downs, C.J.; Sobolewski, M. Cumulative risk assessment as the pathway to public health protection for behavioral neurotoxicity. Neurotoxicology 2025, 108, 400–411.
    64. 64. Chirico, F.; Scoditti, E.; Viora, C.; et al. How occupational mercury neurotoxicity is affected by genetic factors. A systematic review. Appl. Sci. 2020, 10, 7706.
    65. 65. Gundacker, C.; Gencik, M.; Hengstschläger, M. The relevance of the individual genetic background for the toxicokinetics of two significant neurodevelopmental toxicants: Mercury and lead. Mutat. Res. Rev. Mutat. Res. 2010, 705, 130–140.
    66. 66. Ratner, M.H. A critical review of the interrelationships between genetics, neurotoxicant exposure, and age at onset of neurodegenerative diseases. Curr. Top. Toxicol. 2016, 12, 1–10.
    67. 67. Bellinger, D.C. Lead neurotoxicity and socioeconomic status: Conceptual and analytical issues. Neurotoxicology 2008, 29, 828–832.
    68. 68. Eggers, S.; Nagdeo, K.P.; Sachdev, K.; et al. Nutritional Modulation of the Gut Microbiome in Relation to Prenatal Lead-Induced Neurotoxicity: A Review. Nutrients 2025, 17, 3700.
    69. 69. Grant, W.B.; Blake, S.M. Diet’s Role in Modifying Risk of Alzheimer’s Disease: History and Present Understanding. J. Alzheimers Dis. 2023, 96, 1353–1382.
    70. 70. Spencer, P.S.; Palmer, V.S. Interrelationships of undernutrition and neurotoxicity: Food for thought and research attention. Neurotoxicology 2012, 33, 605–616.
    71. 71. Geertsema, J.; Juncker, H.G.; Wilmes, L.; et al. Nutritional interventions to counteract the detrimental consequences of early-life stress. Mol. Psychiatry 2025, 30, 3269–3300. DOI: https://doi.org/10.1038/s41380-025-03020-1
    72. 72. Kordas, K.; Lönnerdal, B.; Stoltzfus, R.J. Interactions between nutrition and environmental exposures: Effects on health outcomes in women and children. J. Nutr. 2007, 137, 2794–2797.
    73. 73. Abouee-Mehrizi, A.; Kashani, M.M.; Rasoulzadeh, Y.; et al. Co-exposure to Toluene and Noise Made Synergistic and Antagonistic Effects on Some Neurotoxic Parameters in New Zealand White Rabbits. Basic Clin. Neurosci. 2023, 14, 813–826.
    74. 74. Angelova, P.R.; Myers, I.; Abramov, A.Y. Carbon monoxide neurotoxicity is triggered by oxidative stress induced by ROS production from three distinct cellular sources. Redox Biol. 2023, 60, 102598.
    75. 75. Hubbs-Tait, L.; Nation, J.R.; Krebs, N.F.; et al. Neurotoxicants, micronutrients, and social environments individual and combined effects on children’s development. Psychol. Sci. Public Interest Suppl. 2005, 6, 57–121. DOI: https://doi.org/10.1111/j.1529-1006.2005.00024.x
    76. 76. Pyatha, S.; Kim, H.; Lee, D.; et al. Co-exposure to lead, mercury, and cadmium induces neurobehavioral impairments in mice by interfering with dopaminergic and serotonergic neurotransmission in the striatum. Front. Public Health 2023, 11, 1265864.
    77. 77. Dórea, J.G. Multiple low-level exposures: Hg interactions with co-occurring neurotoxic substances in early life. Biochim. Biophys. Acta Gen. Subj. 2019, 1863, 129243.
    78. 78. Rechtman, E.; Curtin, P.; Papazaharias, D.M.; et al. Sex-specific associations between co-exposure to multiple metals and visuospatial learning in early adolescence. Transl. Psychiatry 2020, 10, 358. DOI: https://doi.org/10.1038/s41398-020-01041-8
    79. 79. Gaylor, D.W.; Slikker Jr., W. Modeling for Risk Assessment of Neurotoxic Effects. Risk Anal. 1994, 14, 333–338. DOI: https://doi.org/10.1111/j.1539-6924.1994.tb00249.x
    80. 80. Lu, E.H.; Ford, L.C.; Rusyn, I.; et al. Reducing uncertainty in dose-response assessments by incorporating Bayesian benchmark dose modeling and in vitro data on population variability. Risk Anal. 2025, 45, 457–472.
    81. 81. Raffaele, K.C.; Rees, C. Neurotoxicology dose/response assessment for several cholinesterase inhibitors: use of uncertainty factors. Neurotoxicology 1990, 11, 237–256.
    82. 82. Gaylor, D.W.; Kodell, R.L. Percentiles of the product of uncertainty factors for establishing probabilistic reference doses. Risk Anal. 2000, 20, 245–250.
    83. 83. da Silva, A.S.; Santos, R.M.S.; De Marco, P.G.; et al. Neurodevelopmental Outcomes Associated with Early-Life Exposure to Heavy Metals: A Systematic Review. Int. J. Environ. Res. Public Health 2025, 22, 1308.
    84. 84. Knudsen, E.I.; Heckman, J.J.; Cameron, J.L.; et al. Economic, neurobiological, and behavioral perspectives on building America’s future workforce. Proc. Natl. Acad. Sci. USA 2006, 103, 10155–10162.
    ×