Skip to main content

Advertisement

SpringerLink
Log in

Lead exposure and its association with neurological damage: systematic review and meta-analysis

  • Review Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Lead (Pb) is one of the most toxic and abundant elements in the earth’s crust, which is pointed out that the intoxication caused by it may damage biological systems. This systematic review with meta-analysis aimed to evaluate the association between Pb exposure and neurological damage. This work was executed according to PRISMA guidelines, and seven online databases were consulted. Based on the PECO strategy, studies presenting humans as participants (populations) exposed to Pb (exposure) compared to non-exposed to Pb (control) evaluating the neurological impairment (outcome) were included. The quality and risk of bias were verified by Fowkes and Fulton checklist. Two meta-analyses were conducted considering Digit Symbol and Profile Mood tests. The certainty of the evidence was evaluated with the GRADE tool. This review identified 2019 studies, of which 12 were eligible according to the inclusion criteria. Eight were considered with a low risk of bias. All the studies elected showed that exposure to Pb is associated with neurological damage, but the meta-analysis did not show any difference for the evaluated tests, and the certainty of the evidence was considered very low. Nevertheless, the included studies showed that Pb occupational exposure is associated with neurological damage, and the main parameters evaluated for possible neurological damage were related to mnemonic aspects, reaction time, intelligence, attention disorders, and mood changes. Thus, our results revealed that a definitive demonstration of an association of Pb and neurological changes in humans is still a pending issue. Future studies should take into consideration more confident methods to answer this question.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

Not applicable.

References

  • ATSDR U (2005) Toxicological profile for lead. US Department of Health and Human Services. Public Health Service, Atlanta, USA, 582

  • Ayyalasomayajula N, Ajumeera R, Chellu CS, Challa S (2019) Mitigative effects of epigallocatechin gallate in terms of diminishing apoptosis and oxidative stress generated by the combination of Pb and amyloid peptides in human neuronal cells. J Biochem Mol Toxicol 33(11):e22393. https://doi.org/10.1002/jbt.22393

    Article  CAS  Google Scholar 

  • Baker EL, Feldman R, White R, Harley J (1983) The role of occupational Pb exposure in the genesis of psychiatric and behavioral disturbances. Acta Psychiatr Scand 67:38–48. https://doi.org/10.1111/j.1600-0447.1983.tb00940.x

    Article  Google Scholar 

  • Baker E, Feldman R, White R, Harley J, Niles C, Dinse G, Berkey CS (1984) Occupational Pb neurotoxicity: a behavioural and electrophysiological evaluation. Study design and year one results. Occup Environ Med 41:352–361. https://doi.org/10.1136/oem.41.3.352

  • Baker E, White RF, Pothier LJ, Berkey CS, Dinse G, Travers PH, Harley J, Feldman R (1985) Occupational Pb neurotoxicity: improvement in behavioural effects after reduction of exposure. Occup Environ Med 42:507–516. https://doi.org/10.1136/oem.42.8.507

    Article  CAS  Google Scholar 

  • Balbus JM, Stewart W, Bolla KI, Schwartz BS (1998) Simple visual reaction time in organoPb manufacturing workers: influence of the interstimulus interval. Arch Environ Health 53(4):264–270. https://doi.org/10.1080/00039899809605707

    Article  CAS  Google Scholar 

  • Benedict RH, DeLuca J, Phillips G, LaRocca N, Hudson LD, Rudick R (2017) Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis. Mult Scler 23(5):721–733. https://doi.org/10.1177/1352458517690821

    Article  Google Scholar 

  • Borenstein M, Hedges LV, Higgins JP, Rothstein HR (2011) Introduction to meta-analysis. John Wiley & Sons

  • Brasil (2014) Diretrizes Metodológicas: Sistema GRADE–Manual de Graduação da Qualidade da Evidência e Força de Recomendação Para Tomada de Decisão em Saúde. Ministério da Saúde: Brasília

  • Castro MM, Ferreira RO, Fagundes NC, Almeida APCPSC, Maia LC, Lima RR (2020) Association between Psychological Stress and Periodontitis: A Systematic Review. Eur J Dent 14(1):171–179. https://doi.org/10.1055/s-0039-1693507

    Article  Google Scholar 

  • Chen F, Zhou CC, Yang Y, Liu JW, Yan CH (2019) GM1 Ameliorates Pb-Induced Cognitive Deficits and Brain Damage Through Activating the SIRT1/CREB/BDNF Pathway in the Developing Male Rat Hippocampus. Biol Trace Elem Res 190(2):425–436. https://doi.org/10.1007/s12011-018-1569-6

    Article  CAS  Google Scholar 

  • CDC (2012) Fourth national report on human exposure to environmental chemicals: updated tables. Atlanta, GA: Department of Health and Human Services

  • Cordeiro R, Lima FE, Salgado P, Santos C, Constantino L, Malatesta M (1996a) Neurological disorders in workers with low levels of Pb in the blood. II--Neuropsychological disorders. Rev Saude Publica 30(4):358-363. https://doi.org/10.1590/s0034-89101996000400009

  • Cordeiro R, Lima Filho EC, Salgado PE (1996b) Neurological disturbances in workers with low levels of Pb in the blood. I: Peripheral neuropathy. Rev Saude Publica 30(3):248-255. https://doi.org/10.1590/s0034-89101996000300007

  • de Oliveira Ferreira R, de Brito Silva R, Magno MB, Carvalho Almeida APCPS, Fagundes NCF, Maia LC, Lima RR (2019) Does periodontitis represent a risk factor for rheumatoid arthritis? A systematic review and meta-analysis. Therapeutic Adv Musculoskelet Dis 11:1759720X19858514

  • Flora G, Gupta D, Tiwari A (2012) Toxicity of Pb: a review with recent updates. Interdiscip Toxicol 5: 47-58. https://doi.org/10.2478/v10102-012-0009-2

  • Fowkes F, Fulton P (1991) Critical appraisal of published research: introductory guidelines. BMJ (Clinical research ed.) 302(6785): 1136–1140. https://doi.org/10.1136/bmj.302.6785.1136

  • Gomes WR, Devóz PP, Luiz BLC, Grotto D, Batista BL, Barbosa Jr F, Barcelos GRM (2018) Polymorphisms of genes related to metabolism of Pb are associated with the metal body burden and with biomarkers of oxidative stress. Mutat Res Genet Toxicol Environ Mutagen 836: 42-46. https://doi.org/10.1016/j.mrgentox.2018.05.016

  • Higgins JP (2011) Cochrane handbook for systematic reviews of interventions Version 5.1. 0 [updated March 2011]: The Cochrane Collaboration

  • Jeyaratnam J, Devathasan G, Ong C, Phoon W, Wong P (1985) Neurophysiological studies on workers exposed to Pb. Occup Environ Med 42: 173-177. https://doi.org/10.1136/oem.42.3.173

  • Jeyaratnam J, Boey K, Ong C, Chia C, Phoon W (1986) Neuropsychological studies on Pb workers in Singapore. Occup Environ Med 43: 626-629. https://doi.org/10.1136/oem.43.9.626

  • Kabir MT, Uddin MS, Zaman S, Begum Y, Ashraf GM, Bin-Jumah MN, Bungau SG, Mousa SA, Abdel-Daim MM (2021) Molecular Mechanisms of Metal Toxicity in the Pathogenesis of Alzheimer's Disease. Mol Neurobiol 58(1):1-20. https://doi.org/10.1007/s12035-020-02096-w

  • Kasten-Jolly J, Lawrence DA (2018) The cationic (calcium and Pb) and enzyme conundrum. J Toxicol Environ Health B Crit Rev 21(6-8):400-413. https://doi.org/10.1080/10937404.2019.1592728.

  • Khalil N, Morrow LA, Needleman H, Talbott EO, Wilson JW, Cauley JA (2009) Association of cumulative Pb and neurocognitive function in an occupational cohort. Neuropsychology 23(1):10-19. https://doi.org/10.1037/a0013757

  • Langdon D, Amato M, Boringa J, Brochet B, Foley F, Fredrikson S, Hämäläinen P, Hartung H, Krupp L, Penner I (2012) Recommendations for a brief international cognitive assessment for multiple sclerosis (BICAMS). Mult Scler 18: 891-898. https://doi.org/10.1177/1352458511431076

  • Lessler MA (1988) Lead and Lead Poisoning from Antiquity to Modern Times. Ohio J. Science

  • Li N, Qiao M, Zhao Q, Zhang P, Song L, Li L, Cui C (2016) Effects of maternal Pb exposure on RGMa and RGMb expression in the hippocampus and cerebral cortex of mouse pups. Brain Res Bull 127:38-46. https://doi.org/10.1016/j.brainresbull.2016.08.010

  • Liu KS, Hao JH, Zeng Y, Dai FC, Gu PQ (2013) Neurotoxicity and biomarkers of lead exposure: a review. Chin Med Sci J 28(3):178-188. https://doi.org/10.1016/s1001-9294(13)60045-0

  • Maloney B, Bayon BL, Zawia NH, Lahiri DK (2018) Latent consequences of early-life Pb (Pb) exposure and the future: Addressing the Pb crisis. NeuroToxicology 68: 126-132. https://doi.org/10.1016/j.neuro.2018.06.016

  • Mitra P, Sharma S, Purohit P, Sharma P (2017) Clinical and molecular aspects of Pb toxicity: An update. Crit Rev Clin Lab Sci 54(7-8):506-528. https://doi.org/10.1080/10408363.2017.1408562

  • Moher D, Liberati A, Tetzlaff J, Altman DG (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8(5):336-341. https://doi.org/10.1016/j.ijsu.2010.02.007

  • Moreira FR, Moreira JC (2004) A cinética do chumbo no organismo humano e sua importância para a saúde. Ciência & Saúde Coletiva 9: 167-181

    Article  Google Scholar 

  • Murata K, Araki S, Yokoyama K, Nomiyama K, Nomiyama H, Tao YX, Liu SJ (1995) Autonomic and central nervous system effects of Pb in female glass workers in China. Am J Ind Med 28(2):233-244. https://doi.org/10.1002/ajim.4700280208

  • Narayanan SE, Rehuman NA, Harilal S, Vincent A, Rajamma RG, Behl T, Uddin MS, Ashraf GM, Mathew B (2020) Molecular mechanism of zinc neurotoxicity in Alzheimer's disease. Environ Sci Pollut Res Int 27(35): 43542-43552. https://doi.org/10.1007/s11356-020-10477-w

  • Nascimento PC, Castro MML, Magno MB, Almeida APCPSC, Fagundes NCF, Maia LC, Lima RR (2019) Association between periodontitis and cognitive impairment in adults: a systematic review. Front Neurol 10:323. https://doi.org/10.3389/fneur.2019.00323

  • Navas-Acien A, Guallar E, Silbergeld EK, Rothenberg SJ (2007): Pb exposure and cardiovascular disease—a systematic review. Environ Health Perspect 115(3):472-482. https://doi.org/10.1289/ehp.9785

  • Oğuz EF, Yilmaz FM, Tutkun E, Yilmaz ÖH, Ercan M, Sezer S (2018) Serum S100B, NSE, and GRIA1 levels as neurological biomarkers in Pb exposure. Turk J Med Sci 48: 449-454. https://doi.org/10.3906/sag-1511-174

  • Patrick L (2006) Pb toxicity, a review of the literature. Part I: Exposure, evaluation, and treatment. Altern Med Rev 11(1): 2-22.

  • Puty B, Leão LKR, Crespo-Lopez ME, Carvalho APCPS, Fagundes NCF, Maia LC, Lima RR (2019) Association between methylmercury environmental exposure and neurological disorders: A systematic review. J Trace Elem Med Biol 52:100-110. https://doi.org/10.1016/j.jtemb.2018.12.001

  • Schifer TDS, Junior SB, Montano MAE (2005) Aspectos toxicológicos do chumbo. Infarma 17(5-6): 67-71.

  • Schwartz BS, Bolla KI, Stewart W, Ford DP, Agnew J, Frumkin H (1993) Decrements in neurobehavioral performance associated with mixed exposure to organic and inorganic Pb. Am J Epidemiol 137(9):1006-1021. https://doi.org/10.1093/oxfordjournals.aje.a116757

  • Schwartz BS, Stewart W, Bolla KI, Simon D, Bandeen-Roche K, Gordon B, Links JM, Todd A (2000) Past adult Pb exposure is associated with longitudinal decline in cognitive function. Neurology 55: 1144-1150. https://doi.org/10.1212/wnl.55.8.1144

  • Schwartz BS, Lee B-K, Lee G-S, Stewart WF, Lee S-S, Hwang K-Y, Ahn K-D, Kim Y-B, Bolla KI, Simon D (2001) Associations of blood Pb, dimercaptosuccinic acid-chelatable Pb, and tibia Pb with neurobehavioral test scores in South Korean Pb workers. Am J Epidemiol 153(5):453-464. https://doi.org/10.1093/aje/153.5.453

  • Seo J, Lee B-K, Jin S-U, Jang KE, Park JW, Kim Y-T, Park S-J, Jeong KS, Park J, Kim A (2015) Altered executive function in the Pb-exposed brain: A functional magnetic resonance imaging study. Neurotoxicology 50: 1-9. https://doi.org/10.1016/j.neuro.2015.07.002

  • Seppäläinen AM, Hernberg S (1980) Subclinical Pb neuropathy. Am J Ind Med 1: 413-420. https://doi.org/10.1002/ajim.4700010319

  • Tombaugh T, McDowell I, Kristjansson B, Hubley A (1996) Mini-Mental State Examination (MMSE) and the Modified MMSE (3MS): a psychometric comparison and normative data. Psychological Assessment 8(1): 48.

  • Valciukas JA, Lilis R, Eisinger J, Blumberg WE, Fischbein A, Selikoff IJ (1978) Behavioral indicators of Pb neurotoxicity: results of a clinical field survey. Int Arch Occup Environ Health 41(4):217-236. https://doi.org/10.1007/BF00378753

  • Valciukas JA, Lilis R, Singer R, Fischbein A, Anderson HA, Glickman L (1980) Pb exposure and behavioral changes: comparisons of four occupational groups with different levels of Pb absorption. Am J Ind Med 1(3-4):421-426. https://doi.org/10.1002/ajim.4700010320

  • WHO (1986) Diseases caused by Pb and its toxic compounds in early detection of occupation of diseases. World Health Organization (WHO) Geneva: 85-90

  • WHO (1995) Biological indices of Pb exposure and body burden. IPCS. Inorganic Pb, Environmental Health Criteria 165

  • Yi-lan W, Pei-kun L, Zi-qiang C, You-xin L, Qi-ming L, Zhi-qing P, Min S (1985) Effects of occupational Pb exposure. Scandinavian journal of work, environment & health 20-25

  • Yokoyama K, Araki S, Kawakami N, Tkakeshita T (1990) Production of the Japanese edition of profile of mood states (POMS): assessment of reliability and validity. Nihon Koshu Eisei Zasshi 37(11): 913-918

Download references

Acknowledgements

This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) and Pró-Reitoria de Pesquisa e Pós-Graduação da UFPA (PROPESP, UFPA, Brazil).

Code availability

Not applicable

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Código de Financiamento 001. The funder was not involved in the design of the study; data collection, analysis, and interpretation of the data; and the writing of the manuscript.

Author information

Authors and Affiliations

  1. Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, 01 Augusto Correa Street, Guama, Belém, PA, 66075-110, Brazil

    Luciana Guimarães Eiró, Maria Karolina Martins Ferreira, Déborah Ribeiro Frazão, Walessa Alana Bragança Aragão, Renata Duarte Souza-Rodrigues & Rafael Rodrigues Lima

  2. School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

    Nathalia Carolina Fernandes Fagundes

  3. Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Lucianne Cople Maia

Authors
  1. Luciana Guimarães Eiró
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Karolina Martins Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Déborah Ribeiro Frazão
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Walessa Alana Bragança Aragão
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Renata Duarte Souza-Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nathalia Carolina Fernandes Fagundes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lucianne Cople Maia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rafael Rodrigues Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Walessa Alana Bragança Aragão and Déborah Ribeiro Frazão: Methodology, Software; Luciana Guimarães Eiró: Data curation, Writing — Original draft preparation; Maria Karolina Martins Ferreira: Visualization, Investigation; Rafael Rodrigues Lima, Lucianne Cople Maia and Nathalia Carolina Fernandes Fagundes: Supervision; Rafael Rodrigues Lima: Conceptualization; Nathalia Carolina Fernandes Fagundes: Software, Validation; Renata Duarte Souza-Rodrigues, Rafael Rodrigues Lima and Lucianne Cople Maia: Writing — Reviewing and Editing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rafael Rodrigues Lima.

Ethics declarations

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Responsible Editor: Lotfi Aleya

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 26 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Eiró, L.G., Ferreira, M.K.M., Frazão, D.R. et al. Lead exposure and its association with neurological damage: systematic review and meta-analysis. Environ Sci Pollut Res 28, 37001–37015 (2021). https://doi.org/10.1007/s11356-021-13536-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-021-13536-y

Keywords

Search

Navigation