Abstract
Previous studies have shown associations between children’s exposure to phthalates and neurodevelopmental disorders. Whereas the impact of exposure to phthalate alternatives is understudied. This study aimed to evaluate the association of exposure to phthalates/their alternatives with the risk of dyslexia. We recruited 745 children (355 dyslexia and 390 non-dyslexia) via the Tongji Reading Environment and Dyslexia Research Project, and their urine samples were collected. A total of 26 metabolites of phthalates/their alternatives were measured. Multivariate logistic regression and quantile-based g-computation were used to estimate the associations of exposure to the phthalates/their alternatives with dyslexia. More than 80% of the children had 17 related metabolites detected in their urine samples. After adjustment, the association between mono-2-(propyl-6-hydroxy-heptyl) phthalate (OH-MPHP) with the risk of dyslexia was observed. Compared with the lowest quartile of OH-MPHP levels, the odds of dyslexia for the third quartile was 1.93 (95% CI 1.06, 3.57). Regarding mixture analyses, it was found that OH-MPHP contributed the most to the association. Further analyses stratified by sex revealed that this association was only observed in boys. Our results suggested a significantly adverse association of di-2-propylheptyl phthalate exposure with children’s language abilities. It highlights the necessity to prioritize the protection of children’s neurodevelopment by minimizing their exposure to endocrine-disrupting chemicals like di-2-propylheptyl phthalate.
Graphical Abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Benjamin S, Masai E, Kamimura N, Takahashi K, Anderson RC, Faisal PA (2017) Phthalates impact human health: epidemiological evidences and plausible mechanism of action. J Hazard Mater 340:360–383. https://doi.org/10.1016/j.jhazmat.2017.06.036
Bennett DH, Busgang SA, Kannan K, Parsons PJ, Takazawa M, Palmer CD et al (2022) Environmental exposures to pesticides, phthalates, phenols and trace elements are associated with neurodevelopment in the CHARGE study. Environ Int 161:107075. https://doi.org/10.1016/j.envint.2021.107075
Bhat VS, Durham JL, English JC (2014) Derivation of an oral reference dose (RfD) for the plasticizer, di-(2-propylheptyl)phthalate (Palatinol® 10-P). Regul Toxicol Pharmacol 70:65–74. https://doi.org/10.1016/j.yrtph.2014.06.002
Bornehag CG, Lindh C, Reichenberg A, Wikström S, Unenge Hallerback M, Evans SF et al (2018) Association of prenatal phthalate exposure with language development in early childhood. JAMA Pediatr 172:1169–1176. https://doi.org/10.1001/jamapediatrics.2018.3115
Choi J, Knudsen LE, Mizrak S, Joas A (2017) Identification of exposure to environmental chemicals in children and older adults using human biomonitoring data sorted by age: results from a literature review. Int J Hyg Environ Health 220:282–298. https://doi.org/10.1016/j.ijheh.2016.12.006
Chopra V, Harley K, Lahiff M, Eskenazi B (2014) Association between phthalates and attention deficit disorder and learning disability in U.S. children, 6–15 years. Environ Res 128:64–9. https://doi.org/10.1016/j.envres.2013.10.004
Doust C, Fontanillas P, Eising E, Gordon SD, Wang Z, Alagöz G et al (2022) Discovery of 42 genome-wide significant loci associated with dyslexia. Nat Genet 54:1621–1629. https://doi.org/10.1038/s41588-022-01192-y
Eales J, Bethel A, Galloway T, Hopkinson P, Morrissey K, Short RE et al (2022) Human health impacts of exposure to phthalate plasticizers: an overview of reviews. Environ Int 158:106903. https://doi.org/10.1016/j.envint.2021.106903
Engel SM, Wolff MS (2013) Causal inference considerations for endocrine disruptor research in children’s health. Annu Rev Public Health 34:139–158. https://doi.org/10.1146/annurev-publhealth-031811-124556
Ghassabian A, Vandenberg L, Kannan K, Trasande L (2022) Endocrine-disrupting chemicals and child health. Annu Rev Pharmacol Toxicol 62:573–594. https://doi.org/10.1146/annurev-pharmtox-021921-093352
He Z, Shao S, Zhou J, Ke J, Kong R, Guo S et al (2014) Does long time spending on the electronic devices affect the reading abilities? A cross-sectional study among Chinese school-aged children. Res Dev Disabil 35:3645–3654. https://doi.org/10.1016/j.ridd.2014.08.037
Huang PC, Tsai CH, Chen CC, Wu MT, Chen ML, Wang SL et al (2017) Intellectual evaluation of children exposed to phthalate-tainted products after the 2011 Taiwan phthalate episode. Environ Res 156:158–166. https://doi.org/10.1016/j.envres.2017.03.016
Itoh S, Yamazaki K, Suyama S, Ikeda-Araki A, Miyashita C, Ait Bamai Y et al (2022) The association between prenatal perfluoroalkyl substance exposure and symptoms of attention-deficit/hyperactivity disorder in 8-year-old children and the mediating role of thyroid hormones in the Hokkaido study. Environ Int 159:107026. https://doi.org/10.1016/j.envint.2021.107026
Johns LE, Cooper GS, Galizia A, Meeker JD (2015) Exposure assessment issues in epidemiology studies of phthalates. Environ Int 85:27–39. https://doi.org/10.1016/j.envint.2015.08.005
Kang JS, Baek JH, Song MY, Rehman NU, Chung HJ, Lee DK et al (2023) Long-term exposure changes the environmentally relevant bis(2-ethylhexyl) phthalate to be a neuro-hazardous substance disrupting neural homeostasis in emotional and cognitive functions. Environ Pollut 324:121387. https://doi.org/10.1016/j.envpol.2023.121387
Kiess W, Häussler G, Vogel M (2021) Endocrine-disrupting chemicals and child health. Best Pract Res Clin Endocrinol Metab 35:101516. https://doi.org/10.1016/j.beem.2021.101516
Kim JI, Lee J, Lee KS, Lee YA, Shin CH, Hong YC et al (2021) Association of phthalate exposure with autistic traits in children. Environ Int 157:106775. https://doi.org/10.1016/j.envint.2021.106775
Klein D, Kessler W, Pütz C, Semder B, Kirchinger W, Langsch A et al (2018) Single ingestion of di-(2-propylheptyl) phthalate (DPHP) by male volunteers: DPHP in blood and its metabolites in blood and urine. Toxicol Lett 294:105–115. https://doi.org/10.1016/j.toxlet.2018.05.010
Liu L, Wang J, Shao S, Luo X, Kong R, Zhang X et al (2016) Descriptive epidemiology of prenatal and perinatal risk factors in a Chinese population with reading disorder. Sci Rep 6:36697. https://doi.org/10.1038/srep36697
Liu Q, Wan Y, Zhu B, Xie X, Zhu K, Jiang Q et al (2022) Association between urinary propylene oxide metabolite and the risk of dyslexia. Environ Pollut 292:118469. https://doi.org/10.1016/j.envpol.2021.118469
Liu Y, Guo Z, Zhu R, Gou D, Jia PP, Pei DS (2023) An insight into sex-specific neurotoxicity and molecular mechanisms of DEHP: a critical review. Environ Pollut (Barking, Essex: 1987) 316:120673. https://doi.org/10.1016/j.envpol.2022.120673
Loftus CT, Bush NR, Day DB, Ni Y, Tylavsky FA, Karr CJ et al (2021) Exposure to prenatal phthalate mixtures and neurodevelopment in the Conditions Affecting Neurocognitive Development and Learning in Early childhood (CANDLE) study. Environ Int 150:106409. https://doi.org/10.1016/j.envint.2021.106409
Nayebare SR, Karthikraj R, Kannan K (2018) Analysis of terephthalate metabolites in human urine by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). J Chromatogr B Analyt Technol Biomed Life Sci 1092:473–479. https://doi.org/10.1016/j.jchromb.2018.06.044
Odebeatu CC, Taylor T, Fleming LE, Osborne NJ (2019) Phthalates and asthma in children and adults: US NHANES 2007–2012. Environ Sci Pollut Res Int 26:28256–28269. https://doi.org/10.1007/s11356-019-06003-2
Olesen TS, Bleses D, Andersen HR, Grandjean P, Frederiksen H, Trecca F et al (2018) Prenatal phthalate exposure and language development in toddlers from the Odense Child Cohort. Neurotoxicol Teratol 65:34–41. https://doi.org/10.1016/j.ntt.2017.11.004
Pacyga DC, Patti MA, Papandonatos GD, Haggerty DK, Calafat AM, Gardiner JC et al (2023) Associations of individual and cumulative urinary phthalate and replacement biomarkers with gestational weight gain through late pregnancy. Sci Total Environ 855:158788. https://doi.org/10.1016/j.scitotenv.2022.158788
Park S, Zimmerman E, Huerta-Montanez G, Rosario-Pabon Z, Velez-Vega CM, Cordero JF et al (2023) Gestational exposure to phthalates and phthalate replacements in relation to neurodevelopmental delays in early childhood. Toxics 11:ARTN 65. https://doi.org/10.3390/toxics11010065
Perazzo D, Moore R, Kasparian NA, Rodts M, Horowitz-Kraus T, Crosby L et al (2022) Chronic pediatric diseases and risk for reading difficulties: a narrative review with recommendations. Pediatr Res 92:966–978. https://doi.org/10.1038/s41390-022-01934-y
Peterson RL, Pennington BF (2012) Developmental dyslexia. Lancet 379:1997–2007. https://doi.org/10.1016/s0140-6736(12)60198-6
Peterson RL, Pennington BF (2015) Developmental dyslexia. Annu Rev Clin Psychol 11:283–307. https://doi.org/10.1146/annurev-clinpsy-032814-112842
Philippat C, Rolland M, Lyon-Caen S, Pin I, Sakhi AK, Sabaredzovic A et al (2021) Pre- and early post-natal exposure to phthalates and DINCH in a new type of mother-child cohort relying on within-subject pools of repeated urine samples. Environ Pollut (Barking, Essex: 1987) 287:117650. https://doi.org/10.1016/j.envpol.2021.117650
Preece AS, Knutz M, Lindh CH, Bornehag CG, Shu H (2022) Prenatal phthalate exposure and early childhood wheeze in the SELMA study. J Expo Sci Environ Epidemiol 32:303–311. https://doi.org/10.1038/s41370-021-00382-w
Qian X, Li JF, Xu SQ, Wan YJ, Li YY, Jiang YQ et al (2019) Prenatal exposure to phthalates and neurocognitive development in children at two years of age. Environ Int 131:ARTN 105023. https://doi.org/10.1016/j.envint.2019.105023
Radke EG, Braun JM, Nachman RM, Cooper GS (2020) Phthalate exposure and neurodevelopment: a systematic review and meta-analysis of human epidemiological evidence. Environ Int 137:105408. https://doi.org/10.1016/j.envint.2019.105408
Ramos AM, Herring AH, Villanger GD, Thomsen C, Sakhi AK, Cequier E et al (2023) The association of prenatal phthalates, organophosphate pesticides, and organophosphate esters with early child language ability in Norway. Environ Res 115508. https://doi.org/10.1016/j.envres.2023.115508
Saad N et al (2021) Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) alters transcriptional profiles, lipid metabolism and behavior in zebrafish larvae. Heliyon 7:e07951. https://doi.org/10.1016/j.heliyon.2021.e07951
Safarpour S, Ghasemi-Kasman M, Safarpour S, Darban YM (2022) Effects of di-2-ethylhexyl phthalate on central nervous system functions: a narrative review. Curr Neuropharmacol 20:766–776. https://doi.org/10.2174/1570159x19666210713122517
Schaffert A, Karkossa I, Ueberham E, Schlichting R, Walter K, Arnold J et al (2022) Di-(2-ethylhexyl) phthalate substitutes accelerate human adipogenesis through PPARγ activation and cause oxidative stress and impaired metabolic homeostasis in mature adipocytes. Environ Int 164:107279. https://doi.org/10.1016/j.envint.2022.107279
Schildroth S, Valeri L, Kordas K, Shi B, Friedman A, Smith D et al (2024) Assessing the mediating role of iron status on associations between an industry-relevant metal mixture and verbal learning and memory in Italian adolescents. Sci Total Environ 906:167435. https://doi.org/10.1016/j.scitotenv.2023.167435
Schmidtkunz C, Gries W, Weber T, Leng G, Kolossa-Gehring M (2019) Internal exposure of young German adults to di(2-propylheptyl) phthalate (DPHP): trends in 24-h urine samples from the German Environmental Specimen Bank 1999–2017. Int J Hyg Environ Health 222:419–424. https://doi.org/10.1016/j.ijheh.2018.12.008
Schwedler G, Conrad A, Rucic E, Koch HM, Leng G, Schulz C et al (2020) Hexamoll® DINCH and DPHP metabolites in urine of children and adolescents in Germany. Human biomonitoring results of the German Environmental Survey GerES V, 2014–2017. Int J Hyg Environ Health 229:113397. https://doi.org/10.1016/j.ijheh.2019.09.004
Shin HM, Dhar U, Calafat AM, Nguyen V, Schmidt RJ, Hertz-Picciotto I (2020) Temporal trends of exposure to phthalates and phthalate alternatives in California pregnant women during 2007–2013: comparison with other populations. Environ Sci Technol 54:13157–13166. https://doi.org/10.1021/acs.est.0c03857
Shoaff JR, Calafat AM, Schantz SL, Korrick SA (2019) Endocrine disrupting chemical exposure and maladaptive behavior during adolescence. Environ Res 172:231–241. https://doi.org/10.1016/j.envres.2018.12.053
Sjöström Y, Hagström K, Lindh C, Bryngelsson IL, Larsson M, Hagberg J (2023) Exposure to phthalates and DiNCH among preschool children in Sweden: urinary metabolite concentrations and predictors of exposure. Int J Hyg Environ Health 250:114161. https://doi.org/10.1016/j.ijheh.2023.114161
Smith CA, Farmer K, Lee H, Holahan MR, Smith JC (2015) Altered hippocampal lipid profile following acute postnatal exposure to di(2-ethylhexyl) phthalate in rats. Int J Environ Res Public Health 12:13542–13559. https://doi.org/10.3390/ijerph121013542
Stuchlík Fišerová P, Melymuk L, Komprdová K, Domínguez-Romero E, Scheringer M, Kohoutek J et al (2022) Personal care product use and lifestyle affect phthalate and DINCH metabolite levels in teenagers and young adults. Environ Res 213:113675. https://doi.org/10.1016/j.envres.2022.113675
Textor J, van der Zander B, Gilthorpe MS, Liskiewicz M, Ellison GT (2016) Robust causal inference using directed acyclic graphs: the R package ‘dagitty.’ Int J Epidemiol 45:1887–1894. https://doi.org/10.1093/ije/dyw341
Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR Jr, Lee DH et al (2012) Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev 33:378–455. https://doi.org/10.1210/er.2011-1050
Wu H, Kupsco AJ, Deierlein AL, Just AC, Calafat AM, Oken E et al (2020) Trends and patterns of phthalates and phthalate alternatives exposure in pregnant women from Mexico city during 2007–2010. Environ Sci Technol 54:1740–1749. https://doi.org/10.1021/acs.est.9b05836
Xie X, Wan Y, Zhu B, Liu Q, Zhu K, Jiang Q et al (2022) Association between urinary dialkylphosphate metabolites and dyslexia among children from three cities of China: the READ program. Sci Total Environ 814:151852. https://doi.org/10.1016/j.scitotenv.2021.151852
Xu S, Zhang H, Pao PC, Lee A, Wang J, Suen Chan Y et al (2020) Exposure to phthalates impaired neurodevelopment through estrogenic effects and induced DNA damage in neurons. Aquat Toxicol 222:105469. https://doi.org/10.1016/j.aquatox.2020.105469
Xu Y, Jang J, Gye MC (2022) The Xenopus laevis teratogenesis assay for developmental toxicity of phthalate plasticizers and alternatives. Environ Pollut 300:118985. https://doi.org/10.1016/j.envpol.2022.118985
Xue Q, Zhou Y, Gu H, Xie X, Hou F, Liu Q et al (2020) Urine metals concentrations and dyslexia among children in China. Environ Int 139:105707. https://doi.org/10.1016/j.envint.2020.105707
Yang L, Li C, Li X, Zhai M, An Q, Zhang Y et al (2022) Prevalence of developmental dyslexia in primary school children: a systematic review and meta-analysis. Brain Sci 12. https://doi.org/10.3390/brainsci12020240
Ye BS, Leung AOW, Wong MH (2017) The association of environmental toxicants and autism spectrum disorders in children. Environ Pollut 227:234–242. https://doi.org/10.1016/j.envpol.2017.04.039
Zhang YJ, Wu LH, Wang F, Liu LY, Zeng EY, Guo Y (2021) DNA oxidative damage in pregnant women upon exposure to conventional and alternative phthalates. Environ Int 156:106743. https://doi.org/10.1016/j.envint.2021.106743
Zhu K, Wan Y, Zhu B, Wang H, Liu Q, Xie X et al (2023) Association of perchlorate, thiocyanate, and nitrate with dyslexic risk. Chemosphere 325:138349. https://doi.org/10.1016/j.chemosphere.2023.138349
Acknowledgements
The authors would like to thank participants involved in the READ research program.
Funding
The research was supported by the National Key R&D Program of China (2022YFA0806601), the National Natural Science Foundation of China (grant numbers 82173540, 21407117, and 82304170), and the Science and Technology Plan of Shenzhen (JCYJ20190807103409848).
Author information
Authors and Affiliations
Contributions
Qi Jiang: formal analysis, investigation, writing – original draft. Yanjian Wan: conceptualization, resources, methodology, writing – review and editing. Haoxue Wang: conceptualization, investigation, supervision. KaihengZhu: investigation, writing – review and editing. Yanan Feng: methodology, investigation. Zhen Xiang: methodology, formal analysis. Ruidong Liu: methodology. Shuai Zhao: conceptualization, supervision, writing – review and editing. Ying Zhu: formal analysis, Investigation. Ranran Song: conceptualization, supervision, data curation, writing – review and editing.
Corresponding author
Ethics declarations
Ethics approval
The study protocol was agreed upon by the institution of Medical Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology.
Consent to participate
Informed consent was obtained from all respondents.
Consent for publication
The authors consent to publish this research.
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.
Qi Jiang and Yanjian Wan are co-first authors.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Jiang, Q., Wan, Y., Zhu, K. et al. Association of exposure to phthalates and phthalate alternatives with dyslexia in Chinese primary school children. Environ Sci Pollut Res 31, 28392–28403 (2024). https://doi.org/10.1007/s11356-024-32871-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-024-32871-4