{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:30:25Z","timestamp":1791563425899,"version":"4.3.4"},"reference-count":67,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Tire\u2010derived microplastics (TWPs) are now recognized as one of the largest and most persistent sources of environmental micro\u2010 and nanoplastic pollution, yet their implications for human health remain incompletely characterized. TWPs contain complex mixtures of synthetic polymers, metals, polycyclic aromatic hydrocarbons, plasticizers, antioxidants, and transformation products such as 6PPD\u2010quinone. These constituents exhibit chemical reactivity and biological activity relevant to oxidative stress, endothelial injury, inflammation, immune perturbation, and metabolic disruption\u2014processes increasingly linked to chronic disease and components of the inflammothrombotic immunologic response (ITIR). Despite widespread environmental distribution across air, water, soil, and food systems, TWPs remain underexamined within the broader environmental exposome framework. This review synthesizes environmental, toxicologic, and mechanistic evidence on TWPs, integrating data from atmospheric studies, stormwater and sediment analyses, chemical characterization, in\u00a0vitro and in\u00a0vivo models, and emerging microplastic health research. Particular emphasis is placed on oxidative and redox\u2010active constituents, endothelial and vascular responses, immune activation, metabolic effects, and the toxicologic relevance of 6PPD\u2010quinone. Environmental gradients in TWP exposure\u2014especially in high\u2010traffic urban settings\u2014are examined in relation to environmental justice and cumulative risk. Collectively, the evidence indicates that TWPs function as biologically active environmental contaminants capable of engaging multiple mechanistic pathways associated with inflammation, vascular dysfunction, and systemic stress responses. Their ubiquity, persistence, and mechanistic plausibility underscore the need for expanded monitoring, improved analytical methods, and targeted toxicologic and epidemiologic research. TWPs are presented as contributors to sustained ITIR activation, which may increase susceptibility to cardiometabolic and vascular disease. ITIR is increasingly recognized as an established mechanistic framework supported by multiple experimental, clinical, and environmental studies. While definitive causal relationships between TWPs and human disease remain under investigation, the mechanistic plausibility is strong.<\/jats:p>","DOI":"10.1002\/jat.70430","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:28:17Z","timestamp":1789118897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tire\u2010Derived Microplastics as Chemically Complex Environmental Contaminants: Mechanistic Pathways, Exposure Gradients, and Implications for Environmental Health"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9964-1518","authenticated-orcid":false,"given":"Richard M.","family":"Fleming","sequence":"first","affiliation":[{"name":"FMTVDM FRONTIER  Pearland\u2010Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9974-0468","authenticated-orcid":false,"given":"Matthew R.","family":"Fleming","sequence":"additional","affiliation":[{"name":"FMTVDM FRONTIER  Pearland\u2010Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_2_20_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/23748834.2021.1979774"},{"key":"e_1_2_20_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10661\u2010022\u201010021\u20107"},{"key":"e_1_2_20_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s44197\u2010026\u201000609\u20109"},{"key":"e_1_2_20_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2021.126124"},{"key":"e_1_2_20_6_1","volume-title":"Environmental Disaster: World's Biggest Tire Graveyard in Kuwait","author":"Anadolu Agency","year":"2021"},{"key":"e_1_2_20_7_1","doi-asserted-by":"publisher","DOI":"10.30574\/wjarr.2024.21.2.0519"},{"key":"e_1_2_20_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2020.137823"},{"key":"e_1_2_20_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e3181dbece1"},{"key":"e_1_2_20_10_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.7074"},{"key":"e_1_2_20_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/microplastics5020076"},{"key":"e_1_2_20_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2023.131245"},{"key":"e_1_2_20_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.marpolbul.2016.01.006"},{"issue":"12","key":"e_1_2_20_14_1","first-page":"818","article-title":"Air Particulate Matter and Cardiovascular Disease: The Epidemiologic, Biomedical and Clinical Evidence","volume":"29","author":"Du Y.","year":"2016","journal-title":"Biomedical and Environmental Sciences"},{"key":"e_1_2_20_15_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.20237"},{"key":"e_1_2_20_16_1","unstructured":"Fleming R.M andM.R.Fleming.2026. \u201cThe Inflammo Thrombotic Immunologic Response (ITIR): A Unified Mechanism Linking Chronic Disease Immunothrombosis and COVID\u201019 Severity.\u201dhttps:\/\/doi.org\/10.5281\/zenodo.19744072. 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