{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:15:41Z","timestamp":1768569341151,"version":"3.49.0"},"posted":{"date-parts":[[2025,9,22]]},"group-title":"Health Informatics","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Building on evidence linking urinary glyphosate to chronic liver disease (CLD) and hepatocellular carcinoma (HCC), we developed urinary pesticide profiling integrated with machine learning risk prediction (MLRP) to stratify risk in high-exposure populations.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a case\u2013control study within the Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC; 2011\u20132016; n=593): 228 CLD, 116 HCC, and 249 controls. Eight urinary pesticides were quantified by LC\u2013MS\/MS (pendimethalin, oxadiazon, metsulfuron-methyl, butachlor, 2,4-dichlorophenoxyacetic acid [2,4-D], cypermethrin, flocoumafen, bromadiolone). A composite Pesticide Load Score (PLS), with and without glyphosate, estimated burden. Two predictive models were developed: a logistic-regression Pesticide-Informed Liver Cancer Risk Score (PILCRS) and an Extreme Gradient Boosting (XGBoost) classifier that incorporated age, sex, alcohol use, occupation, and PLS. Internal validity used 1,000 bootstrap resamples with optimism-corrected calibration.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>Predicted CLD probability increased from 30% in the lowest PLS quartile to over 70% in the highest, and HCC from 10% to 40% (p&lt;0\ua78f0001). Relative estimates were consistent; the highest versus lowest quartile yielded odds ratios of 2\ua78f84 (95% CI 1\ua78f66\u20134\ua78f91) for CLD and 4\ua78f76 (2\ua78f30\u2013 10\ua78f29) for HCC. Cypermethrin remained independently associated. After optimism correction, both models demonstrated strong discrimination and calibration.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>This framework establishes a scalable, exposure-informed tool for liver disease prediction. Findings underscore pesticide burden as a modifiable risk factor and align with Sustainable Development Goal 3\ua78f9 and WHO\u2013FAO priorities in low- and middle-income countries (LMICs). External validation is essential.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>National Institutes of Health (USA); Thailand Science Research and Innovation.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.09.19.25336162","type":"posted-content","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:30:29Z","timestamp":1758587429000},"source":"Crossref","is-referenced-by-count":0,"title":["Urinary pesticide profiles and liver disease risk in Thailand: a machine-learning risk-prediction model"],"prefix":"10.64898","author":[{"given":"Daxesh P.","family":"Patel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A.","family":"Loffredo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majda","family":"Haznadar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amelia L.","family":"Parker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjarath","family":"Pupacdi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siritida","family":"Rabibhadana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panida","family":"Navasumrit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nirush","family":"Lertprasertsuke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anon","family":"Chotirosniramit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chawalit","family":"Pairojkul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vor","family":"Luvira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ake","family":"Pugkhem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wattana","family":"Sukeepaisarnjaroen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teerapat","family":"Ungtrakul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thaniya","family":"Sricharunrat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kannika","family":"Phornphutkul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank J.","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anuradha","family":"Budhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chulabhorn","family":"Mahidol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin W.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathuros","family":"Ruchirawat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Curtis C.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"TIGER-LC Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025092412201430000_2025.09.19.25336162v1.1","unstructured":"Organization WH. Report of the 17th FAO\/WHO Joint Meeting on Pesticide Management; 2024."},{"issue":"5","key":"2025092412201430000_2025.09.19.25336162v1.2","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1002\/ijc.34300","article-title":"Exposures to pesticides and risk of cancer: Evaluation of recent epidemiological evidence in humans and paths forward","volume":"152","year":"2023","journal-title":"Int J Cancer"},{"key":"2025092412201430000_2025.09.19.25336162v1.3","unstructured":"(IARC) IAfRoC. Agents Classified by the IARC Monographs, Volumes 1\u2013125. 2019 https:\/\/monographs.iarc.who.int\/agents-classified-by-the-iarc\/ (accessed July 18 2025)."},{"key":"2025092412201430000_2025.09.19.25336162v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32345-0"},{"key":"2025092412201430000_2025.09.19.25336162v1.5","unstructured":"Nations U. Goal 3: Ensure healthy lives and promote well-being for all at all ages. 2015. https:\/\/sdgs.un.org\/goals\/goal3 (accessed Jukly 18 2025)."},{"key":"2025092412201430000_2025.09.19.25336162v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2015.12.017"},{"issue":"1","key":"2025092412201430000_2025.09.19.25336162v1.7","doi-asserted-by":"crossref","first-page":"17139","DOI":"10.1038\/s41598-018-35484-3","article-title":"Pendimethalin-induced oxidative stress, DNA damage and activation of anti-inflammatory and apoptotic markers in male rats.","volume":"8","year":"2018","journal-title":"Sci Rep"},{"key":"2025092412201430000_2025.09.19.25336162v1.8","doi-asserted-by":"crossref","unstructured":"Taha MAI , Badawy MEI , Abdel-Razik RK , Younis HM , Abo-El-Saad MM . Mitochondrial dysfunction and oxidative stress in liver of male albino rats after exposing to sub-chronic intoxication of chlorpyrifos, cypermethrin, and imidacloprid. Pestic Biochem Physiol 2021; 178: 104938.","DOI":"10.1016\/j.pestbp.2021.104938"},{"issue":"10","key":"2025092412201430000_2025.09.19.25336162v1.9","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1002\/ijc.35282","article-title":"Associations of chronic liver disease and liver cancer with glyphosate and its metabolites in Thailand","volume":"156","year":"2025","journal-title":"Int J Cancer"},{"issue":"1","key":"2025092412201430000_2025.09.19.25336162v1.10","doi-asserted-by":"crossref","first-page":"11439","DOI":"10.1038\/s41598-022-15800-8","article-title":"Investigation of cypermethrin toxicity in Swiss albino mice with physiological, genetic and biochemical approaches","volume":"12","year":"2022","journal-title":"Sci Rep"},{"key":"2025092412201430000_2025.09.19.25336162v1.11","doi-asserted-by":"crossref","unstructured":"Martins RX , Carvalho M , Maia ME , et al. 2,4-D Herbicide-Induced Hepatotoxicity: Unveiling Disrupted Liver Functions and Associated Biomarkers. Toxics 2024; 12(1).","DOI":"10.3390\/toxics12010035"},{"issue":"3","key":"2025092412201430000_2025.09.19.25336162v1.12","first-page":"177","article-title":"Pesticide exposure and liver cancer: a review","volume":"28","year":"2017","journal-title":"Cancer Causes Control"},{"key":"2025092412201430000_2025.09.19.25336162v1.13","unstructured":"Agency USEP . Cypermethrin; Pesticide Tolerances. Federal Register; 2025."},{"issue":"8","key":"2025092412201430000_2025.09.19.25336162v1.14","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/ijc.35034","article-title":"The landscape of etiological patterns of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in Thailand","volume":"155","year":"2024","journal-title":"Int J Cancer"},{"issue":"2","key":"2025092412201430000_2025.09.19.25336162v1.15","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s11010-021-04303-1","article-title":"Evaluating the effects of anticoagulant rodenticide bromadiolone in Wistar rats co-exposed to vitamin K: impact on blood-liver axis and brain oxidative status","volume":"477","year":"2022","journal-title":"Mol Cell Biochem"},{"key":"2025092412201430000_2025.09.19.25336162v1.16","doi-asserted-by":"crossref","unstructured":"Yang B , Liu Y , Li Y , et al. Exposure to the herbicide butachlor activates hepatic stress signals and disturbs lipid metabolism in mice. Chemosphere 2021; 283: 131226.","DOI":"10.1016\/j.chemosphere.2021.131226"},{"issue":"7","key":"2025092412201430000_2025.09.19.25336162v1.17","first-page":"2034","article-title":"In Silico Analysis to Identify Molecular Targets for Chemicals of Concern: The Case Study of Flocoumafen, an Anticoagulant Pesticide","volume":"40","year":"2021","journal-title":"Environ Toxicol Chem"},{"issue":"1","key":"2025092412201430000_2025.09.19.25336162v1.18","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12940-018-0421-y","article-title":"Safety of Safety Evaluation of Pesticides: developmental neurotoxicity of chlorpyrifos and chlorpyrifos-methyl","volume":"17","year":"2018","journal-title":"Environ Health"},{"key":"2025092412201430000_2025.09.19.25336162v1.19","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.ecoenv.2015.08.022","article-title":"Histopathological and ultramicroscopical changes in gill, liver and kidney of Anabas testudineus (Bloch) after chronic intoxication of almix (metsulfuron methyl 10.1%+chlorimuron ethyl 10.1%) herbicide","volume":"122","year":"2015","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025092412201430000_2025.09.19.25336162v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.envsci.2011.12.005"},{"issue":"1","key":"2025092412201430000_2025.09.19.25336162v1.21","doi-asserted-by":"crossref","first-page":"12663","DOI":"10.1038\/s41598-024-63453-6","article-title":"Impact of metabolic phenotype and alcohol consumption on mortality risk in metabolic dysfunction-associated fatty liver disease: a population-based cohort study","volume":"14","year":"2024","journal-title":"Sci Rep"},{"issue":"5","key":"2025092412201430000_2025.09.19.25336162v1.22","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1080\/10807039.2020.1808777","article-title":"Pesticide use in Thailand: Current situation, health risks, and gaps in research and policy","volume":"27","year":"2021","journal-title":"Hum Ecol Risk Assess"},{"key":"2025092412201430000_2025.09.19.25336162v1.23","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.0901388"},{"key":"2025092412201430000_2025.09.19.25336162v1.24","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.cbi.2016.06.003","article-title":"Effects of pesticide mixtures in human and animal models: An update of the recent literature","volume":"254","year":"2016","journal-title":"Chem Biol Interact"},{"key":"2025092412201430000_2025.09.19.25336162v1.25","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay3164"},{"key":"2025092412201430000_2025.09.19.25336162v1.26","doi-asserted-by":"publisher","DOI":"10.1002\/em.21777"},{"key":"2025092412201430000_2025.09.19.25336162v1.27","doi-asserted-by":"crossref","unstructured":"Chen TQ , Guestrin C. XGBoost: A Scalable Tree Boosting System. Kdd\u201916: Proceedings of the 22nd Acm Sigkdd International Conference on Knowledge Discovery and Data Mining 2016: 785\u201394.","DOI":"10.1145\/2939672.2939785"},{"key":"2025092412201430000_2025.09.19.25336162v1.28","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181c30fb2"},{"key":"2025092412201430000_2025.09.19.25336162v1.29","doi-asserted-by":"publisher","DOI":"10.7326\/M14-0697"},{"key":"2025092412201430000_2025.09.19.25336162v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61602-X"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.09.19.25336162","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:46:29Z","timestamp":1768509989000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.09.19.25336162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":30,"URL":"https:\/\/doi.org\/10.1101\/2025.09.19.25336162","relation":{},"subject":[],"published":{"date-parts":[[2025,9,22]]},"subtype":"preprint"}}