Heavy Metal Contaminations in Herbal Medicines: Determination, Comprehensive Risk Assessments, and Solutions

Heavy Metal Contaminations in Herbal Medicines: Determination, Comprehensive Risk Assessments, and Solutions | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Heavy Metal Contaminations in Herbal Medicines: Determination, Comprehensive Risk Assessments, and Solutions Lu Luo, Bo Wang, Jingwen Jiang, Qin Huang, Zheng Yu, Hui Li, Jiqing Zhang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-53256/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Jan, 2021 Read the published version in Frontiers in Pharmacology → Version 1 posted You are reading this latest preprint version Abstract Background: Heavy metal contamination in herbal medicines is a global threat to human beings especially at levels above known threshold concentrations. Methods: The concentrations of five heavy metals cadmium (Cd), lead (Pb), arsenic (As), mercury (Hg) and copper (Cu) were investigated using Inductively Coupled Plasma Optical Mass Spectrometry (ICP-MS) with 1773 samples. Exposure assessment, Non-carcinogenic risk assessment, and carcinogenic risk assessment were applied to measure their risks in human body. Results: According to Chinese Pharmacopoeia, 30.51% (541) samples were detected with at least one over-limit metal. The over-limit ratio for Pb was 5.75% (102), Cd at 4.96% (88), As at 4.17% (74), Hg at 3.78% (67), and of Cu, 1.75% (31). For exposure assessment, Pb, Cd, As, and Hg have resulted in higher than acceptable risks in 25 kinds of herbs. The maximal Estimated Daily Intake (EDI) of Pb in seven herbs, of Cd in five, of Hg in four, and As in three exceeded their corresponding Provisional Tolerable Daily Intakes (PTDI). In total 25 kinds of herbs present an unacceptable risk as assessed with the HQ (Hazard Quotient) or HI (Hazard Index). Particularly, Plantaginis herba (HI = 11.47) is more than 11 times over the limit. Conclusions: Heavy metal contamination in herbal medicines was borderline or higher than the safety level with the majority of the herbal plants were within acceptable risks. Notably, As posed the highest risk in all indicators including EDI, HI, and CR, inducing the most serious risks in all five metals. Herbal medicines Euodiae fructus, Plantaginis herba, and Desmodii styracifolii were considered the most risk-inducing herbal medicines. Therefore, it is of great advantage to establish universal standards and quality requirements for hazardous elements in herbal medicines so that this natural resource can continue and expand further, to benefit health globally. Clinical Pharmacology heavy metal herbal medicine extrinsic contamination risk assessment Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Full Text Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and accessed as a PDF. Supplementary Files GA.pdf GA.pdf Listofsamples.xlsx Listofsamples.xlsx Supplementarymaterials.docx Supplementarymaterials.docx Cite Share Download PDF Status: Published Journal Publication published 14 Jan, 2021 Read the published version in Frontiers in Pharmacology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-53256","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":1264980,"identity":"01c87c58-fbe8-4957-bac4-00b00ac9167c","order_by":0,"name":"Lu Luo","email":"","orcid":"https://orcid.org/0000-0002-5601-0801","institution":"China Academy of Chinese Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lu","middleName":"","lastName":"Luo","suffix":""},{"id":1264981,"identity":"8f64e908-d12c-435e-bf9a-51f3d0071e4d","order_by":1,"name":"Bo Wang","email":"","orcid":"","institution":"Hubei Institute for 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10:18:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-53256/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-53256/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.3389/fphar.2020.595335","type":"published","date":"2021-01-14T18:28:34+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":1844614,"identity":"d1b24729-780b-4403-9ad1-2b74c0905231","added_by":"auto","created_at":"2020-08-07 21:55:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":106601,"visible":true,"origin":"","legend":"Plotbox showing concentrations of five heavy metals in five medicinal properties. (A) Concentrations of Cu in five medicinal properties. (B) Concentrations of As in five medicinal properties. (C) Concentrations of Cd in five medicinal properties. (D) Concentrations of Hg in five medicinal properties. (E) Concentrations of Pb in five medicinal properties.","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-53256/v1/Figure1.png"},{"id":1844615,"identity":"7d5dd0e0-17cb-4626-ac1c-7c0f660aacfd","added_by":"auto","created_at":"2020-08-07 21:55:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":154471,"visible":true,"origin":"","legend":"Violin plot showing log2 (concentration) values of five heavy metals in 1773 samples and permissible limits in different countries of each heavy metal (see Table S2 for detailed standards of each heavy metal). ","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-53256/v1/Figure2.png"},{"id":1844616,"identity":"ba2cf5b5-a75a-425c-9d87-9e7c798123fd","added_by":"auto","created_at":"2020-08-07 21:55:25","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":14536987,"visible":true,"origin":"","legend":"Heatmap of EDI and HI by mean concentrations detected for five heavy metals in 86 kinds of herbal medicines (A) Heatmap showing log2 (Estimated Daily Intake, EDI) values by mean concentrations detected of five heavy metals in 86 herbal medicines; (B) Heatmap showing log2 (Hazard Index, HI) values by mean concentrations detected of five heavy metals in 86 herbal medicines. ","description":"","filename":"Figure3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-53256/v1/Figure3.jpeg"},{"id":1844617,"identity":"dbdb90a5-b049-4115-8154-aa28d98b6fa3","added_by":"auto","created_at":"2020-08-07 21:55:25","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":161480,"visible":true,"origin":"","legend":"Violin plot of carcinogenic risk (CR) of three carcinogenic metals with maximal, minimal and mean concentrations detected \n(A) Violin plot showing log2 (CR) values of Cd with maximal, minimal and mean concentrations; (B) Violin plot showing log2 (CR) values of As with maximal, minimal and mean concentrations; (C) Violin plot showing log2 (CR) values of Pb with maximal, minimal and mean concentrations; (D) Violin plot showing total log2 (CR) values with maximal, minimal and mean 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could not be completed. However, the latest manuscript can be downloaded and \u003ca href='/article/rs-53256/latest.pdf' target='_blank'\u003e accessed as a PDF.\u003c/a\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"heavy metal, herbal medicine, extrinsic contamination, risk assessment","lastPublishedDoi":"10.21203/rs.3.rs-53256/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-53256/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eHeavy metal contamination in herbal medicines is a global threat to human beings especially at levels above known threshold concentrations.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThe concentrations of five heavy metals cadmium (Cd), lead (Pb), arsenic (As), mercury (Hg) and copper (Cu) were investigated using Inductively Coupled Plasma Optical Mass Spectrometry (ICP-MS) with 1773 samples. Exposure assessment, Non-carcinogenic risk assessment, and carcinogenic risk assessment were applied to measure their risks in human body.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAccording to Chinese Pharmacopoeia, 30.51% (541) samples were detected with at least one over-limit metal. The over-limit ratio for Pb was 5.75% (102), Cd at 4.96% (88), As at 4.17% (74), Hg at 3.78% (67), and of Cu, 1.75% (31). For exposure assessment, Pb, Cd, As, and Hg have resulted in higher than acceptable risks in 25 kinds of herbs. The maximal Estimated Daily Intake (EDI) of Pb in seven herbs, of Cd in five, of Hg in four, and As in three exceeded their corresponding Provisional Tolerable Daily Intakes (PTDI). In total 25 kinds of herbs present an unacceptable risk as assessed with the HQ (Hazard Quotient) or HI (Hazard Index). Particularly, Plantaginis herba (HI = 11.47) is more than 11 times over the limit.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eHeavy metal contamination in herbal medicines was borderline or higher than the safety level with the majority of the herbal plants were within acceptable risks. Notably, As posed the highest risk in all indicators including EDI, HI, and CR, inducing the most serious risks in all five metals. Herbal medicines Euodiae fructus, Plantaginis herba, and Desmodii styracifolii were considered the most risk-inducing herbal medicines. Therefore, it is of great advantage to establish universal standards and quality requirements for hazardous elements in herbal medicines so that this natural resource can continue and expand further, to benefit health globally.\u003c/p\u003e","manuscriptTitle":"Heavy Metal Contaminations in Herbal Medicines: Determination, Comprehensive Risk Assessments, and Solutions","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-08-07 21:55:24","doi":"10.21203/rs.3.rs-53256/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2a5fdd20-d3b7-41ac-a632-c178f7d29e83","owner":[],"postedDate":"August 7th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":260208,"name":"Clinical Pharmacology"}],"tags":[],"updatedAt":"2021-07-22T18:28:35+00:00","versionOfRecord":{"articleIdentity":"rs-53256","link":"https://doi.org/10.3389/fphar.2020.595335","journal":{"identity":"frontiers-in-pharmacology","isVorOnly":true,"title":"Frontiers in Pharmacology"},"publishedOn":"2021-01-14 18:28:34","publishedOnDateReadable":"January 14th, 2021"},"versionCreatedAt":"2020-08-07 21:55:24","video":"","vorDoi":"10.3389/fphar.2020.595335","vorDoiUrl":"https://doi.org/10.3389/fphar.2020.595335","workflowStages":[]},"version":"v1","identity":"rs-53256","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-53256","identity":"rs-53256","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}