Comparative investigation of the potential of glyphosate and glyphosate-based formulations to cause oxidative stress and DNA damage in human skin and liver cell systems.
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| Title: | Comparative investigation of the potential of glyphosate and glyphosate-based formulations to cause oxidative stress and DNA damage in human skin and liver cell systems. |
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| Authors: | Smith-Roe, Stephanie L1 (AUTHOR), DeVito, Michael J1 (AUTHOR), Co, Caroll2 (AUTHOR), Ramaiahgari, Sreenivasa C1 (AUTHOR), Easterling, Michael2 (AUTHOR), Rice, Julie R1 (AUTHOR), Dunlap, Paul E1 (AUTHOR), Crizer, David M1 (AUTHOR), Zhou, Zhifeng1 (AUTHOR), Merrick, Bruce Alex1 (AUTHOR) |
| Source: | Toxicological Sciences. Mar2026, Vol. 209 Issue 3, p1-27. 27p. |
| Subjects: | Oxidative stress, DNA damage, Toxicology, Carcinogenicity, Keratinocytes, Liver cells, National Institute of Environmental Health Sciences, Glyphosate |
| Abstract: | Glyphosate is an herbicide found worldwide in glyphosate-based formulations (GBFs). Although glyphosate appears to have a low toxicity profile for humans and mammals, conflicting reports exist regarding the risk for cancer in humans. US-EPA and European regulatory agencies have described glyphosate as unlikely to pose a carcinogenic hazard to humans. However, the International Agency for Research on Cancer (IARC) classified glyphosate as "probably carcinogenic to humans (Group 2A)," citing "mechanistic data provide strong evidence for genotoxicity and oxidative stress." Given these discrepancies, the Division of Translational Toxicology at NIEHS designed an experimental strategy to expand mechanistic evidence and address critical gaps within existing literature (e.g. mechanistic evaluations of glyphosate alongside GBFs, inclusion of context-defining positive controls). Cell morphology, viability, H2O2, and γH2AX formation were assayed in human keratinocytes (HaCaT), previously cited by IARC, and human hepatocytes (HepaRG) to derive benchmark concentrations and fold-change response metrics. Our findings revealed glyphosate alone was weakly and inconsistently bioactive for oxidative stress and DNA damage when compared with positive controls. In contrast, most of the 13 GBFs evaluated were more clearly bioactive with no apparent correlation to varied glyphosate concentrations. Hierarchical clustering of biological responses revealed some bioactive GBFs to cluster near well-characterized positive controls for oxidative stress, whereas 4 GBFs clustered more similarly to negative controls and glyphosate. Collectively, this study provides a robust dataset with context-defining results that advance our understanding of the hazard potential of GBFs while revealing that glyphosate is likely not a primary driver of oxidative stress from GBF exposures. [ABSTRACT FROM AUTHOR] |
| Copyright of Toxicological Sciences is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 192763956 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Comparative investigation of the potential of glyphosate and glyphosate-based formulations to cause oxidative stress and DNA damage in human skin and liver cell systems. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Smith-Roe%2C+Stephanie+L%22">Smith-Roe, Stephanie L</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22DeVito%2C+Michael+J%22">DeVito, Michael J</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Co%2C+Caroll%22">Co, Caroll</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ramaiahgari%2C+Sreenivasa+C%22">Ramaiahgari, Sreenivasa C</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Easterling%2C+Michael%22">Easterling, Michael</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rice%2C+Julie+R%22">Rice, Julie R</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dunlap%2C+Paul+E%22">Dunlap, Paul E</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Crizer%2C+David+M%22">Crizer, David M</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhou%2C+Zhifeng%22">Zhou, Zhifeng</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Merrick%2C+Bruce+Alex%22">Merrick, Bruce Alex</searchLink><relatesTo>1</relatesTo> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Toxicological+Sciences%22">Toxicological Sciences</searchLink>. Mar2026, Vol. 209 Issue 3, p1-27. 27p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Oxidative+stress%22">Oxidative stress</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+damage%22">DNA damage</searchLink><br /><searchLink fieldCode="DE" term="%22Toxicology%22">Toxicology</searchLink><br /><searchLink fieldCode="DE" term="%22Carcinogenicity%22">Carcinogenicity</searchLink><br /><searchLink fieldCode="DE" term="%22Keratinocytes%22">Keratinocytes</searchLink><br /><searchLink fieldCode="DE" term="%22Liver+cells%22">Liver cells</searchLink><br /><searchLink fieldCode="DE" term="%22National+Institute+of+Environmental+Health+Sciences%22">National Institute of Environmental Health Sciences</searchLink><br /><searchLink fieldCode="DE" term="%22Glyphosate%22">Glyphosate</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Glyphosate is an herbicide found worldwide in glyphosate-based formulations (GBFs). Although glyphosate appears to have a low toxicity profile for humans and mammals, conflicting reports exist regarding the risk for cancer in humans. US-EPA and European regulatory agencies have described glyphosate as unlikely to pose a carcinogenic hazard to humans. However, the International Agency for Research on Cancer (IARC) classified glyphosate as "probably carcinogenic to humans (Group 2A)," citing "mechanistic data provide strong evidence for genotoxicity and oxidative stress." Given these discrepancies, the Division of Translational Toxicology at NIEHS designed an experimental strategy to expand mechanistic evidence and address critical gaps within existing literature (e.g. mechanistic evaluations of glyphosate alongside GBFs, inclusion of context-defining positive controls). Cell morphology, viability, H2O2, and γH2AX formation were assayed in human keratinocytes (HaCaT), previously cited by IARC, and human hepatocytes (HepaRG) to derive benchmark concentrations and fold-change response metrics. Our findings revealed glyphosate alone was weakly and inconsistently bioactive for oxidative stress and DNA damage when compared with positive controls. In contrast, most of the 13 GBFs evaluated were more clearly bioactive with no apparent correlation to varied glyphosate concentrations. Hierarchical clustering of biological responses revealed some bioactive GBFs to cluster near well-characterized positive controls for oxidative stress, whereas 4 GBFs clustered more similarly to negative controls and glyphosate. Collectively, this study provides a robust dataset with context-defining results that advance our understanding of the hazard potential of GBFs while revealing that glyphosate is likely not a primary driver of oxidative stress from GBF exposures. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Toxicological Sciences is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1093/toxsci/kfag029 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 27 StartPage: 1 Subjects: – SubjectFull: Oxidative stress Type: general – SubjectFull: DNA damage Type: general – SubjectFull: Toxicology Type: general – SubjectFull: Carcinogenicity Type: general – SubjectFull: Keratinocytes Type: general – SubjectFull: Liver cells Type: general – SubjectFull: National Institute of Environmental Health Sciences Type: general – SubjectFull: Glyphosate Type: general Titles: – TitleFull: Comparative investigation of the potential of glyphosate and glyphosate-based formulations to cause oxidative stress and DNA damage in human skin and liver cell systems. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Smith-Roe, Stephanie L – PersonEntity: Name: NameFull: DeVito, Michael J – PersonEntity: Name: NameFull: Co, Caroll – PersonEntity: Name: NameFull: Ramaiahgari, Sreenivasa C – PersonEntity: Name: NameFull: Easterling, Michael – PersonEntity: Name: NameFull: Rice, Julie R – PersonEntity: Name: NameFull: Dunlap, Paul E – PersonEntity: Name: NameFull: Crizer, David M – PersonEntity: Name: NameFull: Zhou, Zhifeng – PersonEntity: Name: NameFull: Merrick, Bruce Alex IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 03 Text: Mar2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 10966080 Numbering: – Type: volume Value: 209 – Type: issue Value: 3 Titles: – TitleFull: Toxicological Sciences Type: main |
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