Pub Date : 2025-11-10DOI: 10.1016/j.yrtph.2025.105987
Andressa Glinski , Jessica Zablocki da Luz , Aliciane de Almeida Roque , Tugstênio Lima de Souza , Arandi Ginane Bezerra Junior , Carolina Camargo de Oliveira , Ciro Alberto de Oliveira Ribeiro , Francisco Filipak Neto
Silver nanoparticles (AgNPs) are widely used in nanotechnology products. However, the health risks associated with co-exposure to these emerging contaminants and environmental pollutants, such as non-essential metals, are poorly understood. The present study aimed to investigate the cytotoxicity and toxicological interaction of AgNPs (0.36 and 3.6 μg mL−1) + lead (Pb2+, 25 and 250 μM) and AgNPs + mercury (Hg2+, 15 and 150 μM) using the macrophage cell line RAW 264.7 as a model. Effects were observed after a few hours (4 h) on NO levels, phagocytic activity, and DNA damage. Cell viability (24 h-exposure) was affected mainly by the higher concentrations of the contaminants and their mixtures, preceded by increases in NO levels and DNA damage, but without effects on ROS levels. Co-exposure potentiated some effects (ROS and NO levels and DNA damage), indicating toxicological interaction. These important findings must be further investigated, since the interaction of Pb2+ and Hg2+ with AgNPs from nanoproducts may impair the function of macrophages and represent a health risk for humans.
{"title":"Cytotoxic effects of silver nanoparticles and non-essential metals in murine macrophages","authors":"Andressa Glinski , Jessica Zablocki da Luz , Aliciane de Almeida Roque , Tugstênio Lima de Souza , Arandi Ginane Bezerra Junior , Carolina Camargo de Oliveira , Ciro Alberto de Oliveira Ribeiro , Francisco Filipak Neto","doi":"10.1016/j.yrtph.2025.105987","DOIUrl":"10.1016/j.yrtph.2025.105987","url":null,"abstract":"<div><div>Silver nanoparticles (AgNPs) are widely used in nanotechnology products. However, the health risks associated with co-exposure to these emerging contaminants and environmental pollutants, such as non-essential metals, are poorly understood. The present study aimed to investigate the cytotoxicity and toxicological interaction of AgNPs (0.36 and 3.6 μg mL<sup>−1</sup>) + lead (Pb<sup>2+</sup>, 25 and 250 μM) and AgNPs + mercury (Hg<sup>2+</sup>, 15 and 150 μM) using the macrophage cell line RAW 264.7 as a model. Effects were observed after a few hours (4 h) on NO levels, phagocytic activity, and DNA damage. Cell viability (24 h-exposure) was affected mainly by the higher concentrations of the contaminants and their mixtures, preceded by increases in NO levels and DNA damage, but without effects on ROS levels. Co-exposure potentiated some effects (ROS and NO levels and DNA damage), indicating toxicological interaction. These important findings must be further investigated, since the interaction of Pb<sup>2+</sup> and Hg<sup>2+</sup> with AgNPs from nanoproducts may impair the function of macrophages and represent a health risk for humans.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105987"},"PeriodicalIF":3.5,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145506568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-09DOI: 10.1016/j.yrtph.2025.105984
Felix M. Kluxen , Korinna Wend , Christiane Wiemann , Edgars Felkers , Neil Morgan
A modular non-dietary exposure assessment approach for pesticides (PPPs) is proposed, emphasizing a dose-based prediction of dermal absorption. The Modular Dermal Exposure Model (MODEXMO) defines new nomenclature: exposure, dermal absorption and surface distribution prediction models, respectively abbreviated as EXPREMOs, DAPREMOs, SUDIPREMOs. Approach and nomenclature are generic and can be used for probabilistic models or simulation-based approaches. The modularity aids the integration of refined exposure data and enhances the adaptability of risk assessments to better reflect dynamic real-world scenarios. DAPREMOs could replace relative dermal absorption values (DAVs) by directly predicting internal exposure from external doses with a statistical model. It is well-known that absolute dermal penetration depends primarily on applied dose. EXPREMOs can predict relatively low area doses, since exposure estimates are averaged over large body surfaces, regardless of the actual residue surface distribution. While this has no consequence in the current assessment approach using DAVs, it ignores the exposure scenario-dependent spatial distributions of residue on skin, e.g., due to individual splash events during mixing and loading operations. SUDIPREMOs can refine EXPREMO-assumed default surface areas to provide DAPREMOs with more accurate inputs for different area doses in multiple exposure sub-streams.
{"title":"MODEXMO: A modular non-dietary exposure assessment approach for pesticides using dose-based dermal absorption prediction","authors":"Felix M. Kluxen , Korinna Wend , Christiane Wiemann , Edgars Felkers , Neil Morgan","doi":"10.1016/j.yrtph.2025.105984","DOIUrl":"10.1016/j.yrtph.2025.105984","url":null,"abstract":"<div><div>A modular non-dietary exposure assessment approach for pesticides (PPPs) is proposed, emphasizing a dose-based prediction of dermal absorption. The Modular Dermal Exposure Model (MODEXMO) defines new nomenclature: exposure, dermal absorption and surface distribution prediction models, respectively abbreviated as EXPREMOs, DAPREMOs, SUDIPREMOs. Approach and nomenclature are generic and can be used for probabilistic models or simulation-based approaches. The modularity aids the integration of refined exposure data and enhances the adaptability of risk assessments to better reflect dynamic real-world scenarios. DAPREMOs could replace relative dermal absorption values (DAVs) by directly predicting internal exposure from external doses with a statistical model. It is well-known that absolute dermal penetration depends primarily on applied dose. EXPREMOs can predict relatively low area doses, since exposure estimates are averaged over large body surfaces, regardless of the actual residue surface distribution. While this has no consequence in the current assessment approach using DAVs, it ignores the exposure scenario-dependent spatial distributions of residue on skin, e.g., due to individual splash events during mixing and loading operations. SUDIPREMOs can refine EXPREMO-assumed default surface areas to provide DAPREMOs with more accurate inputs for different area doses in multiple exposure sub-streams.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105984"},"PeriodicalIF":3.5,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1016/j.yrtph.2025.105985
Carole L. Yauk , Anthony M. Lynch , Vasily N. Dobrovolsky , Maik Schuler , Stephanie L. Smith-Roe , Devon Fitzgerald , Jake Higgins , Naveed Honarvar , Frank Le Curieux , Shoji Matsumura , Sheroy Minocherhomji , Leslie Recio , Jesse J. Salk , Kei-ichi Sugiyama , Takayoshi Suzuki , John W. Wills , Francesco Marchetti
Error-corrected sequencing (ECS) is a transformative method for in vivo mutagenicity assessment, enabling direct, highly sensitive measurement of mutation frequency and spectrum. ECS addresses key limitations of the transgenic rodent (TGR) assay, including lack of integration into standard toxicity studies, restricted model availability, and limited alignment with the 3R principles. To support regulatory acceptance, an expert workgroup of the International Workshops on Genotoxicity Testing (IWGT) reviewed ECS technologies and developed consensus recommendations for its inclusion into Organisation for Economic Co-operation and Development (OECD) test guidelines. The working group agreed that ECS: produces results that are concordant with validated TGR assays; can be incorporated into standard ≥28-day repeat-dose toxicity studies; and, data interpretation should be based on overall mutation frequency compared with concurrent vehicle controls. The working group emphasized harmonized data reporting aligned with OECD principles and endorsed study designs that enable quantitative risk assessment. Overall, the working group agreed that ECS offers a significant advancement over current mutagenicity assays by enabling the use of diverse models beyond conventional TGR systems described in OECD test guideline 488. The working group fully supports the application of ECS to generate in vivo mutagenicity data for regulatory submissions and recommends its inclusion in future OECD test guidelines.
{"title":"Application of error-corrected sequencing technologies for in vivo regulatory mutagenicity assessment","authors":"Carole L. Yauk , Anthony M. Lynch , Vasily N. Dobrovolsky , Maik Schuler , Stephanie L. Smith-Roe , Devon Fitzgerald , Jake Higgins , Naveed Honarvar , Frank Le Curieux , Shoji Matsumura , Sheroy Minocherhomji , Leslie Recio , Jesse J. Salk , Kei-ichi Sugiyama , Takayoshi Suzuki , John W. Wills , Francesco Marchetti","doi":"10.1016/j.yrtph.2025.105985","DOIUrl":"10.1016/j.yrtph.2025.105985","url":null,"abstract":"<div><div>Error-corrected sequencing (ECS) is a transformative method for <em>in vivo</em> mutagenicity assessment, enabling direct, highly sensitive measurement of mutation frequency and spectrum. ECS addresses key limitations of the transgenic rodent (TGR) assay, including lack of integration into standard toxicity studies, restricted model availability, and limited alignment with the 3R principles. To support regulatory acceptance, an expert workgroup of the International Workshops on Genotoxicity Testing (IWGT) reviewed ECS technologies and developed consensus recommendations for its inclusion into Organisation for Economic Co-operation and Development (OECD) test guidelines. The working group agreed that ECS: produces results that are concordant with validated TGR assays; can be incorporated into standard ≥28-day repeat-dose toxicity studies; and, data interpretation should be based on overall mutation frequency compared with concurrent vehicle controls. The working group emphasized harmonized data reporting aligned with OECD principles and endorsed study designs that enable quantitative risk assessment. Overall, the working group agreed that ECS offers a significant advancement over current mutagenicity assays by enabling the use of diverse models beyond conventional TGR systems described in OECD test guideline 488. The working group fully supports the application of ECS to generate <em>in vivo</em> mutagenicity data for regulatory submissions and recommends its inclusion in future OECD test guidelines.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105985"},"PeriodicalIF":3.5,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1016/j.yrtph.2025.105983
Kim Z. Travis , Richard W. Lewis , Christine Barreau , Bastian Becker , Philippe F. Kennel
Fluoxapiprolin is a new fungicide developed for the control of oomycetes that damage crops such as tomato, potato, grapes and leafy vegetables. Human safety studies have shown no toxicity clearly attributable to fluoxapiprolin, highlighting its favourable toxicological profile compared to many other fungicides. It meets all human health risk assessment criteria without difficulty. However, fluoxapiprolin was tested up to a Kinetically-Derived Maximum Dose (KMD) rather than the conventional limit dose, making it necessary to justify this approach in the context of regulatory hazard assessment. Official guidance documents encourage the application of KMD approaches under specific conditions. In the case of fluoxapiprolin, oral absorption was shown to become saturated as doses increased, supporting the selection of the high dose in long-term studies based on a KMD rather than using a fixed limit dose. Even if a limit dose had been used, systemic exposure would have been only about twice as high as that observed at the KMD. Given the absence of treatment-related toxicity in any study and the relatively small difference in systemic exposure, the toxicological database is considered sufficient to identify relevant hazards and to support a robust human health risk assessment.
{"title":"Applicability of kinetically-based maximum dose studies for hazard and risk assessments of the fungicide fluoxapiprolin","authors":"Kim Z. Travis , Richard W. Lewis , Christine Barreau , Bastian Becker , Philippe F. Kennel","doi":"10.1016/j.yrtph.2025.105983","DOIUrl":"10.1016/j.yrtph.2025.105983","url":null,"abstract":"<div><div>Fluoxapiprolin is a new fungicide developed for the control of oomycetes that damage crops such as tomato, potato, grapes and leafy vegetables. Human safety studies have shown no toxicity clearly attributable to fluoxapiprolin, highlighting its favourable toxicological profile compared to many other fungicides. It meets all human health risk assessment criteria without difficulty. However, fluoxapiprolin was tested up to a Kinetically-Derived Maximum Dose (KMD) rather than the conventional limit dose, making it necessary to justify this approach in the context of regulatory hazard assessment. Official guidance documents encourage the application of KMD approaches under specific conditions. In the case of fluoxapiprolin, oral absorption was shown to become saturated as doses increased, supporting the selection of the high dose in long-term studies based on a KMD rather than using a fixed limit dose. Even if a limit dose had been used, systemic exposure would have been only about twice as high as that observed at the KMD. Given the absence of treatment-related toxicity in any study and the relatively small difference in systemic exposure, the toxicological database is considered sufficient to identify relevant hazards and to support a robust human health risk assessment.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105983"},"PeriodicalIF":3.5,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1016/j.yrtph.2025.105982
{"title":"Retraction notice to “Repeated dose 28-day oral toxicity study of DEAE-Dextran in mice: An advancement in safety chemotherapeutics” [Regul. Toxicol. Pharm. 88 (2017) 262–272]","authors":"","doi":"10.1016/j.yrtph.2025.105982","DOIUrl":"10.1016/j.yrtph.2025.105982","url":null,"abstract":"","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105982"},"PeriodicalIF":3.5,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-26DOI: 10.1016/j.yrtph.2025.105959
Gina M. Hilton , Penelope A. Fenner-Crisp , William L. Jordan , Amy J. Clippinger , Douglas C. Wolf
The United States Environmental Protection Agency (USEPA) has long championed the use of the most modern toxicity testing approaches to meet its pesticide registration mandates, often collaborating with stakeholders to develop and implement innovative approaches that strengthen environmental and human health protections. Despite these efforts, the adoption of 21st-century testing approaches in pesticide registration has been slowed by various factors, including limited resources, inefficient processes for establishing confidence in new methods, and the retention of outdated data requirements codified in the Code of Federal Regulations. This paper provides a brief overview of the current USEPA legislative landscape for pesticide toxicity testing, describes the progress and remaining challenges in using new testing approaches to fulfill regulatory requirements, and highlights opportunities to address these challenges and enhance protection of human health and the environment.
{"title":"Enhancing pesticide risk assessment processes at the US Environmental Protection Agency","authors":"Gina M. Hilton , Penelope A. Fenner-Crisp , William L. Jordan , Amy J. Clippinger , Douglas C. Wolf","doi":"10.1016/j.yrtph.2025.105959","DOIUrl":"10.1016/j.yrtph.2025.105959","url":null,"abstract":"<div><div>The United States Environmental Protection Agency (USEPA) has long championed the use of the most modern toxicity testing approaches to meet its pesticide registration mandates, often collaborating with stakeholders to develop and implement innovative approaches that strengthen environmental and human health protections. Despite these efforts, the adoption of 21st-century testing approaches in pesticide registration has been slowed by various factors, including limited resources, inefficient processes for establishing confidence in new methods, and the retention of outdated data requirements codified in the Code of Federal Regulations. This paper provides a brief overview of the current USEPA legislative landscape for pesticide toxicity testing, describes the progress and remaining challenges in using new testing approaches to fulfill regulatory requirements, and highlights opportunities to address these challenges and enhance protection of human health and the environment.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105959"},"PeriodicalIF":3.5,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145392475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-25DOI: 10.1016/j.yrtph.2025.105973
Qian Guo , Meirong Shan , Yanhua Fu , Ni Li , Chu Wu , Wei Gao
This study utilized real-world data from the U.S. FDA Adverse Event Reporting System and the WHO VigiAccess database to identify and characterize safety signals associated with fruquintinib, providing insights for clinical practice and regulatory decision-making. Through a retrospective analysis of adverse event (AE) reports for fruquintinib from these two databases, disproportionality analysis methods such as the Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) were employed to detect potential pharmacovigilance signals, with cross-database consistency evaluated. The analysis revealed 4641 and 3909 AEs associated with fruquintinib in the FAERS and VigiAccess databases, respectively. The study identified several AEs not currently documented in the drug label, including dysphonia and pain. In the FAERS database, significant signals were detected in systems not covered by the label, such as blood and lymphatic, psychiatric, immune, reproductive, and ear disorders. Other unreported signals included myelosuppression, headache, dizziness, and dyspnea. In conclusion, this study not only confirmed known adverse reactions to fruquintinib but also uncovered several potential new safety signals. These findings underscore the importance of ongoing post-marketing safety monitoring to optimize the drug's risk-benefit profile. The results provide critical safety information for clinicians managing refractory metastatic colorectal cancer with fruquintinib, supporting more vigilant patient management.
{"title":"Real-world safety of fruquininib in refractory metastatic colorectal cancer: A cross-database study","authors":"Qian Guo , Meirong Shan , Yanhua Fu , Ni Li , Chu Wu , Wei Gao","doi":"10.1016/j.yrtph.2025.105973","DOIUrl":"10.1016/j.yrtph.2025.105973","url":null,"abstract":"<div><div>This study utilized real-world data from the U.S. FDA Adverse Event Reporting System and the WHO VigiAccess database to identify and characterize safety signals associated with fruquintinib, providing insights for clinical practice and regulatory decision-making. Through a retrospective analysis of adverse event (AE) reports for fruquintinib from these two databases, disproportionality analysis methods such as the Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) were employed to detect potential pharmacovigilance signals, with cross-database consistency evaluated. The analysis revealed 4641 and 3909 AEs associated with fruquintinib in the FAERS and VigiAccess databases, respectively. The study identified several AEs not currently documented in the drug label, including dysphonia and pain. In the FAERS database, significant signals were detected in systems not covered by the label, such as blood and lymphatic, psychiatric, immune, reproductive, and ear disorders. Other unreported signals included myelosuppression, headache, dizziness, and dyspnea. In conclusion, this study not only confirmed known adverse reactions to fruquintinib but also uncovered several potential new safety signals. These findings underscore the importance of ongoing post-marketing safety monitoring to optimize the drug's risk-benefit profile. The results provide critical safety information for clinicians managing refractory metastatic colorectal cancer with fruquintinib, supporting more vigilant patient management.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105973"},"PeriodicalIF":3.5,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145424549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-25DOI: 10.1016/j.yrtph.2025.105972
Nina C. Wieland , Daniel M. Figueiredo , Hans Mol , Neus González , Nelson Abrantes , Virginia Aparicio , Isabel Campos , Josefina Contreras , Alcon Francisco , Matjaž Glavan , Tanja Blagus , Vita Dolžan , Paula Harkes , Trine Nørgaard , Vivi Schlünssen , Igor Pasković , Marija Polić Pasković , Martien Graumans , Ad M.J. Ragas , Frans G.M. Russel , Paul T.J. Scheepers
Dietary uptake is estimated using residue data from food commodities and predicting the effect of food processing, such as peeling. The aim of this study was to explore the value of the analysis of duplicate portions supplemented by the analysis of urinary metabolites. Forty-three participants, consuming organic and non-organic diets collected a duplicate portion of food and beverages for 24 h. Urine was collected up to 36 h to account for metabolism and prolonged excretion of metabolites. Pesticide residues were analysed in food portions and urine samples using LC-MS/MS and GC-MS/MS. Multiple pesticide residues were detected per food portion. Out of 183 pesticides, 86 were detected in the diet. Glyphosate and AMPA were detected in 42 % and 30 % of all urine samples, respectively, while detection in the diet was low. A positive relationship between dietary intake and urinary excretion was found for 2,4-D and MCPA. No diet-urine relationship was observed for glyphosate and AMPA, indicating contribution from external routes of exposure. Hazard index (HI) indicated no exposure above the acceptable daily intake (ADI) for all participants. This study demonstrates how DPA combined with urine analysis gives insight into contribution of diet to total pesticide exposure compared to standard monitoring.
{"title":"Relationship between dietary pesticide intake and urinary excretion: a pilot study using duplicate portion analysis","authors":"Nina C. Wieland , Daniel M. Figueiredo , Hans Mol , Neus González , Nelson Abrantes , Virginia Aparicio , Isabel Campos , Josefina Contreras , Alcon Francisco , Matjaž Glavan , Tanja Blagus , Vita Dolžan , Paula Harkes , Trine Nørgaard , Vivi Schlünssen , Igor Pasković , Marija Polić Pasković , Martien Graumans , Ad M.J. Ragas , Frans G.M. Russel , Paul T.J. Scheepers","doi":"10.1016/j.yrtph.2025.105972","DOIUrl":"10.1016/j.yrtph.2025.105972","url":null,"abstract":"<div><div>Dietary uptake is estimated using residue data from food commodities and predicting the effect of food processing, such as peeling. The aim of this study was to explore the value of the analysis of duplicate portions supplemented by the analysis of urinary metabolites. Forty-three participants, consuming organic and non-organic diets collected a duplicate portion of food and beverages for 24 h. Urine was collected up to 36 h to account for metabolism and prolonged excretion of metabolites. Pesticide residues were analysed in food portions and urine samples using LC-MS/MS and GC-MS/MS. Multiple pesticide residues were detected per food portion. Out of 183 pesticides, 86 were detected in the diet. Glyphosate and AMPA were detected in 42 % and 30 % of all urine samples, respectively, while detection in the diet was low. A positive relationship between dietary intake and urinary excretion was found for 2,4-D and MCPA. No diet-urine relationship was observed for glyphosate and AMPA, indicating contribution from external routes of exposure. Hazard index (HI) indicated no exposure above the acceptable daily intake (ADI) for all participants. This study demonstrates how DPA combined with urine analysis gives insight into contribution of diet to total pesticide exposure compared to standard monitoring.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105972"},"PeriodicalIF":3.5,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145424550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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