A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, decanoic acid, CAS Registry Number 334-48-5","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115760","DOIUrl":"10.1016/j.fct.2025.115760","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115760"},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolite identification of ripretinib by UPLC-ESI-MS/MS: in silico prediction, in vitro metabolism, and stability assessment","authors":"Gangireddy Navitha Reddy , Bharath Reddy Gottimukkula , Harshada Anil Bhalerao , Kalpana Talari , Rajesh Sonti","doi":"10.1016/j.fct.2025.115761","DOIUrl":"10.1016/j.fct.2025.115761","url":null,"abstract":"<div><div>Ripretinib (RTB) is a switch-control tyrosine kinase inhibitor for advanced gastrointestinal stromal tumour (GIST) targeting receptor tyrosine kinase (<em>KIT</em>) or Platelet-Derived-Growth-Factor-Alpha (<em>PDGFRα</em>) mutations. Assessment of metabolic stability and characterization of drug metabolites are essential in determining the safety and risk assessment in clinical development. Initial site-of-metabolism predictions and biotransformation pathways were assessed using <em>in silico</em> tools. <em>In vitro</em> microsomal incubations in rat and human liver microsomes revealed Phase I metabolites, mainly by hydroxylation, and de-methylation using UPLC coupled with Orbitrap Exploris 120 HRMS/MS. Metabolic stability assessment showed that RTB has low intrinsic clearance and a relatively long half-life, indicating stable behavior. Furthermore, <em>in silico</em> toxicity predictions suggested an acceptable safety profile for RTB and its metabolites. Results highlighted neurotoxicity as a significant concern for RTB and its metabolites, while metabolite 1 exhibited hepatotoxicity and nephrotoxicity. The current study unveils metabolic profiles of RTB and helps to understand the biotransformation products-related toxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115761"},"PeriodicalIF":3.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A.M. Api , D. Belsito , D. Botelho , M. Bruze , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M.L. Dagli , W. Dekant , C. Deodhar , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , M. Lavelle , I. Lee , D.C. Liebler , H. Moustakas , J. Muldoon , T.M. Penning , Y. Tokura
{"title":"Corrigendum to “RIFM fragrance ingredient safety assessment, 1,3,5-undecatriene, CAS Registry Number 16356-11-9” [Food Chem. Toxicol. (2024 Mar) 183 Suppl 1 114303. doi: 10.1016/j.fct.2023.114303. Epub 2023 Dec 4]","authors":"A.M. Api , D. Belsito , D. Botelho , M. Bruze , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M.L. Dagli , W. Dekant , C. Deodhar , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , M. Lavelle , I. Lee , D.C. Liebler , H. Moustakas , J. Muldoon , T.M. Penning , Y. Tokura","doi":"10.1016/j.fct.2025.115742","DOIUrl":"10.1016/j.fct.2025.115742","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115742"},"PeriodicalIF":3.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer Roberts , Don Caldwell , Tony Zhao , Syed A. Aziz , Jayadev Raju
{"title":"Toxicological responses in F344 rats following repeated dose sub-acute and sub-chronic dietary exposures to the food processing-induced contaminant 2-monochloro-1,3-propanediol (2-MCPD)","authors":"Jennifer Roberts , Don Caldwell , Tony Zhao , Syed A. Aziz , Jayadev Raju","doi":"10.1016/j.fct.2025.115730","DOIUrl":"10.1016/j.fct.2025.115730","url":null,"abstract":"<div><div>In addressing a regulatory toxicological data gap to identify the hazard of the process-induced food contaminant 2-monochloro-1,3-diol (2-MCPD), two independent live bioassays were conducted according to the <em>OECD TG-407</em> and <em>-408</em>. Weanling <em>F344</em> rats (<em>n</em> = 10–12 rats/group/sex) were fed <em>AIN-93G</em> diets containing 2-MCPD to provide estimated daily doses of (a) 0 (control), 25 or 50 mg/kg BW for 28 days, and (b) 0 (control), 0.5, 2, 10 or 40 mg/kg BW for 90 days. Toxicological apical endpoints including histopathology were evaluated. In both studies, compared to the respective controls, the most critical 2-MCPD response was observed in the hearts; with secondary effects in the spleen and kidneys. Relative heart weights were increased in both sexes, together with non-neoplastic lesions in females (at 50 mg/kg BW), and in both males and females (at 40 mg/kg BW g). For the hearts, no-observed adverse effect levels (NOAELs) of 2-MCPD exposure were determined as 50 and 10 mg/kg BW for males, and 25 and 10 mg/kg BW for females, in the <em>28-</em> and <em>90-day studies</em>, respectively. These two regulatory-compliant rodent bioassays provide hazard identification data that strongly determined cardiotoxicity as the primary adverse outcome of 2-MCPD when exposed through the diet.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115730"},"PeriodicalIF":3.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, octanoic acid, CAS Registry Number 124-07-2","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115759","DOIUrl":"10.1016/j.fct.2025.115759","url":null,"abstract":"<div><div>Octanoic acid was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that octanoic acid is not genotoxic. Data on octanoic acid provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. Data show that there are no safety concerns for skin sensitization caused by octanoic acid under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; octanoic acid is not expected to be photoirritating/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to octanoic acid is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; octanoic acid was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use (VoU) in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115759"},"PeriodicalIF":3.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modulative effects of carbon black and polyethylene micro-nanoplastic particles on blood-brain barrier model in vitro","authors":"Justina Pajarskienė , Agnė Vailionytė , Ieva Uogintė , Steigvilė Byčenkienė , Agnė Pociūtė , Edvardas Bagdonas , Rūta Aldonytė","doi":"10.1016/j.fct.2025.115762","DOIUrl":"10.1016/j.fct.2025.115762","url":null,"abstract":"<div><div>Microplastics (MP) and nanoplastics (NP), including low-density polyethylene (LDPE), as well as carbon-based particles such as carbon black (CBP) and black carbon (BC) from incomplete combustion, are widespread environmental pollutants. Their co-occurrence in airborne particulate matter raises concerns about potential impacts on sensitive barriers such as the blood-brain barrier (BBB). This study investigates the effects of CBP and LDPE particles on human cerebral microvascular endothelium hCMEC/D3 cells, an <em>in vitro</em> BBB model. Using a stable NRF2 reporter cell line, we assessed barrier function via transendothelial electrical resistance (TEER), particle uptake through confocal microscopy, and morphological changes using CellProfiler. Inflammatory and oxidative stress responses were also evaluated. CBP exposure increased TEER values, suggesting an occluding effect on barrier integrity. Additionally, CBP enhanced phagocytic activity and reduced <em>IL-1β</em> levels, indicating modulation of inflammation. In contrast, although internalized by cells, LDPE particles had minimal impact on morphology, phagocytosis, inflammation, or barrier function. These findings offer new insights into the cellular responses to airborne pollutants, highlighting the differential effects of CBP and LDPE particles on the BBB and underscoring the need for further studies on their combined impact.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115762"},"PeriodicalIF":3.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"RIFM fragrance ingredient safety assessment, 5-methyl-5-propyl-2-(1-methylbutyl)-1,3-dioxan, CAS Registry Number 80480-24-6","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115763","DOIUrl":"10.1016/j.fct.2025.115763","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115763"},"PeriodicalIF":3.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, spiro[5.5]undec-8-en-1-one, 2,2,7,9-tetramethyl-, CAS Registry Number 502847-01-0","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115748","DOIUrl":"10.1016/j.fct.2025.115748","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115748"},"PeriodicalIF":3.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, p-tolyl 3-methylcrotonate, CAS Registry Number 24700-20-7","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115747","DOIUrl":"10.1016/j.fct.2025.115747","url":null,"abstract":"<div><div><em>p</em>-Tolyl 3-methylcrotonate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that <em>p</em>-tolyl 3-methylcrotonate is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to <em>p</em>-tolyl 3-methylcrotonate is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for non-reactive materials (900 μg/cm<sup>2</sup>); exposure is below the DST. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; <em>p</em>-tolyl 3-methylcrotonate is not expected to be photoirritating/photoallergenic. The environmental endpoints were evaluated; <em>p</em>-tolyl 3-methylcrotonate was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use (VoU) in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115747"},"PeriodicalIF":3.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, p-isopropylacetophenone, CAS Registry Number 645-13-6","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115751","DOIUrl":"10.1016/j.fct.2025.115751","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115751"},"PeriodicalIF":3.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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