{"title":"Utility of in vitro assay data in read-across prediction of nongenotoxic carcinogenicity of pesticides for cytotoxicity-related rat tumors","authors":"Kosuke Mizuno , Jun-ichi Takeshita , Yu Harakawa , Takuomi Hosaka , Ryota Shizu , Kouichi Yoshinari","doi":"10.1016/j.fct.2025.115566","DOIUrl":"10.1016/j.fct.2025.115566","url":null,"abstract":"<div><div>Developing alternative methods for rat carcinogenicity studies remains challenging. This study aimed to establish a read-across method to predict nongenotoxic carcinogenicity in rats using molecular descriptors and <em>in vitro</em> assays. Based on 2-year rat carcinogenicity study results of agrochemicals, 80 compounds that caused benign or malignant tumors in the liver, thyroid, testis, uterus, ovary, breast, nasal cavity, stomach, or bladder/urethra and 46 compounds that did not were selected and subjected to cell-based cytotoxicity assays. Here, we focused on tumors associated with epithelial cell injury (nasal cavity, stomach, and bladder/urethra tumors). The read-across prediction was performed using neighboring substances, which were selected based on the Euclidean distance between the substances calculated using molecular descriptors. In some cases, neighboring substances were further selected based on the concordance of the <em>in vitro</em> assay results. The selection of neighboring substances based on the carcinogenicity-relevant descriptors and then on the cytotoxicity assay data improved the prediction accuracy (balanced accuracy: 0.752–0.821) compared to the accuracy with substances selected based on unselected descriptors alone (balanced accuracy: 0.294–0.582). These results suggest that the combined use of carcinogenicity-relevant descriptors and <em>in vitro</em> assays related to carcinogenic mechanisms is useful for read-across prediction of cytotoxicity-related tumors in rats.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115566"},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124282","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, 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, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment,hydroxycitronellal diethyl acetal, CAS Registry Number 7779-94-4.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, 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, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2025.115563","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115563","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115563"},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126330","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":"Investigating the role of mosquito repellents in atopic dermatitis","authors":"Xiaoxue Wang , Zexin Zhu","doi":"10.1016/j.fct.2025.115571","DOIUrl":"10.1016/j.fct.2025.115571","url":null,"abstract":"<div><div>Mosquito bites are prevalent occurrences among various populations worldwide, mosquito repellent chemical components (MRCCs) have been extensively utilized. MRCCs have been frequently identified in environmental settings nowadays. However, the implications of these compounds on skin conditions, particularly Atopic Dermatitis (AD), are not well understood. In this investigation, we analyzed three commercially available MRCCs: DEET (N,N-diethyl-3-methylbenzamide), IR3535 (ethyl butylacetylaminopropionate), and picaridin (2-(2-hydroxyethyl)-piperidinecarboxylic acid 1-methyl ester). A comprehensive analysis was conducted utilizing various databases to identify potential targets associated with exposure to these MRCCs and their correlation with AD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that exposure to these MRCCs influences inflammation-related pathways. Additionally, molecular docking studies indicated significant binding affinities of DEET, IR3535, and picaridin to critical core targets and receptor proteins. Furthermore, a series of cellular assays were conducted to empirically evaluate the actual effects of these three MRCCs on the induction of AD. The results suggest that MRCCs may facilitate the progression of AD by influencing inflammatory processes. This study provides a conceptual framework for understanding the association between MRCCs and the risk of AD, thereby contributing to the formulation of strategies aimed at mitigating their effects on dermatological disorders.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115571"},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116932","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}
Sven Dänicke , Torsten Krause , Julika Lamp , Karin Knappstein , Dirk von Soosten , Jeannette Kluess , Susanne Kersten , Andreas Beineke , Susanne Bühler , Jana Frahm
{"title":"Effects of exposure of dairy cows to a mixture of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), dioxin-like (dl) polychlorinated biphenyls (PCBs), and non-dl-PCBs during the period of negative and positive energy balance on health traits and on aryl hydrocarbon receptor (AHR)-signaling","authors":"Sven Dänicke , Torsten Krause , Julika Lamp , Karin Knappstein , Dirk von Soosten , Jeannette Kluess , Susanne Kersten , Andreas Beineke , Susanne Bühler , Jana Frahm","doi":"10.1016/j.fct.2025.115560","DOIUrl":"10.1016/j.fct.2025.115560","url":null,"abstract":"<div><div>This study investigated the impact of oral dioxin and PCB exposure on Holstein cows during negative (NEB) and positive (PEB) energy balance. Nine cows were divided into control (CON, n = 4) and exposed (EXP, n = 5) groups. The EXP group received 278/266 pg dioxin-like (dl)-PCB TEQ/kg BW/day and 75/72 ng non-dl-PCBs/kg BW/day for 28 days during both NEB and PEB. Inner exposure and health parameters were assessed. Cholesterol levels increased faster in the EXP group during NEB (p = 0.049). During PEB, CD4<sup>+</sup> cell proportion and mean fluorescence intensity (MFI), along with CD8<sup>+</sup> cell MFI, decreased in the EXP group while increasing in the CON group (p = 0.004, p = 0.05, and p = 0.023, respectively). AHR-signaling mRNA expression was unaffected in subcutaneous adipose tissue, spleen, and peripheral blood mononuclear cells. However, approximately 100 days post-exposure, hepatic AHR and ARNT mRNA expression remained elevated in the EXP group (p = 0.023 each) and correlated positively with liver dioxin and PCB residues (r<sup>2</sup> = 0.43–0.75). Overall, dioxin and PCB effects on the examined endpoints were minor. The long-term implications of the observed T-cell and hepatic AHR-signaling changes require further investigation.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115560"},"PeriodicalIF":3.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116931","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, 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, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, amylcyclohexyl acetate (mixed isomers), CAS Registry Number 67874-72-0.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, 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, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2025.115554","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115554","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115554"},"PeriodicalIF":3.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118422","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}
Jiahui Li , Dan Bi , Ya Nie , Huijuan Wu , Yuting Lei , Siping Yu , Hedong Rong , Yanhong Yang , Zili Lei
{"title":"Loperamide-induced constipation is associated with excessive accumulation of bile acids and cholesterol in the liver of mice; attenuation by hesperidin","authors":"Jiahui Li , Dan Bi , Ya Nie , Huijuan Wu , Yuting Lei , Siping Yu , Hedong Rong , Yanhong Yang , Zili Lei","doi":"10.1016/j.fct.2025.115561","DOIUrl":"10.1016/j.fct.2025.115561","url":null,"abstract":"<div><div>Loperamide, a widely used antidiarrheal agent, frequently induces constipation alongside other adverse effects. This study explored hesperidin's therapeutic potential in alleviating loperamide-induced constipation and its underlying mechanisms. Constipation models were established in HFD- or NFD-fed mice via loperamide administration (5 mg/kg/day). Hesperidin (100 mg/kg/day) significantly increased fecal weight and moisture in constipated mice. Biochemical analyses revealed elevated cholic acid/chenodeoxycholic acid ratios in serum and liver tissues of loperamide-treated HFD mice, indicating bile acids dysregulation. qRT-PCR and Western blot results demonstrated that hesperidin downregulated hepatic expression of cholesterol/bile acids biosynthesis genes (e.g., <em>Hmgcr</em>, <em>Cyp7a1</em>, <em>Ch25h</em>), which were overexpressed in constipated mice. Concurrently, hesperidin enhanced the expression of transporters (<em>Abcg5</em>, <em>Abcb11</em>, <em>Abcc2</em>) responsible for biliary cholesterol and bile acids efflux. Furthermore, hesperidin upregulated hepatic nuclear receptors (FXR/SHP), key regulators of bile acids homeostasis. Hesperidin alleviates loperamide-induced constipation through two parallel mechanisms: decreasing hepatic cholesterol accumulation and enhancing bile acids excretion. This dual action results from coordinated regulation of biosynthesis enzymes and transport proteins. This study highlights hesperidin's potential as an adjunct therapy to counteract loperamide-related constipation.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"203 ","pages":"Article 115561"},"PeriodicalIF":3.9,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101133","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, octanal dimethyl acetal, CAS Registry Number 10022-28-3","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.2025.115555","DOIUrl":"10.1016/j.fct.2025.115555","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115555"},"PeriodicalIF":3.9,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101137","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}
Peter S. Spencer , Valerie S. Palmer , Glen E. Kisby
{"title":"Letter to editor in regard to: Uthra C, Shunmugam S, Nagaraj K, Muralitharan G, Albeshr MF, Velmurugan G. Ultra-fast liquid chromatography detection of β-N-methylamine-l-alanine and its isomers in cycad seeds and cyanobacterial symbionts for neurotoxic risk assessment","authors":"Peter S. Spencer , Valerie S. Palmer , Glen E. Kisby","doi":"10.1016/j.fct.2025.115546","DOIUrl":"10.1016/j.fct.2025.115546","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115546"},"PeriodicalIF":3.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091984","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}
Yanghoon Peter Jung , Suyoung Lim , Seulgi An , Hyunji Kim , Jae-Ho Shin
{"title":"Corrigendum to “A 13-week repeated oral dose toxicity evaluation and a 4-week recovery evaluation of rosemary concentrate containing 50 % ursolic acid in male and female rats” [Food Chem. Toxicol. 197, February (2025) 115308]","authors":"Yanghoon Peter Jung , Suyoung Lim , Seulgi An , Hyunji Kim , Jae-Ho Shin","doi":"10.1016/j.fct.2025.115548","DOIUrl":"10.1016/j.fct.2025.115548","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115548"},"PeriodicalIF":3.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069929","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, linalyl hexanoate, CAS Registry Number 7779-23-9","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.2025.115553","DOIUrl":"10.1016/j.fct.2025.115553","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115553"},"PeriodicalIF":3.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091999","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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