{"title":"A Weight of Evidence Approach to Assess the Human Genotoxicity Risk of Chinese Goldthread Botanical Extract and its Primary Constituent Berberine.","authors":"Bin Sun, Ashley Allemang, Stefan Pfuhler","doi":"10.1016/j.fct.2025.115485","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115485","url":null,"abstract":"<p><p>The genotoxicity potential of Chinese Goldthread Extract (CGPE) was initially explored using the Ames test and in vitro micronucleus assay. CGPE induced gene mutations in the Ames test and micronuclei in TK6 human lymphoblastoid cells, and berberine, present in CGPE above 20%, was identified as the causative phytoconstituent. We confirmed berberine's ability to bind to, and interfere with, human topoisomerase II and bacterial DNA gyrase, enzymes that play a key role in maintaining DNA integrity and conclude that this likely explains the genotoxic effects we observed in the above-mentioned in vitro genotoxicity assays and in an HPRT assay using L5178Y cells. No micronuclei were induced in primary human blood lymphocytes, and in vitro effects were negated when external metabolic activation was included. These factors support a lack of relevance of the positive in vitro findings for human risk assessment. This assumption is further strengthened by comparing human pharmacokinetic Cmax blood levels with in vitro concentrations of berberine that trigger impairment of topo II, a known secondary genotoxicity pathway, revealing a large Margin of Exposure of ≥11900-fold. The overall Weight of Evidence supports the absence of a genotoxicity concern at typical use levels in commercial CGPE and berberine supplements.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115485"},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961958","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}
Ning Tang , Wentao Sun , Jingke Zhang , Xin Ma , Yan Wang
{"title":"Assessing the toxicological effects and mechanism of plasticizer exposure on inflammatory bowel disease based on network toxicology and molecular docking","authors":"Ning Tang , Wentao Sun , Jingke Zhang , Xin Ma , Yan Wang","doi":"10.1016/j.fct.2025.115543","DOIUrl":"10.1016/j.fct.2025.115543","url":null,"abstract":"<div><div>Phthalates (PAEs) are one of the most commonly used plasticizers. Due to their good performance, they are widely used in daily production, such as food packaging, paints, adhesives, children's toys, lubricants and building materials. However, PAEs usually have weak interactions with polymers, which can easily cause environmental pollution in use. These plasticizers have been linked to various health conditions, including inflammatory disorders. They are less intensively studied in the occurrence of inflammation, especially inflammatory bowel disease (IBD), and the necessity to evaluate their pathogenic molecular toxicity is particularly urgent. In this study, network toxicology and molecular docking methods were used to study the toxicological mechanism of IBD induced by four common plasticizers (DBP, DEHP, DEP, DNOP). Potential related targets were predicted using the PharmMapper, SwissStargetPrediction, GeneCards, DisGeNET, OMIM and TTD databases, and 286 related targets were identified. Using Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, binding protein-Protein Interaction (PPI) networks and cytoHubba plug-ins, ten relevant signaling pathways (PI3K-Akt signaling pathway, lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, Proteoglycans in cancer, and so on.) and ten hub genes were identified. Four plasticizers (DBP, DEHP, DEP, DNOP) and the top 10 selected Hub gene targets (SRC, KRAS, PIK3CA, PIK3R1, JAK2, PTPN11, PIK3CD, HRAS, PIK3CG, EGFR) were analyzed by molecular docking. This study provides valuable insights into the molecular mechanisms of plasticizer-induced IBD and highlights the practicality of network toxicology in assessing the toxicity of emerging environmental pollutants. It enhances our understanding of the health risks posed by plasticizers and offers new strategies for mitigating their impact on inflammatory diseases.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115543"},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941325","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, 2-methylundecanal dimethyl acetal, CAS Registry Number 68141-17-3","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.2025.115532","DOIUrl":"10.1016/j.fct.2025.115532","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115532"},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961843","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":"RIFM fragrance ingredient safety assessment, 2-methyl quinoline, CAS Registry Number 91-63-4.","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.2025.115530","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115530","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115530"},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951723","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 , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, hydroxycitronellal dimethyl acetal, CAS Registry number 141-92-4","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 , Y. Thakkar","doi":"10.1016/j.fct.2025.115529","DOIUrl":"10.1016/j.fct.2025.115529","url":null,"abstract":"<div><div>Hydroxycitronellal dimethyl acetal was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog hydroxycitronellal diethyl acetal (CAS # 7779-94-4) show that hydroxycitronellal dimethyl acetal is not expected to be 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 hydroxycitronellal dimethyl acetal is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). Data show that there are no safety concerns for hydroxycitronellal dimethyl acetal for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; hydroxycitronellal dimethyl acetal is not expected to be photoirritating/photoallergenic. The environmental endpoints were evaluated; hydroxycitronellal dimethyl acetal was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients (RQs), 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":"201 ","pages":"Article 115529"},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941393","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}
Xinrong He , Xinyu Han , Yang Yang , Fajie Li , Dongxiao Li , Lianzhong Luo , Hong Liu , Guixia Chen , Xiaomei Chen , Guangming Liu
{"title":"Non-allergenic mixed T cell epitope peptides for preventing Scy p 9 allergic reactions","authors":"Xinrong He , Xinyu Han , Yang Yang , Fajie Li , Dongxiao Li , Lianzhong Luo , Hong Liu , Guixia Chen , Xiaomei Chen , Guangming Liu","doi":"10.1016/j.fct.2025.115512","DOIUrl":"10.1016/j.fct.2025.115512","url":null,"abstract":"<div><div>Filamin c is an allergen with strong IgE-binding activity of <em>Scylla paramamosain</em> (named Scy p 9). In this study, the T cell epitopes of Scy p 9 were identified using the CD4<sup>+</sup>T lymphocyte proliferation assay in the mononuclear cells of the spleen allergic mice. Nine of the thirteen T cell epitope peptides that have been found have the ability to trigger the production of the Th1 cytokine (IFN-γ) and TGF-β. Meanwhile, the findings of the inhibitory Dot blot and basophil activation test of crab allergy patients showed that the mixed nine T cell epitope peptides lacked IgE-binding activity and was unable to stimulate the expression of CD63 and CD203c on the surface of basophils. Non-allergenic mixed T cell epitope peptides (NAMTEP) demonstrate the potential for preventing Scy p 9 allergies. According to the evaluation of the preventive effect of Scy p 9 allergy mouse model, mice challenged with oral administration of Scy p 9 after early injection of NAMTEP did not show any allergic symptoms. NAMTEP inhibited IgE generation and Th2 immune response, preventing Scy p 9 allergy reactions in mice. These results would provide a theoretical foundation for the specific prevention of allergens in crustacean aquatic products.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115512"},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941310","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":"Kaempferol improves recurrent spontaneous abortion outcomes and prevents oxidative stress damage by inhibiting the NF-kB signaling pathway.","authors":"Guangli Xu, Huijuan Li, Lei Fang, Jingjing Guo, Chenyu Zhang, Jing Guo, Shuqing Ren, Ping Chen","doi":"10.1016/j.fct.2025.115540","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115540","url":null,"abstract":"<p><p>Kaempferol (KFL) is a natural flavonoid found in various vegetables and fruits, known for its biological properties such as anti-inflammatory and antioxidant effects. However, there is a lack of research on the potential impact of KFL on recurrent spontaneous abortion (RSA). This study sought to establish an RSA model by mating female CBA/J mice with male DBA/2 mice to assess the influence of KFL on RSA. The results demonstrated that KFL administration leads to a decrease in embryo absorption, reduced inflammation at the maternal-fetal interface, and balanced the T helper 1/T helper 2 ratio, ultimately enhancing pregnancy outcomes. Additionally, KFL was found to enhance placental development, decrease apoptosis, and alleviate oxidative stress in placental tissues of RSA mice. Besides, we investigated the impact of KFL on oxidation-damaged HTR-8/Svneo cells. The findings indicated that KFL mitigates oxidative damage in trophoblast cells by modulating the NF-κB pathway. Furthermore, RNA sequencing revealed that KFL treatment leads to large transcriptome changes in HTR-8/Svneo cells. Overall, the research demonstrated that KFL has the potential to alleviate placental inflammation and oxidative stress, thereby enhancing pregnancy outcomes in RSA mice. The regulatory mechanism of KFL in reducing oxidative damage may be involved in modulating the NF-κB pathway.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115540"},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955267","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, 1,1-diethoxyisooctane, CAS Registry Number 69178-43-4","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.2025.115528","DOIUrl":"10.1016/j.fct.2025.115528","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115528"},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941417","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, 2-isobutylquinoline, CAS registry number 93-19-6","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.2025.115519","DOIUrl":"10.1016/j.fct.2025.115519","url":null,"abstract":"<div><div>2-Isobutylquinoline was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Target data show that 2-isobutylquinoline 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 III material, and the exposure to 2-isobutylquinoline is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). Data from read-across analog quinoline (CAS # 91-22-5) show that there are no safety concerns for 2-isobutylquinoline for skin sensitization under the current declared levels of use. The photoirritation endpoint was evaluated based on data and ultraviolet/visible (UV/Vis) spectra; 2-isobutylquinoline is not photoirritating. The photoallergenicity endpoint was evaluated based on UV/Vis spectra; 2-isobutylquinoline is not photoallergenic. The environmental endpoints were evaluated; 2-isobutylquinoline was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients (RQs), 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":"201 ","pages":"Article 115519"},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941292","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, decanal dimethyl acetal, CAS Registry Number 7779-41-1","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.2025.115515","DOIUrl":"10.1016/j.fct.2025.115515","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115515"},"PeriodicalIF":3.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941392","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}