Pub Date : 2026-01-23DOI: 10.1016/j.fct.2026.115975
Guanjun Nan , Zhengzheng Liu , Xuemei Zhou , Yunzhe Li , Fanli Yang , Rong Lin , Guangde Yang
The global use of Traditional Chinese medicines (TCMs) is increasing, raising concerns regarding contamination by heavy metal(loid)s. Although decoction is a common method of administration, limited research has investigated the transfer of heavy metal(loid)s from medicinal materials to decoctions, particularly for compound formulas, or has performed probabilistic health risk assessments. In this study, six common TCMs (Persicae Semen, Carthami Flos, Rehmanniae Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma, and Paeoniae Radix Alba) were collected from various regions across China. Concentrations of Pb, Cd, Hg, Cu, and As were analyzed in the raw medicinal materials, their single-herb decoctions, and the corresponding compound formula decoction (Taohong Siwu Decoction). The results showed that Hg in some batches exceeded safety limits. Transfer rates of heavy metal(loid)s from medicinal materials to the decoctions varied considerably among elements, ranging from 8.67 % to 65.56 %. Compared with single-herb decoctions, the dissolution of Cu, Pb, and Cd increased in the compound decoction, whereas that Hg decreased. Probabilistic risk assessment indicated no significant non-carcinogenic risk; however, Paeoniae Radix Alba showed a 1.12 % probability of carcinogenic risk above the 1 × 10−4 threshold. Importantly, both heavy metal(loid) levels and the associated health risks were substantially lower in the decoctions than in the raw materials.
{"title":"Probabilistic risk assessment of heavy metal(loid)s in traditional Chinese medicinal materials and their decoctions: Integrating dissolution characteristic with Monte Carlo simulation","authors":"Guanjun Nan , Zhengzheng Liu , Xuemei Zhou , Yunzhe Li , Fanli Yang , Rong Lin , Guangde Yang","doi":"10.1016/j.fct.2026.115975","DOIUrl":"10.1016/j.fct.2026.115975","url":null,"abstract":"<div><div>The global use of Traditional Chinese medicines (TCMs) is increasing, raising concerns regarding contamination by heavy metal(loid)s. Although decoction is a common method of administration, limited research has investigated the transfer of heavy metal(loid)s from medicinal materials to decoctions, particularly for compound formulas, or has performed probabilistic health risk assessments. In this study, six common TCMs (<em>Persicae Semen</em>, <em>Carthami Flos</em>, <em>Rehmanniae Radix</em>, <em>Angelicae Sinensis Radix</em>, <em>Chuanxiong Rhizoma</em>, and <em>Paeoniae Radix Alba</em>) were collected from various regions across China. Concentrations of Pb, Cd, Hg, Cu, and As were analyzed in the raw medicinal materials, their single-herb decoctions, and the corresponding compound formula decoction (Taohong Siwu Decoction). The results showed that Hg in some batches exceeded safety limits. Transfer rates of heavy metal(loid)s from medicinal materials to the decoctions varied considerably among elements, ranging from 8.67 % to 65.56 %. Compared with single-herb decoctions, the dissolution of Cu, Pb, and Cd increased in the compound decoction, whereas that Hg decreased. Probabilistic risk assessment indicated no significant non-carcinogenic risk; however, <em>Paeoniae Radix Alba</em> showed a 1.12 % probability of carcinogenic risk above the 1 × 10<sup>−4</sup> threshold. Importantly, both heavy metal(loid) levels and the associated health risks were substantially lower in the decoctions than in the raw materials.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"210 ","pages":"Article 115975"},"PeriodicalIF":3.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045787","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}
Pub Date : 2026-01-23DOI: 10.1016/j.fct.2026.115976
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, methyl 2-(formylamino)benzoate, CAS Registry Number 41270-80-8.","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.2026.115976","DOIUrl":"10.1016/j.fct.2026.115976","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115976"},"PeriodicalIF":3.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045755","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}
Pub Date : 2026-01-22DOI: 10.1016/j.fct.2026.115968
Pavan K. Jayaswamy , Trupthi Ambrish , Vinay C. Sangamesh , Adithi Kellarai , Prakash Patil , Lobo Manuel Alexander , Praveenkumar Shetty
Background
The balance between Annexin A1 (AnxA1), a pro-resolving mediator, and Annexin A2 (AnxA2), a pro-inflammatory counterpart, is essential for immune homeostasis but remains poorly explored in Alzheimer's disease (AD).
Aim
To evaluate butyrate's ability to restore AnxA1/AnxA2 equilibrium and attenuate tauopathy and neuroinflammation in cellular and aluminum chloride (AlCl3)/d-galactose AD models.
Methods
In vitro, BV2 cells were used to study AnxA1/AnxA2 reciprocity in microglia, while retinoic acid–differentiated C6 cells with a neuron-like phenotype were employed to assess tau phosphorylation and AnxA1/AnxA2 interplay. In vivo, AlCl3/d-galactose rats underwent behavioral testing, Western blotting, ELISA, and immunohistochemistry evaluating butyrate's effects on annexin balance, tau pathology, redox homeostasis, and acetylcholinesterase activity.
Results
In vitro, Aβ1–42 suppressed AnxA1 and elevated AnxA2 in BV2 microglia, increasing TNF-α, and promoted GSK-3α/β–driven tau phosphorylation in differentiated C6 neuron-like cells through AnxA1/AnxA2 reciprocal regulation. Butyrate restored AnxA1, suppressed AnxA2/GSK-3β/TNF-α, and attenuated tau pathology. In vivo, prophylactic butyrate preserved hippocampal cytoarchitecture, improved cognition, reduced amyloid burden, normalized redox balance, inhibited acetylcholinesterase, and re-equilibrated hippocampal/systemic AnxA1/AnxA2 with decreased p-tau.
Conclusion
Butyrate modulates the AnxA1/AnxA2 axis to suppress neuroinflammation and tauopathy, positioning it as a gut-brain axis therapeutic for sporadic AD.
背景：促溶解介质膜联蛋白A1 （AnxA1）和促炎症对应物膜联蛋白A2 （AnxA2）之间的平衡对免疫稳态至关重要，但在阿尔茨海默病（AD）中仍未得到充分研究。目的：评价丁酸盐在细胞和氯化铝(AlCl3)/ d -半乳糖AD模型中恢复AnxA1/AnxA2平衡、减轻牛头病变和神经炎症的能力。方法：体外利用BV2细胞研究小胶质细胞中AnxA1/AnxA2的相互作用，同时利用维甲酸分化的神经元样C6细胞评估tau磷酸化和AnxA1/AnxA2的相互作用。在体内，对AlCl3/ d -半乳糖大鼠进行行为测试、Western blotting、ELISA和免疫组织化学，评估丁酸盐对膜联蛋白平衡、tau病理学、氧化还原稳态和乙酰胆碱酯酶活性的影响。结果：a - β1-42在体外可抑制BV2小胶质细胞中AnxA1，升高AnxA2，升高TNF-α，并通过AnxA1/AnxA2相互调节促进分化的C6神经元样细胞中GSK-3α/β驱动的tau磷酸化。丁酸恢复AnxA1，抑制AnxA2/GSK-3β/TNF-α，减弱tau病理。在体内，预防性丁酸盐保留了海马细胞结构，改善了认知，减少了淀粉样蛋白负担，正常化了氧化还原平衡，抑制了乙酰胆碱酯酶，并通过降低p-tau重新平衡了海马/全身AnxA1/AnxA2。结论：丁酸调节AnxA1/AnxA2轴可抑制神经炎症和牛头病，可作为散发性AD的肠-脑轴治疗药物。
{"title":"Butyrate antagonizes Annexin A2–mediated tauopathy via Annexin A1 reciprocity in Alzheimer's disease","authors":"Pavan K. Jayaswamy , Trupthi Ambrish , Vinay C. Sangamesh , Adithi Kellarai , Prakash Patil , Lobo Manuel Alexander , Praveenkumar Shetty","doi":"10.1016/j.fct.2026.115968","DOIUrl":"10.1016/j.fct.2026.115968","url":null,"abstract":"<div><h3>Background</h3><div>The balance between Annexin A1 (AnxA1), a pro-resolving mediator, and Annexin A2 (AnxA2), a pro-inflammatory counterpart, is essential for immune homeostasis but remains poorly explored in Alzheimer's disease (AD).</div></div><div><h3>Aim</h3><div>To evaluate butyrate's ability to restore AnxA1/AnxA2 equilibrium and attenuate tauopathy and neuroinflammation in cellular and aluminum chloride (AlCl<sub>3</sub>)/<span>d</span>-galactose AD models.</div></div><div><h3>Methods</h3><div><em>In vitro</em>, BV2 cells were used to study AnxA1/AnxA2 reciprocity in microglia, while retinoic acid–differentiated C6 cells with a neuron-like phenotype were employed to assess tau phosphorylation and AnxA1/AnxA2 interplay. <em>In vivo</em>, AlCl<sub>3</sub>/<span>d</span>-galactose rats underwent behavioral testing, Western blotting, ELISA, and immunohistochemistry evaluating butyrate's effects on annexin balance, tau pathology, redox homeostasis, and acetylcholinesterase activity.</div></div><div><h3>Results</h3><div><em>In vitro,</em> Aβ<sub>1</sub>–<sub>42</sub> suppressed AnxA1 and elevated AnxA2 in BV2 microglia, increasing TNF-α, and promoted GSK-3α/β–driven tau phosphorylation in differentiated C6 neuron-like cells through AnxA1/AnxA2 reciprocal regulation. Butyrate restored AnxA1, suppressed AnxA2/GSK-3β/TNF-α, and attenuated tau pathology. <em>In vivo,</em> prophylactic butyrate preserved hippocampal cytoarchitecture, improved cognition, reduced amyloid burden, normalized redox balance, inhibited acetylcholinesterase, and re-equilibrated hippocampal/systemic AnxA1/AnxA2 with decreased p-tau.</div></div><div><h3>Conclusion</h3><div>Butyrate modulates the AnxA1/AnxA2 axis to suppress neuroinflammation and tauopathy, positioning it as a gut-brain axis therapeutic for sporadic AD.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"210 ","pages":"Article 115968"},"PeriodicalIF":3.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043675","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}
Pub Date : 2026-01-22DOI: 10.1016/j.fct.2026.115952
Heather Burleigh-Flayer, Ryan Canatsey, Paul Alan Jean, Linda Lea, Lorna Tempest
Cyclo-di-Badge (CdB) is a by-product of epoxy resin coatings applied to the inside of food cans. By-products are non-intentionally added substances (NIAS) with potential to migrate into food. Due to the lack of data on CdB, studies were conducted to identify potential health hazards. Toxicokinetics study results show negligible amounts of [14C]-CdB excreted in expired air and urine. [14C]-CdB is almost exclusively excreted in the feces with recoveries of ∼100%. The liver plays a role in the excretion of [14C]-CdB with recoveries of ≤7% in the bile with negligible amounts in blood indicating efficient first pass elimination. Genotoxicity tests (Ames and micronucleus) show negative results and the 90-day dietary study results show no adverse effects at levels up to 15,000 ppm (1139 mg/kg). Total recovery of [14C]-CdB in the feces supports the lack of systemic adverse effects in the 90-day dietary study and points to the lack of bioaccumulation potential. To assess risk, the NOAEL of 1139 mg/kg is used to calculate Margin of Safety (MOS) values of 17 (infants), 42 (children), and 247 (adults) indicating acceptable exposures. The lack of adverse effects and risk assessment suggest current CdB levels in canned food are not a concern for human health.
{"title":"Toxicological Evaluation and Risk Assessment of Cyclo-di-Badge, a Non-Intentionally Added Substance (NIAS), found in Epoxy Based Coatings of Food Cans.","authors":"Heather Burleigh-Flayer, Ryan Canatsey, Paul Alan Jean, Linda Lea, Lorna Tempest","doi":"10.1016/j.fct.2026.115952","DOIUrl":"https://doi.org/10.1016/j.fct.2026.115952","url":null,"abstract":"<p><p>Cyclo-di-Badge (CdB) is a by-product of epoxy resin coatings applied to the inside of food cans. By-products are non-intentionally added substances (NIAS) with potential to migrate into food. Due to the lack of data on CdB, studies were conducted to identify potential health hazards. Toxicokinetics study results show negligible amounts of [<sup>14</sup>C]-CdB excreted in expired air and urine. [<sup>14</sup>C]-CdB is almost exclusively excreted in the feces with recoveries of ∼100%. The liver plays a role in the excretion of [<sup>14</sup>C]-CdB with recoveries of ≤7% in the bile with negligible amounts in blood indicating efficient first pass elimination. Genotoxicity tests (Ames and micronucleus) show negative results and the 90-day dietary study results show no adverse effects at levels up to 15,000 ppm (1139 mg/kg). Total recovery of [<sup>14</sup>C]-CdB in the feces supports the lack of systemic adverse effects in the 90-day dietary study and points to the lack of bioaccumulation potential. To assess risk, the NOAEL of 1139 mg/kg is used to calculate Margin of Safety (MOS) values of 17 (infants), 42 (children), and 247 (adults) indicating acceptable exposures. The lack of adverse effects and risk assessment suggest current CdB levels in canned food are not a concern for human health.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115952"},"PeriodicalIF":3.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043687","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}
Pub Date : 2026-01-22DOI: 10.1016/j.fct.2026.115972
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
Naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- is not genotoxic, provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints, and show that there are no safety concerns for naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on data and ultraviolet/visible (UV/Vis) spectra; naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- is not photoirritating/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class III material, and the exposure to naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- is below the TTC (0.47 mg/day). The environmental endpoints were evaluated; naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- 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.
{"title":"Update to RIFM fragrance ingredient safety assessment, naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)-, CAS Registry Number 6790-58-5.","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.2026.115972","DOIUrl":"https://doi.org/10.1016/j.fct.2026.115972","url":null,"abstract":"<p><p>Naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- is not genotoxic, provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints, and show that there are no safety concerns for naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on data and ultraviolet/visible (UV/Vis) spectra; naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- is not photoirritating/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class III material, and the exposure to naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- is below the TTC (0.47 mg/day). The environmental endpoints were evaluated; naphtho[2,1-b]furan, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)- 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.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115972"},"PeriodicalIF":3.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043683","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}
Lactobacillus salivarius AP-32 (namely Ligilactobacillus salivarius AP-32, L. salivarius AP-32), isolated from the human gut, has shown a favorable safety profile. In 14-day acute and 90-day subchronic toxicity studies in rodents, no adverse effects were observed. The maximum tolerated dose was 16 g/kg body weight in the acute study, and the no-observed-adverse-effect level in the 90-day study was 1.88 g/kg body weight. It showed no mutagenicity in vivo or in vitro, including no chromosomal aberrations in mouse spermatogonia, no bone marrow cytotoxicity, and no mutagenic response in the Ames test (5000 μg/mL). L. salivarius AP-32 exhibited γ-hemolysis and bile salt hydrolase activity. It was non-toxic to Caco-2 cells, did not induce cytotoxicity, and demonstrated strong acid and bile tolerance, intestinal adhesion, and antimicrobial activity against Helicobacter pylori, Salmonella enterica subsp. enterica, Escherichia coli, Listeria monocytogenes, and Vibrio parahaemolyticus, while inducing M2 macrophages. Prior research indicated milk and soybean fermentated L. salivarius AP-32 held potential in regulating blood glucose, alleviating neonatal jaundice, and suppressing vaginal and urinary tract pathogens. These findings supported its safety and potential as a probiotic.
{"title":"Safety and toxicity assessment of Lactobacillus salivarius AP-32 with Probiotic potential in vivo and in vitro","authors":"Yu-Hsuan Chin, Yi-Wen Chen, Yen-Yu Huang, Ching-Min Li, Jia-Hung Lin, Yi-Wei Kuo, Chen-Yu Chen, Yen-Feng Lee, Cian-Dai Ciou, Ko-Chiang Hsia, Shin-Yu Tsai, Hsieh-Hsun Ho","doi":"10.1016/j.fct.2026.115970","DOIUrl":"10.1016/j.fct.2026.115970","url":null,"abstract":"<div><div><em>Lactobacillus salivarius</em> AP-32 (namely <em>Ligilactobacillus salivarius</em> AP-32, <em>L. salivarius</em> AP-32), isolated from the human gut, has shown a favorable safety profile. In 14-day acute and 90-day subchronic toxicity studies in rodents, no adverse effects were observed. The maximum tolerated dose was 16 g/kg body weight in the acute study, and the no-observed-adverse-effect level in the 90-day study was 1.88 g/kg body weight. It showed no mutagenicity <em>in vivo</em> or <em>in vitro</em>, including no chromosomal aberrations in mouse spermatogonia, no bone marrow cytotoxicity, and no mutagenic response in the Ames test (5000 μg/mL). <em>L. salivarius</em> AP-32 exhibited γ-hemolysis and bile salt hydrolase activity. It was non-toxic to Caco-2 cells, did not induce cytotoxicity, and demonstrated strong acid and bile tolerance, intestinal adhesion, and antimicrobial activity against <em>Helicobacter pylori</em>, <em>Salmonella enterica</em> subsp. <em>enterica</em>, <em>Escherichia coli</em>, <em>Listeria monocytogenes</em>, and <em>Vibrio parahaemolyticus</em>, while inducing M2 macrophages. Prior research indicated milk and soybean fermentated <em>L. salivarius</em> AP-32 held potential in regulating blood glucose, alleviating neonatal jaundice, and suppressing vaginal and urinary tract pathogens. These findings supported its safety and potential as a probiotic.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"210 ","pages":"Article 115970"},"PeriodicalIF":3.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040036","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}
Pub Date : 2026-01-21DOI: 10.1016/j.fct.2026.115948
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 Natural Complex Substance (NCS) fragrance ingredient safety assessment, laurel leaf oil, CAS Registry Number 8007-48-5, RIFM ID 476-E2.12","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.2026.115948","DOIUrl":"10.1016/j.fct.2026.115948","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"210 ","pages":"Article 115948"},"PeriodicalIF":3.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146027920","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}
Pub Date : 2026-01-20DOI: 10.1016/j.fct.2026.115967
Shaira Shane M. Orencio , Oliver B. Villaflores , Ferry Saputra , Gilbert Audira , Chung-Der Hsiao , Ross D. Vasquez
Tetrandrine, a Stephania-derived bisbenzylisoquinoline alkaloid, shows anticancer activity; however, its mechanisms, cardiotoxicity, and developmental effects are poorly understood. This study investigated tetrandrine's antiangiogenic efficacy and safety liabilities using in silico, in vitro, and in vivo methods. We hypothesized multi-target antiangiogenic activity, but dose-dependent toxicities limiting its therapeutic window.
Molecular docking predicted strong binding to angiogenesis targets: EGFR, MMP-13, and SRPK1. ADMET modeling indicated favorable pharmacokinetics yet moderate toxicity risks, with ProTox-III flagging immunotoxicity. In silico predictions indicated developmentally sensitive adverse effects, mirrored in zebrafish by greater embryonic sensitivity. In vitro assays confirmed MMP-13 inhibition (IC50 = 4.376 ppm). In zebrafish embryos, tetrandrine significantly reduced intersegmental vessel formation, confirming antiangiogenic potential, but revealed higher embryonic sensitivity, indicating a narrow therapeutic window. Cardiac assays showed concentration-dependent increases in heart rate and decreases in stroke volume, revealing cardiotoxicity. Sub-toxic doses preserved locomotor and exploratory activity, suggesting functional safety at lower exposures.
These findings highlight tetrandrine's dual profile: a promising natural antiangiogenic agent with demonstrable efficacy, yet with significant cardiotoxic and developmental liabilities. This study provides crucial mechanistic insight into both its therapeutic and toxicological actions, establishing a translational foundation for its further development.
{"title":"Dual potential of tetrandrine: Antiangiogenic efficacy and safety liabilities revealed through in silico, in vitro, and zebrafish models","authors":"Shaira Shane M. Orencio , Oliver B. Villaflores , Ferry Saputra , Gilbert Audira , Chung-Der Hsiao , Ross D. Vasquez","doi":"10.1016/j.fct.2026.115967","DOIUrl":"10.1016/j.fct.2026.115967","url":null,"abstract":"<div><div>Tetrandrine, a <em>Stephania</em>-derived bisbenzylisoquinoline alkaloid, shows anticancer activity; however, its mechanisms, cardiotoxicity, and developmental effects are poorly understood. This study investigated tetrandrine's antiangiogenic efficacy and safety liabilities using in silico, in vitro, and in vivo methods. We hypothesized multi-target antiangiogenic activity, but dose-dependent toxicities limiting its therapeutic window.</div><div>Molecular docking predicted strong binding to angiogenesis targets: EGFR, MMP-13, and SRPK1. ADMET modeling indicated favorable pharmacokinetics yet moderate toxicity risks, with ProTox-III flagging immunotoxicity. In silico predictions indicated developmentally sensitive adverse effects, mirrored in zebrafish by greater embryonic sensitivity. In vitro assays confirmed MMP-13 inhibition (IC<sub>50</sub> = 4.376 ppm). In zebrafish embryos, tetrandrine significantly reduced intersegmental vessel formation, confirming antiangiogenic potential, but revealed higher embryonic sensitivity, indicating a narrow therapeutic window. Cardiac assays showed concentration-dependent increases in heart rate and decreases in stroke volume, revealing cardiotoxicity. Sub-toxic doses preserved locomotor and exploratory activity, suggesting functional safety at lower exposures.</div><div>These findings highlight tetrandrine's dual profile: a promising natural antiangiogenic agent with demonstrable efficacy, yet with significant cardiotoxic and developmental liabilities. This study provides crucial mechanistic insight into both its therapeutic and toxicological actions, establishing a translational foundation for its further development.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"210 ","pages":"Article 115967"},"PeriodicalIF":3.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146027888","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}
Pub Date : 2026-01-20DOI: 10.1016/j.fct.2026.115961
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
(Z)-2-Penten-1-ol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analogs 2,6-nonadien-1-ol (CAS # 7786-44-9) and trans-2-hexenol (CAS # 928-95-0) show that (Z)-2-penten-1-ol is not expected to be genotoxic. Data on read-across analog allyl alcohol (CAS # 107-18-6) provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. Target data and data from read-across analog allyl alcohol (CAS # 107-18-6) show that there are no safety concerns for (Z)-2-penten-1-ol for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; (Z)-2-penten-1-ol 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 (Z)-2-penten-1-ol is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; (Z)-2-penten-1-ol 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.
{"title":"Update to RIFM fragrance ingredient safety assessment, (Z)-2-penten-1-ol, CAS Registry Number 1576-95-0","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.2026.115961","DOIUrl":"10.1016/j.fct.2026.115961","url":null,"abstract":"<div><div>(Z)-2-Penten-1-ol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analogs 2,6-nonadien-1-ol (CAS # 7786-44-9) and <em>trans</em>-2-hexenol (CAS # 928-95-0) show that (Z)-2-penten-1-ol is not expected to be genotoxic. Data on read-across analog allyl alcohol (CAS # 107-18-6) provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. Target data and data from read-across analog allyl alcohol (CAS # 107-18-6) show that there are no safety concerns for (Z)-2-penten-1-ol for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; (Z)-2-penten-1-ol 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 (Z)-2-penten-1-ol is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; (Z)-2-penten-1-ol 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":"210 ","pages":"Article 115961"},"PeriodicalIF":3.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146027937","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}
Pub Date : 2026-01-20DOI: 10.1016/j.fct.2026.115969
F Peter Guengerich, Samuel M Cohen, Gerhard Eisenbrand, Shoji Fukushima, Nigel J Gooderham, Stephen S Hecht, Ivonne M C M Rietjens, Thomas J Rosol, Jeanne M Davidsen, Christie L Harman, Sean V Taylor
The Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) is conducting a program to re-evaluate the safety of over 250 natural flavor complexes (NFCs) used as flavoring ingredients. This publication, fourteenth in the series, evaluates the safety of NFCs composed primarily of benzaldehyde, methyl salicylate, vanillin and other benzyl derivative compounds. In 2018, the Expert Panel published an update of its safety evaluation procedure for NFCs that was first published in 2005. This procedure relies on a complete constituent characterization of the NFC and organization of the constituents of each NFC into defined congeneric groups. The safety of the NFC is evaluated using the threshold of toxicological concern (TTC) approach using updated estimates of exposure in addition to the evaluation of all relevant safety data on the NFC and its principal constituents. The scope of the safety evaluation contained herein does not include added use in dietary supplements or any products other than food. Eighteen (18) NFCs, derived from the Vanilla, Prunus, Betula, Acacia, Cuminum, Jasminum, Gaultheria, Polianthes and Evernia genera, were affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavor ingredients, based on an evaluation of each NFC and the constituents and congeneric groups therein.
{"title":"lineFEMA GRAS assessment of natural flavor complexes: Vanilla extract, Bitter almond oil, Wintergreen oil and related flavoring ingredients - DRAFT 9.","authors":"F Peter Guengerich, Samuel M Cohen, Gerhard Eisenbrand, Shoji Fukushima, Nigel J Gooderham, Stephen S Hecht, Ivonne M C M Rietjens, Thomas J Rosol, Jeanne M Davidsen, Christie L Harman, Sean V Taylor","doi":"10.1016/j.fct.2026.115969","DOIUrl":"https://doi.org/10.1016/j.fct.2026.115969","url":null,"abstract":"<p><p>The Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) is conducting a program to re-evaluate the safety of over 250 natural flavor complexes (NFCs) used as flavoring ingredients. This publication, fourteenth in the series, evaluates the safety of NFCs composed primarily of benzaldehyde, methyl salicylate, vanillin and other benzyl derivative compounds. In 2018, the Expert Panel published an update of its safety evaluation procedure for NFCs that was first published in 2005. This procedure relies on a complete constituent characterization of the NFC and organization of the constituents of each NFC into defined congeneric groups. The safety of the NFC is evaluated using the threshold of toxicological concern (TTC) approach using updated estimates of exposure in addition to the evaluation of all relevant safety data on the NFC and its principal constituents. The scope of the safety evaluation contained herein does not include added use in dietary supplements or any products other than food. Eighteen (18) NFCs, derived from the Vanilla, Prunus, Betula, Acacia, Cuminum, Jasminum, Gaultheria, Polianthes and Evernia genera, were affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavor ingredients, based on an evaluation of each NFC and the constituents and congeneric groups therein.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115969"},"PeriodicalIF":3.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146027922","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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