Toxicology letters最新文献

{"title":"Review of the genotoxicity of \"Arvin compounds\", drinking water contaminants formed by the degradation of UV-stabilizers in polyolefin pipes.","authors":"Wolfgang Dekant","doi":"10.1016/j.toxlet.2024.11.004","DOIUrl":"https://doi.org/10.1016/j.toxlet.2024.11.004","url":null,"abstract":"<p><p>Polyolefin pipes used in drinking water distribution systems require a number of functional additives to ensure stability and durability. Some of these additives and/or their degradation products may migrate from the pipes into the drinking water. Previously, a number of branched chain alkylphenol degradants have been identified in drinking water; these were termed \"Arvin substances\" and numbered Arvin 1 to 10. As potential genotoxicity is a human health safety concern, the genotoxicity of Arvin substances is reviewed based on comprehensive in vitro and in vivo data available. Results obtained from genotoxicity studies addressing mutagenicity and clastogenicity are available for nine of the ten Arvin substances. These nine Arvin substances were consistently negative in bacterial mutagenicity studies. Divergent results were obtained in clastogenicity assays with some positive responses induced by the branched chain alkylphenols Arvin 1, 2, and 4, often accompanied by significant cytotoxicity. However, Arvin 1, 2, and 4 did not induce micronuclei or genotoxicity in vivo during follow-up testing. The other Arvin compounds did not show genotoxic activity in vitro. In conclusion, regarding human health risk characterization, the Arvin compounds are not considered genotoxic agents based on the available data.</p>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711133","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":"Dose-, stage- and sex- difference of prenatal prednisone exposure on placental morphological and functional development.","authors":"Xiaomeng Zha, Man Fang, Wen Zhong, Liang Chen, Hui Feng, Min Zhang, Hui Wang, Yuanzhen Zhang","doi":"10.1016/j.toxlet.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.toxlet.2024.11.005","url":null,"abstract":"<p><p>Prednisone, a synthetic glucocorticoid, is commonly used to treat autoimmune diseases in pregnant women. However, some studies suggest that the use of prednisone during pregnancy may lead to adverse pregnancy outcomes. In this study, we established PPE mouse models at different doses (0.25, 0.5, 1.0mg/kg·d) and different stages (whole pregnancy, early pregnancy and middle-late pregnancy) and determined outcomes on the placenta and fetus. The results of our study indicated that at the highest dose of 1mg/kg PPE using a GD 0-18 dosing regime, PPE caused placental morphological changes measured as a decrease in placental weight relative to controls and a decrease in the placenta junctional zone (JZ)/labyrinth zone (LZ) ratio. No changes were observed on the fetuses for number of live, stillborn, and absorbed fetuses between the experimental groups and the control group. In the placentas at some doses, there were decreases in cell proliferation markers measured at the RNA and protein level by Western blot and increased apoptosis. Measures of gene expression at the mRNA level showed altered nutrients (including glucose, amino acid, and cholesterol) transport gene expressions with the most significant change associated with the male placentas at high-dose and whole pregnancy PPE group. It was further found that PPE led to the inhibition of the insulin-like growth factor 2 (IGF2)/insulin-like growth factor 1 receptor (IGF1R) signaling pathway, which was well correlated with the indicators of cell proliferation, syncytialization and nutrient (glucose and amino acid) transport indices. In conclusion, PPE can alter placental morphology and nutrient transport function, with differences in effect related to dose, stage and gender. Differential gene expressions measured for genes of the IGF2/IGF1R signaling pathway suggested this pathway may be involved in the effects seen with PPE. This study provides a theoretical and experimental basis for enhancing the understanding of the effects of prednisone use on placenta during human pregnancy but does not currently raise concerns for human use as effects were not seen on the fetuses and while the effects on cell proliferation are informative they were inconsistent and the differential effects on female and male placentas unexplained suggesting that further work is required to elucidate if these findings have relevance for human use of PPE during pregnancy.</p>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695844","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":"Aristolochic acid I promotes renal tubulointerstitial fibrosis by up-regulating expression of indoleamine 2,3-dioxygenase-1 (IDO1)","authors":"Langqun Chen ,&nbsp;Siyu Cheng ,&nbsp;Jiahui Ying ,&nbsp;Qi Zhang ,&nbsp;Chen Wang ,&nbsp;Huimin Wu ,&nbsp;Ying Wang ,&nbsp;Hong Zhang ,&nbsp;Jiahe Wang ,&nbsp;Jing Ye ,&nbsp;Liang Zhang","doi":"10.1016/j.toxlet.2024.11.003","DOIUrl":"10.1016/j.toxlet.2024.11.003","url":null,"abstract":"<div><div>Aristolochic acid I (AAI) is strongly nephrotoxic and can cause \"Aristolochic acid nephropathy (AAN)\". Aristolochic acid nephropathy is characterized by extensive renal interstitial fibrosis. However, the exact mechanism by which it occurs has not been fully elucidated. lt has been reported that indoleamine 2,3-dioxygenase-1 (IDO1) promotes renal fibrosis in renal disorders, but it is unclear how IDO1 functions in AAI-induced kidney fibrosis. In this work, we systematically examined the role of IDO1 in AAI-induced renal tubulointerstitial fibrosis. The results showed that AAI induced upregulation of IDO1 expression in renal tubular epithelial cells and mouse kidney. Inhibition of IDO1 expression reduced the levels of fibrosis-associated markers α-SMA, COL-I and FN and ameliorated renal tubular epithelial cell fibrosis. It also improved renal function, reduced collagen deposition, and ameliorated interstitial fibrosis in mice. Moreover, we discovered that inhibition of IDO1 decreased the expression of the apoptotic protein BAX, raised the expression of BCL-2 protein, and reduced apoptosis. The above studies suggest that IDO1 is a target of action in renal tubulointerstitial fibrosis caused by AAI, and inhibition of IDO1 may be a viable approach for the therapy of AAI-induced renal tubulointerstitial fibrosis.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"402 ","pages":"Pages 44-55"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639973","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":"Activation of mixed lineage kinase 3 by fine particulate matter induces skin inflammation in human keratinocytes","authors":"Jamyeong Koo ,&nbsp;Woo-Jin Sim ,&nbsp;Wonchul Lim ,&nbsp;Tae-Gyu Lim","doi":"10.1016/j.toxlet.2024.11.002","DOIUrl":"10.1016/j.toxlet.2024.11.002","url":null,"abstract":"<div><div>Fine particulate matter (PM_2.5) induces a range of diseases, including skin disorders, through inflammatory responses. In this study, we investigated the novel mechanisms by which PM_2.5 causes skin inflammation in human keratinocytes HaCaT. We observed increased protein expression of cyclooxygenase-2 (COX-2) and the production of prostaglandin E2 (PGE2) in PM_2.5-treated HaCaT cells. To identify the pathways promoting the expression of these inflammatory proteins, we conducted a phospho-kinase antibody array and confirmed that the phosphorylation levels of JNK and p38 were increased by PM_2.5-treated HaCaT cells. Further investigation of the phosphorylation levels of mitogen-activated protein kinases (MAPKs) and upstream signals revealed that PM_2.5 activated the MKK4/7-JNK-c-Jun and MKK3/6-p38-p70^S6K signaling pathways, while the phosphorylation level of ERK1/2 remained unchanged. HaCaT cells treated with PM_2.5 phosphorylated Mixed-lineage kinase 3 (MLK3), an upstream regulator of p38 and JNK. Furthermore, inhibition of ROS production by N-Acetylcysteine (NAC) treatment inhibited MLK3 phosphorylation. Taken together, ROS production induced by PM_2.5 activated the MLK3 signaling pathway and induced skin inflammation.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"402 ","pages":"Pages 38-43"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639970","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":"Nano titanium dioxide induces HaCaT cell pyroptosis via regulating the NLRP3/caspase-1/GSDMD pathway","authors":"Wanting Fu ,&nbsp;Mingxue Liu ,&nbsp;Yu Wang ,&nbsp;Huimin Yang ,&nbsp;Aoqi Ye ,&nbsp;Jianhong Wu ,&nbsp;Yang Li ,&nbsp;Zejun Yu ,&nbsp;Yinsheng Qiu ,&nbsp;Lingyun Xu","doi":"10.1016/j.toxlet.2024.11.001","DOIUrl":"10.1016/j.toxlet.2024.11.001","url":null,"abstract":"<div><div>Nano-titanium dioxide (Nano-TiO₂) is extensively utilized across various industries and has the capacity to penetrate human tissues through multiple biological barriers. The HaCaT cell line, as one of human immortalized keratinocytes, is usually used as a model for studying skin drug toxicology. The objective was to assess the toxic effects of nano-TiO₂ on HaCaT cells and to trigger pyroptosis. We used MTT method to evaluate the effects of three nano-TiO₂ particle sizes (15 nm, 30 nm and 80 nm) on cell viability at different concentrations. Subsequently, we used LDH, Hoechst 33342 and propidium iodide (PI) double staining, scanning electron microscopy (SEM), Western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) to evaluate the effects of different particle sizes on cells at the same concentration. Our findings indicated that HaCaT cell viability diminished with increasing nano-TiO₂ concentrations. Moreover, nano-TiO₂ increased LDH level in cellular supernatant. Fluorescence double staining, SEM, WB and RT-qPCR showed that nano-TiO₂ induced cell membrane damage by activating pyroptosis pathway of NLRP3/caspase-1/GSDMD. These results suggest that nano-TiO₂ toxicity in HaCaT cells is influenced by both dose and particle size, and is associated with the induction of pyroptosis. Frequent and large exposures to nano- TiO₂ in daily life may cause serious health hazards.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"402 ","pages":"Pages 27-37"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639966","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":"Toxicity risk from hip implant CoCrMo particles: The impact of dynamic flow rate on neuronal cells in microfluidic systems","authors":"Matthew Jeffers ,&nbsp;Hemalatha Kanniyappan ,&nbsp;Kai Yuan Cheng ,&nbsp;Saundarya Prithweeraj ,&nbsp;Govindaraj Perumal ,&nbsp;Mark Barba ,&nbsp;Yang Lin ,&nbsp;Mathew T. Mathew","doi":"10.1016/j.toxlet.2024.10.009","DOIUrl":"10.1016/j.toxlet.2024.10.009","url":null,"abstract":"<div><div>In patients with total hip replacements (THRs), wear products in the form of nanoparticles and ions are released, especially around implant failure. In this study, we use N2a cells, a neuroblastoma cell line, to evaluate the effects of different flow rates on neuronal toxicity amidst exposure to CoCrMo particles. We hypothesized that increasing flow rates would increase N2a cell viability and decrease N2a cell-degradation products (DPs) toxicity. We conducted four 24-hour experiments, each with four flow rate conditions, 0, 50, 100, and 200 μL/min, based on the physiological shear stress of the vessels in the human body, to evaluate cell viability, cell morphology, and cell-DPs interaction. Steps included microfluidic channel preparation, N2a cell culturing, CoCrMo particle acquisition, microfluidic system assembly, and dynamic flow neurotoxicity evaluation, which included video microscopy, AlamarBlue, live/dead imaging, DAPI, and ROS assay. The results suggest that fewer neurotoxic reactions and greater viability at higher flow rates supported our hypothesis, although the full range of viable flow rates is yet to be studied. While cell-particle interaction is complex and dynamic, flow rate did modulate toxicity, viability, morphology, and growth environment. The microfluidic system should continue to be developed to study toxicology aspects of implants by simulating <em>in vivo</em> conditions more accurately.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"402 ","pages":"Pages 56-67"},"PeriodicalIF":2.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628822","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":"Neurotoxic and developmental effects of scented incense stick smoke: Network toxicology and zebrafish model study","authors":"Gokul Sudhakaran ,&nbsp;Karthikeyan Ramamurthy ,&nbsp;V.N. Dhaareshwar ,&nbsp;Rajakrishnan Rajagopal ,&nbsp;Ahmed Alfarhan ,&nbsp;Jesu Arockiaraj","doi":"10.1016/j.toxlet.2024.10.008","DOIUrl":"10.1016/j.toxlet.2024.10.008","url":null,"abstract":"<div><div>Burning incense sticks is a traditional practice in many cultures, especially in Southeast Asia. While it is often regarded as sacred and beneficial, modern incense sticks contain various chemicals that can pose health risks. A GCMS analysis of the ICS revealed potential compounds. Network toxicology revealed that ICS contains compounds violating Lipinski's rule of five, leading to potential neurotoxic effects. Key pathways affected include neuroactive ligand-receptor interaction and calcium signaling, associated with neurodegenerative diseases like Parkinson's and Alzheimer's. Significant genes involved are STAT3, BCL2, and MTOR, emphasizing the chemical hazards of ICS exposure. We investigated the toxicity of ICS using zebrafish (<em>Danio rerio</em>) embryos as a mode. ICS exposure resulted in a dose-dependent increase in toxicity. High concentrations (7 and 14 µg/ml) led to immediate mortality, while lower concentrations (0.1, 0.3, 0.5, and 1 µg/ml) caused developmental defects such as yolk sac edema, skeletal malformations, and pericardial edema. Mortality rates increased with higher concentrations, confirming dose-dependent ICS exposure caused hypoactive locomotion, with reduced distance traveled and velocity toxicity. Higher concentrations of ICS led to increased ROS levels and cellular damage, as evidenced by enhanced staining levels. A dose-dependent increase in lipid peroxidation (DPPP assay) and lipid accumulation (Nile red assay) was observed. Higher ICS concentrations led to significant oxidative damage to lipids and increased lipid deposition. Enzymatic assays showed that ICS exposure significantly decreased the activities of antioxidant enzymes SOD and CAT, indicating impaired antioxidant defense, while increasing LDH activity, signaling tissue damage and cytotoxicity. Gene expression analysis revealed downregulation of SOD1 and CAT genes, upregulation of inflammatory genes TNF-α and IL-1β, and increased expression of the apoptotic gene p53 with decreased expression of Bcl-2 and BDNF. These findings highlight ICS's potential to cause oxidative stress, inflammation, apoptosis, and neurodevelopmental impairments.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"402 ","pages":"Pages 15-26"},"PeriodicalIF":2.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508700","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":"Examination of the anabolic activity and mechanisms of action of the combination of Diosgenin and Ecdysterone in C2C12 myotubes","authors":"T. Kostov ,&nbsp;P. Diel ,&nbsp;E. Isenmann","doi":"10.1016/j.toxlet.2024.10.005","DOIUrl":"10.1016/j.toxlet.2024.10.005","url":null,"abstract":"<div><div>Plant steroids such as ecdysterone (ECDY) or diosgenin (DIO) have been associated with anabolic and performance-enhancing effects for years. However, the molecular mechanisms have not yet been extensively studied in skeletal muscle cells. Consequently, the anabolic activity and associated molecular mechanisms of ECDY and DIO alone and in combination were investigated in C2C12 myotubes. Dose-dependent effects of both compounds on myotube diameter, mRNA expression of IGF-1 and PI3KR1 as well as expression of myosin heavy chain (MHC) proteins were analyzed in differentiated C2C12 cells. In addition, the binding affinities to androgen and estrogen receptors were analyzed. Treatment with ECDY and DIO significantly induced hypertrophy of C2C12 myotubes. Partially additive effects were observed. This is supported by the mRNA expression of IGF-1 and PI3KR1 as well as in the expression of MHC. However, no clear statement can be made regarding which combination has the strongest additive effects. Besides the results suggest that, in contrast to ECDY, DIO has antiandrogenic effects and bind on AR. Consequently, it indicate that two different mechanisms of action are activated in ECDY and DIO combinations. However, this must be confirmed in further cell cultures studies and human interventions concerning anti-doping regulations.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"401 ","pages":"Pages 181-189"},"PeriodicalIF":2.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benzo[b]fluoranthene damages coronary artery and affects atherosclerosis markers in mice and umbilical vein endothelial cells","authors":"Hang Luo ,&nbsp;Shanshan Zhao ,&nbsp;Jing Zi ,&nbsp;Yifan Hu ,&nbsp;Yuqin Yao ,&nbsp;Jingyuan Xiong","doi":"10.1016/j.toxlet.2024.10.007","DOIUrl":"10.1016/j.toxlet.2024.10.007","url":null,"abstract":"<div><div>Polycyclic aromatic hydrocarbons (PAHs) exposure is associated with cardiovascular diseases. Toxic effects of PAHs are diverse, while cardiovascular consequences of benzo[<em>b</em>]fluoranthene (B[<em>b</em>]F) are unclear. Here, we reported the impacts of B[<em>b</em>]F on coronary artery and atherosclerosis markers both in mice and umbilical vein endothelial EAhy.926 cells. In mice, we found that B[<em>b</em>]F decreases heart-to-body weight ratio, affects aortic physiology, elevates serum low-density lipoprotein and total cholesterol, increases aortic levels of collagen fiber and atherosclerotic marker vascular cell adhesion molecule-1 (VCAM-1), and downregulates oxidative stress related nuclear factor erythroid 2-related factor 2 (Nrf2). In EAhy.926 cells, we showed that B[<em>b</em>]F inhibits cell proliferation and migration in a dose-dependent manner, induces cell cycle arrest and apoptosis, increases reactive oxygen species, upregulates VCAM-1 level, and suppresses expression of Nrf2. Taken together, our findings reveal that B[<em>b</em>]F exposure may contribute to coronary artery damage and potentially induce atherosclerosis, possibly via the Nrf2-related signaling pathways.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"401 ","pages":"Pages 150-157"},"PeriodicalIF":2.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432867","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":"Are the postmortem concentration changes of the synthetic cannabinoid cumyl-5F-P7AICA and its N-pentanoic acid metabolite dependent on the environmental conditions? – A systematic study following pulmonary administration to pigs","authors":"Nadja Walle ,&nbsp;Adrian A. Doerr ,&nbsp;Benjamin Peters ,&nbsp;Matthias W. Laschke ,&nbsp;Michael D. Menger ,&nbsp;Peter H. Schmidt ,&nbsp;Markus R. Meyer ,&nbsp;Nadine Schaefer","doi":"10.1016/j.toxlet.2024.10.006","DOIUrl":"10.1016/j.toxlet.2024.10.006","url":null,"abstract":"<div><div>The number of fatal cases involving synthetic cannabinoids (SCs) is increasing. However, interpretation of postmortem (PM) toxicological findings is challenging, due to unknown PM intervals and possible redistribution processes or instabilities. Only sparse data on SCs are available. Therefore, a controlled pig study was performed to determine the PM stability of <em>cumyl</em>-5F-P7AICA under different environmental conditions. Ten pigs inhalatively received 200 µg/kg body weight <em>cumyl</em>-5F-P7AICA each. Six hours later, they were euthanized and biopsies of the main tissues and body fluids were taken. Animals were stored in air or water (n=5 each) and samples were repeatedly taken for three days. Quantification of <em>cumyl</em>-5F-P7AICA and its <em>N</em>-pentanoic acid metabolite (NPA) was performed using standard addition or a fully validated method (blood) followed by LC-MS/MS. Time-dependent concentration changes of <em>cumyl</em>-5F-P7AICA were observed in liver, bile fluid and muscle specimens at both conditions. Concentrations of NPA only changed considerably in duodenum content of animals stored in air. Environment-dependent concentrations changes were only observed for <em>cumyl</em>-5F-P7AICA in kidney and the NPA metabolite in duodenum content. Overall, <em>cumyl</em>-5F-P7AICA and its metabolite seem to be quite stable in PM specimens. Hence, also central blood might be analyzed, if no peripheral blood is available.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"401 ","pages":"Pages 170-180"},"PeriodicalIF":2.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}