Toxicology最新文献

{"title":"Occurrence and Ecotoxicological Impacts of Polybrominated Diphenyl Ethers (PBDEs) in Electronic Waste (E-Waste) in Africa: Options for Sustainable and Eco-Friendly Management Strategies","authors":"Emmanuel Sunday Okeke ,&nbsp;Chidiebele Emmanuel Nwankwo ,&nbsp;Timothy Prince Chidike Ezeorba ,&nbsp;Veronica Chisom Iloh ,&nbsp;Adebisi Esther Enochoghene","doi":"10.1016/j.tox.2024.153848","DOIUrl":"10.1016/j.tox.2024.153848","url":null,"abstract":"<div><p>Polybrominated diphenyl ethers (PBDEs) are persistent contaminants used as flame retardants in electronic products. PBDEs are contaminants of concern due to leaching and recalcitrance conferred by the stable and hydrophobic bromide residues. The near absence of legislatures and conscious initiatives to tackle the challenges of PBDEs in Africa has allowed for the indiscriminate use and consequent environmental degradation. Presently, the incidence, ecotoxicity, and remediation of PBDEs in Africa are poorly elucidated. Here, we present a position on the level of contamination, ecotoxicity, and management strategies for PBDEs with regard to Africa. Our review shows that Africa is inundated with PBDEs from the proliferation of e-waste due to factors like the increasing growth in the IT sector worsened by the procurement of second-hand gadgets. An evaluation of the fate of PBDEs in the African environment reveals that the environment is adequately contaminated, although reported in only a few countries like Nigeria and Ghana. Ultrasound-assisted extraction, microwave-assisted extraction, and Soxhlet extraction coupled with specific chromatographic techniques are used in the detection and quantification of PBDEs. Enormous exposure pathways in humans were highlighted with health implications. In terms of the removal of PBDEs, we found a gap in efforts in this direction, as not much success has been reported in Africa. However, we outline eco-friendly methods used elsewhere, including microbial degradation, zerovalent iron, supercritical fluid, and reduce, reuse, recycle, and recovery methods. The need for Africa to make and implement legislatures against PBDEs holds the key to reduced effect on the continent.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200667","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":"Modulation of Ras signaling pathway by exosome miRNAs in T-2 toxin-induced chondrocyte injury","authors":"Chaowei Wang ,&nbsp;Minhan Hu ,&nbsp;Yuequan Yuan ,&nbsp;Xi Lv ,&nbsp;Shujin Li ,&nbsp;Sijie Chen ,&nbsp;Feiyu Zhang ,&nbsp;Yifan Wu ,&nbsp;Yu Zhang ,&nbsp;Yanli Liu ,&nbsp;Feihong Chen ,&nbsp;Xiong Guo ,&nbsp;Yujie Ning ,&nbsp;Xi Wang","doi":"10.1016/j.tox.2024.153858","DOIUrl":"10.1016/j.tox.2024.153858","url":null,"abstract":"<div><p>This study aims to investigate the impact of T-2 toxin on the regulation of downstream target genes and signaling pathways through exosome-released miRNA in the development of cartilage damage in Kashin-Beck disease (KBD). Serum samples from KBD patients and supernatant from C28/I2 cells treated with T-2 toxin were collected for the purpose of comparing the differential expression of exosomal miRNA using absolute quantitative miRNA-seq. Target genes of differential exosomal miRNAs were identified using Targetscan and Miranda databases, followed by GO and KEGG enrichment analyses. Validation of key indicators of chondrocyte injury in KBD was conducted using Real-time quantitative PCR (RT-qPCR) and Immunohistochemical staining (IHC). A total of 20 exosomal miRNAs related to KBD were identified in serum, and 13 in chondrocytes (C28/I2). The identified exosomal miRNAs targeted 48,459 and 60,612 genes, primarily enriched in cell organelles and membranes, cell differentiation, and cytoskeleton in the serum, and the cytoplasm and nucleus, metal ion binding in chondrocyte (C28/I2). The results of the KEGG enrichment analysis indicated that the Ras signaling pathway may play a crucial role in the pathogenesis of KBD. Specifically, the upregulation of hsa-miR-181a-5p and hsa-miR-21–3p, along with the downregulation of hsa-miR-152–3p and hsa-miR-186–5p, were observed. Additionally, T-2 toxin intervention led to a significant downregulation of RALA, REL, and MAPK10 expression. Furthermore, the protein levels of RALA, REL, and MAPK10 were notably decreased in the superficial and middle layers of cartilage tissues from KBD. The induction of differential expression of chondrocyte exosomal miRNAs by T-2 toxin results in the collective regulation of target genes RALA, REL, and MAPK10, ultimately mediating the Ras signaling pathway and causing a disruption in chondrocyte extracellular matrix metabolism, leading to chondrocyte injury.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200664","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":"Fine particulate matter disrupts bile acid homeostasis in hepatocytes via binding to and activating farnesoid X receptor","authors":"Donghui Zhang ,&nbsp;Xinya Liu ,&nbsp;Lanchao Sun ,&nbsp;Daochuan Li ,&nbsp;Jingyue Du ,&nbsp;Huizi Yang ,&nbsp;Dianke Yu ,&nbsp;Chuanhai Li","doi":"10.1016/j.tox.2024.153850","DOIUrl":"10.1016/j.tox.2024.153850","url":null,"abstract":"<div><p>Fine particulate matter (PM_2.5)-induced metabolic disorders have attracted increasing attention, however, the underlying molecular mechanism of PM2.5-induced hepatic bile acid disorder remains unclear. In this study, we investigated the effects of PM_2.5 components on the disruption of bile acid in hepatocytes through farnesoid X receptor (FXR) pathway. The receptor binding assays showed that PM_2.5 extracts bound to FXR directly, with half inhibitory concentration (IC₅₀) value of 21.7 μg/mL. PM_2.5 extracts significantly promoted FXR-mediated transcriptional activity at 12.5 μg/mL. In mouse primary hepatocytes, we found PM_2.5 extracts (100 μg/mL) significantly decreased the total bile acid levels, inhibited the expression of bile acid synthesis gene (Cholesterol 7 alpha-hydroxylase, Cyp7a1), and increased the expression of bile acid transport genes (Multidrug resistance associated protein 2, Abcc2; and Bile salt export pump, Abcb11). Moreover, these alterations were significantly attenuated by knocking down FXR in hepatocytes. We further divided the organic components and water-soluble components from PM_2.5, and found that two components bound to and activated FXR, and decreased the bile acid levels in hepatocytes. In addition, benzo[<em>a</em>]pyrene (B[<em>a</em>]P) and cadmium (Cd) were identified as two bioactive components in PM_2.5-induced bile acid disorders through FXR signaling pathway. Overall, we found PM_2.5 components could bind to and activate FXR, thereby disrupting bile acid synthesis and transport in hepatocytes. These new findings also provide new insights into PM_2.5-induced toxicity through nuclear receptor pathways.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184698","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":"Combined exposure of PS-MPs with NaF induces Sertoli cell death and dysfunction via ferroptosis and apoptosis","authors":"Tan Ma ,&nbsp;Huixian Cheng ,&nbsp;Liang Kong ,&nbsp;Chenghao Shen ,&nbsp;Haibo Jin ,&nbsp;Hongliang Li ,&nbsp;Chun Pan ,&nbsp;Jingyan Liang","doi":"10.1016/j.tox.2024.153849","DOIUrl":"10.1016/j.tox.2024.153849","url":null,"abstract":"<div><p>The individual toxicity of sodium fluoride (NaF) and microplastics (MPs) has been extensively documented. Owing to their high specific surface area, widespread presence and durability, MPs can adsorb a broad spectrum of environmental contaminants into the organism. However, the combined toxicity of NaF and MPs has not been investigated. This study aimed to assess the effects of combined exposure to NaF and MPs on the function of testicular Sertoli cells (SCs) in male mice, and to investigate the underlying molecular mechanisms. The study revealed that combined exposure to NaF and MPs resulted in a decrease in the negative surface charge of MPs, along with an increase in the number of MPs entering the SCs. Through <em>in vivo</em> observation of the testicular pathological structure, spermatogenesis, and cell apoptosis in 180-day-old male mice, we discovered that combined exposure to NaF (80 mg/L) and MPs (10 mg/L) heightened reproductive toxicity compared to the individual exposure groups. This was evidenced by testicular structural defects, impaired spermatogenesis, and increased testicular cell apoptosis. Our <em>in vitro</em> studies showed that NaF (21 μg/mL) and MPs (100 μg/mL) synergistically induced SCs apoptosis and ferroptosis, leading to a reduction in SCs number and dysfunction. This ultimately resulted in structural and functional damage to the testes. Our findings demonstrate, for the first time, the synergistic effects of NaF and MPs on reproductive toxicity in mammals. These insights may provide valuable contributions to co-toxicity studies involving MPs and other environmental pollutants.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184689","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":"c-Jun targets miR-451a to regulate HQ-induced inhibition of erythroid differentiation via the BATF/SETD5/ARHGEF3 axis","authors":"Yanrong Lv ,&nbsp;Xiaoju Ma ,&nbsp;Qing Liu ,&nbsp;Zihao Long ,&nbsp;Shuangqi Li ,&nbsp;Zhaoqing Tan ,&nbsp;Dongsheng Wang ,&nbsp;Xiumei Xing ,&nbsp;Liping Chen ,&nbsp;Wen Chen ,&nbsp;Qing Wang ,&nbsp;Qing Wei ,&nbsp;Mengjun Hou ,&nbsp;Yongmei Xiao","doi":"10.1016/j.tox.2024.153843","DOIUrl":"10.1016/j.tox.2024.153843","url":null,"abstract":"<div><p>Benzene, a widely used industrial chemical, has been clarified to cause hematotoxicity. Our previous study suggested that miR-451a may play a role in benzene-induced impairment of erythroid differentiation. However, the mechanism underlying remains unclear. In this study, we explored the role of miR-451a and its underlying mechanisms in hydroquinone (HQ)-induced suppression of erythroid differentiation in K562 cells. 0, 1.0, 2.5, 5.0, 10.0, and 50 μM HQ treatment of K562 cells resulted in a dose-dependent inhibition of erythroid differentiation, as well as the expression of miR-451a. Bioinformatics analysis was conducted to predict potential target genes of miR-451a and dual-luciferase reporter assays confirmed that miR-451a can directly bind to the 3'-UTR regions of BATF, SETD5, and ARHGEF3 mRNAs. We further demonstrated that over-expression or down-regulation of miR-451a altered the expression of BATF, SETD5, and ARHGEF3, and also modified erythroid differentiation. In addition, BATF, SETD5, and ARHGEF3 were verified to play a role in HQ-induced inhibition of erythroid differentiation in this study. Knockdown of SETD5 and ARHGEF3 reversed HQ-induced suppression of erythroid differentiation while knockdown of BATF had the opposite effect. On the other hand, we also identified c-Jun as a potential transcriptional regulator of miR-451a. Forced expression of c-Jun increased miR-451a expression and reversed the inhibition of erythroid differentiation induced by HQ, whereas knockdown of c-Jun had the opposite effect. And the binding site of c-Jun and miR-451a was verified by dual-luciferase reporter assay. Collectively, our findings indicate that miR-451a and its downstream targets BATF, SETD5, and ARHGEF3 are involved in HQ-induced erythroid differentiation disorder, and c-Jun regulates miR-451a as a transcriptional regulator in this process.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157491","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":"MCF-7 cell - derived exosomes were involved in protecting source cells from the damage caused by tributyltin chloride via transport function","authors":"Yiren Xiong ,&nbsp;Guoqiang Guo ,&nbsp;Hongyi Xian ,&nbsp;Zuqing Hu ,&nbsp;Di Ouyang ,&nbsp;Jiayi He ,&nbsp;Shanshan He ,&nbsp;Renyi Liu ,&nbsp;Zhenjie Gao ,&nbsp;Meilin Tang ,&nbsp;Ying Chen ,&nbsp;Suqin Tan ,&nbsp;Xiaoqi Zhu ,&nbsp;Abudumijiti Abulimiti ,&nbsp;Sujin Zheng ,&nbsp;Hehai Huang ,&nbsp;Dalin Hu","doi":"10.1016/j.tox.2024.153844","DOIUrl":"10.1016/j.tox.2024.153844","url":null,"abstract":"<div><p>Tributyltin chloride (TBTC) is a ubiquitous environmental pollutant with various adverse effects on human health. Exosomes are cell - derived signaling and substance transport vesicles. This investigation aimed to explore whether exosomes could impact the toxic effects caused by TBTC via their transport function. Cytotoxicity, DNA and chromosome damage caused by TBTC on MCF-7 cells were analyzed with CCK-8, flow cytometry, comet assay and micronucleus tests, respectively. Exosomal characterization and quantitative analysis were performed with ultracentrifugation, transmission electron microscope (TEM) and bicinchoninic acid (BCA) methods. TBTC content in exosomes was detected with Liquid Chromatography-Mass Spectrometry (LC-MS). The impacts of exosomal secretion on the toxic effects of TBTC were analyzed. Our data indicated that TBTC caused significant cytotoxicity, DNA and chromosome damage effects on MCF-7 cells, and a significantly increased exosomal secretion. Importantly, TBTC could be transported out of MCF-7 cells by exosomes. Further, when exosomal secretion was blocked with GW4869, the toxic effects of TBTC were significantly exacerbated. We concluded that TBTC promoted exosomal secretion, which in turn transported TBTC out of the source cells to alleviate its toxic effects. This investigation provided a novel insight into the role and mechanism of exosomal release under TBTC stress.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157575","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":"Intratracheal instillation of polyacrylic acid induced pulmonary fibrosis with elevated transforming growth factor-β1 and connective tissue growth factor","authors":"Yasuyuki Higashi ,&nbsp;Chinatsu Nishida ,&nbsp;Taisuke Tomonaga ,&nbsp;Hiroto Izumi ,&nbsp;Naoki Kawai ,&nbsp;Toshiki Morimoto ,&nbsp;Kanako Hara ,&nbsp;Kei Yamasaki ,&nbsp;Akihiro Moriyama ,&nbsp;Jun-ichi Takeshita ,&nbsp;Ke-Yong Wang ,&nbsp;Hidenori Higashi ,&nbsp;Ryohei Ono ,&nbsp;Kazuki Sumiya ,&nbsp;Kazuo Sakurai ,&nbsp;Kazuhiro Yatera ,&nbsp;Yasuo Morimoto","doi":"10.1016/j.tox.2024.153845","DOIUrl":"10.1016/j.tox.2024.153845","url":null,"abstract":"<div><p>We investigated the intratracheal instillation of Polyacrylic acid (PAA) in rats to determine if it would cause pulmonary disorders, and to see what factors would be associated with the pathological changes. Male F344 rats were intratracheally instilled with low (0.2 mg/rat) and high (1.0 mg/rat) doses of PAA. They were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after PAA exposure to examine inflammatory and fibrotic changes in the lungs. There was a persistent increase in the neutrophil count, lactate dehydrogenase (LDH) levels, cytokine-induced neutrophil chemoattractant (CINC) values in bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in lung tissue. Transforming growth factor-beta 1 (TGF-β1), a fibrotic factor, showed a sustained increase in the BALF until 6 months after intratracheal instillation, and connective tissue growth factor (CTGF) in lung tissue was elevated at 3 days after exposure. Histopathological findings in the lung tissue showed persistent (more than one month) inflammation, fibrotic changes, and epithelial-mesenchymal transition (EMT) changes. There was also a strong correlation between TGF-β1 in the BALF and, especially, in the fibrosis score of histopathological specimens. Intratracheal instillation of PAA induced persistent neutrophilic inflammation, fibrosis, and EMT in the rats’ lungs, and TGF-β1 and CTGF appeared to be associated with the persistent fibrosis.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157424","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":"Long-term toxicity evaluation of aristolochic acid-IIIa in mice","authors":"Lianmei Wang ,&nbsp;Yuan Wang ,&nbsp;Yong Zhao ,&nbsp;Chunying Li ,&nbsp;Yan Yi,&nbsp;Jingzhuo Tian,&nbsp;Guiqin Li,&nbsp;Zhong Xian,&nbsp;Fang Wang,&nbsp;Jing Meng,&nbsp;Yushi Zhang,&nbsp;Jiayin Han,&nbsp;Chen Pan,&nbsp;Suyan Liu,&nbsp;Meiting Liu,&nbsp;Chenyue Liu,&nbsp;Aihua Liang","doi":"10.1016/j.tox.2024.153838","DOIUrl":"10.1016/j.tox.2024.153838","url":null,"abstract":"<div><p>Aristolochic acid (AA)-IIIa is an AA analog present in <em>Aristolochiaceae</em> plants. To evaluate the chronic toxicity of AA-IIIa, mice were intragastrically administered with media control, 1 mg/kg AA-IIIa, and 10 mg/kg AA-IIIa, and designated as the control (CTL), AA-IIIa low dose (AA-IIIa-L), and AA-IIIa high dose (AA-IIIa-H) groups, respectively. AA-IIIa was administered three times a week, every other day, for 24 weeks (24-week time point). Thereafter, some mice were sacrificed immediately, while others were sacrificed 29 or 50 weeks after AA-IIIa withdrawal (53- or 74-week time point). Serum and organs were collected for biochemical and pathological analyses, respectively. Whole-genome sequencing was performed on the kidney, liver, and stomach tissues of AA-IIIa-treated mice for single-nucleotide polymorphism (SNP) detection. AA-IIIa-H mice died at 66 weeks, and the remaining mice showed moribund conditions at the 69 weeks. AA-IIIa induced minor kidney tubule injury, fibroblast hyperplasia, and forestomach carcinoma in mice. Bladder, intestine, liver, heart, spleen, lung, and testis tissues were not pathologically altered by AA-IIIa. In addition, AA-IIIa increased the C:G &gt; A:T mutation in the kidney; however, no SNP mutation changes were observed in the liver and forestomach tissues of AA-IIIa-H mice at the 24-week time point compared with control mice. Therefore, we suspect that AA-IIIa is potentially mutagenic for mice after overdose and long-term administration. On the other hand, the forestomach is a unique organ in mice, but it does not exist in humans; thus, we hypothesize that the stomach toxicity induced by AA-IIIa is not a suitable reference for toxicological evaluation in humans. We recommend that <em>Aristolochiaceae</em> plants containing AA-IIIa should be properly supervised, and overdosing and long-term administration of drugs containing AA-IIIa should be avoided.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141144247","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":"Construction of a physiologically based pharmacokinetic model of paclobutrazol and exposure estimation in the human body","authors":"Xiaomeng Li ,&nbsp;Tingting Lian ,&nbsp;Buda Su,&nbsp;Hui Liu,&nbsp;Yuming Wang,&nbsp;Xiaoyan Wu,&nbsp;Junjie He,&nbsp;Yue Wang,&nbsp;Yanyan Xu,&nbsp;Shenshen Yang,&nbsp;Yubo Li","doi":"10.1016/j.tox.2024.153841","DOIUrl":"10.1016/j.tox.2024.153841","url":null,"abstract":"<div><p>Paclobutrazol (PBZ) is a plant growth regulator that can delay plant growth and improve plant resistance and yield. Although it has been widely used in the growth of medicinal plants, human beings may take it by taking traditional Chinese medicine. There are no published studies on PBZ exposure in humans or standardized limits for PBZ in medicinal plants. We measured the solubility, oil–water partition coefficient (logP), and pharmacokinetics of PBZ in rats and established a physiologically based pharmacokinetic (PBPK) model of PBZ in rats. This was followed by extrapolation to healthy Chinese adult males as a theoretical foundation for future risk assessment of PBZ. The results showed that PBZ had low solubility and high fat solubility. Pharmacokinetic experiments showed that PBZ was absorbed rapidly but eliminated slowly in rats. On this basis, the rat PBPK model was successfully constructed and extrapolated to healthy Chinese adult males to predict the plasma concentration–time curve and exposure of PBZ in humans. The construction of the PBPK model of PBZ in this study facilitates the determination of the standard formulation limits and risk assessment of PBZ residues in medicinal plants.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155490","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":"Chemical effects on neural network activity: Comparison of acute versus network formation exposure in microelectrode array assays","authors":"Melissa M. Martin ,&nbsp;Amy F. Carpenter ,&nbsp;Timothy J. Shafer ,&nbsp;Katie Paul Friedman ,&nbsp;Kelly E. Carstens","doi":"10.1016/j.tox.2024.153842","DOIUrl":"10.1016/j.tox.2024.153842","url":null,"abstract":"<div><p>New approach methodologies (NAMs) can address information gaps on potential neurotoxicity or developmental neurotoxicity hazard for data-poor chemicals. Two assays have been previously developed using microelectrode arrays (MEA), a technology which measures neural activity. The MEA acute network function assay (AcN) uses dissociated rat cortical cells cultured at postnatal day 0 and evaluates network activity during a 40-minute chemical exposure on day <em>in vitro</em> (DIV)13 or 15. In contrast, the MEA network formation assay (NFA) uses a developmental exposure paradigm spanning DIV0 through DIV12. Measures of network activity over time at DIV5, 7, 9, and 12 in the NFA are reduced to an estimated area under the curve to facilitate concentration-response evaluation. Here, we evaluated the hypothesis that chemicals with effects in the AcN also perturb the NFA by examining quantitative and qualitative concordance between assays. Out of 243 chemicals screened in both assays, we observed 70.3% concordance between the AcN and NFA after eliminating activity inferred to be cytotoxic (selective activity), with the majority of discordance explained by chemicals that altered selective activity in the AcN but not NFA. The NFA detected more active chemicals when evaluating activity associated with cytotoxicity. Median potency values were lower in the NFA compared to the AcN, but within-chemical potency values were not uniformly lower in the NFA than the AcN. Lastly, the AcN and NFA captured unique bioactivity fingerprints; the AcN was more informative for identifying chemicals with a shared mode of action, while the NFA provided information relevant to developmental exposure. Taken together, this analysis provides a rationale for using both approaches for chemical evaluation with consideration of the context of use, such as screening/ prioritization, hazard identification, or to address questions regarding biological mechanism or function.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094292","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}