Journal of Toxicological Sciences最新文献_第3页

An update on ototoxicity: from a genetic perspective. 耳毒性的最新进展：从遗传学角度看。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.245

Negar Akbari, Fatemeh Mahmoudi Lamooki, Mahmood Rezvani Amin, Seyyed Emran Disnad, Vahid Yousefinejad, Naeem Goharnia

引用次数: 0

Testosterone contributes sex differences of urinary biomarkers for nephrotoxicity in rats. 睾酮有助于大鼠肾毒性尿液生物标志物的性别差异。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.413

Satoshi Tsuji, Aya Hasegawa-Izaki, Bunichiro Ogawa, Hisaharu Yamada

{"title":"Testosterone contributes sex differences of urinary biomarkers for nephrotoxicity in rats.","authors":"Satoshi Tsuji, Aya Hasegawa-Izaki, Bunichiro Ogawa, Hisaharu Yamada","doi":"10.2131/jts.50.413","DOIUrl":"https://doi.org/10.2131/jts.50.413","url":null,"abstract":"Urinary biomarkers have been used widely in non-clinical toxicity studies to detect kidney dysfunction/injury caused by drugs under development. Although their usefulness to evaluate nephrotoxicity has been well studied, knowledge about sex differences in the urinary excretion levels of these biomarkers remains inadequate. We previously demonstrated the existence of sex differences in the excretion levels of urinary biomarkers and that these differences were associated with the endogenous testosterone levels. In this study, testosterone was repeatedly administered subcutaneously to female rats for 4 weeks along with male rats as a comparison control, to investigate how the blood levels of testosterone contribute to the sex differences in the urinary biomarker and renal cortical protein levels. The results showed that the urinary excretion of leucine aminopeptidase (LAP), gamma-glutamyltransferase (γ-GTP), cystatin C (Cys-C), liver-type fatty acid binding protein (L-FABP), and beta2-microglobulin (β2MG) were increased, and the urinary excretion of kidney injury molecule 1 (Kim-1) was decreased. The protein level of megalin, an endocytic receptor, in the renal cortex, was higher in female rats than in male rats, and testosterone treatment led to decrease in the level in the female rats. Our results suggest that the blood testosterone level might be responsible for the sex differences in the urinary excretion levels of low-molecular-weight proteins via regulating the expression level of megalin in the renal cortex.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 8","pages":"413-424"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Estimation of intravenous TTC (TTCiv) for Extractables and Leachables (E&Ls) by applying a modifying factor based on blood concentration predicted using an open-source PBPK model. 应用基于开放源代码PBPK模型预测的血药浓度的修正因子估计静脉中可提取物和可浸出物（e&l）的TTC （TTCiv）

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.471

Tae Hayashi, Akira Kotaki, Asako Fukushima, Tomoko Kawamura, Naruo Katsutani, Takashi Yamada, Akihiko Hirose

{"title":"Estimation of intravenous TTC (TTCiv) for Extractables and Leachables (E&Ls) by applying a modifying factor based on blood concentration predicted using an open-source PBPK model.","authors":"Tae Hayashi, Akira Kotaki, Asako Fukushima, Tomoko Kawamura, Naruo Katsutani, Takashi Yamada, Akihiko Hirose","doi":"10.2131/jts.50.471","DOIUrl":"https://doi.org/10.2131/jts.50.471","url":null,"abstract":"Pharmaceutical manufacturing and storage processes pose the potential risk of chemicals migrating from the packaging materials into pharmaceuticals. These migrants, known as extractables and leachables (E&Ls), consist of various chemicals that may pose a risk to patients during therapeutic use. Although exposure to E&Ls via the intravenous route is of greater concern, there is almost no toxicity information for these chemicals to determine the Permitted Daily Exposure (PDE). The purpose of this study was to establish the Threshold of Toxicological Concern for intravenous route exposure (TTCiv) for risk management of E&Ls contained in pharmaceuticals. First, we derived the oral PDEs of 287 chemicals from a list of 923 known E&Ls. Then, the modifying factor (α) for estimating the intravenous PDE from each oral PDE was calculated based on the ratio of the predicted blood concentrations (area under the curve (AUC) and maximum blood concentration (Cmax)) after oral and intravenous administration using the Integrated Chemical Environment (ICE) PBPK model. Additionally, due to uncertainty of the predictions without bioavailability information, the intravenous PDE was calculated using modifying factor 3 based on the maximum value of the root mean square error (RMSE) reported in varification of the High-Throughput Toxicokinetics (HTTK) model. In conclusion, by analyzing the distribution of the intravenous PDE for 287 chemicals, we propose a TTCiv of 27 µg/day/human, based on the ratio of Cmax. Our route extrapolation approach could contribute to the establishment of scientifically valid TTCs for not only E&Ls, but also for other impurities without toxicity information.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 9","pages":"471-481"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dabrafenib stimulates autophagy in thyroid carcinoma cells via HMGB-1. Dabrafenib通过HMGB-1刺激甲状腺癌细胞自噬。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.273

Xu Wang, Dianchao Wu, Yongqiang Wang, Fengjuan Han, Xue Feng

{"title":"Dabrafenib stimulates autophagy in thyroid carcinoma cells via HMGB-1.","authors":"Xu Wang, Dianchao Wu, Yongqiang Wang, Fengjuan Han, Xue Feng","doi":"10.2131/jts.50.273","DOIUrl":"https://doi.org/10.2131/jts.50.273","url":null,"abstract":"Autophagy has been implicated in the pathophysiology of thyroid cancer and in determining the response of cancer cells to anticancer therapy. Dabrafenib, a BRAF inhibitor, has demonstrated efficacy and safety in several types of cancers. However, it is unknown whether Dabrafenib exerts a protective effect on autophagy in thyroid carcinoma cells. In the current study, our findings demonstrate that treatment with Dabrafenib reduced cell viability and promoted LDH release in SW579 thyroid carcinoma cells. Dabrafenib was then shown to promote autophagy by increasing the level of Beclin1 and the LC3-II/LC3-I ratio while reducing the level of p62. Additionally, exposure to Dabrafenib upregulated the expression of HMGB-1 at both mRNA and protein levels. Interestingly, silencing of HMGB-1 abrogated Dabrafenib-induced autophagy, suggesting that the effects of Dabrafenib are mediated by HMGB-1. Further study revealed that Dabrafenib activated the JAK1/STAT1 signaling pathway and that blockage of the JAK1/STAT1 signaling pathway with its inhibitor Pyridone 6 ameliorated Dabrafenib-induced HMGB-1 upregulation and autophagy, implicating the involvement of the JAK1/STAT1 signaling pathway in this process. Collectively, these findings demonstrate that Dabrafenib induces autophagy in thyroid carcinoma cells via the JAK1/STAT1/HMGB-1 axis. Notably, this effect occurs independently of BRAF V600E mutation status, suggesting a novel therapeutic mechanism.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 6","pages":"273-281"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comprehensive molecular docking on the AlphaFold-predicted protein structure proteome: identifying target protein candidates for puberulic acid. 基于alphafold预测的蛋白质结构蛋白质组的综合分子对接：鉴定青春期少女酸的候选靶蛋白。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.309

Teppei Hayama, Rin Sugawara, Ryo Kamata, Masakazu Sekijima, Kazuki Takeda

{"title":"Comprehensive molecular docking on the AlphaFold-predicted protein structure proteome: identifying target protein candidates for puberulic acid.","authors":"Teppei Hayama, Rin Sugawara, Ryo Kamata, Masakazu Sekijima, Kazuki Takeda","doi":"10.2131/jts.50.309","DOIUrl":"https://doi.org/10.2131/jts.50.309","url":null,"abstract":"Identifying the molecular targets of toxic compounds remains a major challenge in toxicology, particularly when adverse effects occur in off-target organs and the mechanism of action is unknown. To address this issue, a comprehensive computational pipeline was developed to perform high-throughput molecular docking across the entire AlphaFold2-predicted structural proteome of representative organisms such as human and mouse, followed by enrichment analysis to estimate biological processes potentially affected by ligand binding. The pipeline was first evaluated using six known drug-target pairs. In several cases, the known targets were ranked between the top 2 and 250 proteins (top 0.009-1.15%) among more than 21,000 proteins, and displayed docking poses consistent with experimentally observed binding conformations. However, performance was limited for certain targets, such as carbonic anhydrase II with acetazolamide, where the binding pocket was broad, leading to inaccurate docking results. The pipeline was subsequently applied to puberulic acid, a compound suspected of causing severe nephrotoxicity. Screening identified sodium/myo-inositol cotransporter 2 (SLC5A11) as a high-affinity target in both human and mouse, suggesting a mechanism involving disruption of renal osmoregulation. Although docking scores represent only theoretical binding estimates and do not directly imply physiological effects, their distribution was independent of protein length and AlphaFold2 confidence scores (pLDDT), supporting the methodological robustness. This in silico framework enables hypothesis-driven identification of potential target proteins for toxicants or therapeutics and offers a useful tool for predictive toxicology, particularly when experimental data are limited. The pipeline is available at: https://github.com/toxtoxcat/reAlldock.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 7","pages":"309-324"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Slow-releasing hydrogen sulfide donor GYY4137 induces epithelial-mesenchymal transition in A549 human lung adenocarcinoma cells. 缓释硫化氢供体GYY4137诱导A549人肺腺癌细胞上皮-间质转化

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.425

Miu Kajihara, Toshihiko Aki, Takeshi Funakoshi, Kana Unuma

引用次数: 0

Successful multimodal treatment of venlafaxine overdose-induced catecholamine-refractory shock: a case report. 多模式治疗文拉法辛过量致儿茶酚胺难治性休克1例。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.547

Tomoaki Hayakawa, Akimasa Sanagawa, Kazuki Ohashi, Kazuki Kotoge, Ryohei Matsui, Tetsuya Tamura, Jun Monma-Otaki, Yoko Furukawa-Hibi, Tomonori Hattori

{"title":"Successful multimodal treatment of venlafaxine overdose-induced catecholamine-refractory shock: a case report.","authors":"Tomoaki Hayakawa, Akimasa Sanagawa, Kazuki Ohashi, Kazuki Kotoge, Ryohei Matsui, Tetsuya Tamura, Jun Monma-Otaki, Yoko Furukawa-Hibi, Tomonori Hattori","doi":"10.2131/jts.50.547","DOIUrl":"https://doi.org/10.2131/jts.50.547","url":null,"abstract":"Venlafaxine was the first serotonin/noradrenaline reuptake inhibitor used to treat major depressive disorders. Its overdose can cause cardiovascular toxicity and life-threatening cardiogenic shock. We present the case of a 48-year-old woman who experienced venlafaxine overdose-induced cardiogenic shock. Initial treatment included gastric lavage, blood purification therapy, and ventricular assist device use. The serum venlafaxine concentration was 21.4 μg/mL at 12-24 hr after ingestion, which subsequently decreased to 11.0 and 8.4 μg/mL after 1 and 2 days, respectively. This trend in blood concentration exhibited a biphasic elimination pattern. In addition to venlafaxine-induced cardiotoxicity, the patient exhibited peripheral vascular unresponsiveness to catecholamines. Notably, this vascular dysfunction resolved more rapidly than the cardiotoxic effects. Ultimately, the patient was transferred to a psychiatric ward without sequelae. Although venlafaxine overdose-induced cardiotoxicity has been reported, reports on the unresponsiveness of peripheral blood vessels to catecholamines remain lacking. In cases of venlafaxine overdose-induced cardiogenic shock, both left ventricular function may be impaired and peripheral blood vessels may also be unresponsive to catecholamines. Therefore, rapid initiation of extracorporeal life support and multimodal removal of venlafaxine tailored to the clinical situation may contribute to patient survival.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 10","pages":"547-554"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prolyl hydroxylase domain enzymes (isoforms 1-3, PHD1-3), but not factor-inhibiting HIF-1 (FIH-1), interact with the IKK complex and attenuate LPS-activated NF-kappa-B. 脯氨酸羟化酶结构域酶（异构体1-3，PHD1-3），但不抑制因子HIF-1 (FIH-1)，与IKK复合物相互作用并减弱lps激活的nf - κ b。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.105

Akiyoshi Tamura, Koji Kitayama, Mutsumi Adachi, Kentaro Hashimoto, Ami Oguro, Susumu Imaoka

{"title":"Prolyl hydroxylase domain enzymes (isoforms 1-3, PHD1-3), but not factor-inhibiting HIF-1 (FIH-1), interact with the IKK complex and attenuate LPS-activated NF-kappa-B.","authors":"Akiyoshi Tamura, Koji Kitayama, Mutsumi Adachi, Kentaro Hashimoto, Ami Oguro, Susumu Imaoka","doi":"10.2131/jts.50.105","DOIUrl":"10.2131/jts.50.105","url":null,"abstract":"Hypoxia induces the expression of nuclear factor kappa B (NF-kappa-B). NF-kappa-B functions by forming dimers from five main subunits: p65 (RelA), RelB, p52, p50, and c-Rel. In the classical pathway, NF-kappa-B activity is regulated by the degradation-inducing factor I kappa B kinase (IKK). IKK is composed of an α/β isomer and essential modulator NEMO (γ) subunits in the classical pathway, which may be the major pathway for NF-kappa-B signaling. In the present study, we focused on factor-inhibiting HIF-1 (FIH-1) and Prolyl hydroxylase domain enzyme (PHD), which have been identified as oxygen concentration-dependent regulators of HIF-1α. PHD has three isoforms: PHD1, PHD2, and PHD3, which have different affinities towards HIF-1α. We examined the interactions between IKKα/β and PHD1-3 by immunoprecipitation. PHDs efficiently interacted with IKKα/β. Furthermore, the overexpression of PHDs decreased the mRNA level of IL-1β, a downstream factor of NF-kappa-B activated by LPS. The overexpression of PHD1 and PHD2 markedly reduced IKKα/β protein levels; however, the effects of PHD3 were weaker than those of PHD1 and PHD2. Mutants of the active sites of PHD1 and PHD2 did not decrease IKKα/β protein levels, and a mutation in the active site of PHD3 did not affect IKKα/β protein levels. We also attempted to investigate the interactions of FIH-1 with IKKα/β and IκBα by immunoprecipitation, but found none. Moreover, IKKα/β and p65 protein levels were not affected by the overexpression of FIH-1. Collectively, these results suggest that PHDs directly regulated IKK protein levels, while FIH-1 did not affect the NF-kappa-B classical pathway.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 3","pages":"105-116"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reported liver toxicity of food chemicals in rats extrapolated to humans using virtual human-to-rat hepatic concentration ratios generated by pharmacokinetic modeling with machine learning-derived parameters. 通过使用机器学习衍生参数的药代动力学建模产生的虚拟人-大鼠肝脏浓度比，将食品化学物质在大鼠中的肝脏毒性外推到人类。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.205

Koichiro Adachi, Manato Hosoi, Yukia Shimura, Makiko Shimizu, Hiroshi Yamazaki

{"title":"Reported liver toxicity of food chemicals in rats extrapolated to humans using virtual human-to-rat hepatic concentration ratios generated by pharmacokinetic modeling with machine learning-derived parameters.","authors":"Koichiro Adachi, Manato Hosoi, Yukia Shimura, Makiko Shimizu, Hiroshi Yamazaki","doi":"10.2131/jts.50.205","DOIUrl":"https://doi.org/10.2131/jts.50.205","url":null,"abstract":"Pharmacokinetic data are not generally available for evaluating the toxicological potential of food chemicals. A simplified physiologically based pharmacokinetic (PBPK) model has been established to evaluate internal exposures to chemicals in rats or humans with no reference to in vitro or in vivo experimental data. In this study, reported liver toxicity levels in rats were extrapolated to humans using virtual hepatic concentration-time curves (AUC) as the interspecies factor. Virtual liver exposures to 27 lipophilic food chemicals (octanol-water partition coefficient logP >1) with reported rat hepatic lowest-observed-effect levels (LOELs) of ≤1000 mg/kg/day were generated using PBPK models with input parameters obtained entirely in silico via machine learning algorithms. The resulting virtual rat and human liver AUCs were correlated (n = 27, r = 0.52, p < 0.01). However, AUCs for the phenolic compounds emodin, isoeugenol, and tert-butylhydroquinone, which have reported rat LOEL values of ≤300 mg/kg/day, were located outside the relatively wide 95% confidence interval, indicating more extensive hepatic elimination in rats than in humans. In vitro depletion of tert-butylhydroquinone in rat liver fractions via sulfation was confirmed to be faster than that in humans. For emodin, isoeugenol, and tert-butylhydroquinone, human-to-rat AUC ratios ranged from 10- to 13-fold; consequently, their extrapolated human hepatic LOEL values were estimated as ≤30 mg/kg/day, i.e., one order of magnitude smaller than the rat LOELs. Despite the small number of lipophilic food chemicals considered here, the PBPK modeling approach using in silico-generated input parameters for rats and humans has the potential to facilitate toxicological studies.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 5","pages":"205-213"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Construction and evaluation of an open-source database for inhalation-based physiologically based kinetic modeling of selected categories for industrial chemicals. 基于吸入的基于生理动力学建模的工业化学品选定类别的开源数据库的构建和评估。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.57

Shigechika Yamamoto, Kikuo Yoshida, Mariko Matsumoto, Takashi Yamada

{"title":"Construction and evaluation of an open-source database for inhalation-based physiologically based kinetic modeling of selected categories for industrial chemicals.","authors":"Shigechika Yamamoto, Kikuo Yoshida, Mariko Matsumoto, Takashi Yamada","doi":"10.2131/jts.50.57","DOIUrl":"10.2131/jts.50.57","url":null,"abstract":"A physiologically based kinetic (PBK) model is used for predicting chemical concentrations of toxicological concern in target tissues. Such models are important for understanding toxicokinetics. However, it is challenging to obtain chemical-specific empirical parameter values used for PBK modeling. Thus, developing methods predicting these values is necessary. Herein, we researched PBK models of inhalation exposure to industrial chemicals and developed a database of parameters of approximately 200 chemicals in humans and rodents. Next, the chemicals in the database were classified into three categories (I, IIA, and IIB) based on the intermolecular interactions for humans and rats. Quantitative relationships between blood/air and tissue/blood partition coefficients and physicochemical parameters were derived for the chemicals in each category. Regression analyses of blood/air and fat/blood partition coefficients against Henry's law constant and log D at pH 7.4 for chemicals in category IIA for humans, in which van der Waals and dipole-dipole interactions were involved, yielded 0.88 and 0.54 coefficients of determination, respectively. Moreover, these methods worked for other categories and species. The metabolic parameters maximal velocity (Vmax) and Michaelis-Menten constant (Km) of the chemicals that are primarily metabolized by cytochrome P450 were calculated for humans and rats. Multiple regression analyses of logs Vmax and Km against the occurrence frequency of molecular fragments showed good correlations, respectively. The aforementioned models predicted values close to the reported values for test chemicals within the applicability domains. Our approach could also be applied to other chemicals within the domains that are not included in the database.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 2","pages":"57-68"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0