Journal of Toxicological Sciences最新文献

{"title":"Impact of variability of in silico and in vitro octanol/water partition coefficients of compounds on the input parameters and results of simplified human physiologically based pharmacokinetic models after virtual oral administrations.","authors":"Koichiro Adachi, Tsubasa Sasaki, Atsuo Arai, Makiko Shimizu, Hiroshi Yamazaki","doi":"10.2131/jts.49.459","DOIUrl":"https://doi.org/10.2131/jts.49.459","url":null,"abstract":"<p><p>The octanol/water partition coefficient, P (logP), is a hydrophobicity index and is one of the determining factors of the pharmacokinetics of chemical compounds. LogP values obtained from in silico software, open chemistry databases, and in vitro liquid chromatography retention factors may vary. Some chemicals (boscalid, etoxazole, and permethrin) have up to four-order-magnitude differences in in silico/in vitro P values. This study aimed to evaluate the effects of logP values of these three compounds, along with bisphenol A, 1,2-dibromobenzene, tetrabromobisphenol A, trazodone, and triazolam, on the input parameters and output plasma/hepatic concentration-time profiles of simple physiologically based pharmacokinetic (PBPK) models. Although the blood-to-plasma concentration ratios (~0.9-0.6) were slightly affected by variations in logP values, logarithmic plasma unbound fraction values and liver-to-plasma partition coefficients (K_p,h) were, respectively, inversely and linearly correlated with logP values (K_p,h was stable at ~6.7 for logP > 4). LogP was among the input parameters for previously established machine learning systems; consequently, the resulting logarithmic intrinsic clearance values were correlated with logP values in the range 2-8. However, the bioavailability, absorption rate constants, and volumes of distribution were not affected. PBPK-modeled plasma and hepatic maximum concentrations and areas under the concentration-time curves after virtual oral doses were mostly within ~0.5- to ~2-fold ranges, except for substances with low in vitro logP values, e.g., etoxazole and permethrin. These results suggest that in silico logP values are generally suitable for pharmacokinetic modeling; nevertheless, caution is needed for compounds with low in vitro logP values of ~2.</p>","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 10","pages":"459-466"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365662","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}

{"title":"Carcinogenicity of butyraldehyde in rats by a two-year inhalation study.","authors":"Yusuke Furukawa, Hideki Senoh, Shigeyuki Hirai, Kyohei Misumi, Tatsuya Kasai","doi":"10.2131/jts.49.385","DOIUrl":"https://doi.org/10.2131/jts.49.385","url":null,"abstract":"<p><p>We conducted a two-year inhalation study of butyraldehyde using F344/DuCrlCrlj rats. The rats were exposed to 0, 300, 1,000 and 3,000 ppm (v/v) for 6 hr/day, 5 days/ week for 104 weeks using whole-body inhalation chambers. The incidence of squamous cell carcinoma of the nasal cavity was increased in the 3,000 ppm groups of both male and female rats, with Fisher's exact test and the Peto test indicating that the incidence was significant. In addition to squamous cell carcinoma in the nasal cavity, in the 3,000 ppm groups one male had an adenosquamous carcinoma, one male had a carcinosarcoma, one male had a sarcoma NOS (Not Otherwise Specified), and one female had a squamous cell papilloma in the nasal cavity. The combined incidence of squamous cell carcinoma, adenosquamous carcinoma and carcinosarcoma was significantly increased in male rats and the combined incidence of squamous cell papilloma and carcinoma was significantly increased in female. Based on these results, we conclude that there is clear evidence of butyraldehyde carcinogenicity in male and female rats.</p>","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 9","pages":"385-398"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133100","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}

{"title":"Gene expression profiles of neuroinflammatory responses in broad brain regions in rats repeatedly administered with N-methyl-N-nitrosourea for 28 days.","authors":"Xinyu Zou, Yousuke Watanabe, Shunsuke Ozawa, Yuri Ebizuka, Momoka Shobudani, Yuri Sakamaki, Tetsuhito Kigata, Meilan Jin, Fumiyo Saito, Yumi Akahori, Susumu Yamashita, Makoto Shibutani","doi":"10.2131/jts.49.481","DOIUrl":"https://doi.org/10.2131/jts.49.481","url":null,"abstract":"<p><p>N-methyl-N-nitrosourea (MNU) exposure impairs hippocampal neurogenesis in rats. The present study investigated the gene expression profiles that were commonly up or downregulated across different brain substructures in response to repeated MNU administration in rats. Five-week-old rats were orally administered MNU at 0, 5, 15 mg/kg body weight/day for 28 days and subjected to gene expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex and cerebellar vermis. MNU at 15 mg/kg revealed multiple functional clusters of upregulated genes related to immune and inflammatory responses in all brain regions, and also clusters of up or downregulated genes related to regulation of apoptotic process in several regions. Specifically, the upregulated genes commonly found in all four regions were enriched in clusters of \"immune response\" and/or \"inflammatory response\" (Cd74, Ccl3, Fcgr3a, Serping1, Lgals3, Fcgr2b, Hcst, Kcnn4, Tnf, Gpr18, Tyrobp and Cyba) and \"metal-binding proteins\" (Mt1, Mt2A and Apobec1). Meanwhile, downregulated genes common to all four regions (Bmp4, Vcan and Fhit) were included in clusters of \"cell proliferation\", \"glial cell migration\" and \"nucleotide metabolism\". Immunohistochemical analysis of representative gene products revealed that in all brain regions examined, MNU treatment increased metallothionein-I/II ⁺ cells and galectin-3⁺ cells co-expressing Iba1, and also increased Iba1⁺ and CD68⁺ cells. These results suggest that repeated MNU administration in rats causes neuroinflammation and oxidative stress accompanied by apoptosis of neural cell components in the brain, as well as concurrent anti-inflammatory responses for neuroprotection from MNU exposure, involving activation of microglia producing metallothionein-I/II and galectin-3 on these responses.</p>","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 11","pages":"481-495"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576086","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}

{"title":"Puerarin alleviates the high glucose-induced oxidative stress via the RAGE/PKC/NOX4 axis in renal mesangial cells.","authors":"Hongbin Wang, Wei Li","doi":"10.2131/jts.49.497","DOIUrl":"https://doi.org/10.2131/jts.49.497","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a severe microvascular complication of diabetes, of which progression is related to high glucose (HG)-induced oxidative stress in renal mesangial cells. Our study aims to explore the antioxidant activity and the underlying mechanism of Puerarin (Pu) in renal mesangial cells exposed to HG. After the cells finished different treatments, DCFH-DA was used to detect the generation of ROS while the expression of AGE, MDA, SOD, and GSH-PX was measured by the ELISA and corresponding kits. The cell morphology was captured by optical microscopy. The mRNA expressions of RAGE, PKCα, PKCβ, PKCγ, and NOX4 were calculated by RT-PCR assays, while the protein expressions of RAGE, NOX4, and PKCβ were quantified via western blotting. Compared with the normal glucose (NG) group, the ROS level, SOD activity, and GSH-PX expression were markedly reduced in the HG group while the MDA expression was increased in the HG group. Then, Pu treatment was proved to significantly prevent the HG-induced up-regulation of ROS level, MDA expression, and down-regulation of SOD activity and GSH-PX expression. Besides, Pu treatment can notably inhibit the AGE expression and reverse the increased RAGE, PKCβ, and NOX4 expressions by HG environment at both RNA and protein levels. Moreover, the antioxidant effect of Pu against access glucose could not be observed in PKCβ knockdown cells. Pu can alleviate the HG-induced oxidative stress via the RAGE/PKC/NOX4 axis in renal mesangial cells, which innovatively suggests the therapeutic potential of Pu for DN treatment.</p>","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 11","pages":"497-507"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576108","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}

{"title":"Histological differences between the central and peripheral areas of the testes of busulfan-administered mice.","authors":"Hidenobu Miyaso, Satoshi Yokota, Kousuke Suga, Yui Hashimoto, Céline Kouno, Kenta Nagahori, Masahiro Itoh, Satoshi Kitajima","doi":"10.2131/jts.49.139","DOIUrl":"10.2131/jts.49.139","url":null,"abstract":"<p><p>Busulfan is an anticancer drug known to cause serious damage to seminiferous tubules in the testes and deplete germ cells in human and animal models. The testicular artery is anastomosed with deferential and cremasteric arteries and is divided into capsular arteries, which give rise to the centripetal arteries and then recurrent arteries. The arterial blood in the testicular tissue is supplied by such a consequent system of arterial vessels, in order from the peripheral to the central area. As anticancer drugs are generally distributed throughout the whole body via the bloodstream and the running and distribution of arteries differ among the testicular areas, we hypothesized that the efficacy of busulfan differs in different testicular areas, particularly between the central and peripheral areas. In this study, busulfan was intraperitoneally injected at 40 mg/kg body weight into C57BL/6J male mice. After 28 days, in busulfan-treated mice, the diameters of seminiferous tubules were significantly higher in the central than in the peripheral area of the testes. The seminiferous tubular areas also significantly decreased in the peripheral areas compared with the central areas. The number of germ cells per seminiferous tubule was significantly higher in the central than in the peripheral area. Sertoli cell nuclei were detached into the lumen in the peripheral area. The number of Leydig cells was significantly lower in the peripheral areas. These data suggest that the effects of busulfan differ between the central and peripheral areas of the testis at 4 weeks after busulfan administration.</p>","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 4","pages":"139-149"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331804","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}

{"title":"Comparative study of susceptibility to methylmercury cytotoxicity in cell types composing rat peripheral nerves: a higher susceptibility of dorsal root ganglion neurons.","authors":"Eiko Yoshida, Kazuhiro Aoki, Yu Sasaki, Hinako Izuhara, Tsutomu Takahashi, Yasuyuki Fujiwara, Tomoya Fujie, Ke Du, Komyo Eto, Yo Shinoda, Toshiyuki Kaji","doi":"10.2131/jts.49.241","DOIUrl":"https://doi.org/10.2131/jts.49.241","url":null,"abstract":"<p><p>Methylmercury is an environmental polluting organometallic compound that exhibits neurotoxicity, as observed in Minamata disease patients. Methylmercury damages peripheral nerves in Minamata patients, causing more damage to sensory nerves than motor nerves. Peripheral nerves are composed of three cell types: dorsal root ganglion (DRG) cells, anterior horn cells (AHCs), and Schwann cells. In this study, we compared cultured these three cell types derived from the rat for susceptibility to methylmercury cytotoxicity, intracellular accumulation of mercury, expression of L-type amino acid transporter 1 (LAT1), which transports methylmercury into cells, and expression of multidrug resistance-associated protein 2 (MRP2), which transports methylmercury-glutathione conjugates into the extracellular space. Of the cells examined, we found that DRG cells were the most susceptible to methylmercury with markedly higher intracellular accumulation of mercury. The constitutive level of LAT1 was higher and that of MRP2 lower in DRG cells compared with those in AHC and Schwann cells. Additionally, decreased cell viability caused by methylmercury was significantly reduced by either the LAT1 inhibitor, JPH203, or siRNA-mediated knockdown of LAT1. On the other hand, an MRP2 inhibitor, MK571, significantly intensified the decrease in the cell viability caused by methylmercury. Our results provide a cellular basis for sensory neve predominant injury in the peripheral nerves of Minamata disease patients.</p>","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 5","pages":"241-248"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863254","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}

{"title":"Perinatal maternal exposure to high-dose sodium phenobarbital in the modified Comparative Thyroid Assay: no significant reduction in thyroid hormones in pups despite notable effects in dams.","authors":"Hidenori Suto, Keiko Ogata, Kenta Minami, Akira Sato, Naruto Tomiyama, Tadashi Kosaka, Hitoshi Hojo, Naofumi Takahashi, Hiroaki Aoyama, Tomoya Yamada","doi":"10.2131/jts.49.509","DOIUrl":"https://doi.org/10.2131/jts.49.509","url":null,"abstract":"<p><p>We propose a modified Comparative Thyroid Assay (CTA, USEPA) utilizing a smaller number of Sprague-Dawley rats (N=10/group) that assesses brain thyroid hormone (TH) concentrations and periventricular heterotopia while maintaining assay sensitivity. Our recent findings demonstrated that a prenatal test cohort of the modified CTA detected a dose-dependent decrease in maternal serum T3 (up to -26%) and T4 (up to -44%) with sodium phenobarbital (NaPB) exposure at 1000 ppm and 1500 ppm, equivalent to intakes of 60 and 84 mg/kg/day, respectively. On gestation day (GD) 20, fetuses exhibited reduced serum (-26%) and brain (-29%) TH concentrations, although these reductions were not dose dependent. The present study expanded the treatment in a postnatal test cohort, with maternal exposure to NaPB (81-93 mg/kg/day) from GD6 to lactation day (LD) 21. We assessed serum and brain TH concentrations, and periventricular heterotopia in pups on postnatal days (PND) 4, 21, and 28. While LD21 dams showed significant reductions in serum T3 (up to -34%) and T4 (up to -54%), the pups did not exhibit significant TH suppression or periventricular heterotopia at any test point. Instead, a compensatory increase in T4 was observed in serum and brain of PND21 pups. The present study confirmed that perinatal maternal exposure to high doses of NaPB leads to a moderate decrease in maternal TH concentrations; however, the exposure of maternal rats to a similar dose of NaPB did not significantly reduce serum or brain TH concentrations in their postnatal offspring.</p>","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 11","pages":"509-529"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576099","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}

{"title":"Effective in vitro evaluation of the risk of histamine release related to valemetostat tosylate using MRGPRX2-expressing cells.","authors":"Eri Hamamura-Yasuno, Junzo Kinoshita, Koichi Goto, Kazunori Fujimoto, Michael Pignatello, Yoshimi Tsuchiya, Kazuhiko Mori","doi":"10.2131/jts.49.163","DOIUrl":"10.2131/jts.49.163","url":null,"abstract":"<p><p>Mas-related G-protein-coupled receptor X2 (MRGPRX2), expressed on mast cells, is associated with drug-induced pseudo-allergic reactions. Although it is well known that there are differences of sensitivity between species in the pseudo-allergic reactions, no platform for evaluating a human risk of the pseudo-allergic reactions observed in nonclinical studies has been established. Valemetostat tosylate, developed as an anti-cancer drug, induced histamine release in a nonclinical study with dogs. The purpose of the current study was to identify the mechanism and assess the human risk of valemetostat-tosylate-induced histamine release using dog and human MRGPRX2-expressing cells. In an experiment with human or dog MRGPRX2-expressing cells, valemetostat tosylate caused activation of human and dog MRGPRX2. Importantly, the EC₅₀ for dog MRGPRX2 was consistent with the C_max value at which histamine release was observed in dogs. Furthermore, the EC₅₀ for human MRGPRX2 was ca. 27-fold higher than that for dog MRGPRX2, indicating a species difference in histamine-releasing activity. In a clinical trial, histamine release was not observed in patients receiving valemetostat tosylate. In conclusion, an in vitro assay using human and animal MRGPRX2-expressing cells would be an effective platform to investigate the mechanism and predict the human risk of histamine release observed in nonclinical studies.</p>","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 4","pages":"163-174"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331803","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}

{"title":"Simultaneous analysis of caffeine and paraxanthine provides potentially useful indexes in the treatment of acute caffeine intoxication.","authors":"Yoshitaka Yamazaki, Asuka Kaizaki-Mitsumoto, Mariko Sato, Yumiko Inoue, Kazuyuki Miyamoto, Keisuke Suzuki, Munetaka Hayashi, Kenji Dohi, Satoshi Numazawa","doi":"10.2131/jts.49.447","DOIUrl":"https://doi.org/10.2131/jts.49.447","url":null,"abstract":"<p><p>Caffeine (CFF) is efficiently absorbed after ingestion, and approximately 80% of ingested CFF is metabolized to paraxanthine (PXT). Although PXT has approximately twice the adenosine receptor antagonist activity of CFF, there are few reports measuring the metabolite concentrations during CFF intoxication. Furthermore, no studies have examined the efficacy of hemodialysis (HD) on PXT or the indicators that contribute to treatment strategies for patients with acute CFF intoxication. This study analyzed the association between CFF and PXT blood levels, the blood biochemical data, and the vital signs of 27 cases with information on CFF intake and elapsed time data. It was found that HD was not as effective as CFF against PXT in CFF intoxication; however, HD was effective in cases with relatively high PXT concentrations (>10 μg/mL). Simultaneous analysis of CFF and PXT would make it possible to estimate the time elapsed from CFF intake and the risk of hyperCKemia, which may develop in cases left untreated for a prolonged period after ingestion. Therefore, the measurement of PXT, in addition to CFF, is expected to provide useful information for understanding the pathogenesis of CFF intoxication and the development of treatment strategies of acute CFF intoxication.</p>","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 10","pages":"447-457"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365664","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}

{"title":"Novel predictive approaches for drug-induced convulsions in non-human primates using machine learning and heart rate variability analysis.","authors":"Kazuhiro Kuga, Motohiro Shiotani, Kentaro Hori, Hiroshi Mizuno, Yusaku Matsushita, Harushige Ozaki, Kohei Hayashi, Takatomi Kubo, Manabu Kano","doi":"10.2131/jts.49.231","DOIUrl":"https://doi.org/10.2131/jts.49.231","url":null,"abstract":"<p><p>Drug-induced convulsions are a major challenge to drug development because of the lack of reliable biomarkers. Using machine learning, our previous research indicated the potential use of an index derived from heart rate variability (HRV) analysis in non-human primates as a biomarker for convulsions induced by GABA_A receptor antagonists. The present study aimed to explore the application of this methodology to other convulsants and evaluate its specificity by testing non-convulsants that affect the autonomic nervous system. Telemetry-implanted males were administered various convulsants (4-aminopyridine, bupropion, kainic acid, and ranolazine) at different doses. Electrocardiogram data gathered during the pre-dose period were employed as training data, and the convulsive potential was evaluated using HRV and multivariate statistical process control. Our findings show that the Q-statistic-derived convulsive index for 4-aminopyridine increased at doses lower than that of the convulsive dose. Increases were also observed for kainic acid and ranolazine at convulsive doses, whereas bupropion did not change the index up to the highest dose (1/3 of the convulsive dose). When the same analysis was applied to non-convulsants (atropine, atenolol, and clonidine), an increase in the index was noted. Thus, the index elevation appeared to correlate with or even predict alterations in autonomic nerve activity indices, implying that this method might be regarded as a sensitive index to fluctuations within the autonomic nervous system. Despite potential false positives, this methodology offers valuable insights into predicting drug-induced convulsions when the pharmacological profile is used to carefully choose a compound.</p>","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 5","pages":"231-240"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874720","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}