Toxicologic Pathology最新文献_第9页

Toxicologic Pathology Forum Opinion: Interpretation of Gliosis in the Brain and Spinal Cord Observed During Nonclinical Safety Studies. 毒理病理学论坛意见：非临床安全性研究中观察到的大脑和脊髓胶质增生的解释。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-01-01 Epub Date: 2023-04-14 DOI: 10.1177/01926233231164557

Brad Bolon

{"title":"Toxicologic Pathology Forum Opinion: Interpretation of Gliosis in the Brain and Spinal Cord Observed During Nonclinical Safety Studies.","authors":"Brad Bolon","doi":"10.1177/01926233231164557","DOIUrl":"10.1177/01926233231164557","url":null,"abstract":"Gliosis, defined as a nonneoplastic reaction (hypertrophy and/or proliferation) of astrocytes and/or microglial cells, is a frequent finding in the central nervous system (CNS [brain and/or spinal cord]) in nonclinical safety studies. Gliosis in rodents and nonrodents occurs at low incidence as a spontaneous finding and is induced by various test articles (e.g., biomolecules, cell and gene therapies, small molecules) delivered centrally (i.e., by injection or infusion into cerebrospinal fluid or neural tissue) or systemically. Several CNS gliosis patterns occur in nonclinical species. First, gliosis may accompany degeneration and/or necrosis of cells (mainly neurons) or neural parenchyma (neuron processes and myelin). Second, gliosis often follows inflammation (i.e., leukocyte accumulation causing parenchymal damage) or neoplasm formation. Third, gliosis may appear as variably sized, randomly scattered foci of reactive glial cells in the absence of visible parenchymal damage or inflammation. In interpreting test article-related CNS gliosis, adversity is indicated by parenchymal injury (e.g., degeneration, necrosis, or inflammation) and not the mere existence of a glial reaction. In the absence of clear structural damage to the parenchyma, gliosis as a standalone CNS finding should be interpreted as a nonadverse reaction to regional alterations in microenvironmental conditions rather than as evidence of a glial reaction associated with neurotoxicity.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 1-2","pages":"68-76"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9647167","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

Post-Pandemic Pathology Practice. 流行病后病理学实践。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-01-01 Epub Date: 2023-03-29 DOI: 10.1177/01926233231160518

Kenneth A Schafer

引用次数: 1

Investigation of the Proliferative Potential of FGF21 or FGF19 in Liver-Specific FGFR4-Deficient Mice. 研究肝脏特异性 FGFR4 缺失小鼠体内 FGF21 或 FGF19 的增殖潜力

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-01-01 Epub Date: 2023-04-26 DOI: 10.1177/01926233231164097

Kerstin Wäse, Thomas Bartels, Uwe Schwahn, Mostafa Kabiri

{"title":"Investigation of the Proliferative Potential of FGF21 or FGF19 in Liver-Specific FGFR4-Deficient Mice.","authors":"Kerstin Wäse, Thomas Bartels, Uwe Schwahn, Mostafa Kabiri","doi":"10.1177/01926233231164097","DOIUrl":"10.1177/01926233231164097","url":null,"abstract":"Fibroblast growth factor 21 (FGF21) and FGF15/FGF19 belong to the same subgroup of FGFs and are believed to have therapeutic potential in the treatment of type 2 diabetes and associated metabolic dysfunctionalities and pathological conditions. FGF19 has been proposed to induce hyperplasia and liver tumors in FVB mice (named after its susceptibility to Friend leukemia virus B), mediated by the FGF receptor 4 (FGFR4). The goal of this work was to investigate whether FGF21 might also have a potential proliferative effect mediated via FGFR4 using liver-specific Fgfr4 knockout (KO) mice. We conducted a mechanistic 7-day study involving female Fgfr4 fl/fl and Fgfr4 KO mice with a treatment regimen of twice daily or daily subcutaneous injections of FGF21 or FGF19 (positive control), respectively. The Ki-67 liver labeling index (LI) was evaluated by a semi-automated bioimaging analysis. The results showed a statistically significant increase in FGF21- and FGF19-treated Fgfr4 fl/fl mice. Interestingly, in Fgfr4 KO mice, this effect was absent following both treatments of FGF19 and FGF21, indicating that not only the FGFR4 receptor is pivotal for the mediation of hepatocellular proliferation by FGF19 leading finally to liver tumors but it seems also that FGFR4/FGF21 signaling has an impact on the hepatocellular proliferative activity, which does not promote the formation of hepatocellular liver tumors based on the current knowledge.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 1-2","pages":"27-38"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9650358","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

Assessing the Carcinogenicity of Vadadustat, an Oral Hypoxia-Inducible Factor Prolyl-4-Hydroxylase Inhibitor, in Rodents. 评估低氧诱导因子脯氨酰-4-羟化酶口服抑制剂 Vadadustat 在啮齿动物中的致癌性。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-01-01 Epub Date: 2023-05-09 DOI: 10.1177/01926233231168836

Heather Kowalski, Debie Hoivik, Michael Rabinowitz

引用次数: 0

Chronic Inhalation Exposure to Antimony Trioxide Exacerbates the MAPK Signaling in Alveolar Bronchiolar Carcinomas in B6C3F1/N Mice. 慢性吸入三氧化二锑会加剧 B6C3F1/N 小鼠肺泡支气管癌中的 MAPK 信号转导

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2023-01-01 Epub Date: 2023-04-03 DOI: 10.1177/01926233231157322

Thai-Vu T Ton, Hue-Hua L Hong, Ramesh C Kovi, Keith R Shockley, Shyamal D Peddada, Kevin E Gerrish, Kyathanahalli S Janardhan, Gordon Flake, Mathew D Stout, Robert C Sills, Arun R Pandiri

{"title":"Chronic Inhalation Exposure to Antimony Trioxide Exacerbates the MAPK Signaling in Alveolar Bronchiolar Carcinomas in B6C3F1/N Mice.","authors":"Thai-Vu T Ton, Hue-Hua L Hong, Ramesh C Kovi, Keith R Shockley, Shyamal D Peddada, Kevin E Gerrish, Kyathanahalli S Janardhan, Gordon Flake, Mathew D Stout, Robert C Sills, Arun R Pandiri","doi":"10.1177/01926233231157322","DOIUrl":"10.1177/01926233231157322","url":null,"abstract":"Antimony trioxide (AT) is used as a flame retardant in fabrics and plastics. Occupational exposure in miners and smelters is mainly through inhalation and dermal contact. Chronic inhalation exposure to AT particulates in B6C3F1/N mice and Wistar Han rats resulted in increased incidences and tumor multiplicities of alveolar/bronchiolar carcinomas (ABCs). In this study, we demonstrated Kras (43%) and Egfr (46%) hotspot mutations in mouse lung tumors (n = 80) and only Egfr (50%) mutations in rat lung tumors (n = 26). Interestingly, there were no differences in the incidences of these mutations in ABCs from rats and mice at exposure concentrations that did and did not exceed the pulmonary overload threshold. There was increased expression of p44/42 mitogen-activated protein kinase (MAPK) (Erk1/2) protein in ABCs harboring mutations in Kras and/or Egfr, confirming the activation of MAPK signaling. Transcriptomic analysis indicated significant alterations in MAPK signaling such as ephrin receptor signaling and signaling by Rho-family GTPases in AT-exposed ABCs. In addition, there was significant overlap between transcriptomic data from mouse ABCs due to AT exposure and human pulmonary adenocarcinoma data. Collectively, these data suggest chronic AT exposure exacerbates MAPK signaling in ABCs and, thus, may be translationally relevant to human lung cancers.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 1-2","pages":"39-55"},"PeriodicalIF":1.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9640244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Early-Onset albuminuria and Associated Renal Pathology in Leucine-Rich Repeat Kinase 2 Knockout Rats. 富亮氨酸重复激酶 2 基因敲除大鼠的早发性白蛋白尿及相关肾脏病理变化

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-01-01 Epub Date: 2023-04-20 DOI: 10.1177/01926233231162809

Yi-Zhong Gu, Katerina Vlasakova, Glen Miller, Nicholas T Gatto, Paul J Ciaccio, Sabu Kuruvilla, Elizabeth G Besteman, Roger Smith, Spencer J Reynolds, Rupesh P Amin, Warren E Glaab, Gordon Wollenberg, Jose Lebron, Frank D Sistare

{"title":"Early-Onset albuminuria and Associated Renal Pathology in Leucine-Rich Repeat Kinase 2 Knockout Rats.","authors":"Yi-Zhong Gu, Katerina Vlasakova, Glen Miller, Nicholas T Gatto, Paul J Ciaccio, Sabu Kuruvilla, Elizabeth G Besteman, Roger Smith, Spencer J Reynolds, Rupesh P Amin, Warren E Glaab, Gordon Wollenberg, Jose Lebron, Frank D Sistare","doi":"10.1177/01926233231162809","DOIUrl":"10.1177/01926233231162809","url":null,"abstract":"Activating mutations of the leucine-rich repeat kinase 2 (LRRK2) gene are associated with Parkinson disease (PD), prompting development of LRRK2 inhibitors as potential treatment for PD. However, kidney safety concerns have surfaced from LRRK2 knockout (KO) mice and rats and from repeat-dose studies in rodents administered LRRK2 inhibitors. To support drug development of this therapeutic target, we conducted a study of 26 weeks' duration in 2-month-old wild-type and LRRK2 KO Long-Evans Hooded rats to systematically examine the performance of urinary safety biomarkers and to characterize the nature of the morphological changes in the kidneys by light microscopy and by ultrastructural evaluation. Our data reveal the time course of early-onset albuminuria at 3 and 4 months in LRRK2 KO female and male rats, respectively. The increases in urine albumin were not accompanied by concurrent increases in serum creatinine, blood urea nitrogen, or renal safety biomarkers such as kidney injury molecule 1 or clusterin, although morphological alterations in both glomerular and tubular structure were identified by light and transmission electron microscopy at 8 months of age. Diet optimization with controlled food intake attenuated the progression of albuminuria and associated renal changes.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 1-2","pages":"15-26"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678375","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

Assessment of Mouse Liver Histopathology Following Exposure to HFPO-DA With Emphasis on Understanding Mechanisms of Hepatocellular Death. 小鼠暴露于 HFPO-DA 后的肝组织病理学评估，重点是了解肝细胞死亡的机制。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-01-01 Epub Date: 2023-03-29 DOI: 10.1177/01926233231159078

Chad M Thompson, Melissa M Heintz, Jeffrey C Wolf, Roza Cheru, Laurie C Haws, John M Cullen

{"title":"Assessment of Mouse Liver Histopathology Following Exposure to HFPO-DA With Emphasis on Understanding Mechanisms of Hepatocellular Death.","authors":"Chad M Thompson, Melissa M Heintz, Jeffrey C Wolf, Roza Cheru, Laurie C Haws, John M Cullen","doi":"10.1177/01926233231159078","DOIUrl":"10.1177/01926233231159078","url":null,"abstract":"Ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate (HFPO-DA) is a short chain member of per- and polyfluoroalkyl substances (PFAS). To better understand the relevance of histopathological effects seen in livers of mice exposed to HFPO-DA for human health risk assessment, histopathological effects were summarized from hematoxylin and eosin (H&E)-stained sections in several repeat-dose toxicity studies in mice. Findings across studies revealed histopathological changes consistent with peroxisomal proliferation, whereas two reports of steatosis could not be confirmed in the published figures. In addition, mechanisms of hepatocellular death were assessed in H&E sections as well as with the apoptotic marker cleaved caspase-3 (CCasp3) in newly cut sections from archived liver blocks from select studies. A comparison of serially CCasp3 immunolabeled and H&E-stained sections revealed that mechanisms of hepatocellular death cannot be clearly discerned in H&E-stained liver sections alone as several examples of putatively necrotic cells were positive for CCasp3. Published whole genome transcriptomic data were also reevaluated for enrichment of various forms of hepatocellular death in response to HFPO-DA, which revealed enrichment of apoptosis and autophagy, but not ferroptosis, pyroptosis, or necroptosis. These morphological and molecular findings are consistent with transcriptomic evidence for peroxisome proliferator-activated receptor alpha (PPARα) signaling in HFPO-DA exposed mice.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 1-2","pages":"4-14"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5f/85/10.1177_01926233231159078.PMC10278389.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9657655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toxicologic Pathology Forum: Opinion on Approaches for Reporting Toxic and Adverse Dose Levels in Nonclinical Toxicology Studies Supporting the Development of Anticancer Pharmaceuticals. 毒理病理学论坛：关于在支持抗癌药物开发的非临床毒理学研究中报告毒性和不良剂量水平的方法的意见。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-01-01 Epub Date: 2023-01-25 DOI: 10.1177/01926233221146937

Renee R Hukkanen, Tomoyuki Moriyama, Daniel J Patrick, Jonathan Werner

{"title":"Toxicologic Pathology Forum: Opinion on Approaches for Reporting Toxic and Adverse Dose Levels in Nonclinical Toxicology Studies Supporting the Development of Anticancer Pharmaceuticals.","authors":"Renee R Hukkanen, Tomoyuki Moriyama, Daniel J Patrick, Jonathan Werner","doi":"10.1177/01926233221146937","DOIUrl":"10.1177/01926233221146937","url":null,"abstract":"The advancement of an investigational new drug in humans is a significant developmental milestone. In first-in-human (FIH)-enabling toxicology studies, the highest dose without a test article-related adverse effect (no-observed-adverse-effect-level [NOAEL]) serves as the basis for deriving a safe FIH starting dose. For anticancer pharmaceuticals, the FIH dose may be calculated using the highest non-severely toxic dose (HNSTD) in nonrodent models or the dose severely toxic to 10% (STD10) in rodents. Given the practice of reporting the NOAEL, but the lack of regulatory requirements to do so for anticancer pharmaceuticals, we conducted an informal survey of 20 companies to answer the question \"How is our industry reporting toxic/adverse dose levels in FIH-enabling toxicology studies for anticancer indications?\" The data indicated 4 reporting approaches, each providing a path to regulatory acceptance. Within the integrated toxicology study report, 45% of respondents report the HNSTD/STD10, 25% report the NOAEL, 20% report both the HNSTD/STD10 and NOAEL, and 10% do not define either, reserving definitions for regulatory submissions. One reporting approach may be preferred over another for reasons including consistency across indications, repurposing pharmaceuticals, regulatory feedback, or simplicity. The reporting approach should be defined in advance of study initiation, and the pathologist should provide context to support the chosen approach.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 1-2","pages":"81-86"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9647526","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

Pharmacobezoar Formation From HPMC-AS-Containing Spray-Dried Formulations in Nonclinical Safety Studies in Rats. 含hmc - as的喷雾干燥制剂在大鼠体内的非临床安全性研究。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-12-01 DOI: 10.1177/01926233221145112

Hannes Gierke, Teresa Pfrommer, Kerstin Schäfer, Werner Weitschies, Thomas Nolte

{"title":"Pharmacobezoar Formation From HPMC-AS-Containing Spray-Dried Formulations in Nonclinical Safety Studies in Rats.","authors":"Hannes Gierke, Teresa Pfrommer, Kerstin Schäfer, Werner Weitschies, Thomas Nolte","doi":"10.1177/01926233221145112","DOIUrl":"https://doi.org/10.1177/01926233221145112","url":null,"abstract":"Changing the physical state from crystalline to amorphous is an elegant method to increase the bioavailability of poorly soluble new chemical entity (NCE) drug candidates. Subsequently, we report findings from repeat-dose toxicity studies of an NCE formulated as a spray-dried amorphous solid dispersion (SD-ASD) based on hydroxypropyl methylcellulose acetate succinate (HPMC-AS) in rats. At necropsy, agglomerates of SD-ASD were found in the stomach and small intestine, which in reference to literature were termed pharmacobezoars. We interpreted the pH-dependent insolubility of HPMC-AS in the acidic gastric environment to be a precondition for pharmacobezoar formation. Gastric pharmacobezoars were not associated with clinical signs or alterations of clinical pathology parameters. Pharmacobezoar-correlated histopathological findings were limited to the stomach and consisted of atrophy, erosion, ulcer, and inflammation, predominantly of the nonglandular mucosa. Pharmacobezoars in the small intestines induced obstructive ileus with overt clinical signs which required unscheduled euthanasia, prominent alterations of clinical pathology parameters indicative of hypotonic dehydration, degenerative and inflammatory processes in the gastrointestinal tract, and secondary renal findings. The incidence of pharmacobezoars increased with dose and duration of dosing. Besides the relevance of pharmacobezoars to animal welfare, they limit the non-observed adverse effect level in nonclinical testing programs and conclusively their informative value.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"50 8","pages":"920-929"},"PeriodicalIF":1.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10542011","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: 2

Toxicologic Pathology Forum: Opinion on Not Euthanizing Control Animals in the Recovery Phase of Non-Rodent Toxicology Studies. 毒理学病理论坛:关于在非啮齿动物毒理学研究的恢复阶段不对对照动物实施安乐死的意见。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-12-01 DOI: 10.1177/01926233221129214

Kyathanahalli S Janardhan, Radhakrishna Sura, Smita Salian-Mehta, Thierry Flandre, Xavier Palazzi, Doris Zane, Bhanu Singh, Binod Jacob, Renee Rosemary Hukkanen, Muthafar Al-Haddawi, Bindu Bennet, Victoria Laast, Donna Lee, Richard Peterson, Annette Romeike, Frederic Schorsch, Magali Guffroy

{"title":"Toxicologic Pathology Forum: Opinion on Not Euthanizing Control Animals in the Recovery Phase of Non-Rodent Toxicology Studies.","authors":"Kyathanahalli S Janardhan, Radhakrishna Sura, Smita Salian-Mehta, Thierry Flandre, Xavier Palazzi, Doris Zane, Bhanu Singh, Binod Jacob, Renee Rosemary Hukkanen, Muthafar Al-Haddawi, Bindu Bennet, Victoria Laast, Donna Lee, Richard Peterson, Annette Romeike, Frederic Schorsch, Magali Guffroy","doi":"10.1177/01926233221129214","DOIUrl":"https://doi.org/10.1177/01926233221129214","url":null,"abstract":"Nonclinical toxicology studies that are required to support human clinical trials of new drug candidates are generally conducted in a rodent and a non-rodent species. These studies typically contain a vehicle control group and low, intermediate, and high dose test article groups. In addition, a dosing-free recovery phase is sometimes included to determine reversibility of potential toxicities observed during the dosing phase and may include additional animals in the vehicle control and one or more dose groups. Typically, reversibility is determined by comparing the test article-related changes in the dosing phase animals to concurrent recovery phase animals at the same dose level. Therefore, for interpretation of reversibility, it is not always essential to euthanize the recovery vehicle control animals. In the absence of recovery vehicle control tissues, the pathologist's experience, historical control database, digital or glass slide repositories, or literature can be used to interpret the findings in the context of background pathology of the species/strain/age. Therefore, in most studies, the default approach could be not to euthanize recovery vehicle control animals. This article provides opinions on scenarios that may or may not necessitate euthanasia of recovery phase vehicle control animals in nonclinical toxicology studies involving dogs and nonhuman primates.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"50 8","pages":"950-956"},"PeriodicalIF":1.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540407","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: 1