NTP Database Summarization And Evaluation

NTP数据库总结与评估

• 批准号: 7734437
• 负责人: grace e kissling
• 金额: $ 9.63万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7734437
• 关键词: Acids; Arrhythmia; Biological Assay; Caenorhabditis elegans; Caffeine; Canis familiaris; Carcinogenicity Tests; Cardiac; Cells; Chemicals; Chromium Picolinate; Data; Databases; Diet; Dose; Electrocardiogram; Ephedra sinica; Ephedrine; Evaluation; Experimental Designs; Exposure to; Furaldehyde; Future; Genomics; Goals; Growth; Heart; Individual; Investigation; Kidney; Kidney Neoplasms; Laboratory Study; Lamivudine; Lead; Lesion; Longitudinal Studies; Lung Neoplasms; Methane; Methods; Modeling; Movement; National Toxicology Program; Peer Review; Pharmaceutical Preparations; Rattus; Reporting; Reproduction; Rodent; Statistical Methods; Testing; Toxic effect; Toxin; United States National Institutes of Health; Zidovudine; base; carcinogenicity; chemical group; estragole; feeding; interest; isoeugenol; pill; response; technical report

We contributed to NTP Technical Reports on two-year rodent carcinogenicity studies of 5-(hydroxymethyl)-2-furfural, 1,2-dibromo-2,4-dicyanobutane, chromium picolinate monohydrate, isoeugenol, dibromoactonitrile and bromochloroacetic acid. We also contributed to an NTP Toxicity report on short-term rodent studies of estragole. These reports were reviewed and approved by the NTP Technical Reports Subcommittee in February, 2008. We contributed to several smaller studies focused on heart damage resulting from exposure to cardiac toxins, such as AZT, 3TC, ephedrine, caffeine, ma huang, and bis(2-chloroethoxy) methane. We identified several early indicators of heart damage that will prove useful in future studies. Furthermore, we provided the first evidence of a dose-response relationship between ephedrine and heart damage in rodents. The response was exacerbated by concomitant exposure to caffeine. We observed a similar response when ma huang, a 'natural' form of ephedrine, was used in conjunction with caffeine. This information is useful to regulatory agencies because some diet pills contain ephedrine or ma huang and caffeine. An important approach to evaluating and interpreting NTP data is to make comparisons across multiple studies. This year, we undertook two such investigations. 1) We contributed to a summary and characterization of the chemical-induced lung tumors found within the 545 NTP peer-reviewed two-year rodent studies. 2) We investigated the association, in NTP rats, between kidney lesions in short-term studies and chemical-induced kidney tumors in long-term studies. The NTP is interested in reducing, replacing and refining the use of rodents in laboratory studies. We provided advice to the NTP on experimental design and statistical methods for evaluating alternative methods for toxicity and carcinogenicity testing. These include: 1) evaluating electrocardiogram data from a dog model for testing whether drugs prolong the QT wave in the heart beat which may ultimately lead to lethal arrhythmias, and 2) continuing our evaluation of the usefulness of growth, reproduction, feeding, and movement of C. elegans for assessing toxicity. We are also involved in 3) analyzing high throughput data from cell-based assays of chemicals selected by the NTP, that were generated by the NIH Chemical Genomics Center.

我们促进了NTP技术报告，介绍了5年啮齿动物的致癌性研究，可进行5-（羟甲基）-2-毛状，1,2-二纤维瘤-2,4-二氰基丁烷，picolinate picolinate单盐酸铬酸盐，isoeugenol，dibromocartonol，dibromocartonrile和bromohocoticatient酸。我们还为NTP毒性报告做出了贡献，内容涉及雌激素的短期啮齿动物研究。这些报告在2008年2月得到了NTP技术报告小组委员会的审查和批准。 我们促进了几项较小的研究，重点是暴露于心脏毒素的心脏损伤，例如AZT，3TC，麻黄碱，咖啡因，Ma Huang和Bis和Bis（2-氯乙氧基）甲烷。我们确定了心脏损伤的几个早期指标，这些指标将在以后的研究中很有用。 此外，我们还提供了啮齿动物中麻黄碱与心脏损伤之间剂量反应关系的第一个证据。 通过伴随咖啡因的伴随暴露加剧了反应。我们观察到类似的响应，当Ma Huang与咖啡因结合使用“天然”形式的麻黄碱。 该信息对于调节机构很有用，因为某些减肥药含有麻黄碱或黄铁和咖啡因。 评估和解释NTP数据的一种重要方法是在多个研究中进行比较。 今年，我们进行了两项此类调查。 1）我们为在545 NTP同行评审的两年啮齿动物研究中发现的化学诱导的肺肿瘤的摘要和表征做出了贡献。 2）在长期研究中，我们研究了NTP大鼠在NTP大鼠的肾脏病变和化学诱导的肾脏肿瘤之间的关联。 NTP有兴趣减少，更换和完善啮齿动物在实验室研究中的使用。 我们就实验设计和统计方法提供了建议，以评估毒性和致癌性测试的替代方法。其中包括：1）评估来自狗模型的心电图数据，以测试药物是否会延长心跳中的QT波，这最终可能导致致命的心律不齐，2）继续我们评估生长，再生，喂养，饲料和仙女对毒性评估毒性的有用性的评估。 我们还参与了3）分析来自NTP选择的化学物质的高吞吐量数据，这些化学物质是由NIH化学基因组学中心产生的。

项目成果

Occult cardiotoxicity: subtoxic dosage of Bis(2-chloroethoxy)methane impairs cardiac response to simulated ischemic injury.

隐匿性心脏毒性：双（2-氯乙氧基）甲烷的亚毒剂量会损害心脏对模拟缺血性损伤的反应。

• DOI: 10.1080/01926230701230338
• 发表时间: 2007
• 期刊: Toxicologic pathology
• 影响因子: 1.5
• 作者: Golomb,Eliahu;Schneider,Aviva;Houminer,Esther;Dunnick,June;Kissling,Grace;Borman,JosephB;Nyska,Abraham;Schwalb,Herzl
• 通讯作者: Schwalb,Herzl

A comparative immunohistochemical study of spontaneous and chemically induced pheochromocytomas in B6C3F1 mice.

B6C3F1 小鼠自发性和化学诱导的嗜铬细胞瘤的比较免疫组织化学研究。

• DOI: 10.1385/ep:14:1:81
• 发表时间: 2003
• 期刊: Endocrine pathology
• 影响因子: 4.4
• 作者: Hill,GeorgetteD;Pace,Virgilio;Persohn,Elke;Bresser,Christina;Haseman,JosephK;Tischler,ArthurS;Nyska,Abraham
• 通讯作者: Nyska,Abraham

Hepatoblastomas in mice in the US National Toxicology Program (NTP) studies.

美国国家毒理学计划 (NTP) 研究中的小鼠肝母细胞瘤。

• DOI: 10.1080/01926230290105802
• 发表时间: 2002
• 期刊: Toxicologic pathology
• 影响因子: 1.5
• 作者: Turusov,VladimirS;Torii,Mikinori;Sills,RobertC;Willson,GabrielleA;Herbert,RonaldA;Hailey,JamesR;Haseman,JosephK;Boorman,GaryA
• 通讯作者: Boorman,GaryA

A survival-adjusted quantal-response test for analysis of tumor incidence rates in animal carcinogenicity studies.

用于分析动物致癌性研究中肿瘤发生率的生存调整量子反应测试。

• DOI: 10.1289/ehp.8590
• 发表时间: 2006
• 期刊: Environmental health perspectives
• 影响因子: 10.4
• 作者: Peddada,ShyamalD;Kissling,GraceE
• 通讯作者: Kissling,GraceE

N-ethyl-N-nitrosourea (ENU)-induced meningiomatosis and meningioma in p16(INK4a)/p19(ARF) tumor suppressor gene-deficient mice.

N-乙基-N-亚硝基脲 (ENU) 在 p16(INK4a)/p19(ARF) 肿瘤抑制基因缺陷小鼠中诱导脑膜瘤病和脑膜瘤。

• DOI: 10.1080/01926230701584130
• 发表时间: 2007
• 期刊: Toxicologic pathology
• 影响因子: 1.5
• 作者: Morrison,JamesP;Satoh,Hiroshi;Foley,Julie;Horton,JohnL;Dunnick,JuneK;Kissling,GraceE;Malarkey,DavidE
• 通讯作者: Malarkey,DavidE