GENETIC TOXICOLOGY SUPPORT FOR THE NTP AND THE NIEHS

NTP 和 NIEHS 的遗传毒理学支持

• 批准号: 10281726
• 负责人: LESLIE RECIO
• 金额: $ 93.48万
• 依托单位: INTEGRATED LABORATORY SYSTEMS, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-06 至 2021-09-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10281726
• 关键词: Adult; Adverse effects; Aging; Anabolism; Animal Model; Animal Testing; Animals; Biological; Biological Assay; Biological Effect of Chemicals; Biological Monitoring; Biotechnology; Birth; Blood specimen; Botanicals; Brain; Carcinogens; Cells; Chemical Exposure; Chemicals; Chromosomes; Clinic; Clinical; Clinical Research; Colon; Comet Assay; Complication; Congenital Abnormality; Contracts; DNA Damage; DNA Sequence Alteration; DNA sequencing; Data; Databases; Development; Diagnosis; Disasters; Disease; Down Syndrome; Early Diagnosis; Environmental Exposure; Environmental Impact; Erythrocytes; Event; Evolution; Exposure to; Family suidae; Freezing; Frequencies; Future; Gene Expression; Gene Expression Profile; Gene Mutation; Generations; Genes; Genetic; Genetic Diseases; Genomic DNA; Guidelines; Health; Heritability; Human; In Vitro; Induced Mutation; International; Investigation; Kidney; Laboratories; Life; Link; Liver; Malignant Neoplasms; Mammalian Cell; Methods; Micronucleus Tests; Mission; Mitochondrial Diseases; Modeling; Monitor; Mouse Strains; Mus; Mutagenicity Tests; Mutation; Mutation Detection; Mutation Spectra; National Institute of Environmental Health Sciences; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neurologic; Oncology; PI-Glycan; Participant; Pesticides; Pharmaceutical Preparations; Pharmacologic Substance; Process; Protocols documentation; Rattus; Resources; Rivers; Rodent; Sampling; Source; Sprague-Dawley Rats; Stomach; Study models; Symptoms; System; Technology; Testing; Tissue Sample; Tissues; Toxic effect; Toxicity Tests; Toxicogenetics; Toxicology; Translating; United States Environmental Protection Agency; United States Food and Drug Administration; Update; West Virginia; autism spectrum disorder; autistic; base; carcinogenicity; contaminated water; dietary supplements; early life exposure; environmental chemical; exposed human population; flexibility; genetic profiling; genotoxicity; human study; in vitro testing; in vivo; innovation; interest; micronucleus; mutation assay; novel strategies; peripheral blood; reproductive; reproductive toxicity; response; treatment response; tumor

This genetic toxicology testing contract has supported the overall mission of NTP to provide detailed toxicological profiles, including potential for carcinogenicity, of compounds of interest for over 30 years. Assessment of genetic damage, an important factor in the initiation and development of cancer as well as neurodegenerative diseases such as ALS, neurological conditions such as autism, aging processes, birth defects such as Down syndrome, mitochondrial diseases, and other adverse human health effects, is a critical component of any in-depth toxicological profile of a chemical or product. An important complication in assessing the impact of environmentally induced genetic damage is that genetic damage induced early in life, even prior to birth, may not manifest as an adverse health effect until decades later, during adulthood. This delay in manifestation, along with a lack of any immediate symptoms of genetic damage, makes it difficult to link early life exposures that cause genetic damage with adult disease. Because of the importance in understanding potential for induced genetic damage, a detailed characterization of the genotoxic potential of new pharmaceutical and pesticide products, as well as other types of products for which human exposure is a concern, is required by regulatory agencies such as the Food and Drug Administration and the Environmental Protection Agency prior to approval for use. This Genetic Toxicity Testing contract provides information to the NTP on various types of exposure-related genetic damage using universally accepted standard testing protocols as well as innovative approaches, when necessary and applicable, to supplement the information obtained from standard tests. Testing systems employed under this contract include both in vitro (animal and human cell-based, and bacterial) and in vivo (rats and mice) assays. The capabilities of this genetic toxicity testing contract are continuously updated to remain current with the latest scientific approaches in the field and consistent with international guidelines for conducting these kinds of tests. The field is currently undergoing rapid evolution with the many dramatic changes in technological capabilities that are occurring today.

这项遗传毒理学测试合同支持NTP的总体使命，即提供详细的毒理学特征，包括30多年来感兴趣的化合物的潜在致癌性。遗传损伤是引发和发展癌症以及神经退行性疾病（如ALS）、神经系统疾病（如自闭症）、衰老过程、出生缺陷（如唐氏综合症）、线粒体疾病和其他不良人类健康影响的重要因素，评估遗传损伤是化学品或产品任何深入毒理学特征的关键组成部分。在评估环境引起的遗传损伤的影响时，一个重要的复杂因素是，在生命早期，甚至在出生前引起的遗传损伤可能直到几十年后的成年期才表现为对健康的不利影响。这种表现的延迟，沿着缺乏任何遗传损伤的直接症状，使得很难将导致遗传损伤的早期生活暴露与成人疾病联系起来。由于了解潜在的诱导遗传损伤的重要性，监管机构（如食品药品监督管理局和环境保护局）要求在批准使用前详细描述新的药品和农药产品以及其他类型的人类接触产品的潜在遗传毒性。 这项遗传毒性测试合同使用普遍接受的标准测试协议以及必要和适用时的创新方法，向NTP提供有关各种类型与保险有关的遗传损害的信息，以补充从标准测试中获得的信息。本合同所采用的测试系统包括体外（基于动物和人类细胞以及细菌）和体内（大鼠和小鼠）试验。该遗传毒性测试合同的能力不断更新，以保持与该领域最新的科学方法保持一致，并符合进行此类测试的国际准则。该领域目前正在经历快速发展，今天正在发生的技术能力发生了许多巨大的变化。