Triage of Developmental and Reproductive Toxicants using an In vitro to In Vivo Extrapolation (IVIVE)-Toxicokinetic Computational modeling Application
使用体外到体内外推法 (IVIVE) 对发育和生殖毒物进行分类 - 毒代动力学计算模型应用
基本信息
- 批准号:10757140
- 负责人:
- 金额:$ 27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-07 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AgricultureAnimal ModelAnimal TestingAnimalsArea Under CurveBiologicalBiological AssayCase StudyCellsChemicalsComputer ModelsCoupledDataDatabasesDevelopmentDevelopmental ToxicantDocumentationDoseDrug KineticsEffectivenessEmbryoEmbryonic and Fetal DevelopmentEmerging TechnologiesExperimental ModelsFood SafetyGoalsGuidelinesHazard IdentificationHealthHumanIn VitroIndustryKnowledgeLifeMeasurementMethodologyModelingOnline SystemsOutcomePerformancePharmacologic SubstancePhasePhilosophyPhysiologicalPredispositionPregnancyPublic HealthQualifyingRattusReportingRisk AssessmentSafetyScienceSiteTechniquesTeratogensTestingTimeTissuesToxic Environmental SubstancesToxicity TestsToxicokineticsTranslatingTriageWeightWorkWorld Health Organizationchemical safetycommercializationcomputerized toolsconsumer productdata integrationdata streamsdesigndevelopmental toxicitydosimetryenvironmental chemicalexperienceexperimental studyexposed human populationexposure routefetalgraphical user interfacein silicoin vitro Modelin vivomodels and simulationmultidisciplinarynext generationnovel strategiesoutcome predictionpharmacokinetic modelphysiologically based pharmacokineticspragmatic implementationreproductivereproductive toxicityresponsesafety assessmentscreeningsuccesstooltoxicant
项目摘要
PROJECT SUMMARY
A significant shift in the safety assessment of environmental chemicals is ongoing. This shift includes a reduction,
or in some cases elimination, of traditional toxicity testing in animals with the implementation of new approach
methodologies (NAMs). Although these emerging NAMs provide an attractive means for identifying teratogens
and other developmental toxicants, the absence of a quantitative framework for relating in vitro effects to
equivalent in vivo human exposures limits their use for public health. Here, we develop a tiered approach that
integrates existing pharmacokinetic models for pregnancy into a computational application that can be adapted
to current and emerging NAMs for developmental toxicity. The primary aim of the proposed project is to deliver
an out-of-the-box computational solution for predicting the dose-response of possible human health effects by
performing in vitro-to-in vivo extrapolation (IVIVE). In Specific Aim 1, we will design a web based computational
application, DRIIVE for the Developmental and Reproductive In Vitro to In vivo Extrapolation, that will perform
forward- or reverse-dosimetry using physiologically based pharmacokinetic (PBPK) modeling within a tiered
framework bridging multiple levels of biological complexity. This framework will allow us to better account for
chemical space and exposure routes relevant to environmental toxicants. In Specific Aim 2, the work will
culminate in a case study to take industry-relevant compounds through the defined IVIVE workflows and
compare the outcomes to in-life data. Our proposal will reduce the reliance on current in vivo developmental
toxicity and provide a much-needed framework for the next generation of chemical safety assessment.
Successful completion of this Phase I project will result in a model that will undergo further development and
commercialization in Phase II, with the ultimate goal of providing an IVIVE computational model to our customers.
This developmental toxicity product fits into the existing NAM products that we offer that reduce reliance on
current in vivo animal models.
项目摘要
环境化学品的安全评估正在发生重大转变。这种转变包括减少,
或在某些情况下消除传统的动物毒性试验,
方法(NAMs)。虽然这些新兴的NAM为识别致畸剂提供了一种有吸引力的手段
和其他发育毒物,缺乏一个定量框架,
人体体内的等效接触限制了它们在公共卫生方面的使用。在这里,我们开发了一种分层方法,
将现有的妊娠药代动力学模型整合到可调整的计算应用程序中
目前和新出现的NAM的发育毒性。拟议项目的主要目的是提供
一个开箱即用的计算解决方案,用于预测可能的人类健康影响的剂量反应,
进行体外至体内外推(IVIVE)。在具体目标1中,我们将设计一个基于Web的计算
用于发育和生殖体外至体内外推的DRIIVE应用程序,将执行
在分层模型内使用基于生理学的药代动力学(PBPK)建模的正向或反向剂量测定
一个连接生物复杂性多个层次的框架。这一框架将使我们能够更好地解释
与环境毒物有关的化学品空间和接触途径。在具体目标2中,
最终通过案例研究,通过定义的IVIVE工作流程获取行业相关化合物,
将结果与活体数据进行比较。我们的建议将减少对目前体内发育的依赖,
这是一个非常重要的框架,为下一代化学品安全评估提供了一个非常需要的框架。
第一阶段项目的成功完成将产生一个模型,该模型将得到进一步的发展,
我们将在第二阶段进行商业化,最终目标是为我们的客户提供IVIVE计算模型。
这种发育毒性产品适合我们提供的现有NAM产品,
目前的体内动物模型。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Marjory Moreau其他文献
Marjory Moreau的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似海外基金
Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
- 批准号:
495434 - 财政年份:2023
- 资助金额:
$ 27万 - 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
- 批准号:
10586596 - 财政年份:2023
- 资助金额:
$ 27万 - 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
- 批准号:
10590479 - 财政年份:2023
- 资助金额:
$ 27万 - 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
- 批准号:
10642519 - 财政年份:2023
- 资助金额:
$ 27万 - 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
- 批准号:
23K06011 - 财政年份:2023
- 资助金额:
$ 27万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
- 批准号:
10682117 - 财政年份:2023
- 资助金额:
$ 27万 - 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
- 批准号:
10708517 - 财政年份:2023
- 资助金额:
$ 27万 - 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
- 批准号:
10575566 - 财政年份:2023
- 资助金额:
$ 27万 - 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
- 批准号:
23K15696 - 财政年份:2023
- 资助金额:
$ 27万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
- 批准号:
23K15867 - 财政年份:2023
- 资助金额:
$ 27万 - 项目类别:
Grant-in-Aid for Early-Career Scientists