Toxicologic and Metabonomic Characterization of Toxins and Metabolites in Skeletal Tissues for Forensic Prediction of Toxin Exposure Patterns

骨骼组织中毒素和代谢物的毒理学和代谢组学特征，用于毒素暴露模式的法医预测

• 批准号: 327609-2013
• 负责人: Watterson, James
• 金额: $ 2.62万
• 依托单位: Laurentian University of Sudbury
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572069
• 关键词: Toxicologic; Metabonomic; Characterization; Toxins; Metabolites

OBJECTIVES The objective of this research program is to determine the extent to which the circumstances of exposure to a toxin may be differentiated through modeling of quantitative relationships between concentrations of a toxin and metabolites in decomposed skeletal tissues. SCIENTIFIC APPROACH This work will develop quantitative, high throughput mass spectrometric methods to analyze model toxins, their metabolites and endogenous metabolites in decomposed skeletal tissues. The hypothesis is that different patterns of toxin exposure may be differentiated through relationships between relative levels of toxin, toxin metabolites and endogenous metabolites measured in decomposed skeletal tissues. Rats will be exposed to toxin(s) under different dosing patterns, with dose intervals based on the half-life of the toxin in rats. Placebo exposed animals will serve as control groups for each toxin studied. For each pattern of exposure, various postmortem environments (e.g., temperature, humidity, soil conditions, entomological activity and/or degrees of decomposition) will be investigated. Toxins and metabolites will be extracted from bone prior to analysis by chromatography and mass spectrometry. Mathematical relationships between toxin and metabolite levels will be investigated in order to determine if they may be used to predict different patterns of toxin exposure. EXPECTED NOVELTY & SIGNIFICANCE Toxicological analysis of skeletal remains is poorly understood. Discrimination between different patterns of toxin exposure may be possible based on comparison of the mathematical relationship between levels of toxin and metabolites in bone. This would provide an interpretive framework for toxicological measurements in skeletal tissues that is not currently possible, significantly impacting the forensic and environmental sciences.

目标 本研究计划的目的是确定在何种程度上暴露于毒素的情况下，可以区分通过建模的定量关系的毒素和代谢物的浓度在分解的骨骼组织。 科学方法 这项工作将开发定量，高通量质谱方法来分析模型毒素，其代谢产物和内源性代谢产物在分解的骨骼组织。该假说认为，通过在分解的骨骼组织中测量的毒素、毒素代谢物和内源性代谢物的相对水平之间的关系，可以区分毒素暴露的不同模式。大鼠将以不同的给药模式暴露于毒素，给药间隔基于毒素在大鼠中的半衰期。安慰剂暴露动物将作为研究的每种毒素的对照组。对于每种暴露模式，各种死后环境（例如，温度、湿度、土壤条件、昆虫活动和/或分解程度）进行调查。在通过色谱法和质谱法进行分析之前，将从骨中提取毒素和代谢物。 将研究毒素和代谢物水平之间的数学关系，以确定它们是否可用于预测毒素暴露的不同模式。 预期的新奇和重要性 对骨骼遗骸的毒理学分析知之甚少。通过比较骨骼中毒素和代谢物水平之间的数学关系，可以区分不同的毒素暴露模式。这将为目前不可能的骨骼组织毒理学测量提供一个解释性框架，对法医和环境科学产生重大影响。