Development of novel in-vitro chemical tools to simulate gastro-intestinal and lung environments in order to assess bioaccessibility of contaminants

开发新型体​​外化学工具来模拟胃肠道和肺部环境，以评估污染物的生物可及性

• 批准号: RGPIN-2016-06430
• 负责人: Zagury, Gérald
• 金额: $ 1.97万
• 依托单位: École Polytechnique de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=669517
• 关键词: Development; novel; vitro; chemical; tools

Children are regularly exposed to toxic substances such as polycyclic aromatic hydrocarbons (PAHs) and metals via multiple pathways, including contaminated soil ingestion and inhalation of airborne particulate matter (PM). In risk assessment studies conducted on contaminated sites, assuming that 100% of a toxic substance in ingested or inhaled material enters the bloodstream (bioavailable) may lead to unrealistically high risk estimates. On the contrary, using the fraction of an inhaled or ingested pollutant which is soluble in simulated gastrointestinal conditions or simulated lung fluids (bioaccessible), measured via cost effective in-vitro tests, can help environmental engineers and risk assessors to obtain more accurate risk estimates. Such a chemical approach entails, at the same time, a reduction in the use of animal testing which involves strong ethical, technical, and financial issues. In spite of recent progress in chemical*bioavailability research applied to metal contaminated soils, much work is needed to advance the scientific basis for incorporating PAH bioaccessibility testing into contaminated site-specific risk assessments. The objective of my research program is to develop novel and improved in-vitro tools for oral bioaccessibility assessment (ingestion and inhalation) of metals and PAHs in contaminated soils, airborne particulate matter and children's consumer products. More precisely, my work will aim at investigating and challenging recently developed PAH in-vitro bioaccessibility tests (FOREShT and IVG) and at assessing the influence of various food additives and of synthetic lipid sinks on in-vitro chemical bioavailability results using a wide array of industrial PAH-contaminated*soils. In the case of PAH-contaminated sites, the success of this research program will allow for reduced land cleanup costs, following the formulation of more accurate site specific reclamation criteria.*Moreover, this research program brings the prospect of implementing less intrusive and more sustainable remediation approaches. This innovative research program also aims at gaining knowledge on bioaccessibility in simulated lung fluids of PAHs and metals associated with airborne PMs. A novel Gamble's solution containing surfactant lipids specifically developed for PAH, and the existing synthetic interstitial fluids (pH 7.4) and artificial lysosomal fluids (pH 4.5) will be tested. Finally, building on our pioneer work on chemical bioavailability of metals in toys and low-cost jewelry, this research program will also focus on developing a much-needed, semi-continuous and food-containing version of the IVG bioaccessibility test, to simulate prolonged exposure to ingested metallic items.This program will enable the training of highly qualified environmental engineers (1 PDF, 3 PhD, 2 MSc, 6 undergraduates) with a strong knowledge in risk assessment.**

儿童经常通过多种途径接触有毒物质，如多环芳烃（PAH）和金属，包括摄入污染的土壤和吸入空气中的颗粒物（PM）。在对受污染场地进行的风险评估研究中，假设摄入或吸入材料中的有毒物质100%进入血液（生物可利用性）可能导致不切实际的高风险估计。相反，使用吸入或摄入的污染物中可溶于模拟胃肠道条件或模拟肺液（生物可及性）的部分，通过具有成本效益的体外试验测量，可以帮助环境工程师和风险评估人员获得更准确的风险估计。同时，这种化学方法需要减少使用动物试验，这涉及到强烈的道德，技术和财务问题。尽管最近的进展，在化学 * 生物利用度研究应用于金属污染的土壤，需要做很多工作，以推进将多环芳烃生物可及性测试到污染场地的特定风险评估的科学基础。我的研究计划的目标是开发新的和改进的体外工具，用于口腔生物可及性评估（摄入和吸入）的金属和多环芳烃污染的土壤，空气中的颗粒物和儿童消费品。更确切地说，我的工作将旨在调查和挑战最近开发的多环芳烃体外生物可及性测试（FOREShT和IVG），并评估各种食品添加剂和合成脂质汇对体外化学生物利用度结果的影响，使用广泛的工业多环芳烃污染 * 土壤。在多环芳烃污染场地的情况下，这项研究计划的成功将允许在制定更准确的场地特定复垦标准后降低土地清理成本。此外，这项研究计划带来的前景，实施侵入性较低，更可持续的补救办法。这项创新的研究计划还旨在获得有关空气中PM相关的多环芳烃和金属模拟肺液生物可及性的知识。将检测一种含有专门针对PAH开发的表面活性剂脂质的新型Gamble溶液以及现有的合成间质液（pH 7.4）和人工溶酶体液（pH 4.5）。最后，基于我们在玩具和低成本珠宝中金属的化学生物利用度方面的开创性工作，该研究计划还将专注于开发急需的、半连续的和包含食物的IVG生物可及性测试版本，以模拟长时间暴露于摄入的金属物品。（1个PDF，3个博士，2个硕士，6个本科生），具有丰富的风险评估知识。**