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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=681816
• 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，包括摄入受污染的土壤和吸入空气中的颗粒物 (PM)。在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）可能会导致不切实际的高风险估计。相反，使用可溶于模拟胃肠道条件或模拟肺液（生物可访问）的吸入或摄入污染物的分数，通过具有成本效益的体外测试进行测量，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。这种化学方法同时需要减少动物试验的使用，这涉及强烈的伦理、技术和财务问题。尽管最近在应用于金属污染土壤的化学*生物有效性研究方面取得了进展，但仍需要开展大量工作来推进将多环芳烃生物可及性测试纳入污染场地特定风险评估的科学基础。我的研究计划的目标是开发新型和改进的体外工具，用于评估受污染土壤、空气颗粒物和儿童消费品中的金属和多环芳烃的口腔生物可及性（摄入和吸入）。更准确地说，我的工作旨在调查和挑战最近开发的 PAH 体外生物可及性测试（FOREShT 和 IVG），并使用各种工业 PAH 污染*土壤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。就多环芳烃污染场地而言，该研究计划的成功将有助于降低土地清理成本，并制定更准确的特定场地复垦标准。*此外，该研究计划带来了实施侵入性较小且更可持续的修复方法的前景。这项创新研究计划还旨在获取有关模拟肺液中多环芳烃和与空气中颗粒物相关金属的生物可接近性的知识。将测试一种新型 Gamble 溶液，其中含有专为 PAH 开发的表面活性剂脂质，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，以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为基础，该研究计划还将重点开发一种急需的、半连续的、含食品的 IVG 生物可访问性测试版本，以模拟长期暴露于摄入的金属物品。该计划将能够培训高素质的环境工程师（1 PDF、3 博士、2 硕士、6 本科生）具有丰富的风险评估知识。**