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

儿童经常通过多种途径接触到有毒物质，如多环芳烃（PAHs）和金属，包括摄入受污染的土壤和吸入空气中的颗粒物。在对污染场地进行的风险评估研究中，假设摄入或吸入的物质中有毒物质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，通过具有成本效益的体外试验测量吸入或摄入污染物中可溶于模拟胃肠道状况或模拟肺液（生物可及性）的部分，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。与此同时，这种化学方法需要减少动物试验的使用，这涉及到强烈的伦理、技术和财务问题。尽管最近在金属污染土壤的化学生物可利用性研究方面取得了进展，但将多环芳烃生物可利用性测试纳入污染场地特定风险评估的科学基础还需要做大量工作。我的研究计划的目标是开发新的和改进的体外工具，用于口服生物可及性评估（摄入和吸入）的金属和多环芳烃污染土壤，空气中的颗粒物和儿童消费品。更准确地说，我的工作将致力于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），并利用广泛的工业多环芳烃污染土壤评估各种食品添加剂和合成脂汇对体外化学生物利用度结果的影响。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的开垦标准之后减少土地清理成本。此外，该研究项目带来了实施侵入性更低、更可持续的修复方法的前景。这项创新的研究计划还旨在获得与空气传播的pmms相关的多环芳烃和金属在模拟肺液中的生物可及性知识。将测试一种新型甘伯氏溶液，该溶液含有专门针对多环芳烃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，在我们关于玩具和低成本珠宝中金属的化学生物利用度的先驱工作的基础上，本研究项目还将重点开发一种急需的、半连续的、含食物的IVG生物利用度测试，以模拟长期暴露于摄入的金属物品中。该项目将培养具有风险评估知识的高素质环境工程师（1名PDF， 3名博士，2名硕士，6名本科生）。

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 chemicalbioavailability 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-contaminatedsoils. 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.