Development of novel in-vitro chemical tools to simulate gastro-intestinal and lung environments in order to evaluate 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(PM)。在对受污染场地进行的风险评估研究中，假设摄入或吸入的物质中的有毒物质100%进入血液(生物可用)，可能会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的比例，通过经济高效的体外测试来测量，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。这些污染物可溶于模拟的胃肠道环境条件或模拟肺液(生物可及)。与此同时，这种化学试验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。尽管最近在应用于金属污染土壤的化学生物利用度和研究方面取得了进展，但仍有许多工作要做，以推进将多环芳烃生物可获得性测试纳入受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的和改进的体外测试工具，用于口腔生物可及性评估(摄入和吸入)受污染的土壤、空气颗粒物和儿童消费品中的金属和多环芳烃。更准确地说，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试验(FOREShT和IVG)，并使用广泛的工业多环芳烃污染土壤来评估合成脂沉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，随着更准确的场地特定开垦标准的制定，这项研究计划的成功将允许降低土地清理成本。此外，这一研究计划带来了实施侵入性更小、更可持续的补救方法的前景。这项创新的研究计划还旨在获得有关使用Gamble‘s溶液和人造溶酶体液体的多环芳烃和金属在模拟肺液中的生物可达性的知识。最后，在我们最近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的基础上，该研究计划还将专注于开发急需的动态版本的IVG生物可及性测试，以模拟长期接触摄入的物品。总体而言，该计划将能够培训高素质的环境工程师(1名PDF、3名博士、2名硕士、6名本科生)，他们将能够提高知识并开发严格的体外测试，并深入了解这些工具将如何(以及应该)在现场补救和风险评估范围内被环境工程师和科学家使用。

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 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 clean-up 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 using Gamble’s solution and artificial lysosomal fluids. Finally, building on our recent and pioneer work on chemical bioavailability of metals in toys and low-cost jewelry, this research program will also focus on developing a much-needed, dynamic version of the IVG bioaccessibility test, to simulate prolonged exposure to ingested items. Overall, this program will enable the training of highly qualified environmental engineers (1 PDF, 3 PhD, 2 MSc, 6 undergraduates) who will able to advance knowledge and develop rigorous in-vitro tests, with a deep understanding of how these tools will (and should) be used by environmental engineers and scientists within the scope of site remediation and risk assessment.