In-vitro Oral, Inhalation, and Dermal Bioaccessibility and Bioavailability of Metal(loid)s from Polluted Soils and Mine Tailings

由于儿童的生理和发育特性，他们对污染物暴露特别敏感。他们经常接触有毒物质，如金属（类）通过偶然或故意土壤摄入，吸入颗粒物（PM）和皮肤接触污染的土壤。受污染的土壤和尾矿的较细部分，在风蚀或人为活动后悬浮，含有高水平的金属（类金属）。摄入受污染的土壤和吸入灰尘和PM可能会导致污染物在接触胃肠或肺液后释放，具体取决于接触途径。此外，与污染的土壤的皮肤接触可能导致汗液中的土壤结合的金属（类）的溶解以及这些元素通过皮肤的渗透。在暴露之后，不是全部量，而是仅一部分土壤结合的金属（类金属）将变得生物可及，即，溶解在体液中，并且只有一部分生物可利用级分将到达体循环并实际上是生物可利用的。使用合成的胃肠、肺和皮肤表面液体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，体外方法需要减少使用动物试验，这涉及到强烈的伦理，技术和财务问题。 尽管最近在体外口服生物可利用性测定方面取得了进展，但关于通过吸入和皮肤接触与地质材料结合的金属（类金属）的生物可利用性和生物利用度的体外评估存在巨大的知识缺口。本研究计划的目的是开发新的和改进的体外测定法，用于污染土壤和尾矿中金属（类金属）的生物可及性和生物利用度评估（摄入，吸入，皮肤），重点是体外生物利用度评估。这些试验将包括体外暴露于培养的肠和肺细胞（用于口服和吸入途径）以及通过合成皮肤（用于真皮途径）的渗透试验。该研究将确定生物可及金属（loid）的化学形式对肠道（Caco-2）和肺泡细胞（A549）金属（loid）摄取的影响以及潜在的毒性作用。该计划将培养12名高素质的环境工程师（3名博士，3名硕士和6名本科生）。 这项创新的研究计划的目的是为吸入和皮肤生物可及性测定的标准化提供基础，并纳入加拿大的新法规。环境工程师和风险评估人员广泛使用这些先进的体外生物可及性和生物利用性方法，应能改进针对具体地点的风险定性研究，同时取代动物试验，从而减少清理费用，并采用更可持续的补救办法。

Children are particularly sensitive to contaminant exposure due to their physiological and developmental properties. They are regularly exposed to toxic substances such as metal(loid)s via incidental or deliberate soil ingestion, inhalation of particulate matter (PM) and dermal contact with polluted soil. Finer fractions of contaminated soils and mine tailings, suspended following wind erosion or anthropogenic activity, contain high levels of metal(loid)s. Ingestion of contaminated soil and inhalation of dust and PM may cause the release of contaminants following contact with gastro-intestinal or lung fluids depending on the exposure pathway. Additionally, dermal contact with contaminated soil may cause solubilization of soil-bound metal(loid)s in sweat and the permeation of these elements through the skin. After exposure, not the total amount, but only a portion of soil-bound metal(loid)s will become bioaccessible i.e., solubilized in body fluids and only a portion of the bioaccessible fraction will then reach the systemic circulation and be actually bioavailable. The use of synthetic gastro-intestinal, lung, and skin surface fluids can help environmental engineers and risk assessors to obtain more accurate risk estimates. An in vitro 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 on in vitro oral bioaccessibility determination, there is a huge knowledge gap regarding the in vitro assessment of bioaccessibility and bioavailability through inhalation and dermal contact for metal(loid)s bound to geological materials. The objective of this research program is to develop novel and improved in vitro assays for bioaccessibility and bioavailability assessment (ingestion, inhalation, dermal) of metal(loid)s in contaminated soils and mine tailings with an emphasis on in vitro bioavailability assessment. These tests will incorporate in vitro exposure to cultured intestinal and lung cells for oral and inhalation pathways and permeation tests through synthetic skin for dermal pathway. The research will determine the influence of bioaccessible metal(loid)s chemical forms on intestinal (Caco-2) and lung alveolar cells (A549) metal(loid) uptake and the potential toxic effects. This program will enable the training of 12 highly qualified environmental engineers (3 PhD, 3 MSc, and 6 undergraduates). This innovative research program is conducted with the clear intent of providing a basis for standardization of inhalation and dermal bioaccessibility assays and incorporation into new regulations in Canada. The widespread use of these advanced in vitro bioaccessibility and bioavailability methods by environmental engineers and risk-assessors should improve site-specific risk characterization studies, while replacing animal testing.This will allow for reduced clean-up costs and the use of more sustainable remediation approaches.