BACKGROUND The production and use of nanoparticles is growing rapidly due to the unique physical and chemical properties associated with their nano size and large surface area. Since nanoparticles have unique physicochemical properties, their bioactivity upon exposure to workers or consumers is of interest. In this study, the issue of what dose metric (mass dose versus surface area dose) is appropriate for toxicological studies has been addressed. Rats were exposed by intratracheal instillation to various doses of ultrafine or fine TiO2. At 1, 7, or 42 days post-exposure, inflammatory and cytotoxic potential of each particle type was compared on both a mass dosage (mg/rat) as well as an equal surface area dosage (cm2 of particles per cm2 of alveolar epithelium) basis. RESULTS The findings of the study show that on a mass basis the ultrafine particles caused significantly more inflammation and were significantly more cytotoxic than the fine sized particles. However, when doses were equalized based on surface area of particles delivered, the ultrafine particles were only slightly more inflammogenic and cytotoxic when compared to the fine sized particles. Lung burden data indicate that ultrafine TiO2 appears to migrate to the interstitium to a much greater extent than fine TiO2. CONCLUSION This study suggests that surface area of particles may be a more appropriate dose metric for pulmonary toxicity studies than mass of particles.

中文翻译：

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对超细二氧化钛与细二氧化钛气管内滴注的肺反应：颗粒表面积的作用。

背景技术由于与纳米尺寸和大表面积相关的独特物理和化学性质，纳米颗粒的生产和使用正在迅速增长。由于纳米颗粒具有独特的物理化学特性，因此它们在接触工人或消费者时的生物活性令人感兴趣。在这项研究中，已经解决了毒理学研究适合什么剂量指标（质量剂量与表面积剂量）的问题。大鼠通过气管内滴注暴露于不同剂量的超细或细二氧化钛。在暴露后 1、7 或 42 天，在质量剂量（mg/大鼠）和等表面积剂量（每平方厘米肺泡上皮的平方厘米粒子数）上比较每种颗粒类型的炎症和细胞毒性潜力基础。结果 研究结果表明，以质量为基础，超细颗粒引起的炎症明显更多，细胞毒性也明显高于细颗粒。然而，当基于递送的颗粒表面积均衡剂量时，与细颗粒相比，超细颗粒仅具有略微更强的炎症和细胞毒性。肺负荷数据表明，超细 TiO2 似乎比细 TiO2 迁移到间质的程度要大得多。结论 本研究表明，与颗粒质量相比，颗粒表面积可能是肺毒性研究更合适的剂量指标。当根据递送颗粒的表面积来均衡剂量时，与细颗粒相比，超细颗粒仅具有略微更强的炎症和细胞毒性。肺负荷数据表明，超细 TiO2 似乎比细 TiO2 迁移到间质的程度要大得多。结论 本研究表明，与颗粒质量相比，颗粒表面积可能是肺毒性研究更合适的剂量指标。当根据递送颗粒的表面积来均衡剂量时，与细颗粒相比，超细颗粒仅具有略微更强的炎症和细胞毒性。肺负荷数据表明，超细 TiO2 似乎比细 TiO2 迁移到间质的程度要大得多。结论 本研究表明，与颗粒质量相比，颗粒表面积可能是肺毒性研究更合适的剂量指标。