Warheit David B, Hoke Robert A, Finlay Carol, Donner E Maria, Reed Kenneth L, Sayes Christie M
DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19714-0050, USA.
Toxicol Lett. 2007 Jul 10;171(3):99-110. doi: 10.1016/j.toxlet.2007.04.008. Epub 2007 Apr 27.
The development of a risk management system for nanoscale or ultrafine particle-types requires a base set of hazard data. Assessing risk is a function of hazard and exposure data. Previously, we have suggested "parallel tracks" as a strategy for conducting nanoparticle research. On the one hand, mechanistic studies on "representative" nanoparticles could be supported by governmental agencies. Alternatively, with regard to commercial nanoparticles, the environmental, health and safety (EHS) framework would include a minimum base set of toxicity studies which should be supported by the companies that are developing nano-based products. The minimum base set could include the following criteria: substantial particle characterization, pulmonary toxicity studies, acute dermal toxicity and sensitization studies, acute oral and ocular toxicity studies, along with screening type genotoxicity, and aquatic toxicity studies. We report here the toxicity results of a base set of hazard tests on a set of newly developed, well-characterized, ultrafine TiO(2) (uf-TiO(2)) particle-types. In vivo pulmonary toxicity studies in rats demonstrated low inflammatory potential and lung tissue toxicity. Acute dermal irritation studies in rabbits and local lymph node assay results in mice indicated that uf-TiO(2) was not a skin irritant or dermal sensitizer. Acute oral toxicity studies demonstrated very low toxicity and uf-TiO(2) produced short-term and reversible ocular conjunctival redness in rabbits. Genotoxicity tests demonstrated that uf-TiO(2) was negative in both the bacterial reverse mutation test and in an in vitro mammalian chromosome aberration test with Chinese hamster ovary cells. The results of aquatic toxicity screening studies demonstrated that uf-TiO(2) exhibited low concern for aquatic hazard in unaerated, 48h, static acute tests using the water flea, Daphnia magna; exhibited low concern for aquatic hazard in unaerated, 96h, static acute tests using the rainbow trout, Oncorhynchus mykiss; and exhibited medium concern in a 72h acute test using the green algae Pseudokirchneriella subcapitata. To summarize the findings, the results of most of the studies demonstrated low hazard potential in mammals or aquatic species following acute exposures to the ultrafine TiO(2) particle-types tested in this program.
开发针对纳米级或超细颗粒类型的风险管理系统需要一组基本的危害数据。风险评估是危害和暴露数据的函数。此前，我们曾建议采用“并行轨道”策略来开展纳米颗粒研究。一方面，政府机构可支持对“代表性”纳米颗粒进行机理研究。另一方面，对于商业纳米颗粒，环境、健康与安全（EHS）框架应包括一组最低限度的毒性研究基础数据，这些研究应由开发纳米基产品的公司提供支持。最低限度的基础数据集可包括以下标准：颗粒的充分表征、肺部毒性研究、急性皮肤毒性和致敏性研究、急性口服和眼毒性研究，以及筛选类型的遗传毒性和水生毒性研究。我们在此报告了一组新开发的、特征明确的超细TiO₂（uf-TiO₂）颗粒类型的一组基础危害测试的毒性结果。在大鼠体内进行的肺部毒性研究表明其炎症潜力和肺组织毒性较低。在兔子身上进行的急性皮肤刺激性研究以及在小鼠身上进行的局部淋巴结试验结果表明，uf-TiO₂不是皮肤刺激物或皮肤致敏剂。急性口服毒性研究表明其毒性极低，并且uf-TiO₂在兔子身上会产生短期且可逆的眼结膜发红。遗传毒性测试表明，uf-TiO₂在细菌回复突变试验和中国仓鼠卵巢细胞体外哺乳动物染色体畸变试验中均为阴性。水生毒性筛选研究结果表明，在使用大型蚤（Daphnia magna）进行的未曝气48小时静态急性试验中，uf-TiO₂对水生危害影响较低；在使用虹鳟（Oncorhynchus mykiss）进行的未曝气96小时静态急性试验中，uf-TiO₂对水生危害影响较低；而在使用小新月菱形藻（Pseudokirchneriella subcapitata）进行的72小时急性试验中，uf-TiO₂表现出中等影响。总结这些研究结果，在本项目中测试的超细TiO₂颗粒类型急性暴露后，大多数研究结果表明其对哺乳动物或水生物种的危害潜力较低。
