DuPont Haskell Global Centers for Health and Environmental Sciences, 1090 Elkton Road, Newark, DE 19714-0050, United States.
Toxicol Lett. 2013 Jul 4;220(2):193-204. doi: 10.1016/j.toxlet.2013.04.002. Epub 2013 Apr 18.
Due to its multifunctional applications, titanium dioxide particles have widespread use in commerce. The particle-types function as sources of pigment color, in food products, anti-bacterial components, ultraviolet radiation scavengers, catalysts, as well as in cosmetics. Because of its inherent properties in a diverse number of products, exposures may occur via any of the major point-of-entry routes, i.e., inhalation, oral or dermal. Although the majority of TiO2 applications are known to exist in the pigment-grade form, nanoscale forms of TiO2 are also common components in several products. This brief review is designed to identify relevant toxicology and risk-related issues which inform health effects assessments on the various forms of titanium dioxide particles. While there has been an abundance of hazard data generated on titanium dioxide particulates, many of the published reports have limited informational value for assessing health effects due, in large part, to shortcomings in experimental design issues, such as: (1) inadequate material characterization of test samples; (2) questionable relevance of experimental systems employed to simulate human exposures; (3) applications of generally high doses, exclusive focus on acute toxicity endpoints, and a lack of reference benchmark control materials, to afford interpretation of measured results; and/or (4) failure to recognize fundamental differences between hazard and risk concepts. Accordingly, a number of important toxicology issues are identified and integrated herein to provide a more comprehensive assessment of the health risks of different forms of pigment-grade and nanoscale titanium dioxide particles. It is important to note that particle-types of different TiO2 compositions may have variable toxicity potencies, depending upon crystal structure, particle size, particle surface characteristics and surface coatings. In order to develop a more robust health risk evaluation of TiO2 particle exposures, this review focuses on the following issues: (1) Introduction to TiO2 particle chemistry/functionality and importance of robust material characterization of test samples; (2) Implementation of meaningful hazard studies for gauging EHS safety issues – pulmonary bioassay data and development of the Nano Risk Framework for developmental nano TiO2 compounds; (3) Epidemiological study findings on titanium dioxide workers – the most heavily-exposed populations; (4) Methodologies for setting occupational exposure limits including benchmarking or bridging comparisons; and (5) The importance of particle overload data in the lungs of rats as it relates to gauging the relevance of health effects for humans. A comprehensive evaluation of the existing animal and human health data is a necessary prerequisite for facilitating accurate assessments of human health risks to TiO2 exposures.
由于其多功能的应用，二氧化钛颗粒在商业中得到了广泛的应用。这些颗粒类型可用作颜料颜色的来源，存在于食品产品、抗菌成分、紫外线辐射清除剂、催化剂以及化妆品中。由于其在众多产品中的固有特性，暴露可能通过任何主要的进入途径发生，即吸入、口服或皮肤接触。尽管大多数 TiO2 的应用都以颜料级的形式存在，但纳米级的 TiO2 也是几种产品中常见的成分。本综述旨在确定相关的毒理学和风险相关问题，为各种形式的二氧化钛颗粒的健康影响评估提供信息。虽然已经有大量关于二氧化钛颗粒的危害数据，但由于实验设计问题，许多已发表的报告对于评估健康影响的价值有限，这些问题主要包括：（1）测试样品的材料特性描述不充分；（2）用于模拟人体暴露的实验系统的相关性值得怀疑；（3）应用一般高剂量，仅关注急性毒性终点，缺乏参考基准对照材料，以便解释测量结果；和/或（4）未能认识到危害和风险概念之间的根本区别。因此，本文确定并整合了一些重要的毒理学问题，以更全面地评估不同形式的颜料级和纳米级二氧化钛颗粒的健康风险。需要注意的是，不同 TiO2 成分的颗粒类型可能具有不同的毒性效力，这取决于晶体结构、颗粒大小、颗粒表面特性和表面涂层。为了对 TiO2 颗粒暴露进行更稳健的健康风险评估，本综述重点关注以下问题：（1）介绍 TiO2 颗粒的化学/功能和测试样品的稳健材料特性描述的重要性；（2）实施有意义的危害研究，以评估 EHS 安全问题——肺部生物测定数据和发育纳米 TiO2 化合物的纳米风险框架的发展；（3）关于二氧化钛工人的流行病学研究结果——暴露最严重的人群；（4）职业接触限值的制定方法，包括基准或桥接比较；（5）大鼠肺部颗粒过载数据的重要性，因为它与评估人类健康影响的相关性有关。对现有动物和人类健康数据的全面评估是准确评估 TiO2 暴露对人类健康风险的必要前提。
