Categorization of nano-structured titanium dioxide according to physicochemical characteristics and pulmonary toxicity.

Naoki Hashizume,Kenji Kawaguchi,Makoto Nakai,Masashi Gamo,Yoshiyuki Inoue,Kazuhiro Yamamoto,Toshio Kobayashi,Yutaka Oshima,Kazumasa Honda,Takeshi Sasaki,Yasuhiro Tsubokura,Nobuya Imatanaka,Shozo Ajimi

doi:10.1016/j.toxrep.2016.05.005

Abstract

A potentially useful means of predicting the pulmonary risk posed by new forms of nano-structured titanium dioxide (nano-TiO2) is to use the associations between the physicochemical properties and pulmonary toxicity of characterized forms of TiO2. In the present study, we conducted intratracheal administration studies in rats to clarify the associations between the physicochemical characteristics of seven characterized forms of TiO2 and their acute or subacute pulmonary inflammatory toxicity. Examination of the associations between the physicochemical characteristics of the TiO2 and the pulmonary inflammatory responses they induced revealed (1) that differences in the crystallinity or shape of the TiO2 particles were not associated with the acute pulmonary inflammatory response; (2) that particle size was associated with the acute pulmonary inflammatory response; and (3) that TiO2 particles coated with Al(OH)3 induced a greater pulmonary inflammatory response than did non-coated particles. We separated the seven TiO2 into two groups: a group containing the six TiO2 with no surface coating and a group containing the one TiO2 with a surface coating. Intratracheal administration to rats of TiO2 from the first group (i.e., non-coated TiO2) induced only acute pulmonary inflammatory responses, and within this group, the acute pulmonary inflammatory response was equivalent when the particle size was the same, regardless of crystallinity or shape. In contrast, intratracheal administration to rats of the TiO2 from the second group (i.e., the coated TiO2) induced a more severe, subacute pulmonary inflammatory response compared with that produced by the non-coated TiO2. Since alteration of the pulmonary inflammatory response by surface treatment may depend on the coating material used, the pulmonary toxicities of coated TiO2 need to be further evaluated. Overall, the present results demonstrate that physicochemical properties may be useful for predicting the pulmonary risk posed by new nano-TiO2 materials.

Highlights

The European Commission defines a nanomaterial as “a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm–100 nm”The first three authors contributed to the manuscript.[1]
The relationships between the physicochemical characteristics of the TiO2 and the results of the bronchoalveolar lavage fluid (BALF) examination showed that smaller TiO2 particles induced a greater acute pulmonary inflammatory response than did larger TiO2 particles, irrespective of particle crystallinity or shape (Fig. 8A–8F)
Consistent with this result, the frequencies and grades of the histopathological findings at three days after administration of the test materials were greater for the smaller TiO2 particles than for the larger TiO2 particles (Table 2 and Fig. 5)

Summary

Introduction

The European Commission defines a nanomaterial as “a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm–100 nm”The first three authors contributed to the manuscript.[1]. N. Hashizume et al / Toxicology Reports 3 (2016) 490–500 recently regarding the potential health risks posed by nano-TiO2 to consumers, workers, and the environment [4]. Many researchers and regulators are trying to understand the hazards of nano-TiO2 and determine appropriate strategies for the assessment of the pulmonary risk associated with exposure to nano-TiO2 materials. Nano-TiO2 can be manufactured in various forms that have different physicochemical characteristics (e.g., crystallinity, shape, particle size, surface area, and surface modification), which can lead to nanomaterials with the same chemical formula but different pulmonary toxicities [6]. From a regulatory standpoint, it would be beneficial to assess the pulmonary risk of all newly developed nano-TiO2 materials; a program of this size is unrealistic due to the time and money that would be required

Methods

Results

Conclusion