Identification of the mechanisms that drive the toxicity of TiO2 particulates: the contribution of physicochemical characteristics

Abstract

This review focuses on outlining the toxicity of titanium dioxide (TiO2) particulates in vitro and in vivo, in order to understand their ability to detrimentally impact on human health. Evaluating the hazards associated with TiO2 particles is vital as it enables risk assessments to be conducted, by combining this information with knowledge on the likely exposure levels of humans. This review has concentrated on the toxicity of TiO2, due to the fact that the greatest number of studies by far have evaluated the toxicity of TiO2, in comparison to other metal oxide particulates. This derives from historical reasons (whereby the size dependency of particulate toxicity was first realised for TiO2) and due to its widespread application within consumer products (such as sunscreens). The pulmonary and dermal hazards of TiO2 have been a particular focus of the available studies, due to the past use of TiO2 as a (negative) control when assessing the pulmonary toxicity of particulates, and due to its incorporation within consumer products such as sunscreens. Mechanistic processes that are critical to TiO2 particulate toxicity will also be discussed and it is apparent that, in the main, the oxidant driven inflammatory, genotoxic and cytotoxic consequences associated with TiO2 exposure, are inherently linked, and are evident both in vivo and in vitro. The attributes of TiO2 that have been identified as being most likely to drive the observed toxicity include particle size (and therefore surface area), crystallinity (and photocatalytic activity), surface chemistry, and particle aggregation/agglomeration tendency. The experimental set up also influences toxicological outcomes, so that the species (or model) used, route of exposure, experiment duration, particle concentration and light conditions are all able to influence the findings of investigations. In addition, the applicability of the observed findings for particular TiO2 forms, to TiO2 particulates in general, requires consideration. At this time it is inappropriate to consider the findings for one TiO2 form as being representative for TiO2 particulates as a whole, due to the vast number of available TiO2 particulate forms and large variety of potential tissue and cell targets that may be affected by exposure. Thus emphasising that the physicochemical characteristics are fundamental to their toxicity.

Diffusion and reaction pathways of water near fully hydrated TiO2 surfaces from ab initio molecular dynamics

“…Similarly, the layer survival probability is written as (7) or, more simply, P(t, s) = N s (t)/N s (0) ; the ratio between the number of molecules in layer s at time t compared to that at the initial time t = 0. The indicator function I is used to keep track of molecules that stay in each layer.…”

“…7,8 Understanding water adsorption on TiO 2 is the key not only to efficiently split water molecules (as made use of in hydrogen gas production 9 ) but also to optimize adsorption on, and functionalization of, TiO 2 by larger molecules as mediated via strongly bound surface waters. [10][11][12][13][14][15] On the other hand, concerns have been raised with respect to environmental safety and health when TiO 2 is used in medical implants 16 and as engineered nanoparticles in consumer products.…”

A pilot study towards ranking occupational health risk factors emanating from engineered nanoparticles: review of a decade of literature

“…Murashov et al [72] have cited certain conditions to consider with respect to measures addressing not only exposure, namely ambient atmospheric moisture (potential for the production of ENP aerosols), temperature (which infl uences particle mobility), light (it is known that TiO 2 particles can be toxic after activated by UVVisible light [73,74]), but also the presence of other background particles. Unintentionally produced nanoparticles occur in the air we breathe, such as diesel particles and particles produced during machining [75], and can potentially affect the behaviour of nanoaerosols.…”

Maternal Exposure to Particulate Air Pollution and Engineered Nanoparticles: Reproductive and Developmental Effects

“…TiO 2 particles are generally considered to be inert. Physico-chemical characteristics such as particle size, crystal phase, crystalline form and surface modifications determine particulate toxicity (Johnston et al, 2009); in reality, it is therefore difficult to generalise with respect to toxicity of particulate TiO 2 . Nanosized TiO 2 particles have been detected in lung tissue up to four weeks after inhalation exposure (Hougaard et al, 2010), why acute as well as chronic effects of exposure must be considered.…”