Assessment of the in vitro genotoxicity of TiO₂ nanoparticles in a regulatory context

Abstract

A review of in vitro genotoxicity studies on titanium dioxide nanoparticles (TiO-NPs) published between 2010 and 2016 was performed by France in the framework of the CLP Regulation 1272/2008/EC. Neither the few in vivo studies of low quality nor the larger number of acceptable in vitro studies available for genotoxicity allowed France to conclude on the genotoxicity of TiO-NPs. Based on this work, it was decided to compare the acceptable in vitro studies to understand the reasons for the diverging results observed, such as the materials tested or of the protocols used and their inherent interferences. The systematic review performed on in vitro genotoxicity data for TiO-NPs was then restricted to studies with the highest level of confidence among studies following OECD guidelines and the largely applied comet assay. Indeed, the aim of this article is to understand why, even if judged of good quality, the 36 publications selected and analyzed did not lead to a clear picture. Some recommendations to be taken into account before performing new in vitro genotoxicity assays for insoluble particles such as TiO-NPs are proposed. Although secondary genotoxic effects consequent to oxidative stress seem to be the major mechanism responsible for the genotoxicity of TiO-NPs reported in some studies, primary genotoxic effects cannot be excluded. Further studies are needed to clarify the exact mode of action of TiO-NPs and to highlight which physicochemical properties lead to their genotoxicity in vitro to ultimately identify a specific combination of parameters that could represent a risk in vivo.

Genotoxicity assessment of titanium dioxide nanoparticle accumulation of 90 days in the liver of gpt delta transgenic mice

“…Recently, we reported that TiO 2 NPs have no genotoxic effects in the liver and erythrocytes when intravenously injected into gpt delta mice [17], but there are still reports about their positive effect [18,19]. Thus, the genotoxicity of TiO 2 NPs remains unclear [20,21]. TiO 2 NPs in the rodent bloodstream are translocated to the liver and remain in the tissue long-term [22][23][24][25].…”

EFSA statement on the review of the risks related to the exposure to the food additive titanium dioxide (E 171) performed by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES)

“…ANSES, however, supported the conclusions stated by Charles et al (2018) and recommended new in vivo genotoxicity data to be generated.…”

“…The new in vitro studies identified and assessed by ANSES in the current opinion do not call into question the outcome of the review by Charles et al (2018).…”

Is It Safe to Paint Your Wall White? A Case Study on Titanium Dioxide Classification

“…The challenge in interpretation of in vitro genotoxicity results was recently elaborated by Charles et al (2018). The challenge in interpretation of in vitro genotoxicity results was recently elaborated by Charles et al (2018).…”

“…In the present case of TiO 2 classification, ANSES and RAC arrived at different conclusions on the basis of genotoxicity assessments. The challenge in interpretation of in vitro genotoxicity results was recently elaborated by Charles et al (2018). The study sought an explanation of why 36 studies did not lead to a clear picture on TiO 2 genotoxicity.…”