Respiratory sensitization: toxicological point of view on the available assays

Abstract

Respiratory sensitization as a consequence of exposure to chemical products has increased over the last decades, leading to an increase of morbidity. The increased use of synthetic compounds resulted in an exponential growth of substances to which we are potentially exposed on a daily basis. Some of them are known to induce respiratory sensitization, meaning that they can trigger the development of allergies. In the past, animal studies provided useful results for the understanding of mechanisms involved in the development of respiratory allergies. However, the mechanistic understanding of the involved cellular effects is still limited. Currently, no in vitro or in vivo models are validated to identify chemical respiratory sensitizers. Nonetheless, chemical respiratory sensitizers elicit a positive response in validated assays for skin sensitization. In this review, we will discuss how these assays could be used for respiratory sensitization and if necessary, what can be learnt from these assays to develop a model to assess the respiratory sensitizing potential of chemicals. In the last decades, much work has been done to study the respiratory toxicity of inhaled compounds especially in developing in vitro assays grown at the air-liquid interface. We will discuss how possibly the tests currently used to investigate general particle toxicity could be transformed to investigate respiratory sensitization. In the present review, we describe the most known mechanism involved in the sensitization process and the experimental in vivo and alternative in vitro models, which are currently available and how to adapt and improve existing models to study respiratory sensitization.

Electro-mechanical Lung Simulator Using Polymer and Organic Human Lung Equivalents for Realistic Breathing Simulation

“…Simultaneously, up to four cell types may be included. Lung-on-chip technology provides valuable insides about the toxicity of tested substances and in virology studies 12 . The third category of in - silico models currently in use is based on the mathematical simulation of general transport equations 13 .…”

Safety assessment of excipients (SAFE) for orally inhaled drug products

“…To face the challenge of developing an adequate in vitro model of the respiratory tract for safety evaluation, especially to assess nanoparticle (NP) deposition in the lung, the development of complex cell culture systems using two or more cell lines is gaining ground (Chary et al, 2018). But, no systematic data sets for the toxicological assessment of nanoparticles are available due to non-standardized parameters, different testing systems (cells, animals), and the different types and characteristics of the particles themselves (Mahmoudi et al, 2012).…”

Metal nanomaterials: Immune effects and implications of physicochemical properties on sensitization, elicitation, and exacerbation of allergic disease

“…Assessment of respiratory sensitization presents numerous challenges underscored by the absence of validated in vivo , in vitro , or in silico approaches for identification of potential sensitizers. However, biomarkers with proposed utility for in vivo identification of potential respiratory sensitizers following pulmonary exposure include IgE and T H 2 cytokines (de Jong et al 2009; Chary et al 2018). These markers have not been employed for direct evaluation of respiratory sensitization potential by metal nanomaterials; however, numerous studies have reported increased IgE levels following in vivo pulmonary exposure to TiO 2 NP, PtNP, FeNP, AgNP, and ZnO NP (Park et al 2009; Park et al 2010; Cho et al 2011; Huang et al 2015; Seiffert et al 2015).…”