Abstract

The aim of the study was to use multiple in vitro assays to assess the effects of a model irritant, sodium dodecyl sulphate (SDS) (≤10 mM (0.29 %, w/v)), on an in vitro model of the airway, MucilAir™. The use of MucilAir™ in recovery studies was also explored.A 24 h exposure increased IL-8 release at an SDS concentration ≥0.63 mM (0.018 %, w/v). Mucin secretion increased and transepithelial electrical resistance (TEER) decreased at SDS concentrations ≥1.25 mM (0.04 %, w/v). Cytotoxicity (lactate dehydrogenase (LDH) release into basolateral chamber) was observed at SDS concentrations of ≥2.5 mM (0.07 %, w/v). The sensitivity of the assays was IL-8 release > TEER = mucin secretion > LDH release.After 7 days, full or partial recovery was observed for intermediate concentrations of SDS using all assays but not at 5 and 10 mM SDS. Morphologically, erosion and cell loss were observed at these concentrations. Resazurin metabolism at 7 days tended to decrease in a dose-dependent manner at SDS concentrations above 2.5 mM (0.07 %, w/v).Together, these data support a No Observable Effect Level of 0.31 mM (0.009 % w/v) SDS and the use of MucilAir™ as a relevant model for airway toxicity studies.

Highlights

  • The airway epithelial barrier has a role in airway protection and is a key target site for respiratory tract toxicity

  • transepithelial electrical resistance (TEER) values were similar for MucilAirTM tissues within each batch; the TEER values of batches 1, 2 and 3 were 499 ± 34, 346 ± 14 and 638 ± 81 Ω cm2 respectively (mean ± SD; n = 8 and n = 16) (Table 1)

  • MucilAirTM has been widely used in studies of toxicity/irritancy (Sauer et al, 2013; Huang et al, 2013b; Anderson et al, 2013; Frieke Kuper et al, 2015; Kooter et al, 2017; Dankers et al, 2018; Balogh Sivars et al, 2018; Cervena et al, 2019, 2020; Rossner et al, 2019)

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Summary

Introduction

The airway epithelial barrier has a role in airway protection and is a key target site for respiratory tract toxicity. The Organisation for Eco­ nomic Co-operation and Development (OECD) define acute inhalation toxicity as the total adverse effects caused by exposure to a material for

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