Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Pathway-based predictive approaches for non-animal assessment of acute inhalation toxicity

Clippinger, Amy J., Allen, David, Behrsing, Holger, Berube, Kelly ORCID: https://orcid.org/0000-0002-7471-7229, Bolger, Michael B., Casey, Warren, DeLorme, Michael, Gaca, Marianna, Gehen, Sean C, Glover, Kyle, Hayden, Patrick, Hinderliter, Paul, Hotchkiss, Jon A., Iskandar, Anita, Keyser, Brian, Luettich, Karsta, Ma-Hock, Lan, Maione, Anna G., Makena, Patrudu, Melbourne, Jodie, Lawrence, Milchak, Ng, Sheung P., Paini, Alicia, Page, Kathryn, Patlewicz, Grace, Prieto, Pilar, Raabe, Hans, Reinke, Emily N., Roper, Clive, Rose, Jane, Sharma, Monita, Spoo, Wayne, Thorne, Peter S., Wilson, Daniel M. and Jarabek, Annie M. 2018. Pathway-based predictive approaches for non-animal assessment of acute inhalation toxicity. Toxicology in Vitro 52 , pp. 131-145. 10.1016/j.tiv.2018.06.009

[thumbnail of Clippinger Allen et al_TIV_2018_V52_p131-145.pdf]
Preview
PDF - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (591kB) | Preview

Abstract

New approaches are needed to assess the effects of inhaled substances on human health. These approaches will be based on mechanisms of toxicity, an understanding of dosimetry, and the use of in silico modeling and in vitro test methods. In order to accelerate wider implementation of such approaches, development of adverse outcome pathways (AOPs) can help identify and address gaps in our understanding of relevant parameters for model input and mechanisms, and optimize non-animal approaches that can be used to investigate key events of toxicity. This paper describes the AOPs and the toolbox of in vitro and in silico models that can be used to assess the key events leading to toxicity following inhalation exposure. Because the optimal testing strategy will vary depending on the substance of interest, here we present a decision tree approach to identify an appropriate non-animal integrated testing strategy that incorporates consideration of a substance's physicochemical properties, relevant mechanisms of toxicity, and available in silico models and in vitro test methods. This decision tree can facilitate standardization of the testing approaches. Case study examples are presented to provide a basis for proof-of-concept testing to illustrate the utility of non-animal approaches to inform hazard identification and risk assessment of humans exposed to inhaled substances.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Elsevier
ISSN: 0887-2333
Date of First Compliant Deposit: 1 June 2018
Date of Acceptance: 1 June 2018
Last Modified: 06 May 2023 22:50
URI: https://orca.cardiff.ac.uk/id/eprint/111895

Citation Data

Cited 62 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics