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Toxicol In Vitro. 2018 Apr;48:53-70. doi: 10.1016/j.tiv.2017.12.011. Epub 2017 Dec 22.

Alternative approaches for acute inhalation toxicity testing to address global regulatory and non-regulatory data requirements: An international workshop report.

Author information

1
PETA International Science Consortium Ltd., London, UK. Electronic address: amyjc@piscltd.org.uk.
2
Integrated Laboratory Systems, contractor supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods, Research Triangle Park, NC, United States.
3
U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment, Research Triangle Park, NC, United States.
4
Dow AgroSciences, Abingdon, UK.
5
British American Tobacco, London, UK.
6
Dow AgroSciences, Indianapolis, IN, United States.
7
The Dow Chemical Company, Midland, MI, United States.
8
U.S. Environmental Protection Agency, Office of Research and Development, National Center for Computational Toxicology, Research Triangle Park, NC, United States.
9
PETA International Science Consortium Ltd., London, UK.
10
Syngenta, Greensboro, NC, United States.
11
Scitovation LLC, Research Triangle Park, NC, United States.
12
University of Pennsylvania, Philadelphia, PA, United States.
13
U.S. Environmental Protection Agency, Office of Chemical Safety and Pollution Prevention, Office of Pesticide Programs, Washington, DC, United States.
14
ToxMetrics.com, LLC, Midland, MI, United States.
15
Cardiff University, School of Biosciences, Cardiff, Wales, UK.
16
Health and Safety Executive, London, UK.
17
Free University of Brussels-Belgium, Brussels, Belgium.

Abstract

Inhalation toxicity testing, which provides the basis for hazard labeling and risk management of chemicals with potential exposure to the respiratory tract, has traditionally been conducted using animals. Significant research efforts have been directed at the development of mechanistically based, non-animal testing approaches that hold promise to provide human-relevant data and an enhanced understanding of toxicity mechanisms. A September 2016 workshop, "Alternative Approaches for Acute Inhalation Toxicity Testing to Address Global Regulatory and Non-Regulatory Data Requirements", explored current testing requirements and ongoing efforts to achieve global regulatory acceptance for non-animal testing approaches. The importance of using integrated approaches that combine existing data with in vitro and/or computational approaches to generate new data was discussed. Approaches were also proposed to develop a strategy for identifying and overcoming obstacles to replacing animal tests. Attendees noted the importance of dosimetry considerations and of understanding mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Recommendations were made to (1) develop a database of existing acute inhalation toxicity data; (2) prepare a state-of-the-science review of dosimetry determinants, mechanisms of toxicity, and existing approaches to assess acute inhalation toxicity; (3) identify and optimize in silico models; and (4) develop a decision tree/testing strategy, considering physicochemical properties and dosimetry, and conduct proof-of-concept testing. Working groups have been established to implement these recommendations.

KEYWORDS:

Acute inhalation toxicity; Alternative approaches; Dosimetry; Globally harmonized system (GHS) additivity formula; In silico; In vitro

PMID:
29277654
DOI:
10.1016/j.tiv.2017.12.011
[Indexed for MEDLINE]
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