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Citation
Tags
HERO ID
2892
Reference Type
Journal Article
Subtype
Editorial
Title
The relevance of the rat lung response to particle overload for human risk assessment: A workshop consensus report
Author(s)
International Life Sciences Institute :: ILSI
Year
2000
Is Peer Reviewed?
Yes
Journal
Inhalation Toxicology
ISSN:
0895-8378
EISSN:
1091-7691
Volume
12
Issue
1-2
Page Numbers
1-17
Language
English
PMID
10715616
DOI
10.1080/08958370050029725
Web of Science Id
WOS:000085030200001
Abstract
On 23-24 March 1998, the International Life Sciences Institute (ILSI) Risk Science Institute convened a workshop entitled "Relevance of the Rat Lung Response to Particle Overload for Human Risk Assessment." The workshop addressed the numerous study reports of lung tumors in rats resulting from chronic inhalation exposures to poorly soluble, non fibrous particles of low acute toxicity and not directly genotoxic. These poorly soluble particles, indicated by the acronym PSPs (e.g., carbon black, coal dust, diesel soot, nonasbestiform talc, and titanium dioxide), elicit tumors in rats when deposition overwhelms the clearance mechanisms of the lung resulting in a condition referred to as "overload." These PSPs have been shown not to induce tumors in mice and hamsters, and the available data in humans are consistently negative. The objectives were twofold: (1) to provide guidance for risk assessment on the interpretation of neoplastic and nonneoplastic responses of the rat lung to PSPs; and (2) to identify important data gaps in our understanding of the lung responses of rats and other species to PSPs. Utilizing the five critical reviews of relevant literature that follow herein and the combined expertise and experience of the 30 workshop participants, a number of questions were addressed. The consensus views of the workshop participants are presented in this report. Because it is still not known with certainty whether high lung burdens of PSPs can lead to lung cancer in humans via mechanisms similar to those of the rat, in the absence of mechanistic data to the contrary it must be assumed that the rat model can identify potential carcinogenic hazards to humans. Since the apparent responsiveness of the rat model at overload is dependent on coexistent chronic active inflammation and cell proliferation, at lower lung doses where chronic active inflammation and cell proliferation are not present, no lung cancer hazard is anticipated.
Tags
IRIS
•
Asbestos
•
Cobalt
•
Methanol (Non-Cancer)
•
ISA-PM (2009 Final Project Page)
2009 Final
•
ISA-PM (2019)
Peer Input Draft
Chapter 4
1st Draft
Chapter 4
Final ISA
Chapter 4
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