Expert workshop on the hazards and risks of poorly soluble low toxicity particles. (28th January 2020)

• Record Type: Journal Article
• Authors: Driscoll, Kevin E.; Borm, Paul J. A.
• Is Part Of: Inhalation toxicology. Volume 32:Number 2(2020)
• Page Start: 53
• Page End: 62
• Publication Date: 2020-01-28
• Subjects: PSLT -- particles -- lung particle overload -- hazard -- risk -- lung cancer -- inhalation; Pulmonary toxicology -- Animal models -- Periodicals; Pulmonary toxicology -- Periodicals; Air -- Pollution -- Health aspects -- Periodicals; 616.200471
• DOI: 10.1080/08958378.2020.1735581
• Languages: English
• ISSNs: 0895-8378

Abstract

Abstract: 'Lung particle overload' refers to the impaired lung particle clearance and increased particle retention occurring with high lung doses of poorly soluble low toxicity (PSLT) particles. In rats, lung particle overload is associated with inflammation, epithelial hyperplasia, and, in extreme cases, lung cancer. While the human relevance of rat lung tumors occurring under overload has been questioned, recent regulatory decisions have considered these outcomes evidence of possible human hazard. To better understand the state-of-the-science on PSLT toxicology, an Expert Workshop was held to document agreements and differences amongst a panel of highly experienced scientists and regulators. Key outcomes included: a functional definition of PSLTs; agreement the rat is a sensitive model for PSLT inhalation toxicology; identifying lung inflammation as a critical endpoint for PSLT risk assessment; and, agreement rat lung cancer occurring only under conditions of lung particle overload does not imply a cancer hazard for humans under non-overloading exposures. Moreover, when asked – should PSLTs be considered as human lung carcinogens based on rat data alone (and no supporting data from other species), the expert consensus was: 'No. However, the experts noted the current default regulatory position on rat lung overload data alone would be the suspicion of human carcinogen hazard.' The many areas of the expert agreement provide guidance for design, interpretation, and extrapolating PSLT inhalation toxicology studies. Considering the workshop outcomes, the authors recommend guidelines for evaluation and classification of PSLT be reassessed; and, prior decisions on PSLT hazard classification be revisited to determine if they remain appropriate.