Expert workshop on the hazards and risks of poorly soluble low toxicity particles.

Inhalation Toxicology
Kevin E Driscoll, Paul J A Borm

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...Continue Reading

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Citations

Jul 6, 2021·Regulatory Toxicology and Pharmacology : RTP·Heidi StratmannRobert Landsiedel

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