Pulmonary toxicity in rats following inhalation exposure to poorly soluble particles: The issue of impaired clearance and the relevance for human health hazard and risk assessment.

08:00 EDT 8th October 2019 | BioPortfolio

Summary of "Pulmonary toxicity in rats following inhalation exposure to poorly soluble particles: The issue of impaired clearance and the relevance for human health hazard and risk assessment."

Intensive discussions are ongoing about the interpretation of pulmonary effects observed in rats exposed to poorly soluble particles. Alveolar clearance differs between rats and humans and becomes impaired in rats at higher exposure concentrations. Some have doubted the human relevance of toxic effects observed in rats under impaired clearance conditions and have suggested that experimental exposures should stay below concentrations inducing impaired clearance. However, for regulatory purposes, insight in potential health effects at relatively high concentrations is needed to fully understand the hazard. Many aspects of impaired particle clearance remain unclear, hampering human health hazard and risk assessment. For an adequate evaluation of the impact of impaired clearance on pulmonary toxicity, a clear definition of alveolar clearance is needed that enables to quantitatively relate the level of impairment to the induction of adverse pulmonary health effects. Also, information is needed on the mechanism of action and the appropriate dose metric for the pulmonary effects observed. In absence of these data, human hazard and risk assessment can only be performed in a pragmatic way. Unless available data clearly point out otherwise, rat pulmonary toxicity including lung inflammation and tumour formation, needs to be considered relevant for human hazard and risk assessment.


Journal Details

This article was published in the following journal.

Name: Regulatory toxicology and pharmacology : RTP
ISSN: 1096-0295
Pages: 104498


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