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.

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. Regul Toxicol Pharmacol. 2019 Oct 08;:104498 Authors: Bos PMJ, Gosens I, Geraets L, Delmaar C, Cassee FR Abstract 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 ...
Source: Regulatory Toxicology and Pharmacology : RTP - Category: Toxicology Authors: Tags: Regul Toxicol Pharmacol Source Type: research