Inhalation exposure and health effects of copper particles in the context of occupational exposure limit derivation

Copper is a naturally occurring element found in the Earth's crust, soil, water, and air. However, human activities such as smelting, refining, and producing copper-containing products pose a likelihood of occupational inhalation exposure. While copper is an essential element vital to human health, it is also a redox-active metal; thus, exposure beyond tolerable ranges could elicit a toxicological response. Previous occupational exposure limits (OELs) for copper and its compounds have been proposed, but most are based on limited datasets. More recent data available on the health effects of copper inhalation in exposed workforces, the characterization of copper forms in smelters during inhalation exposure, and inhalation effects in rodents have prompted a reevaluation of copper's inhalation toxicity in the context of deriving an up-to-date and more robust OEL. This review examines the toxicological impact of copper inhalation, from its toxicological mode of action to respiratory effects in animal models and humans, in the context of adversity, and identifies relevant points of departure (PoDs) for establishing an OEL. Coupled with data on the rapid clearance of copper from the lung, this information was used in a dosimetric model to quantitatively translate the PoD from the in vivo test model to a human equivalent concentration (HEC) for copper. To address areas of uncertainty and variability, the scientific rationale for chemical-specific versus default assessment factors is discussed.