The majority of data on respiratory effects of inhaled poorly soluble particles (PSP) stems from rat inhalation studies. This relates to the rat-specific effect pattern of ‘lung overload’ for the inhalation toxicity of PSP. The relevance of the rat as a model for the assessment of repeated exposure to PSP for humans has been questioned by a number of analyses since the rat was shown to be particular sensitive towards these effects compared to other rodents, non-human primates and humans. The last comprehensive review was developed in the year 2000 by the ILSI Risk Sciences Institute. Although the ‘lung overload’ phenomena is known for a long time, it has recently become more prominent for the derivation of DNEL under REACH registrations, setting of exposure limits, and for classification and labelling under the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) . The United Nations Sub-Committee of Experts on GHS in 2009 requested further input has been requested from industry.
Terms of reference
- Discuss new information on lung effects and mechanistic interpretation of lung overload in humans and animals (rodents and non-rodents).
- Identify and agree on parameters that characterise lung overload (parameters for animals and humans separate).
- Compare effect levels from animal studies to realistic worker exposure (e.g. deposited dose for humans) on a quantitative basis.
- Review relevance of existing/new epidemiology studies with regard to observed experimental and human respiratory effects.
- Elaborate on the possibility to include possible “lung overload‘ effects from nanomaterial inhalation studies in a separate section of the report (to consider here is that many nanomaterial studies are done via “instillation‘ instead of “inhalation‘ which is a complicating factor).
- Give consideration to the organisation of a workshop to discuss the relevance of rat lung overload for humans in terms of e.g. classification and labelling, and the derivation of DNEL.