Alternative test methods in inhalation toxicology: challenges and opportunities.

Requirements under the new European Union rules regarding Registration, Evaluation & Authorization of Chemicals (REACH) necessitate widespread toxicological safety testing of existing and new chemicals. Given the enormity of new and already in-service chemicals that fall under this new rule, obtaining inhalation toxicity testing data has unique challenges when compared to most biotesting regimes due to the complexity, time and expense involved in conducting standardized inhalation assessments of whole animals. A number of in vitro approaches have been used to obtain respiratory system-related information, but there is no universal or accepted test system to replace inhalation exposure studies. There are many considerations that must be satisfied before adopting any single in vitro bioassay or battery of such assays to substitute for whole animal inhalation data. These considerations relate mostly to the relevance of the bioassay(s) regarding selection of bioassay cell type(s), dose, and fundamental study procedures. There are data in the literature although these have not been well-assessed for such applications, and there exist perhaps more relevant unpublished data in the private sector that could provide guidance on this issue. The formation of a coalition of scientists to assess current knowledge and perhaps to consider a basic comparative study where consensus approaches (with frank discussions of their strengths and weaknesses) would be invaluable to the testing community and to the ultimate protection of human health. In May 2007, a Congress of government, industry, and academic scientists met at the Federal Institute for Risk Assessment (BfR), Berlin, on the subject of Alternative Test Methods in Inhalation Toxicology. The stimulus for the meeting arose from the European Union's (EU) recent implementation of the new REACH safety testing requirements for commercial chemicals and products. Attendees at the meeting presented a panoply of data and perspectives on the state of the science on alternative testing methods and how these might aid safety assessments of inhaled materials. The focus of many presentations was on the fundamental attributes of inhalation toxicology and how these are translated or otherwise addressed in alternative in vitro test methods. There was recognition of the needs and the potential for progress through collaboration, but there remains a clear need for continued discussion and proactive support to a broad-based comparative study. The present discussion provides one perspective of this complex issue and how the science community might collaborate to develop acceptable alternative approaches based in science that have utility in inhalation toxicological assessments.