The Evaluation of Inhalation Studies for Exposure Quality: A Case Study with Formaldehyde
The inherent complexity of generating and monitoring a test article in an inhalation chamber can make inhalation toxicity testing challenging. We have developed a process for evaluating seven key elements of exposure quality in inhalation chamber studies: 1) test article characterization, 2) generation method, 3) analytical method, 4) chamber concentrations, 5) particle size characteristics, 6) chamber type, and 7) controls. For each study, exposure deficiencies are documented, and a study is given an overall rating (Robust, Adequate, or Poor) for the quality of its exposure characterization and documentation. In combination with the systematic consideration of experimental features other than exposure, these ratings can inform the utility of a study for use in hazard identification and/or exposure-response analysis. The exposure quality evaluations of 204 formaldehyde inhalation studies are presented as a case study. Of these, 34% were rated Robust because they had detailed exposure documentation and no serious deficiencies in the key elements of exposure quality. Another 19% of studies with minor uncertainties or limitations were rated Adequate, and 47% were rated Poor due to multiple serious exposure deficiencies. This formaldehyde case study illustrates the need to carefully consider the exposure quality of inhalation toxicity studies when their results are used to support hazard and risk assessment.