Estimates of carbon nanotube deposition in the lung: improving quality and robustness

Carbon nanotube (CNT) in vivo inhalation studies are increasingly providing estimates of the quantity of material deposited in the lung, generally estimated using standard formulae and pulmonary deposition models. These models have typically been developed and validated using data from studies using sphere-like particles. Given the importance of particle morphology to pulmonary deposition, the appropriateness of such an approach was explored to identify any potential limitations. Aerosolized CNT particles typically form 'fiber-like' and/or 'broadly spherical' agglomerates. A review of currently used deposition models indicates that none have been directly validated against results for CNT, however, models for spherical particles have been extensively validated against a wide range of particle sizes and materials and are thus expected to provide reasonable estimates for most 'broadly spherical' CNT particles, although experimental confirmation of this would be of benefit, especially given their low density. The validation of fiber deposition models is significantly less extensive and, in general, focused on larger particles, e.g. asbestos. This raises concerns about the accuracy of deposition estimates for 'fiber-like' CNT particles and recommendations are made for future research to address this. An appreciation of the uncertainties on CNT deposition estimates is important for their interpretation and thus it is recommended that model sensitivity and uncertainty assessments be undertaken. Issues surrounding the measurement and derivation of model input data are also addressed, including instrument responses and particle density assessment options. Recommendations are also made for aerosol characterization to 'future-proof' CNT inhalation studies regarding advances in deposition modeling and toxicological understanding.