We thank Dr Kuehl for his comments and his support for our attempts to standardise the calculation of delivered dose in non-clinical aerosol inhalation studies.
We recognise that the AIT formula provides RMV figures for small animals that do not differ markedly from those provided by some other formulae and that it is only for larger animals that differences become apparent. This is in line with experimental data from dosimetry studies in dogs using radiolabelled aerosols in which the actual measured lung dose is underestimated by the standard dose calculations using an RMV derived from Bide’s formula. Both the AIT and Bide formulae are based on allometric analysis and within-species comparisons are of limited relevance.
In addition, the data set used for the AIT calculation uses data from GLP-compliant studies using the restraint methods that are used to dose animals by inhalation, and therefore the formula derived from this data set is more appropriate for use in GLP regulatory studies than any of the other available formulae for calculation of RMV.
We therefore recommend the adoption of the AIT formula for calculation of RMV in all non-clinical aerosol inhalation studies.
Colin John Hardy, PhD
Huntingdon Life Sciences
Alconbury, Cambridgeshire, United Kingdom