Association of Inhalation Toxicologists (AIT) working party recommendation for standard delivered dose calculation and expression in non-clinical aerosol inhalation toxicology studies with pharmaceuticals

Inhal Toxicol. 2008 Oct;20(13):1179-89. doi: 10.1080/08958370802207318.

Abstract

There are many ways in which the dose can be expressed in inhalation toxicology studies. This can lead to confusion when comparing results from studies performed in different laboratories. A working party of the Association of Inhalation Toxicologists has reviewed this subject in detail and has collected data from 10 inhalation laboratories and used these data to determine a new algorithm for the calculation of Respiratory Minute Volume (RMV), one of the most important factors in the calculation of delivered dose. The recommendations of the working party for regulatory inhalation toxicology studies with pharmaceuticals are as follows: 1. The dose should be reported as the delivered dose calculated according to the formula: DD = C x RMV x D(xIF)/BW, where DD = delivered dose (mg/Kg); C = concentration of substance in air (mg/L); RMV =respiratory minute volume or the volume of air inhaled in one minute (L/min); D = duration of exposure (min); IF = proportion by weight of particles that are inhalable by the test species, the inhalable fraction (inclusion of this parameter is not essential provided that the aerosol has reasonable respirability for the intended species. If it is included, the way in which it is determined should be clearly stated); BW = bodyweight (Kg). 2. The RMV for mice, rats, dogs and cynomolgus monkeys should be calculated according to the formula:RMV(L/min) = 0.608 x BW(Kg)(0.852). 3. If deposited dose or the amount of material actually retained inthe respiratory tract is presented as supplementary information,the way in which it is calculated should be clearly stated.4. Dose should always be presented in mg/Kg but may also bepresented in other ways, such as mg/unit body surface area, as supplementary information.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols / administration & dosage*
  • Animals
  • Biomedical Research / methods
  • Biomedical Research / standards*
  • Dogs
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Inhalation Exposure / standards*
  • Macaca fascicularis
  • Mice
  • Pharmaceutical Preparations / administration & dosage*
  • Rats
  • Societies, Scientific / standards
  • Toxicology / methods
  • Toxicology / standards*

Substances

  • Aerosols
  • Pharmaceutical Preparations