A novel sulfur mustard (HD) vapor inhalation exposure system for accurate inhaled dose delivery

J Pharmacol Toxicol Methods. 2015 Jan-Feb:71:120-8. doi: 10.1016/j.vascn.2014.09.009. Epub 2014 Oct 5.

Abstract

Introduction: A custom designed HD exposure system was used to deliver controlled inhaled doses to an animal model through an endotracheal tube.

Methods: Target HD vapor challenges were generated by a temperature controlled bubbler/aerosol trap, while concentration was monitored near real-time by gas chromatography. Animal breathing parameters were monitored real-time by an in-line pneumotach, pressure transducer, and Buxco pulmonary analysis computer/software. For each exposure, the challenge atmosphere was allowed to stabilize at the desired concentration while the anesthetized animal was provided humidity controlled clean air. Once the target concentration was achieved and stable, a portion of the challenge atmosphere was drawn past the endotracheal tube, where the animal inhaled the exposure ad libitum. During the exposure, HD vapor concentration and animal weight were used to calculate the needed inhaled volume to achieve the target inhaled dose (μg/kg). The exposures were halted when the inhaled volume was achieved.

Results: The exposure system successfully controlled HD concentrations from 22.2 to 278mg/m(3) and accurately delivered inhaled doses between 49.3 and 1120μg/kg with actual administered doses being within 4% of the target level.

Discussion: This exposure system administers specific HD inhaled doses to evaluate physiological effects and for evaluation of potential medical countermeasure treatments.

Keywords: Dosimetry; Inhalation exposure; Inhaled dose; Methods; Sulfur mustard vapor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / instrumentation*
  • Inhalation Exposure
  • Mustard Gas / administration & dosage*
  • Mustard Gas / adverse effects

Substances

  • Mustard Gas