Ventilation of Ambulatory Rats Exposed to Methanol Vapor in a Flow-Through Exposure System: Measurement and Input to Toxicokinetic Models

Abstract

Ventilation parameters (minute ventilation, V̇; tidal volume, V_t; and breathing frequency, f) of female Sprague-Dawley rats were measured during an 8-h exposure to methanol vapor at concentrations of 1000, 5000, 10, 000, 15, 000 and 20, 000 ppm. Rats were exposed individually in a flow-through chamber that permitted simultaneous measurement of ventilation, methanol extraction from the airstream by the animal, and blood methanol concentration. Compared to the whole-body plethysmography with nose-only exposure (WBP) system, the total ventilation of rats in this study was approximately half; the V_t was approximately the same, but f was about 50% lower than reported in WBP exposed rats. The hourly ventilation decreased slightly with increasing blood methanol concentration up to 2000 mg/L; at concentrations exceeding 2000 mg/L, the hourly ventilation decreased more significantly. The exposure system method studied simultaneously yielded information on the extraction of methanol from the airstream, efficiency of absorption of methanol vapor during inhalation exposure, and the resulting systemic methanol concentration, which may then be used to provide input to a toxicokinetic model for inhaled methanol.