Biological Effects of Short-Term, High-Concentration Exposure to Methyl Isocyanate. III. Influence on Gas Exchange in the Guinea Pig Lung

Abstract

The influence of methyl isocyanate (MIC) inhalation on the gas exchange function of the lungs in guinea pigs was studied by measuring arterial blood gases, pH, and tracheal pressure during constant-volume, artificial ventilation with air or lOO1 02 at 40 and 120 min after exposure. A 15 min exposure to MIC at concentrations of 240 to 628 ppm caused a marked reduction in Pao2 and PHa and an elevated tracheal pressure during artificial ventilation. The low Pao2 was only slightly elevated when the animals were ventilated with 100% 02. Although the dry-wet lung weight ratio was reduced at the highest exposure concentration, the effect was not severe and no significant increase in lung water was found at the lower concentrations. MIC inhalation caused severe pulmonary blood shunting and ventilation/perfusion imbalance. This, in turn, led to hypoxemia, metabolic acidosis, and tissue hypoxia, which could produce death. The pulmonary gas exchange deficit likely resulted from bronchial and bronchiolar obstruction caused by sloughed epithelium and other debris from intra-and extrapulmonary airways.

Biological effects of short-term, high-concentration exposure to methyl isocyanate. V. Morphologic evaluation of rat and guinea pig lungs.

“…The morphologic changes induced by high exposure concentrations of MIC vapor in the lungs of rats and guinea pigs support the biological effects observed in other studies conducted by UCC (6,8,9). In the controlled ventilation studies (8), we have shown that within minutes there is an increase in intratracheal pressure with marked shifts in both blood gases and pH.…”

“…This airway obstruction resulted in changes in the blood gases and pH (8), which resulted in a shift in the oxygen dissociation curve of hemoglobin (9) that very likely caused further tissue hypoxia with the resulting death of the animal.…”

Biological Effects of Short-Term, High-Concentration Exposure to Methyl Isocyanate. I. Study Objectives and Inhalation Exposure Design

“…The results indicated the development of a condition of severe acidosis. This led to a series of controlled ventilation experiments with guinea pigs to further study the effect of MIC on the gas exchange functions of the lungs (18). Also, the effect of exposure on the oxyhemoglobin dissociation curve was explored to assist in interpreting the respiratory function data (13).…”

“…Both 15 min) and high in concentration (a target concentration range of 25-3500 ppm). In general, rats were exposed in groups of four to five and guinea pigs in groups of three to four, although for some experiments guinea pigs were exposed individually or in pairs (13,18,22). Food and water were provided ad libitum except during inhalation exposures.…”

“…The lowest MIC concentrations (100 ppm for rats and 25 ppm for guinea pigs) caused no mortality between 4 and 16 hr postexposure (Table 2) and were considered unlikely to cause any deaths since these concentrations were below the lower limit of the 95% confidence interval of the 15-min LC50 values. MIC concentrations that caused approxi- Several studies performed by Union Carbide Corporation (13,18,22) involved the exposure of guinea pigs to a target MIC concentration of 675 ppm for 15 min. This exposure condition caused approximately 50% mortality during or within 10 min postexposure ( Table 1).…”