Biological Effects of Short-Term, High-Concentration Exposure to Methyl Isocyanate. II. Blood Chemistry and Hematologic Evaluations

• Published in: Environmental health perspectives 1987-06, Vol.72, p.21-28
• Main Authors: Troup, Catherine M., Dodd, Darol E., Fowler, Edward H., Frank, Fred R.
• Format: Article
• Language: English
• Subjects: Animals; Blood; Blood - drug effects; Chemical hazards; Cholinesterase Inhibitors; Creatine Kinase - blood; Cyanates - administration & dosage; Cyanates - toxicity; Erythrocytes; Erythrocytes - drug effects; Erythrocytes - enzymology; Female; Guinea Pigs; Hemoglobins; Humans; In Vitro Techniques; Inhalation; Isocyanates; Leukocyte Count; Lung - drug effects; Lung - pathology; Lungs; Male; Neutrophils - drug effects; Rats; Rats, Inbred Strains; The Toxicity of Methyl Isocyanate. March 12-13, 1986. Research Triangle Park, NC; Vapors
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.877221

Human, rat, and guinea pig packed erythrocytes exposed to 100, 500, or 1000 ppm of methyl isocyanate (MIC) vapor in vitro showed a concentration-related inhibition of cholinesterase (ChE) activity. Rat and guinea pig packed erythrocytes showed an almost complete inhibition of ChE activity at 2000 ppm. In vitro exposures of human and guinea pig blood to 1000 or 2000 ppm of MIC vapor resulted in qualitative alterations in the electrophoretic mobility of hemoglobin (Hb) as measured by citrated agar electrophoresis. In rats and guinea pigs, neither IV injection of liquid MIC nor in vivo exposure to 1000 ppm of MIC by inhalation resulted in any inhibition of erythrocyte ChE activity or alteration in Hb electrophoretic mobility. As a result of these observations, it was concluded that neither ChE inhibition nor structural alteration of Hb were major contributing factors to death resulting from MIC exposure. Rats and guinea pigs receiving IV injections of liquid MIC showed an increase in creatine kinase (CK) levels. This increase could not be attributed to a specific isoenzyme of CK by ion exchange chromatography. Rats exposed to 100, 600, or 1000 ppm of MIC and guinea pigs exposed to 25, 125, or 225 ppm of MIC and bled immediately following a 15-min exposure or at 1, 2, 4, or 16 hr postexposure had the following alterations in blood parameters: a) an increase in CK, b) increases in hemoglobin concentration and hematocrit, c) reticulocytosis (rats only), d) neutrophilia, e) a decrease in blood pH and Po2, and f) an increase in blood Pco2. These findings indicate the occurrence of generalized hypoxic injury with concomitant pathophysiologic alterations, e.g., increases in hemoglobin and hematocrit concentrations.