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Methyl isocyanate inhalation induces tissue factor-dependent activation of coagulation in rats
- Source :
- Drug Chem Toxicol
- Publication Year :
- 2018
-
Abstract
- Methyl isocyanate (MIC) is a highly toxic industrial chemical causing acute lethality after inhalation. The objective of this study was to determine whether alterations in hemostasis also occur in the immediate hours after exposure. Male rats were exposed to MIC (125-500 ppm) by nose-only vapor inhalation for 30 min. Arterial O(2) saturation was monitored prior to exposure, and hourly thereafter. Rats were euthanized at 1, 2, 4 and 8 hr and plasma analyzed for recalcification clotting time, Tissue Factor (TF) activity and protein levels. Hypoxemia, as assessed by pulse oximetry, was an early feature of MIC inhalation. In contrast to sham or low (125 ppm) concentrations, 250 and 500 ppm MIC caused significant declines in blood oxygen saturation (% SpO2) at 1 hr, which remained at deficit during the post exposure period. Commensurate with hypoxemia, plasma clotting time was significantly accelerated 1 hr after MIC inhalation (sham treatment: 955 ± 62.8 seconds; 125 ppm MIC: 790 ± 62 seconds; 250 ppm: 676 ± 28.0 seconds; 500 ppm: 581 ± 175 seconds). This procoagulant effect was transient, with no difference observed between sham and all MIC groups by 8 hr. Similarly, elevated TF activity and protein were detected in plasma 1 hr after MIC inhalation, each of which showed a progressive decline back to control levels at later timepoints. This study demonstrates that MIC inhalation resulted in hypoxemia and transient hypercoagulability of blood. Accelerated clotting occurred rapidly and was likely due to intravascular TF, which initiates the extrinsic coagulation pathway.
- Subjects :
- Male
Health, Toxicology and Mutagenesis
010501 environmental sciences
Pharmacology
Methyl isocyanate
Toxicology
01 natural sciences
Article
Hypoxemia
Thromboplastin
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
Tissue factor
0302 clinical medicine
medicine
Animals
Respiratory system
Hypoxia
Blood Coagulation
0105 earth and related environmental sciences
Inhalation Exposure
Chemical Health and Safety
medicine.diagnostic_test
Inhalation
Dose-Response Relationship, Drug
Public Health, Environmental and Occupational Health
General Medicine
Rats
Oxygen
Pulse oximetry
chemistry
Clotting time
Hemostasis
medicine.symptom
030217 neurology & neurosurgery
Isocyanates
Subjects
Details
- ISSN :
- 15256014
- Volume :
- 42
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Drug and chemical toxicology
- Accession number :
- edsair.doi.dedup.....45eaa34fbc10ee635070338b67f67781