Gas chromatographic studies of the carbamylation of haemoglobin by methyl isocyanate in rats and rabbits.
Carbamylation of the N-terminal valine of haemoglobin with methyl isocyanate in rats and rabbits has been demonstrated in vitro and in vivo by gas chromatography. N-Methylcarbamylated haemoglobin, converted by cyclization into 3-methyl-5-isopropylhydantoin, has been quantified by gas chromatography. Standard hydantoin was synthesized, chemically characterized and used for calibration. The method is simple and reliable in the concentration range 0.06-2 nmol. Carbamylation of haemoglobin by methyl isocyanate in vivo in rats can be identified only above a dose of 1.05 mg/l in inhalation exposures. It is inferred that methyl isocyanate in the "active" form crosses the alveolar and erythrocyte membranes and carbamylates the haemoglobin.
Ramachandran
P K
PK
Defence Research and Development Establishment, Gwalior, India.
Gandhe
B R
BR
Venkateswaran
K S
KS
Kaushik
M P
MP
Vijayaraghavan
R
R
Agarwal
G S
GS
Gopalan
N
N
Suryanarayana
M V
MV
Shinde
S K
SK
Sriramachari
S
S
D000818:Animals; D000986:Antisickling Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002849:Chromatography, Gas; D003485:Cyanates / Q000138:chemical synthesis / Q000494:pharmacology*; D006454:Hemoglobins / Q000032:analysis*; D006461:Hemolysis / Q000187:drug effects; D066298:In Vitro Techniques; D017953:Isocyanates; D011817:Rabbits; D051381:Rats
D000986:Antisickling Agents; D003485:Cyanates; D006454:Hemoglobins; D017953:Isocyanates; C008461:methyl isocyanate