M. Eto, J. Casida, Tadako Eto
Apr 1, 1962
Citations
5
Influential Citations
157
Citations
Quality indicators
Journal
Biochemical pharmacology
Abstract
Abstract Tri- o -cresyl phosphate is metabolized in rats by hydroxylation and cyclization of the hydroxymethyl derivatives. Indirect evidence was obtained for two intermediates, di-( o -cresyl) mono- o -hydroxymethylphenyl phosphate and di-( o -hydroxymethyl-phenyl)mono- o -cresyl phosphate. These intermediates cyclize spontaneously. The principal cyclic phosphate formed was 2-( o -cresyl)-4H-1:3:2-benzodioxaphosphoran-2-one, as ascertained by isolation and synthesis. Evidence is also presented for 2-( o -hydroxymethylphenyl)-4H-1:3:2-benzodioxaphosphoran-2-one and 2-( o -hydroxy-benzyl)-4H-1:3:2-benzodioxaphosphoran-2-one, as either metabolites or products formed on spontaneous cyclization. The primary cyclic metabolite (see above) hydrolyses in mild alkali or reacts with chymotrypsin by cleavage of the cyclic phosphate at the P—O-aryl bond. The deleterious biological activity of tri - o -cresyl phosphate appears to result from esterase inhibition by these cyclic phosphate metabolites.