Portal de Periódicos da CAPES

Toxicity of 3,4-dichloroaniline to male wistar rats blood cells

1995; Elsevier BV; Volume: 31; Linguagem: Inglês

10.1016/1043-6618(95)86834-8

1096-1186

Antonino Donato, Loreana Sanches Silveira, Lúcia Guilhermino, Amadeu M.V.M. Soares, A.P. Carvalho, Mafalda Cunha de Castro Pinheiro Lopes,

Pharmacogenetics and Drug Metabolism

Toxic signs after ip doses of 200 to 800 mg/kg of the herbicide propanil in mice included central nervous system depression, loss of righting reflex, cyanosis and death at the higher doses. Pretreatment with triorthotolyl phosphate (TOTP), an esterase inhibitor, prevented cyanosis but slightly enhanced the CNS depressant actions of propanil. Propanil and a probable hydrolytic metabolite, 3,4-dichloroaniline (DCA), produced methemoglobinemia in mice. Comparison of the time- and dose-response relationships for equimolar doses of propanil and DCA showed that DCA was more potent and had a faster onset of methemoglobin production than propanil. The hydrolysis of propanil to yield 3,4-dichloroaniline by liver homogenates was completely inhibited 18 hr after mice were given 125 mg/kg of TOTP. Methemoglobin formation after propanil was inhibited in mice pretreated with 125 mg/kg of TOTP, but TOTP did not affect DCA-induced methemoglobinemia. Inhibition of propanil-amidase activity and propanil-induced methemoglobinemia had similar TOTP dose- and time-response relationships. Pretreatment with SKF-525A inhibited and phenobarbital pretreatment slightly increased both propanil- and DCA-induced methemoglobin formation. Neither pretreatment affected normal liver propanilamidase activity. These findings indicate that propanil-induced methemoglobinemia is dependent upon the metabolism of propanil by a coupled hydrolytic-oxidase enzyme system. The acute toxicity-TOTP interaction experiments indicate that methemoglobinemia can account for the cyanotic appearance of propanil-poisoned mice, but that methemoglobin formation is apparently not responsible for loss of righting reflex and death.