2,4-Diamino-6-methylphenol

THE IP ADMIN OF 4,6-DIAMINO-O-CRESOL (33 MG/KG) OR 4,6-DIAMINO-2-SEC-BUTYLPHENOL (43 MG/KG) PRODUCED A LETHAL METHEMOGLOBINEMIA WITHIN 15-20 MINUTES. THE INTRARUMINAL ADMIN INDUCED A LESS DRAMATIC METHEMOGLOBINEMIA. HEMOLYSIS & ACUTE NEPHROSIS WERE OBSERVED IN A PROLONGED EXPERIMENT. APPARENTLY, THE DIAMINOPHENOL METABOLITES ARE RESPONSIBLE FOR THE METHEMOGLOBIN FORMATION IN DINITROPHENOL (DNOC OR DNBP) POISONINGS.

2-METHYL-4,6-DINITROPHENOL SHOWED HIGHER TOXICITY TO SHEEP THAN 2-(1-METHYLPROPYL)-4,6-DINITROPHENOL FOLLOWING ORAL ADMIN (70 MG/KG); HOWEVER, DYSPNEA & HYPERTHERMIA WERE CAUSED BY THEIR RESPECTIVE DIAMINO METABOLITES, 2-METHYL-4,6-DIAMINOPHENOL & 2-(1-METHYLPROPYL)-4,6-DIAMINOPHENOL. THE METABOLITES ALSO CAUSED METHEMOGLOBINEMIA, HYPOTHERMIA, & HEMOCONCENTRATION.

Diamino metabolites of DNOC ... were active inducers of methemoglobin formation in vitro at a concentration of 5 x 10-4 M. Marked hemoglobinemia was observed almost immediately in a goat given an intraperitoneal injection of 2-methyl-4,6-diamino phenol (DAOC) at 33 mg free amine/kg, and the goat died within 45 min. A slower and less pronounced development of methemoglobinemia developed following ruminal administration of the same dose of DAOC. Hemoconcentration was observed in both cases, and hemolysis and nephrotic lesions were found in the latter. Intraperitoneal administration of both compounds to pigs produced immediate methemoglobinemia and death within 1 hr. The results confirm the hypothesis that methemoglobinemia following dinitrophenol poisoning in ruminants may be due to the diaminophenol metabolites.

RUMEN MICROFLORA FROM ADULT SHEEP WERE CAPABLE OF DETOXIFYING 4,6-DINITRO-O-CRESOL (DNOC), REDUCING THIS COMPOUND TO 6-AMINO-4-NITRO-O-CRESOL & THEN TO 4,6-DIAMINO-O-CRESOL.

4,6-DINITRO-O-CRESOL (DNOC) ADMIN ORALLY TO RATS WAS ELIMINATED SLOWLY, WITH REDN BEING THE MAJOR METABOLIC PATHWAY. IN THE RAT & RABBIT INITIAL REDN OF THE NITRO GROUP, FOLLOWED BY ACETYLATION &/OR CONJUGATION ARE THE MAJOR STEPS INVOLVED IN THE BIOTRANSFORMATION OF DNOC. POSSIBLE METABOLIC RELATION OF THE BIOTRANSFORMATION PRODUCTS, INCLUDING 2,4-DIAMINO-6-METHYLPHENOL, OF DNOC ARE OUTLINED.

THE METABOLISM OF DINITROPHENOLS & THEIR RESPECTIVE MONOAMINE DERIVATIVES WAS STUDIED IN RAT CECAL INCUBATES. ALL OF THE COMPOUNDS WERE REDUCED TO THEIR CORRESPONDING DIAMINO METABOLITES. THE RESULTS ARE DISCUSSED IN RELATION TO THE COMPARATIVE TOXICOLOGY OF DINITROPHENOLS WITH REGARD TO INTESTINAL METABOLITES.