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Effects of Methemoglobin Versus Potassium Cyanide Intoxication. (2000)

Abstract
The effect of pre-existing levels of blood methemoglobin (10-12%) induced by WR 6026 on the ability of the Beagle dog to resist lethal cyanide potassium cyanide intoxication was investigated. Five groups of five dogs each were administered WR 6026 one daily for at least four consecutive days and then given an intravenous injection of KCN at a level of 1X lethal dose 50, 2XLD50, 3.5LD50 or 4XLD50 when the blood methemoglobin injection level had decreased to 10-12%. The number of surviving animals following cyanide administration in each group was then compared to the LD50 mortality cure for cyanide determined in animals not previously administered WR 6026 in an attempt to establish a 'protective index' for a 10-12% methemoglobin level. All animals injected with cyanide at 1XLD50, 2XLD50 or 3XLD50 survived the challenge, while the five animals injected with cyanide at 4XLD50 died following the injection. For four animals injected with cyanide at 3.5XLD50, two died and two survived. Analysis of the data showed an ED50 value of 6.48 mg/kg. This value was 3.5 times greater than the LD50 value (1.85 mg/kg) obtained with a single injection of KCN non-induced ('normal') methemoglobin levels. Thus, a protective index of 3.5 was established for a 10-12% blood methemoglobin level induced by WR6026 administration.

Publication details
Contributors FOOD AND DRUG RESEARCH LABS INC WAVERLYNY
Repository Defense Technical Information Center OAI-PMH Repository (United States)
Keywords TOXICOLOGY, PHARMACOLOGY, *METHEMOGLOBIN, *CYANIDES, *INTOXICATION, *POTASSIUM COMPOUNDS, *ANTIDOTES, BLOOD, INDEXES, INJECTION, DOGS, PROTECTION., WR 6026 Chemotherapeutic Agent, PE62734A, AS875, WU086.
Language eng