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Comparison of antidotal efficacy of chelating agents upon acute toxicity of Co(II) in mice.
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1985
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Pharmaceutical SciencePharmacotherapyToxicological MechanismAntidotal EfficacyOxidative StressMedicinal ChemistryToxicologyRadiation OncologyClinical ToxicologyIp AdministrationBiochemistryPoisoningDrug DevelopmentExperimental ToxicologyPharmacologyRelative EfficacyAcute CobaltNatural SciencesDrug DiscoveryMedicineAcute Toxicity
The relative efficacy of 14 chelating agents in alleviating acute cobalt (II) chloride (ip) intoxication has been determined. For a level of 0.70 mmol/kg ip of CoCl2 (slightly higher than its LD50), the ip administration of chelating agents at a 2:1 and 5:1 mole ratio resulted in a significant antidotal action for L-cysteine, N-acetyl-cysteine, L-histidine,glutathione,D,L-penicillamine, DMSA, DTPA and EDTA. For a level of 1.18 mmol/kg ip of CoCl2 (slightly higher than its LD99) only L-cysteine, N-acetylcysteine,glutathione, DMSA, DTPA and EDTA resulted in a significant enhancement of the survival rate. The therapeutic indices of these compounds were respectively: 8.3, 11.8, 10.9, 9.1, 20.5 and 26.4; with EDTA and DTPA being the most effective. However, due to their low toxicity, N-acetylcysteine and glutathione should be considered as possible alternatives.