Relative efficacy of chelating agents as antidotes for acute nickel(II) acetate intoxication

The relative efficacy of 14 chelating agents in alleviating acute nickel(II) acetate (ip) intoxication has been determined. The LD50 for ip nickel(II) acetate in mice was found to be 45.7 mg/kg with a 95% confidence limit of 39.2--53.3 mg/kg. For a level of 62 mg/kg ip of nickel(II) acetate (i.e. approximately LD90 or greater), the most effective antidotes were D-penicillamine and Na2CaEDTA, but several other chelating agents with rather different arrangements of donor atoms were almost as effective. The acetylation of the amino group in penicillamine to give N-Acetyl-D,L-penicillamine effectively destroys the antidotal action, as would be expected if coordination to the nitrogen were essential to the process.