In 2 studies, parenteral administration of
diethyldithiocarbamate 50-100 mg/kg to rats immediately following
nickel carbonyl exposure ensured the survival of all animals: Mortality fell from 73% to 8% when
diethyldithiocarbamate was administered
at 10 minutes in a third study. In the same study, there was no protection when
diethyldithiocarbamate was administered at 6 hours, and the mortality was greater, though not significantly different, when
diethyldithiocarbamate was administered at 24 hours. In another study in mice, total protection was afforded by
diethyldithiocarbamate given at 8 hours but this protection was limited when
diethyldithiocarbamate was administered at 24 hours, with
diethyldithiocarbamate 100 mg/kg apparently being less protective than
diethyldithiocarbamate 50 mg/kg. In 3 studies, oral
diethyldithiocarbamate administration was less effective than parenteral administration. There are no adequately controlled clinical studies of the use of
diethyldithiocarbamate in acute
nickel carbonyl poisoning despite claims that this
therapy has been effective in the treatment of several hundred such patients.
Disulfiram, a metabolite of
diethyldithiocarbamate, offered complete protection against
nickel carbonyl-induced toxicity when administered in a dose of 1000 mg/kg to rats immediately following
nickel carbonyl exposure. In contrast,
disulfiram 500 mg/kg offered no protection and
disulfiram 1500 mg/kg appeared to enhance mortality, possibly by increasing brain
nickel accumulation.
CONCLUSION: