Effects of lipophilic complex formation on the disposition of nickel in experimental animals.

Dithiocarbamates, thiuram sulphides, xanthates, pyridinethiones and halogenated 8-hydroxyquinolines are groups of compounds which can form lipophilic complexes with Ni2+. These compounds are widely used as drugs and pesticides, and in industry. We have exposed rodents (mice, rats) and fish (brown trout) to substances belonging to these groups of compounds together with 63Ni2+ (as 63NiCl2) and then examined the uptake of the 63Ni2+ in the tissues of the animals. One dithiocarbamate--sodium diethyldithiocarbamate, which is used clinically in nickel carbonyl intoxications--was also examined with regard to effects on the tissue disposition of the metal in mice exposed to 63Ni(CO)4. The studies with 63Ni2+ showed that some of the complexing substances examined caused highly increased tissue levels of the metal in the animals. However, the enhancing effect varied with different complexing compounds. A facilitated penetration of the lipophilic 63Ni2+ complexes across the cellular membranes may underlie the increments in the tissue levels of the metal, but the effects on the disposition of the 63Ni2+ may vary depending on the lipophilicity and the stability of the complexes. In mice exposed to 63Ni(CO)4 by inhalation, sodium diethyldithiocarbamate decreased the levels of the metal in tissues such as the lung, brain and heart. These tissues are targets in nickel carbonyl intoxications and will attain high levels of the metal following inhalation of the compound. The nickel is present in nickel carbonyl as Ni0, but will be oxidized to Ni2+ in the tissues. The experiments presented here indicate that the diethyldithiocarbamate is able to reach and bind the intracellular Ni2+ in the critical target tissues and this property may underlie the ability of the compound to act as an antidote in nickel carbonyl intoxications. However, the ability of diethyldithiocarbamate to act as a nickel antidote may be limited to nickel carbonyl. Generally, the increased uptake of nickel induced by the compounds forming lipophilic complexes with the metal may imply risks of noxious combination effects.