Effects of sodium pyridinethione on the uptake and distribution of nickel, cadmium and zinc in pregnant and non-pregnant mice.

Oral administration of sodium pyridinethione together with 63Ni2+, 109Cd2+ or 65Zn2+ to non-pregnant mice resulted in very markedly increased levels of the metals in several tissues in comparison with animals given the metals alone. For 63Ni2+ the sodium pyridinethione induced a strong labelling of the pancreatic islets and of the melanin of pigmented tissues. A considerable radioactivity was also obtained in the peripheral and central nervous system. For 109Cd2+ a strong radioactivity was observed in the red pulp of the spleen and the neurohypophysis and, in addition, in the liver and the kidney. For 65Zn2+ the distribution pictures in mice given 65Zn2+ only were similar to those seen in mice given the metal together with sodium pyridinethione, although the radioactivity in all tissues of the latter animals was much higher than in the former. All 3 metals were shown to form lipophilic complexes with pyridinethione (the nickel and zinc complexes being more lipophilic than the cadmium complex) and a facilitated penetration of the complexed metals through the cellular membranes is probably important for the observed results. Differences in the stability of the complexes in the body may be one factor of importance for the marked differences in the obtained distribution pictures but other factors may also be involved, as discussed in the paper. Experiments in pregnant mice showed markedly increased levels of 63Ni2+ and 65Zn2+ in the foetuses as a result of the sodium pyridinethione administration, whereas for 109Cd2+ only a small increase was observed. Our results suggest that effects on the disposition of metals may be important for the toxicity of the pyridinethiones.