Chelate antidotal efficacy in acute zinc intoxication
Basinger, M.A.; Jones, M.M.
Research Communications in Chemical Pathology and Pharmacology 33(2): 263-272
1981
ISSN/ISBN: 0034-5164 PMID: 7302374 Document Number: 176603
The ability of several structural types of chelating agents to antagonize i.p. administration of 50 mg/kg ZnSO4 was examined in mice. LD50 of i.p. ZnSO4 in mice was 36.1 mg/kg with a 95% confidence interval of 34.8-37.4 mg/kg. When given at a chelating agent to Zn(II) ratio of 10 to 1, 20 min after administration of Zn, the structures that provided the most effective antidotal activity were EDTA, 2,3-dimercaptosuccinic acid, diethylenetriaminepentaacetate (NA3CaDTPA), cyclohexanediaminetetraacetate (Na2CaCDTA), D-penicillamine and sodium-2,3-dimercaptopropane-1-sulfonate. Triethylenetetramine (TTT .cntdot. 2HCl) under these conditions was not an antidote. Acute Zn(II) intoxication was antagonized by a variety of combinations of donor types. Calcium ethyleneglycol-bis-(.beta.-aminoethylether)-N,N'-tetraacetate (CaEGTA) at this level was not an antidote and appeared to be toxic. The behavior of mice with the most effective antidotes indicated that these compounds, if given simultaneously with Zn, were capable of antagonizing larger amounts of ZnSO4. The fact that the effective chelating agents possessed such a variety of donor groups was consistent with the fact that Zn(II) formed stable coordinate bonds to O, N and S donor atoms. Results were also presented in which the chelating agent to Zn ratio was < 10; in these cases the most effective antidotes were still able to antagonize the lethal action of ZnSO4.