71.

Bersworth Chemical Co. The versenes for exacting chemical control of cations in solution. Technical Bulletin No. 2, 4th ed. 1952; 102 pp. (1313) [This is a manufacturer's pamphlet describing Versenes (EDTA) and their applications. Appended is a summary of toxicity data. The acute toxicity of EDTA varies with the species of animal, rapidity of injection and the route of administration. For rapid (15 sec) intravenous (iv) injection the LD50 ranges from 30-100 mg/kg death being produced by hypercalcemic tetany due to the chelating action of EDTA on the systemic Ca. EDTA has been given to humans by the iv route by injections over several hours. Up to 12 g of material was given in this way over a period of 2 days with no toxic manifestations. Over 60% of the EDTA appeared in the urine as the Ca complex. The compound does not appear to have cumulative toxicity. Subcutaneously (sc) administered, the hypocalcemic action is slow. There is a moderate amount of percutaneous absorption as demonstrated in humans. The ointments and solutions containing 5% of EDTA showed no primary irritation when patch tested on a group of children and adults. Three per cent and lower solutions are without irritation when used for irrigation in the kidney, bladder, or in the rectum for anemia. Oral administration to animals at 19% or less of total food intake had no effect on the growth of animals for a period of 3 mo, nor up to the level of 0.5% for 1 yr and 0.25% for 2 yr. The toxic effects observed at high levels of EDTA feeding have included diarrhea, anorexia, general inactivity, loss of healthy appearance of the fur and evidence of dehydration. At necropsy no significant changes were observed.
CaNa2EDTA when tested in mice, rats, pigeons, rabbits, dogs and humans is without the acute hypercalcemic toxicity shown by EDTA. The LD50 iv ranged from 1500 mg/kg-3000 mg/kg. In man doses ranging up to a total of 200 g over periods up to 20 days for this quantity produced no evidence of toxicity. Cutaneous application to humans in solutions or ointments of up to 15% CaEDTA was without evidence of primary irritation. By oral administration its toxicity was ~1/3 of EDTA. MgNa2EDTA has a toxicity similar to that of EDTA; iv infusion of 0.5 g to a series of 8 patients showed marked hypotensive effect but no toxic reactions. On the basis of experiments the degree of detoxification achieved by EDTA is as follows: Pb, detoxification 3.3, Be, 4.0, Cu, 4.0, Ca, 9.5, Co, 21, Ni, 38.]

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