The principal toxicity of CaNa2EDTA is related to the metal chelates it forms. In mice, the intraperitoneal (IP) LD50 values of various CaNa2EDTA metal chelates are CaNa2EDTA, 14.3 mmol/kg; lead EDTA, 3.1 mmol/kg; and mercury EDTA, 0.01 mmol/kg.
When CaNa2EDTA is given to patients with lead poisoning, the resultant sites of major renal toxicity are the proximal convoluted tubule, the distal convoluted tubule, and the glomeruli, possibly caused by the release of lead in the kidneys during excretion.30 Of the 130 children who received both dimercaprol and CaNa2EDTA, 13% had biochemical evidence of nephrotoxicity, and 3% developed acute oliguric renal failure, which resolved over time; none needed hemodialysis.36 Other studies failed to demonstrate any cases of renal failure in more than 1000 patient courses of therapy when CaNa2EDTA was given in divided daily doses of 1000 mg/m2 intravenously (IV) over 1 hour every 6 hours.34 Because lead toxicity causes renal damage independent of chelation, it is important to monitor renal function closely during CaNa2EDTA administration and to adjust the dose and schedule appropriately.37,38 Nephrotoxicity may be minimized by limiting the total daily dose of CaNa2EDTA to 1 g in children or to 2 g in adults, although higher doses may be needed to treat lead encephalopathy. Continuous infusion while maintaining good hydration increases efficacy and decreases toxicity.37 Because the administration of disodium EDTA can lead to life-threatening hypocalcemia and death, CaNa2EDTA is the preparation of choice for lead toxicity and hypocalcemia is no longer a clinical concern.4,9 Other adverse clinical effects of CaNa2EDTA, most of which are uncommon, include malaise, fatigue, thirst, chills, fever, myalgias, headache, anorexia, urinary frequency and urgency, sneezing, nasal congestion, lacrimation, glycosuria, anemia, transient hypotension, increased prothrombin time, and inverted T waves.11,30 Various mucocutaneous lesions in two patients included cheilosis and sore throat, magenta tongue, and papular lesions over the face, trunk and extremities, attributed to zinc deficiency.7 Mild increases in alanine aminotransferase and aspartate aminotransferase, which are usually reversible, and decreases in alkaline phosphatase are frequently reported. Extravasation may result in the development of painful calcinosis at the injection site.40,44 Depletion of endogenous metals, particularly zinc, and perhaps iron, and manganese, can result from chronic therapy.12,47 An animal study suggests that gastrointestinal lead absorption may be enhanced by either IP or oral administration of CaNa2EDTA29; consequently, removal of lead from the environment should always remain the first strategy in the management of lead toxicity. In the event of exposure to a new lead source, decontamination of the gastrointestinal tract must complement chelation.35