Safety evaluation studies of calcium EDTA

Abstract

Listen

Translate article

Abstract The acute oral LD 50 of calcium EDTA for the rat was found to be 10.0 ± 0.74 g per kilogram body weight and for the rabbit and dog, approximately 7 and 12 g, respectively. The acute toxicity in rats was not altered by prior feeding of a diet suboptimal in respect to calcium, iron, copper, and manganese. In 2-year feeding studies with rats receiving diets containing calcium EDTA at levels to provide 50, 125, or 250 mg per kilogram body weight, no adverse effects on growth or food efficiency were observed. Hematologic examinations conducted periodically, and determination of prothrombin time, blood sugar, NPN, and serum calcium were likewise normal throughout the test period. Responses similar to those seen in the parent generation were observed in the rats of the three succeeding generations maintained on the same diet. Under the stresses of repeated pregnancies and lactation, no adverse effect of calcium EDTA was observed as measured by any of the usual indexes of reproduction or lactation efficiency. At autopsy neither gross examination nor the weights of the major organs disclosed any significant differences between the test and control groups. The histopathologic findings likewise revealed no consistent or dose-related effects. Observations on the incidence and severity of dental caries, and “line tests” of the tibias failed to suggest any evidence of an adverse effect on the calcification processes. Determinations of the xanthine oxidase content in liver tissue at autopsy, and on carbonic anhydrase content of the blood, revealed no significant changes resulting from chronic ingestion of calcium EDTA. The normal physiologic responses and behavior of the rats, even under the stresses of reproduction through successive generations, are consistent with the lack of effect of the chelating agent on these or other important metallo-enzyme systems. Groups of dogs were fed diets furnishing 0, 50, 100, and 250 mg of calcium EDTA per kilogram body weight for 1 year. Every dog gained weight during the test period, regardless of dietary treatment. The hematologic findings suggest that the dogs at all dosage levels were in an even better state of health after 1 year of test feeding than they were initially. No significant deviations from normal or control values were noted throughout the test period in urine or in blood chemistry, including the values for prothrombin time. Roentgenographic examinations of the rib cages and leg bones of the dogs in the highest dosage group and of the femurs of all dogs at or near the termination of the test period showed no evidence of osseous change. All dogs survived the 1-year test period. No gross aberrations were seen at autopsy, and the weights of the liver, kidneys, spleen, heart, adrenals, and gonads were all within normal limits. Histopathologic findings of the liver, kidneys, and pituitary of all dogs and of the adrenals and 12 additional organs in the dogs of the highest dosage group were negative.