Abstract:
CHD-FA is a safe, heavy metal free carbohydrate derived fulvic acid. For registration purposes, pharmaceuticals require a comprehensive assessment of their genotoxic potential. A standard battery of tests usually includes a (i) bacterial reverse mutation test (Ames test) and an evaluation of chromosomal damage using the micronucleus (MN) assay. Micronuclei are expressed in dividing cells that either contain chromosome breaks lacking centromeres (acentric fragments) and/or whole chromosomes that are unable to travel to the spindle poles during mitosis. Methods: (i) The Ames test was used to test for the genotoxic potential of CHD-FA at the highest non toxic concentration. This test was done using susceptible bacterial strains of Salmonella typhimurium. Diagnostic mutagens were included for each strain to test for the revertant potential. (ii) CHD-FA was buffered to a pH of 5.5 for the MN assay. In this test CHD-FA was compared to an unfiltered product thereof. The concentrations tested were calculated according to the degree of toxicity for lymphocytes. Cells were collected from healthy non-smoking volunteers, fixed and stained with acridine orange and scored using a fluorescence microscope. Results: (i) FA was not mutagenic at the concentrations tested to any of the bacterial strains used in the Ames test when compared to the spontaneous revertant counts. (ii) Both filtered and unfiltered CHD-FA compared closely to the negative control with respect to the number or lack of micronuclei observed. Conclusion: This study indicated no genotoxicity above background for both filtered (determined by the Ames test and the MN assay) and unfiltered (in the case of the MN assay only) CHD-FA.
