Genetic toxicology of ethylenediaminetetraacetic acid (EDTA)

EDTA and its salts have a number of applications in medicine and pharmacy. EDTA is used to remove calcium from the human body, and serves as an anticoagulant and as a detoxicant after poisoning by heavy metals. It is often used in analytical chemistry for complexometric titrations and many other purposes. Because the compound is of rather low toxicity, it is used as a food additive to bind metal ions. EDTA affects the inhibition of DNA synthesis in primary cultures of mammalian cells. This may be due to impairment of enzymes involved in DNA replication. Some early studies have shown that EDTA leads to morphological changes of chromatin and chromosome structure in plant and animal cells. These alterations consist of dispersion or swelling of chromosomes or a loss of interphase chromatin structure. For several test systems, a low chromosome-breaking activity of EDTA has been reported. A weak activity in the induction of gene mutations has also been observed. It is well established that EDTA influences chromosome breakage by mutagenic agents. In particular, when applied in combination with chemical mutagens, EDTA enhances mutagen-induced aberration frequencies. Furthermore, the chelating agent is able to increase the incidence of meiotic crossing-over. This has been demonstrated for many gene loci in Drosophila melanogaster, Chlamydomonas reinhardi, Neurospora crassa and Zea mays. EDTA interferes with DNA repair processes that take place after exposure to mutagens. In E. coli or Micrococcus radiodurans as well as in Chinese hamster cells, the fast repair component detectable after treatment with ionizing radiation or bleomycin is inhibited by EDTA. In plant cells exposed to gamma-rays, EDTA inhibits unscheduled DNA synthesis. The mechanism by which EDTA causes these effects remains poorly understood. The sequestering of metal ions by the chelating agent is obviously responsible for functional and structural alterations of the genetic material. Although EDTA produces a whole set of genetic effects it seems to be a harmless compound to man as far as genotoxicity is concerned. The data presently at hand, however, are not sufficient for a reliable risk assessment.