Tetrapotassium ethylenediaminetetraacetate

Endpoint summary

Description of key information

There are no repeated dose studies with K4EDTA available. However, under physiological conditions (pH 7-9) any EDTA salt as well as edetic acid will dissociate into the sodium cations and the respective anionic species of edetic acid depending on the dissociation equilibria of edetic acid. Under the assumption of this equivalence it is likely that all EDTA salt chelate ions in vivo. (For read-across justification also refer to section 13)

A 90 day study with Na2H2EDTA as well as 2 years feeding studies with Na3EDTA on rats and mice provide reliable toxicological information for an overall NOAEL of about 500 mg/kg bw.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Oral route:

A 90 days feeding study of Na2EDTA in rats revealed a NOAEL of 500 mg/kg bw (Wynn, 1970). Groups of 10 male Holzman rats received 1, 5 and 10% (respectively 500 mg/kg bw; 2,500 mg/kg bw and 5,000 mg/kg bw) Na2EDTA in the diet for 90 days. The mid and high dose animals expressed a significant decrease of body weights and food consumption. Dose dependent mortality was evident by 20% in the 5% and 60% in the 10% group. In these groups animals exhibited diarrhea and were emaciated. Water consumption was increased. In the upper dose there was an intermittent decrease of hematocrite and hemoglobin levels, livers appeared to be pale. Histological investigation failed to reveal any pathological alteration. From this investigation, a NOAEL of 500 mg/kg/day equivalent to 1% in diet can be deduced for male rats. It should be noted that in this study no complete clinical biochemistry has been performed as required by OECD 408 guideline.

A two year feeding study with (Na3EDTA x 3H2O) to rats revealed a NOAEL of 500 mg/kg/day (corresponding to 7,500 ppm in the diet) (NTIS, 1977). In this feeding study with two dose levels 3,750 ppm and 7,500 ppm (corresponding to approximately 250 and 500 mg/kg/day) no substance related toxic effects could be observed.

The same study at the same dose levels (3,750 ppm and 7,500 ppm; corresponding to approximately 469 and 938 mg/kg/day) conducted with mice showed a NOAEL of 938 mg/kg bw/day. There were also no treatment related changes.

A one month feeding study of Na2EDTA in rats revealed a NOAEL of 1,125 mg/kg bw (this corresponds to 2.25% in the diet) (Kawamata, 1980). In this study test substance was incorporated at levels of 1, 2.25 and 5% in the diet (this corresponds to 500, 1125 and 2500 mg/kg bw). 15 rats per sex and dose level were exposed over a period of one month. At the upper dose level body weight decrease, some mortalities and a reduction of total leucocytes and lymphocytes as well as an increase of bound urine nitrogen (BUN) and a decrease Ca serum levels were found. Pathological investigation at this dose level revealed a decrease of liver, spleen and thymus weight. Some parakeratosis was detected in the oesophagus and forestomach by histopathology.

Justification for classification or non-classification

Based on the results obtained in the toxicity studies and taking into account the provisions laid down in Council Directive 67/548/EEC and CLP, a classification as Xn (R48/20) and STOT RE Cat 2 (H373) is justified.