Tetrapotassium ethylenediaminetetraacetate

Endpoint summary

Description of key information

Based on read-across approach with EDTA 2Na, the same conclusions can be drawn for EDTA 4K on skin sensitisation: despite rather negative in vivo results, conflicting human data can not be ruled, so that overall these results do not warrant a labeling according to EU or GHS critieria.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The Magnusson Klingman Test according to OECD Test Guideline 406 using Na2EDTA (purity 91%) was chosen as key study. This test was performed under GLP by BASF (2000). 10 test animal and 5 control animals were used. A 0.5% substance concentration in corn oil was used for intradermal induction and a 30% test concentration for topical induction. Control animals were treated with corn oil as vehicle control. The challenge was conducted with 30% Na2EDTA in corn oil. 3/10 test animals showed a discrete patchy erythema 24 h after patch removal, after 48 h 0/10 showed a patchy erythema. 7 days later a rechallenge was conducted using 30% substance in corn oil. 1/10 test animals exhibited a discrete patchy erythema after 24 h, which was reversible within 48 h. Control animals did not exhibit skin reaction after challenge or rechallenge. The positive control group using 20% mercaptobenzodiazol induced positive skin sensitisation reactions in 7/10 animals at the 24 and 48 h reading.

With Na3EDTA a Repeated Insult Patch Test gave a negative result (0/10 animals) (Henck 1980). Within 10 days the animals received 4 topical treatments (0.1 ml) of 10% Na3EDTA in dipropyleneglycolmethylether; at the third treatment Freud's adjuvants was injected additionally. 2 weeks after the last treatment the challenge was conducted using 10% Na3EDTA in dipropyleneglykolmethylether. Within the same test Henck et al also tested for cross-sensitisation between the known skin sensitizer ethylenediamine (EDA) and Na3EDTA. Animals were sensitized with EDA and challenged topically with Na3EDTA on the one flank and EDA on the other. None of the animals reacted positive after the challenge with Na3EDTA, but all of the animals which were challenge with EDA showed a slight to marked erythema and slight edema. Therefore it was concluded that Na3EDTA does not cross-sensitize with EDA.

Human data:

2 reports of skin sensitization by Na4EDTA are available: A 78-year old woman with recurrent leg ulcers yielded a positive response on two occasions to a 1% concentration of Na4EDTA in water (de Groot, 1986). A group of 50 persons included normal volunteers and patients of assorted dermatoses. All subjects were patch tested with 1% or 0.1% EDTA in petrolatum. Three cases reacted to EDTA (test concentration 0.1% or 1% aqueous EDTA). In all instances, positive reactions were confirmed on retesting. One patient developed a periorbital edema with vesiculation of the eyelids tested positive after having used a popular ophthalmic solution containing among other substances 0.1% Na4EDTA. Another patient had a generalized eczematous dermatitis of 4-year duration and had been treated with many unidentified topical medications. A third person was the only volunteer who reacted positive (Raymond and Gross, 1969).

Additionally, several reports on human skin sensitisation using edetic acid or other Na salts of EDTA are available: 2/529 dermatitis patients reacted positive to EDTA (Angelini, 1985). In another study after patch testing with 1% EDTA 0.9% of 215 subjects reacted positive towards EDTA (Rudner, 1977). In further patch tests using Na2EDTA 13/743 or 10/345 patients reacted positive (Penvy1980, 1981). However, in the studies of Penvy a 10% solution was used not a 1% solution as usual. Therefore these result may only suggest irritation not contact allergy. In studies of Fisher (1986) hundreds of patients were tested without a single positive response.

Migrated from Short description of key information:

No skin sensitisation studies on Na4EDTA are available. However, Na4EDTA shows similar properties as other Na salts of EDTA, therefore studies using Na2EDTA and Na3EDTA have been used for read across. (For read-across justification also refer to section 13)

In the OECD 406 guideline study with Na2EDTA 3/10 animals guinea pigs showed a patch erythema after the first challenge and 1/10 after the second challenge.

The reports on humans are conflicting and in case of the positive results it can not be ruled out that the reactions reflected irritation rather than sensitisation. However, overall these results do not warrant a labeling according to EU or GHS critieria, which was also confirmed by the independent evaluation of the MAK Commission for the Investigation of Health Hazards of Chemical Compounds in the work area (MAK, 46. Lieferung, 2009).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

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 has not to be done with respect to sensitisation.