Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The Magnusson Kligman 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 animals 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:

Several reports on human skin sensitisation 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 rather than contact allergy. In studies of Fisher (1986) hunderts of patients were tested without a single positive response.


Migrated from Short description of key information:
No skin sensitisation studies on edetic acid are available. However, except for acute toxic and local effects H4EDTA shows similar properties as Na salts of EDTA, therefore studies using Na2EDTA and Na3EDTA have been used for read across.
In the OECD 406 guideline study with Na2EDTA 3/10 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)
Additional information:

6/22 patients with stable asthma developed bronchoconstriction after inhaling 4 ml of a nebuliser containing EDTA (0.5 g/l) and benzalkonium bromide (0.25 g/l) as preservatives together with the bronchodilatator ipratropium bromide. When these six subjects inhaled 4 ml EDTA and benzalkonium bromide free ipratropium bromide solution all subjects showed bronchodilatation. Inhalation of EDTA and benzalkonium bromide administered separately (EDTA solutions containing 0.25-10 g/l) produced dose related bronchoconstriction which persisted for longer than 60 minutes. The cumulative geometric mean (range) of a 20% fall in FEV, (forced expiratory volume) was 2.40 g/l (1.2-12.8) for edetic acid. Although the mechanism by which edetic acid causes bronchoconstriction is uncertain, it probably relates to

its action as a chelator of calcium ions (Beasley, 1987). However in a study by the same group (Beasly, 1989) those results could not be confirmed. EDTA (0.5 g/l) did not influence the bronchodilator effect of a single dose inhaled Duovent with fenoterol (0.31 g/l) and ipratropium bromide (0.13 g/l). However, the airway effects of repeated inhalations of EDTA were not investigated

In letters from industry (BASF-Letter, 2001) no adverse acute or chronic respiratory health effects from exposure to EDTA or Na4EDTA have been observed in workers.

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.