Cobalt disodium ethylenediaminetetraacetate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

The chelating effect of sodium EDTA in nickel-allergic patients was investigated. It could be shown how EDTA has a blocking effect for skin irritant reaction (eczema) on humans.

Data source

Reference

Reference Type:

publication

Title:

Chelating effect of EDTA on nickel

Author:

Van Ketel, W.G. and Bruynzeel, D.P.

Year:

1984

Bibliographic source:

Contact dermatitis, 11/5, 311-314

Materials and methods

Principles of method if other than guideline:

Study on humans in order to investigate an EDTA effect which prevent the dermatitis-provoking potential of nickel.

GLP compliance:

not specified

Test material

Test material information

1

Reference substance name:

Nickel sulphate

EC Number:

232-104-9

EC Name:

Nickel sulphate

Cas Number:

7786-81-4

Molecular formula:

H2O4S.Ni

IUPAC Name:

nickel(2+) sulfate

Specific details on test material used for the study:

aqueous nickel sulphate (prepared by the hospital pharmacist)

In vitro test system

Test system:

human skin model

Remarks:

upper back of 17 nickel-allergic female patients

Source species:

human

Cell type:

other: human skin cells

Vehicle:

water

Details on test system:

The right half of the upper back was lightly rubbed with a cream containing 10% EDTA (w/w) (disodium salt of ethylenediamine tetra acetate) in cetomacrogol cream FNA. After 15 min, when the cream was no longer visible, 3 concentrations of aqueous nickel sulphate were patch tested in the pretreated area. The left upper back was pretreated in a similar way with cetomacrogol cream FNA without EDTA. The same concentrations of nickel sulphate were patch tested in this area. Patch testing was performed with the Silver Patch Testers. The reactions were graded according to the ICDRG after 48 and 72 h.

Control samples:

yes, concurrent positive control

other: 10% EDTA in cetomacrogol cream

Amount/concentration applied:

0.01% (24.4 ppm), 0.1% (244 ppm), 1% (2440 ppm)

Duration of treatment / exposure:

The reactions were graded after 48 and 72 h

Results and discussion

In vitro

Results

Results 1

Irritation / corrosion parameter:

penetration time (in minutes)

Remarks:

After 2880 and 4320 min

Run / experiment:

1-6, 8-14 and 16

Positive controls validity:

not specified

Remarks on result:

no indication of irritation

Remarks:

at 2440 ppm nickel sulphate

Results 2

Irritation / corrosion parameter:

penetration time (in minutes)

Remarks:

After 2880 and 4320 min

Run / experiment:

7, 15 and 17

Positive controls validity:

not specified

Remarks on result:

positive indication of irritation

Remarks:

slight reaction was observed

Applicant's summary and conclusion

Conclusions:

The blocking effect of the 10% EDTA cream appeared to be significant in comparison with that of the cream base only (p < 0.01). In most patients, 10% EDTA does chelate nickel sulphate in 0.01% (24.2 ppm), 0.1% (244 ppm) and 1% (2440 ppm) by reducing the dermatitis-provoking potential of nickel. A barrier cream with 10% EDTA might be of help in nickel-allergic patients with eczema of the hands.

Executive summary:

In the area pretreated with 10% EDTA in cetomacrogol cream FNA, only 3 of 17 patients showed a + positive reaction to 1% (2440 ppm) nickel sulphate. 3 patients showed no reaction to any concentration of nickel sulphate in either area. The reactivity to nickel sulphate in the area pretreated with 10% EDTA appeared to be far less than in the control area (rank sum test p < 0.01). No irritant reactions to the 10% EDTA cream were observed.