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Toxicological information

Skin irritation / corrosion

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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

Reference
Name:
Unnamed
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

Resultsopen allclose all
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
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.