Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Sensitisation data (human)

Currently viewing:

Administrative data

sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published data, information on methods and results is sufficient to make an assessment
Reason / purpose for cross-reference:
reference to other study

Data source

Reference Type:
A cream containing the chelator DTPA (diethylenetriaminepenta-acetic acid) can prevent contact allergic reactions to metals
Wohrl, S.
Bibliographic source:
224-8. [Contact dermatitis]

Materials and methods

Type of sensitisation studied:
Study type:
study with volunteers
Test guideline
no guideline followed
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)
EC Number:
EC Name:
N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)
Cas Number:
Molecular formula:
2-[bis({2-[bis(carboxymethyl)amino]ethyl})amino]acetic acid
Details on test material:
- Name of test material: 10% DTPA (oil-in-water emulsion; hydrocream HY/Excipial HydrocremeA, Spirig, Switzerland; 35% lipids/64% water) )


Type of population:
not specified
Ethical approval:
not specified
- Number of subjects exposed: 45 subjects
- Sex: 41 female + 4 male
- Age: mean age 34 years (range 14-56 years)
- Race: no data
- Demographic information: no data
Clinical history:
- History of allergy or casuistics for study subject or populations: Subjects tested positive in patch tests to nickel, cobalt, copper, palladium and/or chromium
- Symptoms, onset and progress of the disease: no data
- Exposure history: no data
- Aggravating factors both in home and workplace: no data
- Family history: no data
- Medical history (for respiratory hypersensitivity): no data
- Any other allergic or airway disorders: no data
- Smoking history: no data
Route of administration:
Details on study design:
TYPE OF TEST(S) USED: patch test

- Type of application: no data
- Description of patch: 2 identical blocks consisting of 8 circular areas of 3 cm2 each were tested on the left and right outer upper arms.
- Vehicle / solvent: yes
- Concentrations: nickel sulfate (NiSO4 2.5% and 5% pet.), palladium chloride (PdCl2 1% pet.), cobalt chloride (CoCl2 1% pet.), potassium dichromate (Cr2K2O7 0.5% pet.) and copper sulfate (CuSO4 5% pet.).
- Volume applied: no data
- Testing/scoring schedule: 3 days post application
- Removal of test substance: no data

- Grading/Scoring system: ICDRG criteria
- Statistical analysis: yes All patients showing any positive skin reactions upon re-testing (either to allergen and/or allergen+HY and/or allergen+HY-DTPA) were considered for the statistical analysis. The sign test was used to judge whether the occurrence of an allergic skin reaction was prevented with the DTPA-containing vehicle. The Wilcoxon signed rank test was employed to ask whether the severity of the ACD could be reduced.

The samples were randomized and applied in the following manner: each of the 6 tested substances was tested on a non pre-treated patch and on a patch pre-treated with 0.02 ml of the DTPA-containing vehicle. 2 patches were pretreated with the vehicle alone and exposed to 2.5% and 5% NiSO4, respectively. On the remaining 2 fields the vehicle and the vehicle with DTPA were tested as negative controls. The pre-treated areas were let dry for 10 min, before single patches using the Cura test system (Lohmann GmbH & Co KG, Germany) were applied. The reading was done after 3 days by a 3rd party following the ICDRG criteria.

Results and discussion

Results of examinations:
Pre-treating the skin with DTPA-HY reduced the clinical reaction to 2.5% nickel in a highly significant way, showing positive skin reactions in only 1 out of 28 persons. DTPA is the active agent in DTPA-HY because HY alone was not able to protect the skin in comparison with the nickel positive control (24 v 25 positive skin reactions out of 28). Doubling the concentration of nickel to 5% reduced the protective effect while still being statistically highly significant. DTPA-HY pre-treatment prevented positive tests in 17/32 subjects. Again HY alone had no protective effect as 28 out of 32 persons had a positive skin reaction v 30 with nickel alone (positive control).
Focusing on the severity of the allergic reaction, the number of +++ reactions decreased from 8 to 1 when using 2.5% nickel. The reduction was even more pronounced with 5% nickel: 16 +++ reactions versus 1 +++ reaction following DTPA-HY pre-treatment. With both concentrations of nickel this was a highly significant result.
20 individuals qualified as being sensitized to cobalt. Of 19 individuals with a positive patch test to 1% cobalt, 14 showed no signs of allergic reaction
after pre-treatment with DTPA-HY. This was a highly significant reduction. Additionally DTPA-HY decreased the severity of the skin reaction in a highly significant way. No +++ reactions were seen on the pre-treated sites in comparison with 6 +++ on the positive controls. As copper is a rare allergen only 14 individuals could be recruited to this sub-group. 13 out of 14 patients had a positive patch test to copper. Pretreatment with DTPA-HY significantly decreased the number to 5 positive patch test results. Also the severity of the patch test reactions was reduced significantly.
No effect was detected in the context of palladium hypersensitivity. 7 of 23 pre-treated sites gave no positive test result in comparison with 6 in the positive controls.
DTPA-HY had no significant protecting effect in the context of chromium sensitization. 6 out of 13 subjects with pre-treatment and 4 without pretreatment remained without a positive patch test reaction.
HY alone and HY-DTPA (negative controls) did not provoke skin irritation in any case.

Any other information on results incl. tables


Applicant's summary and conclusion

Under the conditions of the study, the results showed that diethylenetriaminepentaacetic acid/hydrocream (HY-DTPA) is an effective protective barrier cream in metal-sensitive subjects.