N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published data, information on methods and results is sufficient to make an assessment

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

A cream containing the chelator DTPA (diethylenetriaminepenta-acetic acid) can prevent contact allergic reactions to metals

Author:

Wohrl, S.

Year:

2001

Bibliographic source:

224-8. [Contact dermatitis]

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Not applicable

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)

EC Number:

200-652-8

EC Name:

N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)

Cas Number:

67-43-6

Molecular formula:

C14H23N3O10

IUPAC Name:

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) )

Method

Type of population:

not specified

Ethical approval:

not specified

Subjects:

- 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

Controls:

yes

Route of administration:

dermal

Details on study design:

TYPE OF TEST(S) USED: patch test

ADMINISTRATION
- 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

EXAMINATIONS
- 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

none

Applicant's summary and conclusion

Conclusions:

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.