Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989-08-18 to 1989-08-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP study performed according to European guideline used in 1989. The study design is quite different from the present-day guideline. But it is considered as valid.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: Liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Abbaye de Bellefontaine, 49122 BEGROLLES en Mauges, FRANCE.
- Weight at study initiation: average weight 2.5 ± 0.2 kg at the start of the experiment.
- Housing: Upon receipt, the animals received a preventive treatment for coccidiosis by administration of a Mucoxid (R) solution at the dose of 140 mg/kg/d at a volume of 10 ml/kg (Véda-Cogla, 45140 Saint Jean de la Ruelle, FRANCE). Observation was performed at the time of delivery of the animals and daily during the acclimatisation period. Animals were housed individually in cages of standard size. These cages were placed in an air-conditioned (20 ± 3°C) animal house kept at 50 ± 20 % relative humidity. These parameters are recorded in each room. Non recycled air is filtered by absolute filters. The artificial day/night cycle was 12 hours light and 12 hours darkness.
- Diet: "Lapins entretien référence 112 C" from U.A.R. 91360 VILLEMOISSON SUR ORGE, was available ad libitum. A certificate of analysis (including the main contaminants) is provided by the supplier for every batch.
- Water: free access to tap water filtered by 0.22 micron filter membrane. Drinking water was available ad libitum in bottles. A specimen of water is regularly sent to a laboratory for bacteriological and chemical analysis (Laboratoire Municipal et Régional de Rouen, 76000 ROUEN, FRANCE.
- Acclimation period:For at least 5 days before the treatment, in the area where the experiment took place.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
24 hours before the test, the treatment region of each rabbit was shaved over an sufficient area. Only animal with a skin free from any traces of irritation are retained for the experiment. 0.5 mL of the substance (as supplied) was added on an hydrophilic gauze patch (6 cm2) applied to the skin of the right flank region. The left flank did not receive any substance and served as a control.
The substance and the gauze patch were maintained in contact with the skin by a semi-occlusive aerated and non-allergenic adhesive dressing . The animals were fitted with this pad for 4 hours (animal n.1, n.2 and n.3) and for 3 min. (animal n.4) and they are kept in restraining cages.
When the dressing was removed , the test substance was not rinsed off.
Duration of treatment / exposure:
A first patch was applied and removed after 4 hours of exposure (animal N. 1, 2 an 3) and a second patch was removed after three minutes of exposure (animal 4).
Observation period:
The responses were graded at 1 hour and 24 h following the patch removal. Then the animals were sacrified.
Number of animals:
4 animals
Details on study design:
The test item was applied once only, at a duration of exposure of 4 hours (exposure of 3 animals).
The test item was applied once at a duration of three minutes (exposure of one animal).
The cutaneous reactions were evaluated for Erythema and Oedema formation. As skin necrosis and a serious oedema was observed after 1h and 24 hours following the patch removal, the observation of the animals was no longer continued and the animals were sacrified.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: Observation after 1h and 24h
Max. score:
4
Reversibility:
other: animal sacrified following the observation at 24 hour
Remarks on result:
other: Necrosis following 4 hours of exposure
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: Observation after 1h and 24h
Max. score:
4
Reversibility:
other: animal sacrified following the observation at 24
Remarks on result:
other: Necrosis following 4 hours of exposure
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: Observation after 1h and 24h
Max. score:
4
Reversibility:
other: animal sacrified following the observation at 24
Remarks on result:
other: Necrosis following 4 hours of exposure
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: Observation after 1h and 24h
Max. score:
4
Reversibility:
other: animal sacrified following the observation at 24
Remarks on result:
other: Necrosis following 3 min. of exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: Observation after 1h and 24h
Score:
4
Max. score:
4
Reversibility:
other: animal sacrified following the observation at 24
Remarks on result:
other: 4 hours of exposure
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: Observation after 1h and 24h
Score:
4
Max. score:
4
Reversibility:
other: animal sacrified following the observation at 24
Remarks on result:
other: 4 hours of exposure
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: Observation after 1h and 24h
Score:
4
Max. score:
4
Reversibility:
other: animal sacrified following the observation at 24
Remarks on result:
other: 4 hours of exposure
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: Observation after 1h and 24h
Score:
4
Max. score:
4
Reversibility:
other: animal sacrified following the observation at 24
Remarks on result:
other: 3 min. of exposure
Irritant / corrosive response data:
One hour and 24 hours after the patch removal, a skin necrosis and a serious oedema was observed in all treated animals following 3min. or 4 hours of exposure. All animals were sacrified after 24 hours.

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions, the substance dimethoxy-2,2 ethylamine (HF 88035) was found to be corrosive cat. 1A for the skin of the rabbit.
Executive summary:

Any irritant property and/or degree of corrosion of the substance dimethoxy-2,2 ethylamine (HF 88035) was evaluated in the rabbit following a single semi-occluded application to intact skin in accordance with the method B4 of Commission Directive 84/449/CEE and following the GLP.

4 animals were used for the study.

0.5 mL of HF 88035 was applied on the skin via an absorbent gauze. Adjacent surfaces of untreated skin served as a control for the trial. Semi-occlusive dressings held the test item in place for 3 minutes on the skin of 1 animal and for 4 hours on the skin of 3 animals.

The application of the test item induces necrosis and severe oedema in all animal following 3min or 4 hours of exposure to the substance. This effects were evaluated 1h and 24 hours after removal of the dressing. Due to the importance of the reactions, the animals were sacrified after the 24 -hour scoring period.

On the basis of the necrosis observed after 3 min. of exposure to the test substance, the substance is considered as corrosive category 1A