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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 April 2012 to 29 August 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
yes
Remarks:
(no information is given on the analytical purity)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
(1998)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Crl: KBL (NZW)
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 13-14 weeks old
- Weight at study initiation: > 2 kg
- Housing: semi barrier in an air-conditioned room in ABS - plastic rabbit cages, floor 4200 cm²
- Diet: autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 1410), rich in crude fibre, ad libitum
- Water: tap water (drinking water, municipal residue control, microbiological controls at regular intervals), ad libitum
- Acclimation period: at least 5 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18±3 (recommendations of TVT, GV-SOLAS)
- Humidity (%): 55±10
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated right side of the dorsal area of the trunk served as control
Amount / concentration applied:
A dose of 0.5 ml of the test item was applied to each test site.
Duration of treatment / exposure:
The test item was held in contact with the skin throughout a 4-hour period.
Observation period:
Animal no. 1 was observed for 11 days after the patch removal.
Animals no. 2 and 3 were observed for 9 days after the patch removal.
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the trunk, approximately 6 cm²
- Type of wrap if used: gauze patch immobilised with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing: None stated in the study report

SCORING SYSTEM: Draize Scoring System

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 11 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
over all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
Slight irritant effects (erythema grade 1) were observed on the intact skin of the three female rabbits (strain NZW) after a contact time
of 4 hours. These signs of irritation were reversible within 11 days in animal no. 1 and within 9 days in animals no. 2 and 3.
The application area was not rinsed.

Other effects:
Neither mortalities nor significant clinical signs of toxicity were observed.
There were no significant body weight changes during the contact and observation period.

Any other information on results incl. tables

Table 2: Dermal Irritation Evaluation

Animal
No.

Application
Site

Irritation (hours after patch removal)

1 hour

24 hours

48 hours

72 hours

T

C

T

C

T

C

T

C

1

Erythema

0

0

1

0

1

0

1

0

Oedema

0

0

0

0

0

0

0

0

2

Erythema

0

0

1

0

1

0

1

0

Oedema

0

0

0

0

0

0

0

0

3

Erythema

0

0

1

0

1

0

1

0

Oedema

0

0

0

0

0

0

0

0

T = test item;       C = control;        0 – 3 = grade

 

Animal
No.

Application
Site

Irritation (days after patch removal)

4 days

5 days

6 days

7 days

T

C

T

C

T

C

T

C

1

Erythema

1

0

1

0

1

0

1

0

Oedema

0

0

0

0

0

0

0

0

2

Erythema

1

0

1

0

1

0

1

0

Oedema

0

0

0

0

0

0

0

0

3

Erythema

1

0

1

0

1

0

1

0

Oedema

0

0

0

0

0

0

0

0

T = test item;       C = control;        0 – 3 = grade

Animal
No.

Application
Site

Irritation (days after patch removal)

8 days

9 days

10 days

11 days

T

C

T

C

T

C

T

C

1

Erythema

1

0

1

0

1

0

0

0

Oedema

0

0

0

0

0

0

0

0

2

Erythema

1

0

0

0

--

--

--

--

Oedema

0

0

0

0

--

--

--

--

3

Erythema

1

0

0

0

--

--

--

--

Oedema

0

0

0

0

--

--

--

--

T = test item;       C = control;        0 – 3 = grade

Table 3: Individual Data

Individual Systemic and Local Findings - Animal No. 1

Time after
Patch Removal

Systemic Findings

Specific Local Findings (apart from erythema/oedema)

Comments

1 hour

nsf

nsf

-

24 hours

nsf

nsf

-

48 hours

nsf

nsf

-

72 hours

nsf

nsf

-

4 days

nsf

nsf

-

5 days

nsf

nsf

-

6 days

nsf

nsf

-

7 days

nsf

nsf

-

8 days

nsf

nsf

-

9 days

nsf

nsf

-

10 days

nsf

nsf

-

11 days

nsf

nsf

-

Individual Systemic and Local Findings - Animal No. 2

Time after
Patch Removal

Systemic Findings

Specific Local Findings (apart from erythema/oedema)

Comments

1 hour

nsf

nsf

-

24 hours

nsf

nsf

-

48 hours

nsf

nsf

-

72 hours

nsf

nsf

-

4 days

nsf

nsf

-

5 days

nsf

nsf

-

6 days

nsf

nsf

-

7 days

nsf

nsf

-

8 days

nsf

nsf

-

9 days

nsf

nsf

-

Individual Systemic and Local Findings - Animal No. 3

Time after
Patch Removal

Systemic Findings

Specific Local Findings (apart from erythema/oedema)

Comments

1 hour

nsf

nsf

-

24 hours

nsf

nsf

-

48 hours

nsf

nsf

-

72 hours

nsf

nsf

-

4 days

nsf

nsf

-

5 days

nsf

nsf

-

6 days

nsf

nsf

-

7 days

nsf

nsf

-

8 days

nsf

nsf

-

9 days

nsf

nsf

-

nsf = no specific findings

Table 4: Absolute Body Weights in kg

 

Animal No. 1

Animal No. 2

Animal No. 3

Start of Study
(weight in kg)

3.2

3.1

3.4

72 Hours after Application (weight in kg)

3.2

3.1

3.5

End of Study
(weight in kg)

3.3

3.3

3.5

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
In an acute dermal irritation/corrosion study, conducted according to the OECD TG 404, and in compliance with GLP, the single dermal application of the test item N-[3-(dimethoxymethylsilyl)-2-methylpropyl]ethylenediamine to three rabbits at a dose of 0.5 ml showed very slight irritant but no corrosive effects which were resolved within 11 days of patch removal. Based on this result, there are no classification and no obligatory labelling requirements for skin irritation per the Annex VI of Commission Directive 2001/59/EC, Annex I of Regulation (EC) 1272/2008, and GHS (Globally Harmonized Classification System).
Executive summary:

Summary Results

The study was performed in order to assess the potential of the test item to induce acute dermal irritation/corrosion when applied directly to the skin of rabbits. Animals were exposed to 0.5 ml of the test item by application onto clipped skin for four hours using a semi-occlusive dressing. The test sites were assessed one, 24, 48, and 72 hours following patch removal. Three male New Zealand White rabbits (Crl: KBL (NZW)) were selected for testing. An initial test was conducted with one of the animals to determine if the test item produced significant irritation. The test item was applied to the two remaining animals selected for testing when the initial test showed that the test item was neither corrosive nor a severe irritant. During the initial test and confirmatory test, no irritation was observed one hour following patch removal. However, 10 days post application; animal no. 1 (initial test) had a grade 1 erythema score. Animal nos. 2 and 3 (confirmatory test) had a grade 1 erythema score for 8 days post application.  For animal no. 1 (initial test), the erythema was no longer apparent within 11 days after patch removal. For animal nos. 2 and 3 (confirmatory test), the erythema was no longer apparent within 9 days after patch removal.

Table 5: Average Scores – (24, 48, 72 h reading)

Mean Value Irritation Scores

Animal No.

Mean 24 – 72 hours

Erythema

Oedema

1

1

0

2

1

0

3

1

0

Total Mean Value

1

0

No mortalities, significant body weight changes, or significant clinical signs of toxicity were observed during the experimental period. The experimental phase for the initial test was terminated 11 days after patch removal. The experimental phase for the confirmatory test was terminated 9 days after patch removal.

Conclusion

Under the conditions of the present study, the single dermal application of the test item N-[3-(dimethoxymethylsilyl)-2-methylpropyl]ethylenediamine to three rabbits at a dose of 0.5 ml showed very slight irritant but no corrosive effects which were resolved within 11 days of patch removal.  Based on this conclusion, there are no classification and no obligatory labelling requirements for skin irritation per the Annex VI of Commission Directive 2001/59/EC, Annex I of Regulation (EC) 1272/2008, and GHS (Globally Harmonized Classification System).