N-[3-(dimethoxymethylsilyl)-2-methylpropyl]ethylenediamine

Skin irritation / corrosion

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(2002)

Deviations:

yes

Remarks:

(no information is given on the analytical purity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

(1998)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(dimethoxymethylsilyl)-2-methylpropyl]ethylenediamine

EC Number:

245-642-4

EC Name:

N-[3-(dimethoxymethylsilyl)-2-methylpropyl]ethylenediamine

Cas Number:

23410-40-4

Molecular formula:

C9H24N2O2Si

IUPAC Name:

N-{3-[dimethoxy(methyl)silyl]-2-methylpropyl}ethane-1,2-diamine

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 11 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 9 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 9 days

Results 4

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).