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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:
2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guidelance study under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
GLP compliance:
yes
Remarks:
statement

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
N-[2-[2-(dimethylamine) ethoxy] ethyl]-N-methyl-I ,3-
Batch 19902-1
Purity >92%
Expiry date 31 October 2006

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 6 weeks
- Weight at study initiation: 1.0 Kg
- Diet :Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day.
- Water :Free access to tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature of 21.0 ± 3.0
- Humidity (%):30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light):12 hours artificial fluorescent light and 12 hours darkness per day

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: dorsal fur was clipped with electric clippers
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml of the substance/ pure material
Duration of treatment / exposure:
There were 3 sites prepared on the single animal. The time of exposure was 3 mins-1 hr - 1 hr.
Observation period:
Immediately and 1 h after removal of the patch.
Number of animals:
1
Details on study design:
Test animal received of 0.5 ml of the test substance to the intact, clipped skin of one flank using a Metalline patch# of 2x3 cm. The patch was mounted on Micropore tape', which was wrapped around the abdomen and secured with Coban elastic bandage.The dressing was removed 3 minutes after application
Since no signs of severe skin reactions (i.e. necrosis or corrosion) were observed and it was considered that exposure could be continued humanely, two samples of 0.5 ml of the test substance were then applied to separate skin-sites on the intact, clipped skin of the same animal, using an identical procedure and one sample per dressing. One of the dressings was removed after a 1-hour exposure.
Since signs of severe skin reactions (necrosis) were observed after 1 hour of exposure, the remaining dressing was removed immediately. After skin reading, the study was terminated. No further testing was performed.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 3 min
Score:
1
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 3 min
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 h
Score:
4
Max. score:
4
Remarks on result:
other: assessed immediately after removal of patch
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 h
Score:
0
Max. score:
4
Remarks on result:
other: Assessed immediately after removal of the patch
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 h
Score:
4
Max. score:
4
Remarks on result:
other: Assessed 1 hr after removal of the patch
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 h
Score:
0
Max. score:
4
Remarks on result:
other: Assessed 1 h after the removal of the patch
Other effects:
Dark discoloration and signs of necrosis were observed immediately after the removal of the 1 h patch.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive)
Remarks:
Migrated information Corrosive > 3 min and < 1 h exposure Criteria used for interpretation of results: EU
Conclusions:
Substance was found to be corrosive > 3 min and < 1 h exposure and it is classified as category 1B.
Executive summary:

One rabbit was exposed to three samples of 0.5 ml of N42-[2 -(DlMETHYLAMINE)ETHOXY]ETHYL)-N-METHYL- ,3-PROPANEDIAMINE applied to separate skin-sites on intact, clipped skin using a semi-occlusive dressing. The exposure periods were 3 minutes, 1 hour and 1 hour, respectively. Skin reactions were assessed immediately after removal of the dressings andlor after 1 hour. Since severe skin reactions were noted after one hour of exposure, the animal was sacrificed for humane reasons.

Three minutes exposure to Nj2-12-(DIMETHYLAMINE)ETHOXY]ETHYL)-N-METHYL- ,3 -PROPANEDIAMINE resulted in very slight erythema and no oedema in the treated skin-areas of the rabbit, noted immediately after removal of the dressing and after 1 hour.

One hour of exposure resulted in severe erythema and brown discoloration (signs of necrosis) covering the entire application site and seen immediately after removal of the dressings.

Severe necrosis was observed during the observation period, indicating that corrosion of the skin had occurred by dermal application of N42-12-(DIMETHYLAMINE)ETHOXY]ETHYL)-NMETHYL- 1,3-PROPANEDIAMINE to the intact rabbit skin after one hour of exposure.

Based on these results and according to the:

- OECD Harmonized Integrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances (OECD, 1998), N42-12 -(DIMETHYLAMINE)ETHOXV]ETHYL}-N-METHYL-1,3-PROPANEDIAMINE should be

classified as : skin corrosive (Class 1 B).

- EC criteria for classification and labeling requirements for dangerous substances and preparations (Council Directive 67/548lEEC), N42-[2-(DIMETHYLAMINE)ETHOXY]ETHYL)-N-METHYL-1,3-PROPANEDIAMINE should be labeled as: causes burns (R 34).

- criteria for transport and packaging labeling as specified in Accord Europken Relatif (ADR) ), Appendix A, Class 8, N-(2-[2-(DIMETHYLAMlNE)ETHOXY]ETHYL)-N-METHYL-1,3 -PROPANEDIAMINE should be classified in packaging group I1 (irritating substances).

- criteria for transport and packaging labeling as specified in International Maritime Dangerous Goods code, Vol. IV, General introduction to Class 8 - Corrosives section 2.1, Amdt. 28-96. N42-12-(DIMETHYLAMlNE)ETHOXV]ETHYL)-N-METHYL- ,3-PROPANEDIAMINE should be classified in packaging group I1 (preparations and substances presenting medium

danger).