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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:
1990-08-22 - 1990-09-05
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Well documented GLP study performed according to a method similar to OECD Guideline 404 with the following deviations: an occlusive dressing was used (instead of semi-occlusive). Furthermore, next to application of the test substance on intact shaved skin, also abraded skin was tested.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
occlusive dressing used (instead of semi-occlusive); abraded skin was tested
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
4-methylmorpholine
EC Number:
203-640-0
EC Name:
4-methylmorpholine
Cas Number:
109-02-4
Molecular formula:
C5H11NO
IUPAC Name:
4-methylmorpholine
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): 6398-24-20, Project #90-005
- Substance type: clear, colorless liquid
- Physical state: liquid
- Lot No.: 90-005
- Purity: responsibility of the sponsor
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hare-Marland, Hewitt, NJ, USA
- Age at study initiation: adult animals
- Weight at study initiation: males 2129-2507 g (mean 2351 g); females 2170-2633 g (mean 2468 g)
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): not indicated
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact shaved skin
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/site


Duration of treatment / exposure:
The test substance was kept in contact with the skin on the upper dorsal site (intact) for four hours and at the lower dorsal sites (intact and abraded) for twenty four hours.
Observation period:
Dermal irritation was scored at 30-60 minutes, 24, 48 and 72 hours and on Days 4 through 14 after patch removal. Dermal irritation of the lower dorsal sites (intact and abraded) were scored at 24, 48 and 72 hours and on Days 4 through 14 after application of the test material.
Number of animals:
6 (3 males and 3 females)
Details on study design:
TEST SITE
- Area of exposure: one intact site on the upper dorsal trunk and at two sites, one intact and one abraded, on the lower dorsal trunk of the animal.
- Type of wrap if used: All application sites were clipped free of hair. The abraded site was prepared using a burred needle; the abrasion penetrated the stratum corneum but not the derma. Following the application of the test material, gauze patches were applied to each of the sites then wrapped with a rubber dam and an elastic bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
At the end of each exposure period, the sites were wiped with water and gauze and observed for erythema and edema.

SCORING SYSTEM: Draize evaluation of dermal irritation

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: application on intact shaved skin (upper dorsal area)
Irritant / corrosive response data:
Moderate to severe erythema and edema were observed at the 30-60 minute observation period on the upper dorsal site. Severe erythema and edema were observed at the 24, 48 and 72 hours and on days 4 through 14 on the upper dorsal site. Severe erythema and edema were observed at the 24, 48 and 72 hours and on days 4 through 14 on the lower dorsal sites. Necrosis of the skin was observed at each application site at the 24, 48 and 72 hours and on days 4 through 14 observation periods at each application site. Sloughing of the skin at the application site was observed at the day 14 observation period on the upper dorsal site and at the day 13 and 14 observation periods at the lower dorsal sites. The study was terminated following the day 14 observation period.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
Based on the test results and according to the criteria of the CLP Regulation, the substance is classified as category 1 corrosive.