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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:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Well documented guideline study (OECD 404), conducted under GLP-like conditions.In accordance to OECD Guideline 404 of 1981, "Acute Dermal Irritation/Corrosion", a 4 hour application time was used, but additional application times (3 min and 1 h) were also used.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982
Reference Type:
publication
Title:
Studies on the design of animal tests for the corrosiveness of industrial chemicals
Author:
Potokar, M. et al.
Year:
1985
Bibliographic source:
Food Chem. Toxicol. 23, 615-617.

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
in accordance to OECD Guideline 404 of 1981, "Acute Dermal Irritation/Corrosion", a 4 hour application time was used, but additional application times (3 min and 1 h) were also used.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diaethylaethanolamin
- Physical state: liquid
- Analytical purity: > 99 %

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach Germany
- Weight at study initiation: male: 2.91 kg; female: 2.74 kg
- Housing: single
- Diet: Ovator Solikanin 4 mm (MUSKATOR-WERKE, Düsseldorf, Germany, ad libitum
- Water: on week days, purified water ad libitum; on weekends, tap water ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
other: varied with exposure time, see below for details
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin area served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
3 min, 1 h or 4 h
Observation period:
7 days
Number of animals:
Two males and four females were used for the 3 min application time. 
Three males and three females were used for 1hour and 4 hour application times.
Details on study design:
Dorsal and lateral regions of the trunk were used as the application sites (3x3 cm per application site). 0.5 mL/patch of test item was used. Two males and four females were treated for 3 minutes whereas three males and three females were treated for 1 hour and 4 hours. Each animal had 4 sites of application (except for the 3 min application; in this case, each animal had 2 application sites, one treated occlusively and the other under semi-occlusive conditions), namely, a site for 1 hr application under occlusive conditions, a site for 4 hr application under occlusive conditions, a site for 1 hr application under semi-occlusive conditions and a site for 4 hr application, under semi-occlusive conditions. After treatment the patches were removed, and the treated area was rinsed with a polyethylene glycol 400 solution or a polyethylene glycol 400/water (1:1) solution and dried. Observations were made 1 hr after the removal of the patch, and at 24, 48 and 72 hr, as well as 7 days after start of application.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
4 hours of treatment, semi-occlusive
Basis:
mean
Remarks:
out of 6 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: all animals displayed erythema grade 4 at day 7
Irritation parameter:
edema score
Remarks:
4 hours of treatment, semi-occlusive
Basis:
mean
Remarks:
out of 6 animals
Time point:
other: 24 h - 48 h - 72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: at day 7, all animals still displayed edema graded 1
Irritant / corrosive response data:
Overview of findings following 1 and 4 hours of application:
After 1 hr and 4 hr occlusive and semi-occlusive exposure severe erythema, eschar formation and necrosis were observed. Very slight to slight edema was also observed. By day 7 after application the findings were not reversed. The score for erythema after the 4 hr occlusive exposure was always a 4 at all times, with the exception of one reading of 3 at 1 h. The scores for edema after the 4 hr occlusive exposure was 2 in all animals 1 hr  after patch removal; 24 hr after the start scores of 2 were seen in 5  animals and a score of 3  was seen in 1 animal; 48 hr after the start  scores of 1 were seen in 2 animals, and scores of 2 were seen in 4  animals; the same scores were seen at 72 hr after the start; and at 7  days 3 animals had a score of 1, and 3 had a score of 2. The scores for erythema after the 4 hr semi-occlusive exposure were reported to be: 2-3 at 1 hr after patch removal; 3-4 at 24 hr after the start; and thereafter it was observed to have a score of 4. The scores for edema after the 4 hr semi-occlusive exposure were reported to be: 1 in 1 animal and 2 in 5 animals one hr after patch removal; 1 in 3 animals and 2 in 3 animals 24 hr after the start; 1 in 2 animals and 2 in 4 animals 48 hr after the start; 1 in 4 animals and 2 in 2 animals 72 hr after the start; and 7 d after the start a score of 1 was reported in all 6 animals. Necrosis was confirmed histologically. In this regard, in the semi-occlusive 1 hr application group full thickness necrosis was seen in 2/6 animals; in the 4 hr application group full thickness necrosis was seen in 5/6 animals.  In the occlusive 1 hr application group full thickness necrosis was seen in 3/6 animals; in the 4 hr application group full thickness necrosis was seen in all animals.

Findings considered for assessment of the skin irritating potential of the test item:
Only the findings obtained after 24, 48 and 72 h, referring to the 4 hour application under semi-occlusive conditions were considered for the purpose of assessment. The mean scores, the absence of reversibility, and the histologically-confirmed necrosis clearly indicate that the test item is corrosive.
Other effects:
3 min application:
After a 3 min occlusive exposure, as well as semi-occlusive exposure only slight erythema was observed. It was reversible by the end of the experiment. Some scaling was observed on day 7.

Any other information on results incl. tables

Mean erythema score:

occlusive:

 Exposure time  3 min  1 h  4 h  24 h  48 h 72 h  day 7
 3 min 1/1/1/1/1/1 - - 1/1/1/1/1/1 1/1/1/1/1/1 1/1/1/1/1/1 0/0/0/0/0/0
 1 h - 3/2/2/3/3/4 - 4/2/2/4/3/4 4/4/4/4/4/4 4/4/4/4/4/4 4/4/4/4/4/4
 4 h - 4/4/4/4/3/4 - 4/4/4/4/4/4 4/4/4/4/4/4 4/4/4/4/4/4 4/4/4/4/4/4

semiocclusive:

 Exposure time  3 min  1 h  4 h  24 h  48 h 72 h  day 7    
 3 min 1/1/1/1/1/1 - - 1/1/1/1/1/1 1/1/1/1/1/1 1/1/1/1/1/1 0/0/0/0/0/0    
 1 h - 3/2/3/4/3/3 - 4/2/2/4/3/2 4/2/2/4/4/2 4/2/4/4/4/4 4/2/4/4/4/4    
 4 h - - 3/3/3/3/2/3 4/4/4/4/3/4 4/4/4/4/4/4 4/4/4/4/4/4 4/4/4/4/4/4    

Mean edema score:

occlusive:

 Exposure time  3 min  1 h  4 h  24 h  48 h 72 h  day 7    
 3 min 0/0/0/0/0/0 - - 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0    
 1 h - 1/2/2/2/2/2 - 1/2/2/1/2/2 1/2/2/1/1/1 1/2/2/2/1/1  1/1/1/1/1/1    
 4 h - - 2/2/2/2/2/2 2/2/2/2/2/3 2/2/2/2/1/1 2/2/2/2/1/1  2/1/2/2/1/1    

semiocclusive:

 Exposure time  3 min  1 h  4 h  24 h  48 h 72 h  day 7    
 3 min 0/0/0/0/0/0 - - 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0     
 1 h - - 1/2/2/2/2/2 1/1/2/1/1/2 1/1/2/2/1/1 1/1/1/1/1/1     
 4 h - - 2/2/2/2/1/2 2/1/2/1/1/2 2/2/2/2/1/1 1/2/2/1/1/1 1/1/1/1/1/1     

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information