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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions- incomplete characterization of the test substance (no data on test substance purity available)- no GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
Test material is N, N, N' Trimethylaminoethyl-Ethanolamin

Test animals

Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Gaukler; D - 6050 Offenbach/Main, FRG
Weight at study initiation: 3.42 kg (male), 2.98 (females)
Housing: individually in stainless steel cages with wire mesh floors
Diet: Kliba 341, 4 mm, Klingentalmuehle AG, CH 4303, Kaiseraugst, Switzerland; available ad libitum
Water: about 250 mL tap water per animal per day; available ad libitum
Acclimation period: at least 8 days
ENVIRONMENTAL CONDITIONS
Temperature (°C): 20 - 24
Humidity (%): 30 -70
Photoperiod: 12 hours light/dark cycle

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
Amount(s) applied: 0.5 mL applied on a 2.5 x 2.5 cm test patch
Concentration: undiluted
Duration of treatment / exposure:
3 minutes and 1 hour and 4 hours
Observation period:
15 days for animals treated treated for 3 minutes and 1 hour.. Readings were performed 4, 24, 48, 72 hours, 8 and 15 days after beginning of application.
8 days for animals treated for 4 hours. Readings were performed 4, 24, 48, 72 hours, 8 days after beginning of application.
Number of animals:
3 animals per incubation duration
Details on study design:
TEST SITE- Shavings: performed at least 15 hours before treatment
Site of exposure: upper third of the back or flanks
Area of exposure: coverage: 2.5 cm x 2.5 cm
Type of wrap if used: test patches were secured in position with a porous dressing (four layers of absorbent gauze + porous bandage)
REMOVAL OF TEST SUBSTANCE
Washing: yes (with lutrol and lutrol/water (1:1))
Time after start of exposure: 3 minutes and 1 hour
SCORING SYSTEM: Draize method (see below)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
(exposure duration of 4 hours)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Remarks:
Scaling observed at 8 days.
Irritation parameter:
erythema score
Remarks:
(exposure duration of 4 hours)
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Remarks:
Scaling observed at 8 days.
Irritation parameter:
erythema score
Remarks:
(exposure duration of 4 hours)
Basis:
animal #3
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
(exposure duration of 4 hours)
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
(exposure duration of 4 hours)
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Score after 4/24/48/72 hours and 8 days = 2/2/1/0/0
Irritation parameter:
edema score
Remarks:
(exposure duration of 4 hours)
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
(exposure duration of 1 hour)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
(exposure duration of 1 hour)
Basis:
animal: # 2 and 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
(exposure duration of 1 hour)
Basis:
mean
Remarks:
of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
(exposure duration of 3 minutes)
Basis:
mean
Remarks:
of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
(exposure duration of 3 minutes)
Basis:
mean
Remarks:
of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Other effects:
Following the 4-hour exposure, necrosis was noted in one animal at 48 and 72 hours. At 8 days this was noted as superficial necrosis by gross pathological examinaition. Haemorrhage was noted in the same animal at 4 hour and 24 hours following exposure. Scaling was observed in the remaining two animals following the 4-hour exposure.

Any other information on results incl. tables

Observations following 3 minute exposure:

Animal number

Observation

4 hours

24 hours

48 hours

72 hours

8 days

15 days

E

O

E

O

E

O

E

O

E

O

E

O

Animal 1

0

0

0

0

0

0

0

0

0

0

0

0

Animal 2

0

0

0

0

0

0

0

0

0

0

0

0

Animal 3

1

0

0

0

0

0

0

0

0

0

0

0

E            Erythema
O           Oedema

Observations following 1 hour exposure:

Animal number

Observation

4 hours

24 hours

48 hours

72 hours

8 days

15 days

E

O

E

O

E

O

E

O

E

O

E

O

Animal 1

1

0

2

0

3

0

3

0

3

0

0

0

Animal 2

1

0

0

0

0

0

0

0

0

0

0

0

Animal 3

1

0

0

0

0

0

0

0

0

0

0

0

E            Erythema
O           Oedema

Observations following 4 hour exposure:

Animal number

Observation

4 hours

24 hours

48 hours

72 hours

8 days

E

O

E

O

E

O

E

O

E

O

Animal 1

1

0

2e

1a

2e

0

2e

0

0f

0

Animal 2

1e

2a

2e

2a

2e

1a

1e

0

0f

0

Animal 3

2e

1a, b

2e

2a, b

4c

1a

4c

1a

4d, g

1a

E            Erythema
O           Oedema

a            Oedema extending beyond area of exposure
b            Haemorrhage
c            Necrosis
d            Superficial necrosis
e            Erythema extending beyond area of exposure
f             Scaling



Applicant's summary and conclusion

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
For the animals exposed for 4 hours, the mean erythema score (24/48/72 hours) was 2.3 and the mean oedema score was 0.89 (24/48/72 hours). Since necrosis was noted at 48 and 72 hours in one animal exposed for 4 hours and the study was terminated on Day 8 thereby the observation period was less than 21 days this did not allow for assessment of reversibility of the damage. The test material is considered to be corrosive to skin (category 1C) under CLP.
Executive summary:

An in vivo skin irriation study was conducted in accordance with OECD 404 with test material N, N, N' trimethylaminoethyl-Ethanolamin. The test sites (2.5 cm x 2.5 cm) of Vienna white rabbits were shaved at least 15 hours prior to the addition of 0.5 mL of the test material with semi-occlusive coverage. Three animals were treated for each of three induction times (3 minutes, 1 hour and 4 hours). Following 3 minute exposure, no erythema or oedema was observed in any of the animals at 24, 48 or 72 hour observations. Following 1 hour exposure, erythema was observed in one animal only (mean of 2.7 at 24/48/72 hour) which was reversible within 15 days; no erythema was noted in the remaining two animals. Oedema was not observed for any animals following 1 hour exposure. Following 4 hour exposure, very slight to severe or very severe erythema and none to well defined oedema was obsvered for all animals. This was reversible in two animals within 72 hours, but was irreversible in one animal for at least 8 days (the end of the observation period). Necrosis was noted in the latter animal at 48 and 72 hours. Gross histopathological examination at 8 days confirmed this was superficial necrosis, but since no further information was presented in the report and the study was terminated early this prevented assessment of the reversibility of the damage within 21 days. On the basis of the necrosis, the test material is considered to be corrosive to the skin (Category 1C).