Registration Dossier

Administrative data

Description of key information

In vivo studies of skin irritation/corrosion and eye irritation are available for the submission substances. Waivers are provided for in vitro studies of skin irritation/corrosion and eye irritation due to the availability of in vivo data.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Specific details on test material used for the study:
Test material is N, N, N' Trimethylaminoethyl-Ethanolamin
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
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)
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.

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



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).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye 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
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Specific details on test material used for the study:
N, N, N Trimethylaminoethyl-Ethanolamin
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
Source: Gaukler; D - 6050 Offenbach/Main, FRG
Weight at study initiation: 2.46 kg (male), 2.88 (female)
Housing: individually in stainless steel cages with wire mesh walk floors
Diet: Kliba 341, 4 mm, Klingentalmuehle AG, CH 4303, Kaiseraugst, Switzerland; available ad libitum (ca. 130 g per day per animal)
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 (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: left eye (untreated)
Amount / concentration applied:
Amount applied: 0.1 mL applied in to the conjuctival sac of the right eye.
Duration of treatment / exposure:
Eyes were not washed after application.
Observation period (in vivo):
15 days- Reading were performed 1, 24, 48, 72 hours, 8 and 15 days after application.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE- Washing (if done): no
SCORING SYSTEM: Draize method
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
within 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 8 and 15 days
Score:
>= 4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
not reversible
Remarks:
within 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks:
within 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Remarks:
72 hour assessment could not be made
Basis:
animal #3
Time point:
24/48 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks:
within 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks:
within 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
no indication of irritation
Other effects:
See table 2: Table of symptoms

Observations

Parameter

Observation period

Animal 1

Animal 2

Animal 3

Cornea

1 hour

1

1

1

24 hours

1

1

2

48 hours

1

1

2

72 hours

1

2

3

8 days

2

3

4

15 days

2

2

4

Iris

1 hour

0

0

0

24 hours

0

1

1

48 hours

0

1

1

72 hours

1

1

a

8 days

1

1

a

15 days

b

b

a

Conjunctivae

1 hour

2

2

2

24 hours

2

2

2

48 hours

2

2

2

72 hours

2

2

2

8 days

2

2

2

15 days

1

2

1

Chemosis

1 hour

2

2

2

24 hours

1

2

2

48 hours

1

2

2

72 hours

1

2

2

8 days

0

1

1

15 days

0

0

0

a       reading cannot be made due to severe corneal opacity

b       reading cannot be made due to marginal vascularisation of the cornea

Table of symptoms

 

Animal 1

Animal 2

Animal 3

Discharge of blood

≥ 24 h – 48 h

≥ 1 h – 72 h

≥ 1 h – 72 h

Loss of corneal tissue

-

≥ 72 h – 8 d

≥ 1 h – 8 d

Loss of hair at margins of eyelids

-

≥ 8 – 15 d

≥ 8 – 15 d

Marginal vascularisation of the cornea

15 d

≥ 8 – 15 d

≥ 8 – 15 d

Pupil contracted

≥ 1 h – 8 d

≥ 1 h – 8 d

≥ 1 h – 48 h

Pannus

15 d

-

-

Small retractions in the eyelid

15 d

≥ 24 h – 15 d

≥ 72 h – 15 d

Suppuration

72 h

≥ 48 h – 15 d

≥ 48 h – 15 d

Staphyloma

-

15 d

15 d

After 15 days, the study was discontinued because of serious irritation effects on the eyes.

Interpretation of results:
Category 1 (irreversible effects on the eye)
Conclusions:
For the animals exposed for 4 hours, the mean corneal score (24/48/72 hours) was 1.6, the mean conjunctivae score was 0.89 (24/48/72 hours) and the the mean chemosis score was 1.7 (24/48/72 hours). The mean iris score was 0.7 based on 2 animals (24/48/72 hours) and a score of 1 was assigned at both 24 and 48 hours for the third animal. Based on the corneal opacity score of 4 for one animal at 8 and 15 days and the irreversible damage, the test material is considered to cause serious eye damage (Category 1) according to CLP
Executive summary:

An in vivo eye irriation study was conducted in accordance with OECD 405 with test material N, N, N' Trimethylaminoethyl-Ethanolamin. The eyes of three Vienna white rabbits were instillated with 0.1 mL of test material. The test material was not removed. Observations were made 1, 24, 48 and 72 hours and 8 and 15 days after application. The material showed a mean value of 1.6 (24/48/72 hours) for corneal opacity, 2.0 (24/48/72 hours) for conjunctivae and 1.7 (24/48/72 hours) for chemosis. Due to the extent of corneal damage, iritis readings for 1 animal could not be made at 72 hours, however the mean for the remaining two animals was 0.7 (24/48/72 hours) with readings for the former animal were 1 at 24 and 48 hours. With the exception of chemosis which was reversible within at least 15 days, the damage was irreversible. The severity of cornea opacity increased for all three animals between 72 hours and 8 days and worsened or remained the same by 15 days; the opacity score for one rabbit was 4 at 8 and 15 days after installation. On the basis of the corneal opacity and the irreversible damage, the test material is considered to cause serious eye damage (Category 1).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

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).

Eye irritation

An in vivo eye irriation study was conducted in accordance with OECD 405 with test material N, N, N' Trimethylaminoethyl-Ethanolamin. The eyes of three Vienna white rabbits were instillated with 0.1 mL of test material. The test material was not removed. Observations were made 1, 24, 48 and 72 hours and 8 and 15 days after application. The material showed a mean value of 1.6 (24/48/72 hours) for corneal opacity, 2.0 (24/48/72 hours) for conjunctivae and 1.7 (24/48/72 hours) for chemosis. Due to the extent of corneal damage, iritis readings for 1 animal could not be made at 72 hours, however the mean for the remaining two animals was 0.7 (24/48/72 hours) with readings for the former animal were 1 at 24 and 48 hours. With the exception of chemosis which was reversible within at least 15 days, the damage was irreversible. The severity of cornea opacity increased for all three animals between 72 hours and 8 days and worsened or remained the same by 15 days; the opacity score for one rabbit was 4 at 8 and 15 days after installation. On the basis of the corneal opacity and the irreversible damage, the test material is considered to cause serious eye damage (Category 1).

Justification for classification or non-classification

N, N, N' trimethylaminoethyl-Ethanolamne is classified as skin corrosive (category 1C) based on the irreversible nature of the skin damage in two/three animals and the absence of further histopathological details that the necrosis was superficial.

N, N, N' trimethylaminoethyl-Ethanolamne is classified as causes serious eye damage (category 1) based on the irreversible nature of the eye damage and the extent of corneal opacity in one animal at 8 and 15 days following installation.