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Description of key information

- Skin irritation: test substance: TMA HCl; 2 rabbits; transient skin irritation reactions triggered C&L in one out of 2 animals. The effects observed were fully reversible within 5 days (Key study 1).
- Eye: irritating: test substance: TMA HCl; 2 rabbits; transient eye irritation reactions triggered C&L in 2 tested animals. The effects observed were fully reversible within 7 days (Key Study 2).

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
Study period:
31. May 1967 - 05. Jun 1967
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (1, 5, 15 min and 20 h exposure duration, no 72 h reading, 7-d observation period, 60% aqueous solution of test substance).
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
(limited documentation, 1, 5, 15 min and 20 h exposure duration, no 72 h-reading, observation period 7 d, 2 animals, 60% aqueous solution of test substance)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.56 and 3.58 kg
no additional information given
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: other: untreated site served as control
Amount / concentration applied:
test substance (approx. 60% aqueous solution; 0.2 – 1% Trimethylamin)
Duration of treatment / exposure:
1, 5, 15 min and 20 h
Observation period:
7 d (readings after treatement: 24 h, 48 h, 5 d and 7 d)

Number of animals:
2 (females)
Details on study design:
TEST SITE
- Area of exposure: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was washed with Lutrol (conc.) and 50% in water.
- Time after start of exposure: 1, 5, 15 min or 20 h.

SCORING SYSTEM: evaluation was performed according to the Draize Scoring System
Irritation parameter:
erythema score
Remarks:
(20 h exposure)
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: slight, line-like necrosis at day 5, scaling at day 7
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Irritation parameter:
erythema score
Remarks:
(20 h exposure)
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: see 'Remarks'
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Irritation parameter:
edema score
Remarks:
(20 h exposure)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: slight, line-like necrosis at day 5, scaling at day 7
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Irritation parameter:
edema score
Remarks:
(20 h exposure)
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: see 'Remarks'
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Other effects:
Body weights (day 0 - day 7):
animal#1: 3.58 kg - 3.36 kg
animal#2: 3.56 kg - 3.34 kg

 Table 1: Details on results: Skin irritation

Exposure

Reading

Animal#1

Animal#2

Erythema

Edema

Remarks

Erythema

Edema

Remarks

1 min

All timepoints

0

0

-

0

0

-

5 min

All timepoints

0

0

-

0

0

-

15 min

All timepoints

0

0

-

0

0

-

20 h

24 h

3

2

-

1

0

-

48 h

3

2

-

0

0

-

5 d

0

0

Line-like necrosis

0

0

-

7 d

0

0

Scaling

0

0

-

Mean (24, 48 h)

3.0

2.0

-

0.5

0.0

-

Because of the strong differences between the 2 animals after test substance application, the assessment is based on the reaction of animal#1 in a worst case scenario.

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test substance is considered as skin-irritant. Despite of restrictions regarding the actual guideline, the study is considered suitable for assessment
Executive summary:

In a primary dermal irritation study performed according to a protocol similar to the OECD test guideline 404, the test substance (approx. 60% aqueous solution; 0.2 – 1% Trimethylamin) was applied to the intact skin of 2 rabbits (Vienna White) under occlusive conditions for 1, 5, 15 min and 20 h. Erythema (mean scores (24 – 48 h): 3.00 and 0.50) was observed, but was fully reversible within 5 d and 48 h, respectively. Edema (scores: 2.00 and 0.00) was reversible within 5 d. The scores of one animal are above the threshold of classification, thus in a worst case scenario with regard to this animal, the test substance is considered irritant. The conditions were very harsh compared to the conditions requested by the guideline (20 h instead of 4 h treatment, occlusive instead of semiocclusive treatment) and no 72 h scoring was performed. But as the test substance concentration was only 60% and a strong reaction was observed in 1 of 2 animals, an irritant potential of the test substance is assumed. Besides the observed erythema, line-like necrosis was described on day 5. As on day 7 only scaling is reported, it is not considered to be of relevance for classification.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31. May 1967 - 05. Jun 1967
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (limited documentation, 0.05 mL application amount, no 72 h scoring, 60% aqueous solution of test substance)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(limited documentation, application amount 0.05 mL, no 72 h scoring)
Principles of method if other than guideline:
Method: BASF-Test
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.07 and 3.04 kg

no additional information given
Vehicle:
unchanged (no vehicle)
Controls:
other: the other eye served as control (NaCl-treated)
Amount / concentration applied:
0.05 mL
Duration of treatment / exposure:
one single application
Observation period (in vivo):
5 and 7 d (readings after treatment: 10 min, 1 h, 3 h, 24 h, 48 h, 5 d (and 7 d))

Number of animals or in vitro replicates:
2 (1 male, 1 female)
Details on study design:
SCORING SYSTEM: evaluation was performed according to the Draize Scoring System.

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
(out of two animals)
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: see 'Remarks'
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
(out of 2 animals)
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: see 'Remarks'
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
(out of 2 animals)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: see 'Remarks'
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
(out of 2 animals)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: see 'Remarks'
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: see 'Remarks'
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: see 'Remarks'
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
(out of 2 animals)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: see 'Remarks'
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
(out of two animals)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: see 'Remarks'
Remarks:
This value was derived for the following time points: mean over 24 and 48 h. 72 hours were not evaluated.
Irritant / corrosive response data:
Increased secretion 10 minutes after application in both animals.
Smeary secretion 3 h after application in both animals.

 Table 1: Details on results: Eye irritation

Reading

Animal#1

Animal#2

Cornea

Iris

Conj.

Chemosis

Cornea

Iris

Conj.

Chemosis

10 min

1

0

2

3

1

0

1

3

1 h

1

0

2

3

1

0

2

3

3 h

1

0

2

3

1

0

2

3

24 h

1

0

1

0

1

0

2

0

48 h

1

0

1

0

1

0

2

0

5 d

0

0

0

0

1

0

2

0

7 d

-

-

-

-

0

0

0

0

Mean (24, 48 h)

1.0

0.0

1.0

0.0

1.0

0.0

2.0

0.0

Conj.: conjunctivae score

Although no 72 h scoring was performed, an overestimation of the effects is not assumed because only 0.05 mL was applicated and the test substance was not pure but 60 - 65% in water.

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
Single application of test substance caused irritating reactions in rabbits eye. Although the current guideline requires that 0.1 mL of the undiluted test substance should be evaluated in 3 animals, the study is considered suitable for assessment.
Executive summary:

The eye irritation potential of the test substance (approx. 60% aqueous solution; 0.2 – 1% Trimethylamine) was determined in a procedure similar to that described in the OECD test guideline 405. A single application of 0.05 mL of the undiluted test substance caused irritating reactions in the eyes of 2 rabbits. The effects on cornea (mean score: 1.00) and conjunctivae (mean score: 1.00 and 2.00) were reversible within 7 d, respectively.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

In a primary dermal irritation study performed according to a protocol similar to the OECD test guideline 404, Trimethylamine hydrochloride (approx. 60% aqueous solution; 0.2 – 1% Trimethylamine) was applied to the intact skin of 2 rabbits (Vienna White) under occlusive conditions for 1, 5, 15 min and 20 h (Key study 1, 1967). Erythema mean scores at 24 -h and 48 -h time reading points were 3.00 and 0.50 for animal 1 and 2, respectively. The irritation reactions were fully reversible within 5 d and 48 h, respectively. Edema scores were 2.00 and 0.00 in animal 1 and 2, respectively. Edema was reversible within 5 d. The scores of one animal are above the threshold of classification, thus in a worst case scenario with regard to this animal, the test substance is considered irritant. The conditions were very harsh compared to the conditions requested by the guideline (20 h instead of 4 h treatment, occlusive instead of semiocclusive treatment) and no 72 h scoring was performed. However, as the test substance concentration was only 60% and a strong reaction was observed in 1 of 2 animals, an irritant potential of the test substance is assumed. Besides the observed erythema, line-like necrosis was described on day 5 in one animal. As on day 7 only scaling is reported, it is not considered to be of relevance for classification. Despite of restrictions regarding the actual guideline, the study is considered suitable for assessment. 

 

 Eye irritation

The eye irritation potential of Trimethylamine hydrochloride (approx. 60% aqueous solution; 0.2 – 1% Trimethylamine) was determined in a procedure similar to that described in the OECD test guideline 405 (Key study 1, 1967). A single application of 0.05 mL of the undiluted test substance caused irritation reactions in the eyes of 2 rabbits. Eye irritation scores were recored after treatment at the following time points: 10 min, 1 h, 3 h, 24 h, 48 h, 5 d and 7d. Strong (score = 3) conjunctival swelling was observed in the treated eyes of both animals in the first 3 hours after application but was reversible within 24 h.The effects on cornea (mean score at 24 and 48 hours: 1.00 in both animals) and conjunctivae (mean score at 24 and 48 hours: 1.00 and 2.00 in animal 1 and 2, respectively) were reversible within 7 d. Iritis and chemosis scores were 0.0 in the eyes of both animals. Although the current guideline requires that 0.1 mL of the undiluted test substance should be evaluated in 3 animals, the study is considered suitable for assessment.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available.

Justification for selection of eye irritation endpoint:
Only one study available.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation

According to the classification criteria outlined in the section 3.2.2.2. (Guidance on the Application of CLP criteria, 2015), if the mean value of ≥ 2.3 - ≤ 4.0 was reached for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal, the classification as Skin Irritant would be assigned. Two animals instead of three were tested in the skin irritation study with Trimethylamine hydrochloride. Besides this, there was no 72 -h reading point of skin reactions. The highest mean values (at 24 –h and 48 -h reading points) for erythema and oedema were 3.0 and 2.0, respectively, in one animal. The scores in another animal were under the cut-off values. All skin irritation scores were reversible within 5 days. In a worst case scenario with regard to the animal with positive skin reactions, Trimethylamine hydrochloride is considered to be irritating to skin. In accordance with the criteria of EU CLP Regulation (EC) No. 1272/2008, the classification and labelling of Trimethylamine hydrochloride as a skin irritant in Cat 2 (H315: Causes skin irritation) is considered appropriate.

Eye irritation

According to the classification criteria outlined in the section 3.3.2.2. (Guidance on the Application of CLP criteria, 2015), if a substance cause positive but reversible reactions such as corneal opacity (score ≥ 1), iritis (score ≥ 1), conjunctival redness (score ≥ 2) or conjunctival oedema (chemosis) (score ≥ 2) in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after application, the classification as Eye Irritant (Category 2) is assigned. Two animals instead of three were tested in the eye irritation study with Trimethylamine hydrochloride. Besides this, the reading after 72 hours after treatment was not conducted. The average irritation scores over 24 and 48 hours for corneal opacity were 1.0 in two tested animals. Conjunctivae mean scores of 1.0 and 2.0 were yielded for animal 1 and 2, respectively. Iritis and chemosis mean scores were 0.0 in both animals. All irritation reactions were reversible within 7 days. Based on the scores of 1 for corneal opacity in both animals, Trimethylamine hydrochloride is classified into Cat 2 (H319: Causes serious eye irritation) according to Regulation (EC) No. 1272/2008.