Registration Dossier

Administrative data

Description of key information

Testing for irritation and corrosion of the skin in rabbits revealed the test substance to be skin irritating, whereas no eye irritating effect could be confirmed.

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:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 12 May 1981
GLP compliance:
not specified
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach/Main, Germany
- Age at study initiation: no data
- Weight at study initiation: male: 2.89 kg, mean weight females: 2.96 kg
- Housing: individually
- Diet: KLIBA 341 (Klingentalmühle AG, Kaiseraugst, Switzerland), ca. 130 g/animal/day
- Water: tap water, ca. 250 mL/animal/day
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animals
Amount / concentration applied:
undiluted; 0.5 ml test substance
Duration of treatment / exposure:
4 h
Observation period:
8 days
Number of animals:
3 (1 male, 2 females)
Details on study design:
TEST SITE
- Area of exposure: upper third of the dorsal region or the flank
- Type of wrap if used: 4 layers of gauze and a porous-bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lutrol and lutrol /water (1:1) after removing the exposure patch

SCORING SYSTEM:
according to Draize
Erythema:
0       no erythema
1       very slight erythema (barely perceptible)
2       well-defined erythema
3       moderate to serious erythema
4       severe erythema (beet redness) with slight eschar formation (injuries in depth)

Edema:
0       no edema
1       very slight edema (barely perceptible)
2       slight edema (edges of area well-defined by definite raising)
3       moderate edema (raised approx. 1 mm)
4       severe edema (raised more than 1 mm, extending beyond the area of exposure)
Irritation parameter:
erythema score
Basis:
mean
Remarks:
:individual scores 1.3 / 2.7 / 2.7
Time point:
24/48/72 h
Score:
ca. 2.2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: scaling in 2 out of 3 animals at the end of the observation period
Irritation parameter:
edema score
Basis:
mean
Remarks:
: individual scores 0.0 / 0.3 / 0.3
Time point:
24/48/72 h
Score:
ca. 0.2
Max. score:
4
Reversibility:
fully reversible within: 48 hours

Reading Time

Animal No.

Erythema

Oedema

4 h

1

1

0

 

2

2

1

 

3

2

1

24 h

1

2

0

 

2

3

1

 

3

3

1

48 h

1

1

0

 

2

2

0

 

3

3

0

72 h

1

1

0

 

2

3

0

 

3

2

0

8 d

1*

0

0

 

2*

2

0

 

3

2

0

*Scaling

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under these test conditions there was irritation to the skin with the undiluted test substance.
Executive summary:

Three rabbits (one male, two females) were exposed dermally to single doses of 0.5 mL of undiluted test substance (purity about >=98.5%, test item was soaked into gauze patch (2.5 cm x 2.5 cm = 0.5 mL fluid) for 4 hours. The residual test item was wiped with lutrol and lutrol/water (1:1) and grading was performed according to Draize. Examinations for dermal reactions were carried out at 4, 24, 48, 72 hours, as well as 8 days following initiation of the exposure.

After 4-h exposure 3/3 animals showed well defined erythemas (overall 24 -48 -72 h mean score 2.2) and 2/3 animals slight edema (score 1 each) after 4 and 24 h, but not at later time points. Erythemas were still present after 8 d (2/3 animals, score 2 each). Two animals showed scaling at the end of the 8 d observation period (one animal with erythema and one animal without erythema, the second animal with erythema did not reveal scaling).

Based on the given results the test item was considered to be irritating to skin under the test conditions (BASF AG, 1985).

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenach, Germany
- Weight at study initiation: 2.78, 2.66, 2.78 kg
- Housing: single
- Diet: KLIBA 341, 4mm; klingentalmuehle AG, CH, ad libitum
- Water: ad libitum
- Acclimation period: at least 8 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye
Amount / concentration applied:
undiluted
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml


Duration of treatment / exposure:
Single application - eyes were not washed out
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.9
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Maximum score is the sum of individual findings for one animal.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Given score is the mean value for all three time points.
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Given score is the mean value for all three time points.
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Given score is the mean value for all three time points.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation

Findings animal1/animal2/animal3:

 Time     Conjunctiva                 
Opacity  Iritis Erythema Chemosis              
1 h 0/0/0    0/0/0   2/2/2  0/0/0              
24 h 0/0/0  0/0/0  2/1/2  0/0/0              
48 h 0/0/0  0/0/0  1/1/1  0/0/0              

72 h

0/0/0    0/0/0  0/0/0  0/0/0              

Mean values over 24, 48, and 72 h:

Animal1:Opacity: 0; Iritis: 0; Erythema: 1; Chemosis: 0

Animal2:Opacity: 0; Iritis: 0; Erythema: 0.7; Chemosis: 0

Animal3:Opacity: 0; Iritis: 0; Erythema: 1; Chemosis: 0

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this test the test item was not irritating to eyes according to the criteria of the Regulation (EC) No 1272/2008.
Executive summary:

A reliable experimental study was performed with three rabbits (BASF AG, 1985; similar to OECD 405, RL 2, key study). Animals were exposed to 0.1 mL of neat test item and were observed for 72 hours. At the 1, 24, 48 and 72 h reading there were no effects on the cornea, iris and no conjunctivia chemosis was observed (score 0 for all endpoints at all time points). Only a mean conjuctiva redness score of 0.9 (mean of all animals; 24 -48 -72 h) was observed, effects were fully reversible within 72 h, thus the test item is not irritating to the eyes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

Skin irritation/corrosion has been investigated in several studies. In a reliable study which was performed similar to OECD TG 404 three rabbits were exposed to 0.5 mL of tributylamine (purity about 98.5%; test item was soaked into gauze patch) for 4 hours on the clipped skin. At the end of the exposure period the residual test item was wiped with lutrol and lutrol/water (1:1) and grading was performed according to Draize. Examinations for dermal reactions were carried out at 4, 24, 48, 72 hours, as well as 8 days following initiation of the exposure. After 4-h exposure 3/3 animals showed well defined erythemas (overall 24 -48 -72 h mean score 2.2) and 2/3 animals slight edema (score 1 each) after 4 and 24 h, but not at later time points. Erythemas were still present after 8 d (2/3 animals, score 2 each). Two animals showed scaling at the end of the 8 d observation period (one animal with erythema and one animal without erythema, the second animal with erythema did not reveal scaling). Based on the given results the test item was considered to be irritating to skin under the test conditions (BASF AG, 1985).

In another reliable study (BASF AG, 1982, RL2, OECD 404) four rabbits were exposed dermally to single doses of 0.5 ml of undiluted test substance (purity not mentioned, skin was carefully clipped at least 15 hours prior to dosing, test item was soaked into gauze patch (2.54 x 2.54 cm = 0.5 ml fluid) for 3 minutes or 1 hour. The residual test item was wiped with lutrol and lutrol/water (1:1) and grading was performed according to Draize. Examinations for dermal reactions were carried out at 24, 48 hours, as well as after 7 days and 14 respectively 15 days following initiation of the exposure. After 3-min exposure 3/4 animals showed slight to well defined erythemas (1x score 1 and 2x score 2) and 2/4 had slight edemas (with score 1 each) after 24 h, which subsided over time. 3/4 animals exhibited scurf by the end of the observation period.

After 1 -h exposure 4/4 animals showed well defined erythemas (score 2 each) and 4/4 and 3/4 animals slight edema (score 1 each) after 24 and 48 h, respectively, which subsided over time. Erythemas were still present after 8 d (3/4 score 1, 1/4 score 2), yet not fully reversible until the end of the observation period (2/4 score 1 after 14/15 d). All animals exhibited scurf by the end of the observation period. Based on the given results the test item was considered to be irritating to skin under the test conditions.

Several less reliable studies were performed on the irritation and corrosion potential of the skin, but with the exception of Sidorin et al. (1984, rat/mouse, RL 3) and Hoechst (1989, rabbit, RL3) they all report less severe outcome (irritating to the skin, non irritating to the skin) than the key study does. The studies named in detail are Carpenter et al. (1974, rabbit, RL 3), Sidorin et al. (1984, rat, RL 3), TAMINCO (ICL ltd, 1957; rabbit, RL 3) and Arkema (1976, rabbit, RL 4).

Based on the findings of the two BASF studies with short- and long-term exposure and taking into account the information from the less reliable studies it is concluded that tributylamine is a skin irritant.

 

Eye irritation:

The irritation potential to the eye of the test substance was analysed as well. A realiable experimental study performed (BASF AG, 1985; OECD 405, rabbit, RL 2, key study) revealed only a conjuctiva score of 0.9 (mean of all animals; 24 -48 -72 h) and the observed effects were fully reversible within 72 h, thus the test item is not irritating to the eyes.

Carpenter et al. (1974; rabbit, RL 3) could not confirm this findings, they state that the test item is probably irritating. In total this study can not be assessed because of insufficient data on the study design (not according to guideline, major deficiencies in reporting) as well as no conclusion can be drawn because of insufficient data presented . This is also true for another study reported by Latven (Arkema, 1976; rabbit RL 4), which states that the test item is practically not irritating to the eye and is therefore in line with the key study.

Respiratory irritation:

Studies on acute inhalation toxicity indicate that the substance causes respiratory irritation: After acute exposure clinical signs and necropsy findings typical for respiratory irritating effects were described like watery and bloody nasal secretion, intermittant and rale respiration, bloody regions of the lungs, lung congestion and edema.

Justification for classification or non-classification

Based on the existing test results it is concluded that the substance should be classified as skin irritant (Cat. 2) according to Regulation (EC) No 1272/2008.

Based on the available data on the irritation of the eye no classification is required according to Regulation (EC) No. 1272/2008.