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Description of key information

4,4'-Thiobis(6-tert-butyl-3-cresol) was tested in albino rabbits for eye and skin irritation. The studies were not performed under GLP conditions or according to the current guidelines. However, the studies performed at Sunimoto were well performed and documented.

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:
February 28 - April 4, 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Although the study was quite old and not performed under GLP conditions, the described study method was comparable to OECD Guideline 404.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
not under GLP conditions, study dates 1986
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Japan Lab Animals Co., Ltd.
- Age at study initiation: not mentioned.
- Weight at study initiation: 2.05-2.47 kg
- Housing: individual metal mesh-bottomed suspenses cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 - 42 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 27
- Humidity (%): 45 - 75
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
physiological saline
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:
4 hours
Observation period:
4.5, 24, 48, 72 hours and 1 week
Number of animals:
3 rabbits
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage:
- Type of wrap if used: lint clot with PBS plus surgical tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, gauze with water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize criteria
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 4.5 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: (non) wounded test site
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: (non) wounded test site
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: (non) wounded test site
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
1.6
Max. score:
2
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: non wounded test site
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: wounded test site
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 week
Score:
0
Max. score:
0
Remarks on result:
other: (non) wounded test site
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 4.5 h
Score:
0.6
Max. score:
1
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: non wounded test site
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 4.5 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: wounded test site
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h
Score:
1.6
Max. score:
2
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: (non) wounded test site
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: (non) wounded test site
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 h
Score:
0.6
Max. score:
1
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: non wounded test site
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: wounded test site
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 week
Score:
0
Max. score:
0
Remarks on result:
other: (non) wounded test site
Irritant / corrosive response data:
4.5 hours after the application of Slz WX-R, all of the cases (3 cases) showed erythema and edema in both the wounded site and the non-wounded site with a strength level of 1, at approximately the same extent for both findings. By 24 hours after application, the erythema had increased in intensity to a strength level of 2 in all of the cases, while the edema ranged in strength from 1 to 2. However, these local reactions gradually lessened, and by 1 week after application, all of the local reactions had disappeared.
The primary irritation rate that was calculated based on the above-noted results was 2.83, indicating that Slz WX-R will show moderate irritation of rabbit skin.
Other effects:
none

none

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A study in 3 rabbits revealed that Slz WX-R 6 was moderately irritanting after 4-hour exposure. The study was not performed according to the general guidelines for acute dermal irritation/corrosion under GLP conditions, but was well performed and documented and as such considered reliable with minor restrictions.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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:
February 28 - April 4, 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Although the study was quite old and not performed under GLP conditions, the described study method was comparable to OECD Guideline 405.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
not under GLP conditions, study dates 1986
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Japan Lab Animals Co., Ltd.
- Age at study initiation: not mentioned.
- Weight at study initiation: 2.05-2.47 kg
- Housing: individual metal mesh-bottomed suspenses cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 - 42 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 27
- Humidity (%): 45 - 75
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: other eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
1, 24, 48, 72, (96 hours, 1 week): with or without washing after 30 seconds for 1 minute
Observation period (in vivo):
1, 24, 48, 72, (96 hours, 1 week)
Number of animals or in vitro replicates:
3 with washing; 3 without washing
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, in one group
- Time after start of exposure: 30 seconds

SCORING SYSTEM: Criteria of Draize
Irritation parameter:
cornea opacity score
Remarks:
non-washed group
Basis:
mean
Time point:
other: 1 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: Score: 10.0, 6.7, 6.7, 1.7, 0 resp. at t = 24, 48, 72, 96 h, 1 week
Irritation parameter:
iris score
Remarks:
non-washed group
Basis:
mean
Time point:
other: 1 h
Score:
1.7
Max. score:
5
Reversibility:
fully reversible within: 96 hours
Remarks on result:
other: Score: 5.0, 1.7, 1.7, 0, 0 resp. at t= 24, 48, 72, 96 h, 1 week
Irritation parameter:
conjunctivae score
Remarks:
non-washed group
Basis:
mean
Time point:
other: 1 h
Score:
6
Max. score:
6
Reversibility:
fully reversible within: 96 hours
Remarks on result:
other: Score: 12.7, 4.0, 0.7, 0, 0 resp. at t = 24, 48, 72, 96 h, 1 week
Irritation parameter:
cornea opacity score
Remarks:
washed group
Basis:
mean
Time point:
other: 1 h
Score:
0
Max. score:
0
Remarks on result:
other: Score: 0, 0, 0 resp. at t = 24, 48, 72 h
Irritation parameter:
iris score
Remarks:
washed group
Basis:
mean
Time point:
other: 1 h
Score:
0
Max. score:
0
Remarks on result:
other: Score: 0, 0, 0 resp. at t = 24, 48, 72 h
Irritation parameter:
conjunctivae score
Remarks:
washed group
Basis:
mean
Time point:
other: 1 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Score: 2.7, 0, 0 resp. at t = 24, 48, 72 h
Irritant / corrosive response data:
In the non-washed group (3 animals), all of the cases showed conjunctival redness with a strength level of 1 and conjunctival edema with a strength level of 2 at 1 hour after Slz WX-R application, while 1 case showed iris hyperemia with a strength level of 1. No change in the strength of the conjunctival hyperemia was observed at 24 hours after application, but in all of the cases, the strength of the conjunctival redness increased to a level of 2. Further, 2 cases newly developed iris hyperemia with a strength level of 1, and all of the cases showed corneal opacity with a strength level of 1 and a breadth of 1 to 4 as well as eye discharge with a strength level of 2 to 3. These local reactions gradually lessened, with only 1 case showing corneal opacity with a strength level of 1 and a breadth of 1 at 96 hours after application. After 1 week, all of the local reactions had disappeared. In the washed group (3 animals), all of the cases showed conjunctival redness and conjunctival edema with a strength level of 1 at 1 hour after Slz WX-R application. By 24 hours after application, the conjunctival redness had disappeared in 1 case, and the conjunctival edema also disappeared in 2 cases. However, 1 case newly developed eye discharge with a strength level of 1. All of these local reactions disappeared by 48 hours after application.
Based on the above-noted results, the mean total scores for the local reactions in each tissue were calculated. The maximum value up to 72 hours after application was 27.7 at 24 hours after application in the non-washed group and 4.0 at 1 hour after application in the washed group. These results indicated that Slz WX-R showed moderate irritation of rabbit eyes in the non-washed group, with only extremely mild irritation in the washed group, demonstrating the effects of washing.
Other effects:
none

none

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A study in 3 rabbits revealed that Slz WX-R 6 was moderately irritanting when the eyes were not washed and extremely mild irritating when the eyes were washed after 30 seconds of exposure. The study was not performed according to the general guidelines for acute eye irritation/corrosion under GLP conditions, but was well performed and documented and as such considered reliable with minor restrictions.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Data are available from two dermal irritation/corrosion studies in albino rabbits; these studies do not meet the requirements of the current guidelines, however, one of the studies (Sunitomo, 1986) was well performed and documented.

Data are available from two eye irritation/corrosion studies in albino rabbits; these studies do not meet the requirements of the current guidelines, however one of the studies (Sunitomo, 1986) was well performed and documented.

The results of these studies indicate that the substance should not be classified as a skin irritant or as an eye irritant in accordance with the CLP Regulation.


Justification for selection of skin irritation / corrosion endpoint:
Most well documented study, conducted using methods that are similar to those described in OECD Guideline 404.

Justification for selection of eye irritation endpoint:
Most well documented study, conducted using methods that are similar to those described in OECD Guideline 405.

Justification for classification or non-classification

The available studies do not warrant a DSD/CLP classification for irritation.