Registration Dossier

Administrative data

Description of key information

Skin:

1,1'-(1,1,2,2-tetramethylethylene)dibenzene resulted in a primary irritation index of 0 (erythema and edema score over 24/48/72 h = 0) when applied to the intact rabbit skin.

Eye:

1,1'-(1,1,2,2-tetramethylethylene)dibenzene resulted in a slight conjunctivae redness which was reversible within at least 72 h (mean score 24/48/72 h: 0.33 - 0.67) when applied to the rabbits eye. No adverse effects were observed for parameters cornea, iris and discharge (score 0 in all animals).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1993-02-23 to 1993-02-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted May 12, 1981
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
84/449/EEC
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: Approx. 12 weeks
- Weight at study initiation: 2410 - 2674 g
- Housing: Individually in labelled cages with perforated floors and equipped with an automatic drinking system.
- Diet: Standard laboratory rabbit diet (LKK-20, peller diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 g per day.
- Water: Free access to tap-water diluted with decalcified water.
- Acclimation period: at least five days before start of treatment under test conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated contralateral flank served as negative control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g, using a moistened Scotchpak-non-woven patch.
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: dorsal
- coverage: 10 cm x 15 cm were shaved, treatment area 2 x 3 cm.
- Type of wrap if used: elastic bandage (Coban, 3M, St. Paul, USA)

REMOVAL OF TEST SUBSTANCE
- Washing: The remaining test substance was removed using a tissue moistened with tap-water and subsequently dried with a tissue.
- Time after start of exposure: 4 h

SCORING SYSTEM: according to OECD and EU Guidelines (Draize system).
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No skin irritation was caused by the test substance after a 4 hour dermal application. There was no evidence of a corrosive effect on the skin.
Other effects:
No staining of the treated skin by the test substance was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
1,1'-(1,1,2,2-tetramethylethylene)dibenzene resulted in a primary irritation index of 0 (erythema and edema score over 24/48/72 h = 0), when applied to the intact rabbit skin.
Executive summary:

1,1'-(1,1,2,2-tetramethylethylene)dibenzene was applied onto shaved skin of three albino rabbits (New Zealand White) using semi-occlusive dressings for 4 hours, followed by four observations at approximately 1, 24, 48 and 72 hours after removal of the dressings and remaining test substance. The study was performed according to OECD 404 and Regulation (EC) No 440/2008 Method B.4. Under the conditions of this study, no skin irritation was caused by 1,1'-(1,1,2,2-tetramethylethylene)dibenzene and no corrosive effect occurred on the skin in any of the three rabbits. In the area of application, no staining of the treated skin by 1,1'-(1,1,2,2-tetramethylethylene)dibenzene was observed. No signs of intoxication were observed during the study period. 1,1'-(1,1,2,2-tetramethylethylene)dibenzene resulted in a primary irritation index of 0 (erythema and edema score over 24 /48/72 h = 0), when applied to the intact rabbit skin and is thus classified as not irritating to the skin.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded skin
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g
Duration of treatment / exposure:
24 h
Observation period:
72 h
Number of animals:
6 animals (intact skin)
6 animals (abraded skin)
No information on sex.
Details on study design:
TEST SITE
- Area of exposure: 1 inch x 1 inch
- Type of wrap if used: The patches are fixed to the application site by means of adhesive tape and the entire trunk of the rabbits is wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatile substances.

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 24 h

SCORING SYSTEM: according to Draize
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24/72 h
Score:
0.167
Max. score:
4
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24/72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24/72 h
Score:
0.083
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24/72 h
Score:
0
Max. score:
4
Remarks on result:
other: abraded skin
Irritant / corrosive response data:
After 4 hours two out of twelve rabbits showed very slight erythema. After 52 hours one out of twelve rabbits showed very slight erythema of the treated skin.
Other effects:
none
Interpretation of results:
GHS criteria not met
Conclusions:
1,1'-(1,1,2,2-tetramethylethylene)dibenzene is not irritating when applied to intact and abraded rabbit skin.
Executive summary:

In a primary dermal irritation study, New Zealand White rabbits (6 aminals) were dermally exposed to 0.5 g of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene for 24 hours to the intact and abraded skin. Animals then were observed for 3 days. Irritation was scored by the method of Draize. Mean erythema scores of 0.167 and 0.083 (24/72 h) and mean edema scores of 0 (24/72 h) were noted. Thus, in this study, 1,1'-(1,1,2,2-tetramethylethylene)dibenzene is not a dermal irritant.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1993-02-24 to 1993-02-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted February 24, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
84/449/EEC
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: Approx. 12 weeks
- Weight at study initiation: 2689 - 2993 g
- Housing: Individually in labelled cages with perforated floors and equipped with an automatic drinking system.
- Diet: Standard laboratory rabbit diet (LKK-20, peller diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 g per day.
- Water: Free access to tap-water diluted with decalcified water.
- Acclimation period: at least five days before start of treatment under test conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as reference control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 64 ± 1 mg per animal
Duration of treatment / exposure:
single treatment for 24 h
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
SCORING SYSTEM: according to EU and OECD guidelines (Draize system)

TOOL USED TO ASSESS SCORE: fluorescein, pocket flash light
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.56
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Instillation of the test substance into one eye of each of the three male albino rabbits affected the conjunctivae. The irritation of the conjunctivae had resolved within 48 h in one animal and within 72 h after instillation in the two other animals. Treatment of the eyes with 2% fluorescein, 24 h after test substance instillation revealed no corneal epithelial damage in any of the animals.
There was no evidence of ocular corrosion.
Other effects:
No staining of per-ocular tissues by the test substance was observed. No toxic symptoms were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
1,1'-(1,1,2,2-tetramethylethylene)dibenzene resulted in a slight conjunctivae redness which was reversible within at least 72 h (mean score 24/48/72 h: 0.33 - 0.67), when applied to the rabbits eye. No adverse effects were observed for parameters cornea, iris and discharge (score 0 in all animals).
Executive summary:

The eye irritation potential of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene was assessed according to OECD guideline 405 and EU method B.5. The test item was instilled into one eye of each of three male albino rabbits (New Zealand White), followed by four observations at approximately 1, 24, 48 and 72 h after test substance administration. Under the conditions of the study, 1,1'-(1,1,2,2-tetramethylethylene)dibenzene resulted in adverse effects on the conjunctivae in all three animals, which had resolved within 48 - 72 h after instillation (mean score 24/48/72 h: 0.33 - 0.67). Ocular corrosion was not observed in any of the rabbits. No signs of systemic intoxication were observed during the study period. In conclusion, 1,1'-(1,1,2,2-tetramethylethylene)dibenzene was considered as not irritating to the eye.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
The animals were caged individually and received no hay or other extraneous material that might enter the eyes.
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 mg
Duration of treatment / exposure:
single treatment
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
6 animals (sex not specified).
Details on study design:
SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: Ocular reactions were read using a binocular magnifying glass.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(6 animals)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
(6 animals)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(6 animals)
Time point:
24/48/72 h
Score:
0.78
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(6 animals)
Time point:
24/48/72 h
Score:
0.56
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
After 24 hours the eye effects caused by the test material consisted of slight to moderate redness and slight swelling of the conjunctivae. After 72 hours these eye effects had cleared up completely.
Interpretation of results:
GHS criteria not met
Conclusions:
1,1'-(1,1,2,2-tetramethylethylene)dibenzene resulted in a slight to moderate irritation which was reversible within at least 72 h (mean score 24/48/72 h: conjunctivae = 0.78, chemosis = 0.56) when applied to the rabbits eye. No adverse effects were observed for parameters cornea and iris (score 0 in all 6 animals).
Executive summary:

In a primary eye irritation study, 100 mg 1,1'-(1,1,2,2-tetramethylethylene)dibenzene were instilled into the conjunctival sac of 6 New Zealand White rabbits. Animals then were observed for 3 days. Irritation was scored by the method of Draize.

1,1'-(1,1,2,2-tetramethylethylene)dibenzene resulted in a slight to moderate irritation which was reversible within at least 72 h (mean score 24/48/72 h: conjunctivae = 0.78, chemosis = 0.56) when applied to the rabbits eye. No adverse effects were observed for parameters cornea and iris (score 0 in all 6 animals). Thus, in this study, 1,1'-(1,1,2,2-tetramethylethylene)dibenzene is not an eye irritant.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin:

- Key study

1,1'-(1,1,2,2-tetramethylethylene)dibenzene was applied onto shaved skin of three albino rabbits (New Zealand White) using semi-occlusive dressings for 4 hours, followed by four observations at approximately 1, 24, 48 and 72 hours after removal of the dressings and remaining test substance. The study was performed according to OECD 404 and Regulation (EC) No 440/2008 Method B.4. Under the conditions of this study, no skin irritation was caused by 1,1'-(1,1,2,2-tetramethylethylene)dibenzene and no corrosive effect occurred on the skin in any of the three rabbits. In the area of application, no staining of the treated skin by 1,1'-(1,1,2,2-tetramethylethylene)dibenzene was observed. No signs of intoxication were observed during the study period. 1,1'-(1,1,2,2-tetramethylethylene)dibenzene resulted in a primary irritation index of 0 (erythema and edema score over 24 /48/72 h = 0), when applied to the intact rabbit skin and is thus classified as not irritating to the skin.

- Supporting study

In a primary dermal irritation study, New Zealand White rabbits (6 aminals) were dermally exposed to 0.5 g of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene for 24 hours to the intact and abraded skin. Animals then were observed for 3 days. Irritation was scored by the method of Draize. Mean erythema scores of 0.167 and 0.083 (24/72 h) and mean edema scores of 0 (24/72 h) were noted. Thus, in this study, 1,1'-(1,1,2,2-tetramethylethylene)dibenzene is not a dermal irritant.

Eye:

- Key study

The eye irritation potential of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene was assessed according to OECD guideline 405 and EU method B.5. The test item was instilled into one eye of each of three male albino rabbits (New Zealand White), followed by four observations at approximately 1, 24, 48 and 72 h after test substance administration. Under the conditions of the study, 1,1'-(1,1,2,2-tetramethylethylene)dibenzene resulted in adverse effects on the conjunctivae in all three animals, which had resolved within 48 - 72 h after instillation (mean score 24/48/72 h: 0.33 - 0.67). Ocular corrosion was not observed in any of the rabbits. No signs of systemic intoxication were observed during the study period. In conclusion, 1,1'-(1,1,2,2-tetramethylethylene)dibenzene was considered as not irritating to the eye.

- Supporting study

In a primary eye irritation study, 100 mg 1,1'-(1,1,2,2-tetramethylethylene)dibenzene were instilled into the conjunctival sac of 6 New Zealand White rabbits. Animals then were observed for 3 days. Irritation was scored by the method of Draize.

1,1'-(1,1,2,2-tetramethylethylene)dibenzene resulted in a slight to moderate irritation which was reversible within at least 72 h (mean score 24/48/72 h: conjunctivae = 0.78, chemosis = 0.56) when applied to the rabbits eye. No adverse effects were observed for parameters cornea and iris (score 0 in all 6 animals). Thus, in this study, 1,1'-(1,1,2,2-tetramethylethylene)dibenzene is not an eye irritant.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No. 1272/2008. As a result the substance is not considered to be classified for skin corrosion/irritation and eye damage/irritation under Regulation (EC) No. 1272/2008, as amended for the twelfth time in Regulation (EU) No. 2019/521.