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Administrative data

Description of key information

Oral:

The LD50 of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene in the rat after oral administration (gavage) is greater than 2000 mg/kg bw.

Dermal:

No local or systemic toxic effects related to administration of the test substance were noted from clinical observations or post-mortem-examination at a dose of 2000 mg of the test substance per kg body weight. No mortality occurred.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1993-02-04 to 1993-02-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted February 24, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
84/449/EEC
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: males: 249 - 299 g; females: 196 - 191 g
- Fasting period before study: yes, 18 h before treatment
- Acclimation period: at least one week
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: standard vehicle according to guideline

DOSAGE PREPARATION:
The test item was granulated using a mortar and pestle, subsequently weighed into a glass beaker on a Mettler tarred analytical balance and corn oil was added. Adjustment was made for the specific gravity of the vehicle. A weight/weight suspension was prepared using a magnetic stirrer. The preparation was made immediately prior to dosing.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Motality/Viability: At least three times each day
Body Weights: Test days 1 (pre-administration), 8 and 15
Clinical Signs: Each animal was examined for changes to treatment with particular attention paid to changes in behaviour, respiration, motility, body posture, motor susceptibility, skin, eyes, nose and fur. Observations (including mortality/viability) were performed four times during day 1 and once daily during days 2 - 15.
- Necropsy of survivors performed: yes, all animals.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured during the study period.
Clinical signs:
No clinical signs were observed during the study period.
Body weight:
The body weight gain shown by the animals over the study period was considered similar to that expected of normal untreated animals of the same age and strain, although low body weight gain was noted in two females over the second week.
Gross pathology:
Macroscopic post mortem examinations of the animals at termination did not reveal any abnormalities.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene in the rat after oral administration (gavage) is greater than 2000 mg/kg bw.
Executive summary:

The oral toxicity of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene was assessed according to OECD guideline 401 and EU method B.1. The test item was administered to one group of 3 male and 3 female Wistar rats by oral gavage, at a single dose of 2000 mg/kg bw. No mortality occurred, no clinical signs were observed and no macroscopic abnormalities were seen at necropsy. Based on these observations, the estimated acute oral toxicity LD50 of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene in rats of both sexes observed for a period of 15 days is greater than 2000 mg/kg bw.

Endpoint:
acute toxicity: oral
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:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, The Netherlands
- Age at study initiation: young adult
- Weight at study initiation: males = 121 - 148 g, females = 115 - 133 g
- Fasting period before study: yes
- Housing: The rats were housed in groups of five, males and females separated, in stainless steel cages with grid-bottom and front.
- Diet: The rats received stock diet ad libitum.
- Water: Tap water was freely available at all times by means of an automatic, watering system.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24
- Humidity (%): 40 - 60
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25 % (v/v)
- Amount of vehicle: 20 mL/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
After treatment, the rats were observed frequently for signs of intoxication during the first 4 post-treatment hours and thereafter at least once daily throughout a 14-day observation period. The individual body weights were recorded on day 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
Clinical observations during the first 4 post-treatment hours and in the remaining part of the observation period did not reveal any sign of intoxication.
Body weight:
The individual body weights on day 7 and 14 indicated normal growth.
Gross pathology:
Macroscopic examination of the survivors at autopsy did not reveal any treatment-related gross alterations.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene in the rat after oral administration (gavage) is greater than 5000 mg/kg bw.
Executive summary:

In an acute oral toxicity study, groups of fasted, young adult Wistar rats (10/sex) were given a single oral dose of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene in polyethylene glycol at a limit doses 5000 mg/kg bw and observed for 14 days. The study was performed according to OECD 401. Clinical observations during the first 4 post-treatment hours and in the remaining part of the observation period did not reveal any sign of intoxication. No deaths occurred. The individual body weights on day 7 and 14 indicated normal growth. Macroscopic examination of the survivors at autopsy did not reveal any treatment-related gross alterations. The oral LD50 value is greater than 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2011-09-22 to 2011-11-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 1997
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
30 May 2008
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, 97633 Sulzfeld, Germany
- Age at study initiation: Approximately 8 weeks (males) and 12 weeks (females)
- Weight at study initiation: males: 271 - 288 g; females: 222 - 244 g
- Fasting period before study: no
- Housing: Single caging in Makrolon cages type III (37.5 cm x 21.5 cm bottom area, 18 cm height). Wire mesh lids. Sanitation of cages once a week
- Diet: Ssniff R/M-H maintenance diet for rats and mice (item V1534-300) ad libitum, supplied by Ssniff Spezialdiäten GmbH, 59494 Soest, Germany
- Water: Tap water, from an automatic watering system, ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: Mean of 20.85 °C (continuous control and recording)
- Humidity: Mean of 41.49 % (continuous control and recording)
- Air changes: 12 per hour.
- Photoperiod: Artificial light from 6 a.m. to 6 p.m.

IN-LIFE DATES: From: 2011-10-11 To: 2011-10-25
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 6.5 x 8 cm
- % coverage: 10 % of estimated body surface
- Type of wrap if used: semi-occlusive dressing (Fixomull Stretch, Fa. Beiersdorf)

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test substance was wiped off using wet cellulose tissue
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: The amounts of the test substance were calculated and weighed for each individual using the body weights determined on the day of the administration
- For solids, paste formed: no
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed 0 - 0.5, > 0.5 - 1, > 1 - 2, > 2 - 4 and > 4 - 6 hours after administration of the test substance (p.a.) and then at least once a day for a total of 2 weeks.
Body weights were determined
• before administration.
• 7 days p.a.
• 14 days p.a.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived until the scheduled termination of the study.
Clinical signs:
General findings: All animals did not show any clinical signs during the entire observation period. Observations of skin condition: Exposed skin was not found to be altered by the test substance.
Body weight:
All animals gained weight in both weeks p.a.
Gross pathology:
No abnormal findings were made in the animals at terminal necropsy.
Other findings:
No noteworthy sex difference in the response to the test substance was derived from clinical observations or post-mortem findings.
Interpretation of results:
GHS criteria not met
Conclusions:
No local or systemic toxic effects related to administration of the test substance were noted from clinical observations or post mortem examination at a dose of 2000 mg of the test substance per kg body weight. No mortality occurred.
Executive summary:

The test item 1,1'-(1,1,2,2-tetramethylethylene)dibenzene was tested in an acute dermal toxicity study in rats according to OECD guideline 402 and EU method B.3. The test item was administered once topically on an area of approximately 6.5 cm x 8 cm on the dorsal thoracic region of 5 male and 5 female Sprague Dawley rats. The dose was 2000 mg per kg body weight. A cellulose patch with the calculated amount of the test substance on the surface and soaked with deionised water to get optimal contact with the skin, was applied to the test site and held in place by fixing marginally with non-irritating tape. The test site was covered by a semi-occlusive dressing. The duration of the exposure was 24 hours. No local or systemic toxic effects related to administration of the test substance were noted from clinical observations or post-mortem examination at a dose of 2000 mg of the test substance per kg body weight. No mortality occurred. Therefore, the LD50 dermal was estimated to be > 2000 mg /kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Additional information

Oral:

- Key study

The oral toxicity of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene was assessed according to OECD guideline 401 and EU method B.1. The test item was administered to one group of 3 male and 3 female Wistar rats by oral gavage, at a single dose of 2000 mg/kg bw. No mortality occurred, no clinical signs were observed and no macroscopic abnormalities were seen at necropsy. Based on these observations, the estimated acute oral toxicity LD50 of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene in rats of both sexes observed for a period of 15 days is greater than 2000 mg/kg bw.

- Supporting study

In an acute oral toxicity study, groups of fasted, young adult Wistar rats (10/sex) were given a single oral dose of 1,1'-(1,1,2,2-tetramethylethylene)dibenzene in polyethylene glycol at a limit doses 5000 mg/kg bw and observed for 14 days. The study was performed according to OECD 401. Clinical observations during the first 4 post-treatment hours and in the remaining part of the observation period did not reveal any sign of intoxication. No deaths occurred. The individual body weights on day 7 and 14 indicated normal growth. Macroscopic examination of the survivors at autopsy did not reveal any treatment-related gross alterations. The oral LD50 value is greater than 5000 mg/kg bw.

Inhalation:

Additional testing by inhalation route is not applicable as data for oral and dermal toxicity study are available. According to the REACH Regulation No. 1907/2006, Annex VIII, 8.5.1 only information on two application routes needs to be provided, with test item administration via the most appropriate route. Additionally, the vapour pressure of the test item is very low (calculated as 0.0153 Pa at 20 °C resp. 0.0265 Pa at 25 °C) and exposure via inhalation route is not expected.

Dermal:

The test item 1,1'-(1,1,2,2-tetramethylethylene)dibenzene was tested in an acute dermal toxicity study in rats according to OECD guideline 402 and EU method B.3. The test item was administered once topically on an area of approximately 6.5 cm x 8 cm on the dorsal thoracic region of 5 male and 5 female Sprague Dawley rats. The dose was 2000 mg per kg body weight. A cellulose patch with the calculated amount of the test substance on the surface and soaked with deionised water to get optimal contact with the skin, was applied to the test site and held in place by fixing marginally with non-irritating tape. The test site was covered by a semi-occlusive dressing. The duration of the exposure was 24 hours. No local or systemic toxic effects related to administration of the test substance were noted from clinical observations or post-mortem examination at a dose of 2000 mg of the test substance per kg body weight. No mortality occurred. Therefore, the LD50 dermal was estimated to be > 2000 mg /kg body weight.

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. The LD50 was greater than 2000 mg/kg bw for oral and dermal exposure. As a result the substance is not considered to be classified for acute oral toxicity and acute dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the twelfth time in Regulation (EU) No. 2019/521.