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Description of key information

In an acute oral toxicity study with cyclohexylidenebis[tert-butyl] peroxide in rats a LD50 value of 16653 mg/kg bw with a confidence interval of 11912 to 23279 mg/kg bw was determined. No acute inhalation study is available. In an acute dermal toxicity study with cyclohexylidenebis[tert-butyl] peroxide in rabbits a LD50 value of > 2000 mg/kg bw was determined.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978-07-24
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP or guideline compliant study (although similar to present OECD guideline)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Industries, Inc., Indianapolis, Indiana, USA
- Weight at study initiation: 200 - 253 g
- Fasting period before study: rats were fasted overnight before dosing (ca. 18 h)
- Housing: 5 animals/sex/cage; hanging wire-mesh cages
- Diet: Purina laboratory Chow, ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
Temperature and humidity controlled quarters were used for housing.
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle: 10 mL/kg bw (6810, 8260 mg/kg bw), 20 mL/kg bw (10000, 12100, 14700, 17800 mg/kg bw), 30 mL/kg bw (21500 mg/kg bw)

MAXIMUM DOSE VOLUME APPLIED: 30 mL/kg bw
Doses:
6810, 8260, 10000, 12100, 14700, 17800, 21500 mg/kg bw
No. of animals per sex per dose:
five rats/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 4 hours following dosing at 24 hours and daily thereafter for 14 days
- Necropsy of survivors performed: no
- Other examinations performed: body weight: recorded prior to dosing and at days 7 and 14
Statistics:
Statistics were performed using Thompson and Weil (1952).
Sex:
female
Dose descriptor:
LD50
Effect level:
13 342 mg/kg bw
Based on:
test mat.
95% CL:
10 895 - 16 338
Sex:
male
Dose descriptor:
LD50
Effect level:
> 21 500 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
16 653 mg/kg bw
Based on:
test mat.
95% CL:
11 912 - 23 279
Mortality:
No deaths occurred in dosing group 6.810 mg/kg bw. In dose group 8.260 mg/kg bw one animal died (female). 10.000 and 12.100 mg/kg bw caused a death to two out of ten animals (one male and female). In dosing group 14.700 mg/kg bw six rats died (two males, four females). The two highest dosing groups 17.800 mg/kg bw and 21.500 mg/kg bw caused the death of five animals each (one male, 4 females; two males, three females).
Clinical signs:
NA
Body weight:
All surviving rats gained weight during the study.
Gross pathology:
NA
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity study on Sprague-Dawley rats treated with 1,1-bis(tert-butylperoxy)cyclohexane resulted in a LD50 of above 2000 mg/kg bw for male and female rats.
Executive summary:

The acute oral toxicity of 1,1-Di(t-butyl peroxy) cyclohexane was evaluated in Sprague-Dawley rats. The test material was administered orally by gavage as a solution in com oil at the following dosage levels to male and female rats: 6810, 8260, 10000, 12100, 14700, 17800 and 21500 mg/kg.The rats were observed for mortality, only, during the first four hours following dosing, at 24 hours and daily thereafter for a total of 14 days. Body weights were recorded immediately prior to dosing (control weight) and at 7 and 14 days. All surviving rats gained weight during the study. The LD50 value for male and female animals was determined to be 16653 mg/kg bw with a 95 % confidence interval of 11912 to 23279 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
16 653 mg/kg bw
Quality of whole database:
The study is considered reliable with restrictions and equivalent to OECD 401.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
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:
2004-2005
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24th February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
31st July 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source/Breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 321 +/- 10 g for the males and 211 +/- 4 g for the females
- Fasting period before study: no data
- Housing: individually in polycarbonate cages with stainless steel lid (35.5 cm x 23.5 cm x 19.3 cm)
- Diet: free access to adapted pelleted diet
- Water: Drinking water filtered by a FG Millipore membrane (0.2 micron) was provided ad libitium.
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature: 22+/- 2 °C
- Humidity: 30 to 70 %
- Air changes: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod: 12 h light/12 h dark

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 cm x 7 cm for males and 5 cm x 6 cm for the females
- Type of wrap if used: an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage

TEST MATERIAL
- Amount(s) applied: 2.41 mL/kg
- Constant volume or concentration used: yes

Duration of exposure:
single
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day 15. Type, time of onset and duration of clinical signs were recorded for each animal individually. From day 2, any local cutaneous reaction was recorded.
The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs and no cutaneous reactions were observed during the study.
Body weight:
A slightly reduced body weight gain was seen in 2/5 females during the second week of the study.
Gross pathology:
Macroscopic examination of main organs of the animals revealed no apparent abnormalities.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD0 of the test item cyclohexylidenebis[tert-butyl] peroxide is higher than or equal to 2000 mg/kg in rats.
Executive summary:

The acute dermal toxicity of the test item cyclohexylidenebis[tert-butyl] peroxide was evaluated in rats according to OECD guideline No. 402 and EU method B.3. The test item was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females).

The application was performed with diluted test item at the dose-level of 2000 mg/kg, taking into consideration that its specific gravity was 0.83 g/mL. The test site was then covered by a semi-occlusive dressing for 24 hours.

Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test item. All animals were subjected to necropsy.

No clinical signs, no cutaneous reactions and no deaths were observed during the study. A slightly reduced body weight gain was seen in 2/5 females during the second week of the study. The overall body weight gain of the other animals was similar to that of CIT historical control animals. No apparent abnormalities were observed at necropsy in any animal.

The dermal LD0 of the test item cyclohexylidenebis[tert-butyl] peroxide is higher than or equal to 2000 mg/kg in rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
GLP study according to OECD/EU guideline. The study is considered as reliable without restrictions.

Additional information

Acute toxicity: oral

The acute oral toxicity of 1,1-Di(t-butyl peroxy) cyclohexane was evaluated in Sprague-Dawley rats. The test material was administered orally by gavage as a solution in com oil at the following dosage levels to male and female rats: 6810, 8260, 10000, 12100, 14700, 17800 and 21500 mg/kg.The rats were observed for mortality, only, during the first four hours following dosing, at 24 hours and daily thereafter for a total of 14 days. Body weights were recorded immediately prior to dosing (control weight) and at 7 and 14 days. All surviving rats gained weight during the study. The LD50 value for male and female animals was determined to be 16653 mg/kg bw with a 95 % confidence interval of 11912 to 23279 mg/kg bw.

Acute toxicty: inhalation

Additional testing by inhalation route is not applicable as data for oral and dermal toxicity study were 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 low (92 Pa at 58°C) and exposure via inhalation route is not expected.

Acute toxicity: dermal

The acute dermal toxicity of the test item cyclohexylidenebis[tert-butyl] peroxide was evaluated in Sprague-Dawley rats (males and females) according to OECD guideline No. 402 and EU method B.3. Diluted test item at the dose-level of 2000 mg/kg was applied (specific gravity: 0.83 g/mL). Semi-occlusive dressing for 24 hours. No clinical signs, no cutaneous reactions and no deaths were observed during the study. A slightly reduced body weight gain was seen in 2/5 females during the second week of the study. Overall body weight gain was similar to that of historical control animals. Thus, the dermal LD0 of the test item cyclohexylidenebis[tert-butyl] peroxide is higher than or equal to 2000 mg/kg in rats.


Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Based on the experimental data available the test item is not classified for acute oral, inhalation and dermal toxicity accodring to Regulation (EC) No 1272/2008 (CLP) .

The substance contains up to 25 % isododecane as stabilizer which is classified as aspiration toxicity cat. 1. Based on the kinematic viscosity of the substance and in accordance with the section 3.10.3 of Annex I of Regulation (EC) No 1272/2008 (CLP) the substance has to be classified as aspiration toxicity cat. 1, H304: May be fatal if swallowed and enters airways.