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Description of key information

Tert-Butylperoxy-3,5,5-trimethylhexanoat was tested for acute toxicity by oral, inhalation and dermal application in fixed dose studies in the rat. The studies revealed an LD50 (oral) value of 12905 mg/kg bw an LC50 value (4 h, inhalation) of greater than 0.8 mg/L (800 mg/m³) and an LD50 (dermal) of greater than 2000 mg/kg bw.

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:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Institute's colony
- Weight at study initiation: Males: 219 to 348 g; females: 137 to 200 g
- Fasting period before study: Before dosing the rats were fasted overnight
- Housing: In groups of five in screen-bottomed stainless steel cages in a well-ventilated room, maintained at 23 - 25°C
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
NA
Doses:
12.1, 14.5, 17.4, 20.1, 25 mL/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
After treatment the rats received stock diet and tap water ad libitum. They were observed for signs of intoxication during a 14 day period, after which autopsies were carried out on the survivors. The LD50 was calculated according to the method of Weil (Biometrics 6 (1952) 249-263).
Statistics:
Not performed
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 14.5 - < 17.4 mL/kg bw
Remarks on result:
other: Calculated based on relative density of 0.89 g/mL
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 12 905 - < 15 486 mg/kg bw
Mortality:
Deaths occurred between 9 hours and 6 days after dosing. Thereafter, the survivors recovered gradually and looked quite healthy again at the end of the observation period.
Clinical signs:
other: Within a few hours after treatment the rats showed sluggishness and decreased activity. Thereafter slight diarrhoea, humpback behaviour, rough coats and loss of consciousness were frequently observed.
Gross pathology:
Macroscopic examination of the survivors revealed no treatment-related gross alterations.

The doses applied and the mortality-figures are shown in the table below:


 
















































dose (mL/kg)



mortality



number



%



males



females



12.1



0/5



3/5



30



14.5



1/5



3/5



40



17.4



5/5



3/5



80



20.8



4/5



5/5



80



25



5/5



5/5



100


Interpretation of results:
not classified
Conclusions:
From the mortality-figures the LD50 of tert-Butylperoxy-3,5,5-trimethylhexanoat was between 14.5 and 17.4 mL/kg bw, corresponding to 12905 - 15486 mg/kg bw. Therefore, the material can be classified as relatively harmless.
Executive summary:

Young adult albino rats (Wistar derived) from the Institute's colony were used to determine the acute oral toxicity of tert-Butylperoxy-3,5,5-trimethylhexanoat. After some preliminary observations, the test material was given undiluted by gavage to groups of five males and five females in single doses of 12.1, 14.5, 17.4, 20.1 or 25 mL/kg bw. After treatment the rats received stock diet and tap water ad libitum. They were observed for signs of intoxication during a 14 day period, after which autopsies were carried out on the survivors.

Within a few hours after treatment the rats showed sluggishness and decreased activity. Thereafter slight diarrhoea, humpback behaviour, rough coats and loss of consciousness were frequently observed. Deaths occurred between 9 hours and 6 days after dosing. Thereafter, the survivors recovered gradually and looked quite healthy again at the end of the observation period. Macroscopic examination of the survivors revealed no treatment-related gross alterations.

From the mortality-figures the LD50 of tert-Butylperoxy-3,5,5-trimethylhexanoat was between 14.5 and 17.4 mL/kg bw, corresponding to 12905 - 15486 mg/kg bw. Therefore, the material can be classified as relatively harmless.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
12 905 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system 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: about 235 g, females: about 160 g
- Housing: stainless steel/ glass exposure chamber; five male and five female rats in separate wire screen cages
Route of administration:
inhalation: mist
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel/ glass aerodynamic nozzle nebulizer
- Exposure chamber volume: 1.5 m3
- Airflow rate: 3 m3/ h

TEST ATMOSPHERE
- Brief description of analytical method used: Samples of the atmosphere were drawn through a Bergshoeff air-sampler filled with xylene and subsequently analysed by gas-liquid chromatography with the aid of an Intersmat gaschromatograph with a QF-1 (4.8% diglycerol on a chromosorb G-AW-DMCS) stainless-steel column.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
No data
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: no
Statistics:
not performed
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.8 mg/L air
Exp. duration:
4 h
Mortality:
No mortality occurred
Other findings:
During the first half hour of the exposure period the rats were somewhat restless. This symptom gradually disappeared and after one hour all rats were asleep. This situation continued throughout the remainder of the exposure period.
Since no mortality occurred during the 4 hours of the exposure and the subsequent observation period, the 4 hour LC 50 could not be determined.
Interpretation of results:
not classified
Conclusions:
The results of the present acute inhalation study lead to the conclusion that the 4-hour LC 50 of tert-Butylperoxy-3,5,5-trimethylhexanoat is higher than 0.8 mg/L of air.
Executive summary:

The acute inhalation toxicity of tert-Butylperoxy-3,5,5-trimethylhexanoat was studied by exposing rats for 4 hours to an aerosol of the undiluted substance at a concentration of 0.8 mg/L of air.

No mortality occurred and no signs of intoxication were observed.

It was concluded that the 4 -hour LC 50 of tert-butyl 3,5,5-trimethylperoxyhexanoate was higher than 0.8 mg/L of air.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
800 mg/m³ air

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:
1998-06-24 to 1998-07-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Iffa Crédo, 69210 L'Arbresle, France
- Age and Weight at study initiation: On the day of treatment, the animals were approximately 8 weeks old, and had a mean body weight ± standard deviation of 255 ± 3 g for the males and 222 ± 11 g for the females.
- Fasting period before study:
- Housing: During the acclimatization period, four to seven animals of the same sex were housed in polycarbonate cages (48 cm x 27 cm x 20 cm). During the treatment period, the animals were housed individually in polycarbonate cages (35.5 cm x 23.5 cm x 19.3 cm)
- Diet: All the animals had free access to A04 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France).
- Water: Drinking water filtered by FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimatization: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 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: females: 5 cm x 6 cm; males: 5 cm x 7 cm
- % coverage: approximately 10 %
- Type of wrap if used: A hydrophilic gauze pad was applied to the skin. The test substance and the gauze pad were held in contact with the skin for 24 hours by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At least once a day until day 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not performed
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No death occurred during the study
Clinical signs:
other: No clinical signs and no cutaneous reactions were observed during the study.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions, the dermal LD0 of the test substance tert-Butylperoxy-3,5,5-trimethylhexanoat is equal to or higher than 2000 mg/kg in rats.
Executive summary:

Tert-Butylperoxy-3,5,5-trimethylhexanoat was tested in a single dermal application to rats. The application was performed with the undiluted test substance at the dose of 2000 mg/kg, taking into consideration that its specific gravity was 0.89. 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 substance. All animals were subjected to necropsy.

No death occurred at 2000 mg/kg. No clinical signs were observed. The body weight gain of one female was reduced between day 1 and 15 and another female lost weight during this same period. The overall body gain of the other animals was not affected by treatment with the test substance. No cutaneous reactions were observed. No apparent abnormalities were observed at necropsy.

Under these experimental conditions, the dermal LD0 of the test substance tert-Butylperoxy-3,5,5-trimethylhexanoat is equal to or higher than 2000 mg/kg in rats.

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

Additional information

Oral:


TBPIN was examined in an acute toxicity studysimilar or equivalent to OECD guideline 401. Five males and five females were administered with the test substance by gavage in single doses of 12.1, 14.5, 17.4, 20.1 or 25 mL/kg bw. No mortality and adverse effects were observed during the 14 days observation period and not in the autopsies. The LD50 was 12905 mg/kg bw.


 


Oral LD50: 12905 mg/kg bw


 


Dermal:


TBPIN was examined in an acute dermal toxicity study according to EU method B.3 and OECD guideline no. 402. Five male and five female Sprague-Dawley rats were treated in a semi-occlusive dressing with the undiluted test substance at a dose level of 2000 mg/kg. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test substance. All animals were subjected to necropsy.


No death occurred at the examined dose level of 2000 mg/kg and no clinical signs were observed. The body weight gain of one female was reduced between day 1 and 15 and another female lost weight during this same period. The overall body gain of the other animals was not affected by treatment with the test substance. No cutaneous reactions were observed. No apparent abnormalities were observed at necropsy. Under the study conditions, a dermal LD50 of greater than 2000 mg/kg was determined.


 


Dermal LD50: > 2000 mg/kg bw


 


Inhalation:


The acute inhalation toxicity was studied by exposing rats for 4 hours to aerosols of the diluted test substance at a concentration of 0.8 mg/L of air in a study which was performed similarly or to EU method B.2.No mortality occurred and no signs of intoxication were observed. It was concluded that the 4-hour LC 50 of TBPIN was higher than 0.8 mg/L (800 mg/m³) air.


 


Inhalation LC50 (4h): > 800 mg/m³

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. Based on available data the test item is not classified for acute toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the seventeenth time in Regulation (EU) 2021/849.