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Administrative data

Description of key information

Tert.-Butylperoxy-2-ethylhexanoatwas tested for acute toxicity by oral, inhalation and dermal application in fixed dose studies in the rat. These studies revealed LD50 (oral) of > 10000 mg/kg bw, a LD50 (dermal) of 16.82 g/kg bw and a LC50 (inhalation) of 42.2 mg/L air (42200 mg/m³ air).

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
NA
GLP compliance:
not specified
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: Harlan Industries, Inc. Indianapolis, Indiana
Housing: rats were housed by sex in 5 rats per cage, in temperature and humidity controlled quarters
Conditioning period: 8 days prior to study initiation
Fasting period: about 18 h over night prior to oral administration
Body weights prior to administration: males 210 - 250 g; females 210 - 250 g
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
NA
Doses:
10000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Rats were observed for mortality during the first four hours after administration and daily for a total of 14 days. Body weights were recorded immediately prior to dosing (control weight) and at 7 and 14 days.
Statistics:
NA
Preliminary study:
No preliminary study
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 10 000 mg/kg bw
Mortality:
None of the ten rats died during the 14 day study period. The minimum lethal dose by the oral route of administration was found to be greater than
10000 mg/kg bw.
Clinical signs:
NA
Body weight:
No adverse effects on body weight observed.
Gross pathology:
NA
Other findings:
NA

No remarks

Interpretation of results:
GHS criteria not met
Conclusions:
None of the test animals died during the 14 day study period. Thus the LD50 > 10000 mg/kg bw.
Executive summary:

Tert.-Butylperoxy- 2-ethylhexanoat was administered to 5 male and 5 female Sprague-Dawley rats at a dose of 10000 mg/kg bw. The test material was administered orally by gavage as a solution in corn oil. The rats were observed for mortality during the first four hours after administration and daily thereafter for a total of 14 days. Body weights were recorded immediately prior to dosing (control weights) and at 7 and 14 days.

None of the animals died during the 14 day study period. Thus, the minimum lethal dose as well as the LD50 are > 10000 mg/kg bw. No adverse effects related to the body weights were observed. The LD0 was >= 10000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
10 000 mg/kg bw
Quality of whole database:
Although the study was not conducted in compliance with GLP and the respective OECD guideline, the data available are considered sufficient for the assessment of acute oral toxicity of the test substance.

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:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
May 1981
Deviations:
yes
Remarks:
only limited data about analytics
Principles of method if other than guideline:
NA
GLP compliance:
no
Test type:
other: standard acute method
Limit test:
no
Species:
rat
Strain:
other: Charles River CD
Sex:
male/female
Details on test animals and environmental conditions:
- Weight: male 216 to 300 g; females 200 to 299 g
- Housing: wire-mesh cages
- Diet and water (e.g. ad libitum): Purina Laboratory Chow and water (ad libitum)
- Acclimation period: 4 hour


Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
- Exposure apparatus: FMI LAB pump
- Exposure chamber volume: 160-liter cubical
- Rate of air: 8 L/min
- Pressure in air chamber: 10 psig


Analytical verification of test atmosphere concentrations:
no
Remarks:
The individual concentrations of the compound in the chamber atmosphere were calculated from the ratio of the rate of liquid dissemination to the rate of total chamber airflow.
Duration of exposure:
4 h
Concentrations:
"metered" conc.: 9.2, 20.8, 46.5 and 103.4 mg/L
No. of animals per sex per dose:
5 animals per sex per dose (total: 20 animals)
Control animals:
not specified
Details on study design:
95 % confidence limits
Preliminary study:
No preliminary study
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
42.2 mg/L air
95% CL:
28.4 - 62.9
Exp. duration:
4 h
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
42.2 mg/L air
95% CL:
25.2 - 70.7
Exp. duration:
4 h
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
42.2 mg/L air
95% CL:
30.8 - 58
Exp. duration:
4 h
Mortality:
All animals (5 male, 5 females) died during the 14 day study period at the chamber concentration of 103.4 mg/L.
Further animals (6 animals) died at the chamber concentrations of 20.8 (1 female) and 46.5 mg/L (2 females, 3 male).
Clinical signs:
Exposure concentration (103.4 mg/L): By 30 minutes of exposure, a nasal discharge was observed in all rats. Slight dyspnoea was observed in 4 rats by 3 hours of exposure and in all rats by 4 hours of exposure. Redness was observed in the ears and the paws of all rats shortly after exposure. Four male and 4 female rats were found dead on day 1 postexposure. The two remaining rats exhibited decreased activity, slow breathing, slight dyspnoea and prostration.

Exposure concentration (46.5 mg/L): After 60 minutes of exposure a nasal discharge was seen in all male rats. By 3.5 hours of exposure, nasal discharge was seen in 4 female rats and slight dyspnoea was seen in 4 male and 3 female rats. Slight dyspnoea was seen in all rats by the end of the 4-hour exposure. The slight dyspnoea persisted and erythema developed shortly after exposure. Two male rats and 1 female rat were found dead on day 1 postexposure. Prostration, slow breathing and decreased activity were observed in 1 male and 1 female rat on day 1 postexposure. The male rat was found dead on day 2 postexposure and the female rat on day 3 postexposure. The remaining rats exhibited slight dyspnoea for 3-7 days postexposure but all appeared normal by the end of the 14 day observation period.
Exposure concentration (20.8 mg/L): A nasal discharge was observed in 8 rats by 30 minutes of exposure and in all rats by 60 minutes of exposure. by 2.5 hours, slight dyspnoea was noted in rats. Slight dyspnoea was observed in all rats by 3.5 hours and persisted until day 2 postexposure. One female rat exhibited prostration on day 1 postexposure and was found dead on day 2 postexposure. No other rats died during the 14-day observation period.
Exposure concentration (9.2 mg/L): A nasal discharge was observed in 1 male rat by 1.5 hours of exposure and in 3 additional rats by 3.5 hours. Slight dyspnoea was observed in 4 male rats by the end of the 4-hour exposure. This condition persisted for periods up to 6 days postexposure.
Body weight:
Exposure concentration (103.4 mg/L): A slight body weight loss was observed for day 1 postexposure.
Exposure concentration (46.5 mg/L): A slight body weight loss was observed for day 1 postexposure. This condition persisted for 7 days in the surviving rats.
Exposure concentration (20.8 mg/L): A slight body weight loss was observed in all rats for day 1 postexposure.
Exposure concentration (9.2 mg/L): A slight body weight loss was observed for day 1 postexposure which persisted for 5 days for 3 male rats and 14 days for 1 female rat.
Gross pathology:
Exposure concentration (103.4 mg/L): Necropsy of the rats revealed red patches in the lungs.
Exposure concentration (46.5 mg/L): Necropsy of the rats which died revealed pink lungs with dark red patches.
Exposure concentration (20.8 mg/L): Necropsy of the 1 female rat revealed 2 large red patches on the left lung.
Other findings:
NA

No remarks

Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 was calculated to be 42.2 mg/L with 95% confidence limits of 30.8 and 58.0 mg/L.
Executive summary:

Four groups of male and female rats were exposed to the aerosol and vapour atmospheres of tert.-Butylperoxy- 2-ethylhexanoat. The four "metered" concentrations were 103.4, 46.5, 20.8 and 9.2 mg/L, respectively. During the 4 -hour exposures, nasal discharge and slight dyspnoea were observed in all groups of rats. Redness of ears and paws developed shortly after exposure in all rats exposed to 103.4 and 46.5 mg/L. Death occurred in all groups on 1 or 2 days postexposure at concentrations above 9.2 mg/L.

The LC50 was calculated to be 42.2 mg/L with 95% confidence limits of 30.8 and 58.0 mg/L.

Necropsy of the rats that died during the observation period revealed red patches in the lungs.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
42 200 mg/m³
Quality of whole database:
Although the study was not conducted in compliance with GLP and the respective OECD guideline, the data available are considered sufficient for the assessment of acute toxicity by inhalation of the test substance.

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:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
NA
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
Source: H.A.R.E. Rabbits for Research, Hewitt, New Jersey or Kuiper's Rabbit Ranch, Gary, Indiana
Housing: rabbits were individually housed in hanging wire-mesh cages in temperature and humidity controlled quarters
Conditioning period: 13 days prior to study initiation
Diet: ad libitum
Water: ad libitum
Body weights prior to administration: 2300 to 2804 g
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back of each rabbit
- % coverage: 20 - 30 % of the body surface
- Type of wrap if used: the application sites were wrapped with gauze bandaging and overwrapped with Saran Wrap. The entire application area was then wrapped with Several layers of 75 mm Elastoplast tape. A collar was also applied.


REMOVAL OF TEST SUBSTANCE
- 24 hours following application, the bandages and collars were removed and the test sites were washed with tepid tap water


Duration of exposure:
24 hours
Doses:
2.5, 5, 10 and 20 g/kg bw
No. of animals per sex per dose:
2 animals per sex per dose (total: 8 animals)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: pharmaceutical signs, mortality, dermal irritation
Statistics:
95% Confidence limits
Preliminary study:
No preliminary study
Sex:
female
Dose descriptor:
LD50
Effect level:
14 142 mg/kg bw
95% CL:
> 7 071 - < 28 284
Sex:
male
Dose descriptor:
LD50
Effect level:
20 000 mg/kg bw
95% CL:
> 10 000 - < 40 000
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
16 818 mg/kg bw
95% CL:
> 11 892 - < 23 784
Mortality:
3 animals (2 females, 1 male) died during the 14 day study period at a dosage level of 20 g.
Clinical signs:
NA
Body weight:
NA
Gross pathology:
NA
Other findings:
NA

No remarks

Interpretation of results:
GHS criteria not met
Conclusions:
Eight male and 8 female New Zealand White rabbits were used for this study. The rabbits were divided into 4 groups of 2 male and 2 female rabbits each. The test material was applied once only to the backs of the rabbits at the following dosage levels: 2.5, 5, 10 and 20 g/kg.
Based upon the data obtained, the acute dermal LD50 values and 95% confidence limits (CL) were estimated to be as follows:
male rabbits: 20 g/kg bw with 95%CL of 10 - 40 g/kg bw
female rabbits: 14.14 g/kg bw with 95%CL of 7.07 - 28.28 g/kg bw
Combined male and female rabbits: 16.82 g/kg with 95%CL of 11.89 - 23.78 g/kg
Executive summary:

Tert.-Butylperoxy- 2-ethylhexanoat was tested to eight male and 8 female New Zealand White rabbits were used for this study. The rabbits were divided into 4 groups of 2 male and 2 female rabbits each. The test material was applied once only to the backs of the rabbits at the following dosage levels: 2.5, 5, 10 and 20 g/kg.

Based upon the data obtained, the acute dermal LD50 values and 95% confidence limits (CL) were estimated to be as follows:

male rabbits: 20 g/kg bw with 95%CL of 10 - 40 g/kg bw

female rabbits: 14.14 g/kg bw with 95%CL of 7.07 - 28.28 g/kg bw

Combined male and female rabbits: 16.82 g/kg with 95%CL of 11.89 - 23.78 g/kg

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
16 820 mg/kg bw
Quality of whole database:
Although the study was not conducted in compliance with GLP and the respective OECD guideline, the data available are considered sufficient for the assessment of acute dermal toxicity of the test substance.

Additional information

Oral:

Tert.-Butylperoxy-2-ethylhexanoat was assumed in an acute toxicity study, similar to OECD guideline 401.

Five male and 5 female Sprague-Dawley rats were treated with tert.-Butylperoxy-2-ethylhexanoat by single oral (gavage) administration at a dose level of 10000 mg/kg bw using corn oil as a vehicle.

The rats were observed for mortality during the first four hours after administration and daily thereafter for a total of 14 days. Body weights were recorded immediately prior to dosing (control weights) and at 7 and 14 days. None of the animals died during the 14 day study period. Thus, the minimum lethal dose as well as the LD50 were > 10000 mg/kg bw. No adverse effects related to the body weights were observed. The LD0 was >= 10000 mg/kg bw.

Oral LD50: > 10000 mg/kg bw

Dermal:

Tert.-Butylperoxy-2-ethylhexanoat was examined in an acute dermal toxicity study, similar to OECD Guideline 402. Eight male and eight female New Zealand White rabbits were treated with tert.-Butylperoxy-2-ethylhexanoate at dosage levels up to 2000 mg/kg bw. The exposure period was 24 hours. Animals were observed for 14 days after treatment. Based upon the data obtained, the acute dermal LD50-values 20000 mg/kg bw for male and 14142 mg/kg bw for female.

Dermal LD50: 20000 mg/kg bw (male); 14142 mg/kg bw (female)

Inhalation:

In the first study, four groups of male and female rats were exposed to aerosol of tert.-Butylperoxy-2-ethylhexanoat.

Concentrations were 103.4, 46.5, 20.8 and 9.2 mg/L, respectively. Nasal discharge and slight dyspnoea were observed in all groups of rats. Redness of ears and paws developed shortly after exposure in all rats exposed to 103.4 and 46.5 mg/L. Death occurred in all groups on 1 or 2 days postexposure at concentrations above 9.2 mg/L. The LC50 was calculated to be 42.2 mg/L with 95% confidence limits of 30.8 and 58.0 mg/L. Necropsy of the rats that died during the observation period revealed red patches in the lungs.

In the second study, tert-butyl 2 -ethylperoxyhexanoate showed a LC50 of > 200 mg/L and LC0 >= 200 mg/L. In this study, tert.-Butylperoxy-2-ethylhexanoat was examined for acute inhalation toxicity in ten male Spartan rats. Animals were exposed to a single aerosol concentration of 200 mg/L for 4 hours.

Inhalation LC50 (4h): 42200 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 on acute oral, dermal and inhalation toxicity, the test item does not require classification according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.