tert-butyl peroxypivalate

Endpoint summary

Description of key information

In an acute oral toxicits study with TBPPI in rats a combinded LD50 value of 4169 mg/kg bw was determined. The 4 hours LC50 was calculated to be 7.79 mg/L with 95 % confidence limits of 5.89 and 10.28 mg/L (exposure to mist). In an acute dermal toxicits study with TBPPI in rabbits a LD50 value of 2500 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:

July 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD TG 201

Principles of method if other than guideline:

5 doses were applied orally by gavage to rats, which were observed the following 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Industries, Inc. Indianapolis; Indiana
- Weight at study initiation: 200 to 248 g
- Fasting period before study: overnight period before administration of test item
- Housing: 5 rats per sex per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 8 days

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL to 20 mL

MAXIMUM DOSE VOLUME APPLIED: 20 mL

Doses:

1585; 2512; 3980; 6308 and 10000 mg/kg bw

No. of animals per sex per dose:

5 per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: during the first 4 hours, at 24 h and daily for a total of 14 days
- Frequency of weighing: prior to dosing and on day 7 and 14
- Necropsy of survivors performed: no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 169 mg/kg bw

Based on:

test mat.

95% CL:

> 3 587 - < 4 845

Mortality:

1585 mg/kg bw : 0/10
2512 mg/kg bw: 0/10
3980 mg/kg bw: 4/10
6308 mg/kg bw: 10/10
10000 mg/kg bw: 10/10

Clinical signs:

other: no data

Gross pathology:

no data

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicits study with TBPPI in rats a combinded LD50 value of 4169 mg/kg bw was determined.

Executive summary:

Twenty-five male and twenty- five female rats of the Sprague Dawley strain were used for an acute oral toxicity study. The test material was administered orally by gavage as a solution in corn oil at the following dosage levels to male and female rats: 1585; 2512; 3980 and 10000 mg/kg bw. Five rats of each sex were used at each dosage level. All the dosage levels were administered at a volume of 10 mL/ kg except for the high dose, which was administed at a volume of 20 mL/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 and at 7 and 14 days.

No animal died at the two lowest dosage levels. Four females died at the dosage level of 3980 mg/kg bw and all animals died in the two highest dosage levels.

The combined male and female acute oral LD50 value was 4169 mg/kg bw and the 95th confidence interval was 3587 - 4845 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

4 169 mg/kg bw

Quality of whole database:

sumilar to OECD 401/non-GLP

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

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Rats were exposed to a vapour atmosphere of the test item in an acute inhalation toxicity study.

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Charles River CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: male: 216 - 292 grams and female: 209 - 286 grams
- Housing: individually in compartmented wire-mesh exposure cages
- Diet: purina laboratory chow ad libitum
- Water: water ad libitum
- Acclimation period: at least week

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: a FMI Lab pump or a Harvard infusion pump
- Exposure chamber volume: 160 L
- Source and rate of air: 8 L/min

TEST ATMOSPHERE
- Brief description of analytical method used: The invidual concentratins 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.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

2.0, 4.2, 8.3, 17.1 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights were recorded prior to the 4 hour exposure and at 24 and 48 hours in order to detect any latent effects following the exposure.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

7.79 mg/L air (analytical)

Based on:

test mat.

95% CL:

5.89 - 10.28

Exp. duration:

4 h

Sex:

male

Dose descriptor:

LC50

Effect level:

5.07 mg/L air (analytical)

Based on:

test mat.

95% CL:

3.81 - 6.75

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Effect level:

> 8.3 - < 17.1 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: by inspection only as data were not suitable for calculation

Mortality:

At the concentration of 2.0 mg/L, no mortality was observed. At the concentration of 4.2 mg/L, one male rat died. At the concentration of 8.3 mg/L, five male rats died. At the concentration of 17.1 mg/L, all animals died.

Clinical signs:

other: Slight to marked dyspnea was observed in all groups of rats at the concentrations above 2.0 mg/L.

Body weight:

All rats lost weight following the exposures.

Gross pathology:

Necropsy of the dead rats revealed reddened lungs with dark red patches and discoloration of the liver.

Interpretation of results:

GHS criteria not met

Conclusions:

The 4 hours LC50 was calculated to be 7.79 mg/l with 95 % confidence limits of 5.89 and 10.28 mg/L (aerosol exposure).

Executive summary:

Tert-butyl peroxypivalate was tested in an acute inhalation toxicity study. Four groups of 5 male and 5 female rats were exposed to an aerosol atmosphere of tert-butyl peroxypivalate. The four "metered" concentrations were 17.1, 8.3, 4.2, 2.0 mg/L respectively. Slight to marked dyspnea and deaths were observed in all groups of rats at concentrations above 2.0 mg/L. All rats lost weight following the exposures. Necropsy of the dead rats revealed reddened lungs with dark red patches and discoloration of the liver. The 4 hours LC50 was calculated to be 7.79 mg/l with 95 % confidence limits of 5.89 and 10.28 mg/L.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

7 790 mg/m³ air

Physical form:

inhalation: aerosol

Quality of whole database:

similar to OECD 403/non-GLP

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:

July 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

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

5 doses were applied once only to the backs of rabbits for 24 hours and were observed the following 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: H.A.R.E. Rabbits for Research, Hewitt, New Jersey
- Weight at study initiation: 2300 to 2805 g
- Housing: individually in hanging wire-mesh cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 12 days

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- % coverage: 20 - 30% of body surface
- Type of wrap if used: gauze banding

REMOVAL OF TEST SUBSTANCE
- Washing: tepid tap water
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

1250; 2500; 5000; 10000 and 20000 mg/kg bw

No. of animals per sex per dose:

2 animals per sex per dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 24 hours and daily for 14 days
- Frequency of weighing: prior to test material administration and on day 7 and 14
- Necropsy of died animals performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 500 mg/kg bw

Based on:

test mat.

95% CL:

> 1 301 - < 4 806

Mortality:

1250 mg/kg bw: 1/4
2500 mg/kg bw: 1/4
5000 mg/kg bw: 4/4
10000 mg/kg bw: 4/4
20000 mg/kg bw : 4/4

Clinical signs:

other: Animals exposed up to 2500 mg/kg bw showed dermal irritations like moderate to marked erythema, edema, desquamation and necrosis, which were not reversible until day 14.

Gross pathology:

The animals died during the test exposed to doses higher than 5000 mg/ kg bw showed dermal irritation and ulceration and hyperemia of mucose of the stomach and discoloration of the liver. Males were more sensitive to the test item than females.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study with TBPPI in rabbits a LD50 value of 2500 mg/kg bw was determined.

Executive summary:

Twenty male and twenty female New Zealand White rabbits were used for an acute dermal toxicity study with TBPPI. The rabbits were divided into five groups of 2 male and 2 female rabbits each. The hair was removed from the back of each rabbit (20 -30% of the body surface) with an electric clipper. The test material was applied once only to the backs of the rabbits at the following dosage levels: 1250; 2500; 5000; 10000 and 20000 mg/ kg bw. Following dosing, the application sites were wrapped with gauze bandaging and overwrapped with Saran Wrap. 24 hours following application, the bandages were removed and the test sites were washed with tepid tap water. The rabbits were observed at 24 hours and daily thereafter for a total of 14 days for pharmacotoxic signs, mortality and dermal irritation. Body weights were recorded immediately prior to the test material administration and at 7 and 14 days of the observation period. All rabbits which died on study were subjected to gross necropsy examination.

All animals exposed to 5000 mg/kg bw and higher died during the testing period. One female and one male rabbit died in the lowest and the 2500 mg/kg bw dose level respectivly. In all surviving animals moderate to marked dermal irritation and necrosis occured and were not reversible until 14 days. Necropsy of died animals showed ulceration and hyperemia of the mucosa of the stomach and discoloration of the liver. No adverse effects on body weights of surviving animals could be observed.

The acute dermal LD50 values were 2500 mg/kg bw in males and females and the 95th confidence limits were 1250 - 5000 mg/kg bw in males and 625 - 10000 mg/kg bw in females.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Quality of whole database:

similar to OECD 402/GLP

Additional information

Oral:

Twenty-five male and twenty- five female rats of the Sprague Dawley strain were used for an acute oral toxicity study. The test material was administered orally by gavage as a solution in corn oil at the following dosage levels to male and female rats: 1585; 2512; 3980 and 10000 mg/kg bw. Five rats of each sex were used at each dosage level. All the dosage levels were administered at a volume of 10 mL/ kg except for the high dose, which was administed at a volume of 20 mL/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 and at 7 and 14 days. No animal died at the two lowest dosage levels. Four females died at the dosage level of 3,980 mg/kg bw and all animals died in the two highest dosage levels. The combined male and female acute oral LD50 value was 4169 mg/kg bw and the 95th confidence interval was 3587 - 4845 mg/kg bw.

 

Inhalation:

Tert-butyl peroxypivalate was tested in an acute inhalation toxicity study. Four groups of 5 male and 5 female rats were exposed to an aerosol atmosphere of tert-butyl peroxypivalate. The four "metered" concentrations were 17.1, 8.3, 4.2, 2.0 mg/L respectively. Slight to marked dyspnea and deaths were observed in all groups of rats at concentrations above 2.0 mg/L. All rats lost weight following the exposures. Necropsy of the dead rats revealed reddened lungs with dark red patches and discoloration of the liver. The 4 hours LC50 was calculated to be 7.79 mg/L with 95 % confidence limits of 5.89 and 10.28 mg/L. Furthermore, an acute inhalation toxicity study, published by Gage J.C. (1970) is available. Tert- butyl peroxypivalate was irritant to the eyes and respiratory tract but no mortality was observed with a concentration of 200 ppm (corresponding to 1.45 mg/L).

 

Dermal:

Twenty male and twenty female New Zealand White rabbits were used for an acute dermal toxicity study with TBPPI. The rabbits were divided into five groups of 2 male and 2 female rabbits each. The hair was removed from the back of each rabbit (20 -30% of the body surface) with an electric clipper. The test material was applied once only to the backs of the rabbits at the following dosage levels: 1250; 2500; 5000; 10000 and 20000 mg/ kg bw. Following dosing, the application sites were wrapped with gauze bandaging and overwrapped with Saran Wrap. 24 hours following application, the bandages were removed and the test sites were washed with tepid tap water. The rabbits were observed at 24 hours and daily thereafter for a total of 14 days for pharmacotoxic signs, mortality and dermal irritation. Body weights were recorded immediately prior to the test material administration and at 7 and 14 days of the observation period. All rabbits which died on study were subjected to gross necropsy examination. All animals exposed to 5000 mg/kg bw and higher died during the testing period. One female and one male rabbit died in the lowest and the 2500 mg/kg bw dose level respectivly. In all surviving animals moderate to marked dermal irritation and necrosis occured and were not reversible until 14 days. Necropsy of died animals showed ulceration and hyperemia of the mucosa of the stomach and discoloration of the liver. No adverse effects on body weights of surviving animals could be observed. The acute dermal LD50 values were 2500 mg/kg bw in males and females and the 95th confidence limits were 1250 - 5000 mg/kg bw in males and 625- 10000 mg/kg bw in females.

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 eighteenth time in Regulation (EU) 2022/692.

The substance contains up to 26 % 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 with as aspiration toxicity Cat. 1, H304: May be fatal if swallowed and enters airways.