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Administrative data

Description of key information

Two acute oral toxicity studies are available in which animals were dosed up to 10 g/kg bw. The lowest LD50 from these studies is 4270 mg/kg bw. An acute inhalation toxicity study in rats shows that exposure to Tert- Amyl peroxypivalate at a concentration of 9.5 g/m3 air during four hours did not result in mortality or in any other major sign of intoxication. The dermal LD50 is greater than 2000 mg/kg. Since one death is observed at 2000 mg/kg.

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:
Date: September 25, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
other: Conducted in accordance with the regulations for Good Laboratory Practices as described by the FDA (21 CFR Part 58) and FDRL Standard Operating Procedures
Principles of method if other than guideline:
Animals were individually housed in wire mesh bottom cages in environment controlled rooms as per "Guide for the care and Use of Laboratory Animals" DREW .Publication No. (NIH) 78-23.
Animals were fasted overnight {approximately 18 hours ) prior to receiving a single oral dose of the test article.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
FDRL Test Article ID: 81-0558
Sponsor Test Article ID: TA-54M75; tert-amyl peroxypivalate 75% in odorless mineral spirit
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
A sufficient number of young adult male and female Sprague-Dawley rats were purchased from Charles River Breeding Laboratories, Wilmington, MA. After an acclimation period of approximately 3 - 5 days , the animals were assigned to groups of one male and one female at five dose levels for the preliminary study, and a sufficient number of males and females at five dose levels for the principal study.

Animals were individually housed in wire mesh bottom cage s in environment controlled rooms as per "Guide for the Care and Use of Laboratory Animals" DHEW Publication No. (NIH) 78-23.
Animals were fasted overnight (approximately 18 hours) prior to receiving a single oral dose of the test article.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
Preliminary:
1.0, 1.5, 2.24, 3.34 and 5.0 mg/kg.

Main:
3.0, 3.41, 3.87, 4.40 and 5.0 mg/kg
No. of animals per sex per dose:
Preliminary
1 male and 1 female per dose.

Main
5 males and 5 females per dose.
Control animals:
not specified
Details on study design:
Observations
All animals on the main study were observed for 15 days. They were observed three times on the day of dosing, twice on the fol lowing day and once daily for the remainder of the study. All gross or visible toxic or pharmacological effects were recorded. Body weights were recorded initially and on day 15 or at death.

Sacrifice and Necropsy
All animals that died during the study were subjected to a gross necropsy. All abnormalities were recorded.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4.27 other: g/kg bw
Based on:
test mat.
95% CL:
>= 3.85 - <= 5.18
Mortality:
Preliminary:
Mortality = 2/2 at 5.0 mg/kg

Main:
Mortality at: 3.0 mg/kg = 1/10
3.41 mg/kg = 3/10
3.87 mg/kg = 2/10
4.40 mg/kg = 5/10
5.0 mg/kg = 8/10
Clinical signs:
See table in "Any Other Information on Results"
Body weight:
See table in "Any Other Information on Results"
Gross pathology:
See table in "Any Other Information on Results"

Preliminary search

Dosage level (g/kg)

1.0

1.5

2.24

3.34

5.0

Mortality after 7 days

0/2

0/2

0/2

0/2

2/2

Two rats per dosage level

LD50Assay

Dosage Level

g/kg

Time of Death

Cumulative Mortality

Day

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

3.0

0

0

0

0

0

1

0

0

0

0

0

0

0

0

0

1/10

3.41

1

0

2

0

0

0

0

0

0

0

0

0

0

0

0

3/10

3.87

0

0

0

0

1

0

1

0

0

0

0

0

0

0

0

2/10

4.40

0

1

4

0

0

0

0

0

0

0

0

0

0

0

0

5/10

5.0

1

2

2

2

1

0

0

0

0

0

0

0

0

0

0

8/10

Ten rats (5 male and 5 female) per dosage level.

Mean Body weight data

Sex and Dosage Level

g/kg

Initial (grams)

Day 15 (grams)

At Death (grams)

Male

3.0

243.4 ± 7.8 (5)

307.6 ± 12.3 (5)

-

3.41

248.6 ± 16.8 (5)

325.2 ± 20.1 (5)

-

3.87

288.6 ± 37.1 (5)

347.6 ± 42.9 (5)

-

4.40

287.6 ± 22.5 (5)

341.2 ± 27.0 (5)

-

5.0

284.8 ± 30.6 (5)

366.0 (1)

252.8 ± 41.1 (4)

Female

3.0

230.8 ± 7.0 (5)

267.0 ± 8.1 (4)

186.0 (1)

3.41

216.8 ± 21.5 (5)

261.0 ± 55.2 (2)

201.3 ± 11.1 (3)

3.87

203.8 ± 10.8 (5)

242.7 ± 22.0 (3)

164.5 ± 9.2 (2)

4.40

198.8 ± 12.1 (5)

-

181.6 ± 10.9 (5)

5.0

211.0 ± 11.9 (5)

242.0 (1)

194.5 ± 13.2 (4)

Summary of observations

Dosage Level g/kg

Clinical Observations

Necropsy Observations

2.0

Decreased activity

(5M & 5F),

Salivation (3M & 3F) ,

Ataxia (5M & 5F) ,

Diarrhoea (4M & 3F) ,

Urinary incontinence

(1M & 3F), Deaths (1F)

Intestines: contain

blood like viscous

liquid (1F) .

3.41

Decreased activity

(5M & 5F),

Ataxia (5M & 5F),

Diarrhoea (3M & 4F),

Deaths (3F).

Intestines: contain

blood like viscous

liquid (1F) .

3.87

Decreased activity

(5M & 5F),

Ataxia (5M & 5F) ,

Diarrhoea (3M & 5F),

Rectal area red in

color (3M & 5F),

Urinary incontinence

(3M & 4F),

Salivation (2M & 2F),

Deaths (2F).

Intestines: contain

blood like viscous

liquid (2F).

4.40

Decreased ac tivity

(5M & 5F),

Ataxia (5M & 5F),

Diarrhoea (3M & 3F),

Salivation (2M & 2F),

Lacrimation (4F),

Deaths (5F) .

Intestines: contain

bloodlike viscous

liquid (3F).

Bladder: contains bloodlike liquid (2F).

5.0

Decreased activity

(5M & 5F),

Ataxia (5M & 5F),

Diarrhoea (4M & 5F),

Urinary incontinence

(4M & 1F),

Rectal area red in

color (3M & 3F),

Lacrimation (3M & 1F),

Deaths (4M & 4F) .

Intestines: contain

bloodlike viscous

liquid (3F).

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The oral LD50 is 4270 mg/kg. This warrants classification in category 5 according to GHS criteria (table 3.1.1 note g-ii).
Executive summary:

Acute Oral LD50 (g /kg): 4.27

95% Confidence Intervals: 3.85 - 5.18

Slope: 8.58

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
4 270 mg/kg bw
Quality of whole database:
two K2 studies are available

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:
other: Non-GLP study with adequate details. No COA however the test article was described as tert-amyl peroxypivalate.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Five male a.nd five female SPF-reared rats (Cpb: WU, Wistar Random) were obtained from the Central Institute for the Breeding of Laboratory Animals TNO, Zeist, The Netherlands. At the beginning of the study the mean body weight of the males was 16.8 g and that of the females 142 g. During the observation period the animals were kept in stainless steel cages. (5 to a cage), which were suspended in an open rack in an animal room. They received ad libitum the Institute's stock diet for rats and bottled unfluoridated water. During the exposure. the animals were deprived o.f water and food. The temperature and the relative humidity in the animal room were set and controlled at 21 +/- 1 °C and 50 - 60 per cent, respectively.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
The animals w.ere exposed in a stainless steel exposure chamber having a capacity of 1.5 m3 under dynamic airflow conditions. Through a glass door at the front of the exposure chamber the animals could be observed continuously durtng the exposure period. The front door is provided with several openings for taking samples of the test atmosphere at different locations.

During the exposure the animals were housed in wire mesh stainless steel
cages, which were suspended in a rack in the exposure chamber. Individual
housing was used to prevent crowding and to minimise filtration of
inspired air by the animals' fur.

Tert- Amylperoxypivalate was dispersed to a fine mist by means of a
stainless steel glass aerodynamic nozzle nebuliser, operated at a
pressure of 5 atm giving an airflow rate of 2.2 m3/h. The nebuliser was
provided with a baffle in order to prevent the larger droplets from
entering into the test atmosphere of the inhalation chamber. The mist was
passed through the exposure chamber with a total airflow of 2.4m3/h.

The concentration of Tert- Amyl peroxypivalate in a sample of the test
atmosphere was determined according to a method provided by the sponsor.
A sample of the test atmosphere was obtained by passing a measured quantity
of this air through an impinger filled with xylene.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
9.5 g/m3 air
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The animals were exposed to the test material for 4 hours. After the exosure period the animals were returned to their living cages for an observation period of 2 weeks. During this period the body weight of the animals was recorded at days 1, 2, 4, 7 and 14. At the end of the observation period the animals were killed by exsanguination from the abdominal aorta under ether anaesthesia, autopsied and examined for gross pathological changes.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 9 500 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the exposure period and the subsequent observation period of 14 days.
Clinical signs:
other: During the last two hours of the exposure period the animals showed laboured respiration, but they recovered completely whithin a couple of hours after termination other exposure.
Body weight:
Both males and females lost body weight during the first day of the observation period, and thereafter they grew in a normal way.
Gross pathology:
Gross examination at autopsy did not reveal any abnormalities that were considered to be treatment-related.
Interpretation of results:
GHS criteria not met
Conclusions:
The results of the present acute inhalation toxicity study in rats allow the conclusion that exposure to Tert- Amyl peroxypivalate at a concentration of 9.5 g/m3 air during four hours did not result in mortality or in any other major sign of intoxication.
Executive summary:

1. The acute inhalation toxicity of Tert- Amyl peroxypivalate was studied by exposing male and female rats one single time for 4 hours. to an atmosphere containing an aerosol of Tert-Amyl peroxypivalate.

2. Exposure of rats to the maximum attainable concentration of 9.5 g/m3 air did not result in mortality or any other major sign of intoxication.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
one K2 study is 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:
Date: September 24, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
other: Conducted in accordance with the regulations for Good Laboratory Practices as described by the FDA (21 CFR Part 58) and FDRL Standard Operating Procedures.
GLP compliance:
yes
Test type:
standard acute method
Specific details on test material used for the study:
FDRL Test Article ID: 81-0558
Sponsor Test Article ID: TA-54M75; tert-amyl peroxypivalate 75% in odorless mineral spirit
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
Five male and 5 female adult New Zealand White rabbits, weighing between 2.0 and 4.0 kg, were purchased from H.A.R.E. - Rabbits for Research, Hewitt, N.J. for use in this-study. H.A.R.E. - Rabbits is a USDA approved supplier.
All animals were acclimated a minimum of 5 days. During this acclimation period, the rabbits were examined with respect to their general health to assure their suitability as test animals. The rabbits were housed individually
in wire mesh bottom cages. NIH Animal Feed A (certified) and water were provided ad libitum. Animals were identified by use of ear tags and cage cards.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The back and flanks of each rabbit were clipped free of fur with electrical clippers not more than 24 hours before study initiation. The clipped area constituted approximately 30 percent of the total body surface.
On the day of testing and just prior to the application of the test article, abrasion of the skin was performed on the exposure sites of 3 males and 2 female rabbits. The skin of the remaining 2 male and 3 female rabbits was left intact. Abrasions were made with the point of a 22 gauge disposable hypodermic needle. The abrasions were minor incisions through the stratum corneurn that were not sufficiently deep enough to disturb the derma or to produce bleeding.
The test article was administered under an occlusive binder at a level of 2.0 g/kg. The occlusive binder consisted of a layer of plastic wrap, a protective cloth and stockinette binder, all securely held in place with masking tape. The occlusive binder is applied to maintain contact and minimize evaporation of the applied test article.
If the test article was solid, it was moistened with physiological saline, (1 ml saline per 1 g of test article) before dermal application. Liquid test articles are administered as received.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
no
Details on study design:
After an exposure period of 24 hours the occlusive binders were-removed. The exposure sites were then gently wiped with clean gauze to remove as much nonabsorbed test article as possible. Observations for mortality, local reactions, and toxicological findings were recorded for a total of 14 days. Body weights were recorded on the initial day of testing, day 8 and at study termination or day of death.
Only those animals that died during the progress of the study were subjected to a gross necropsy.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
95% CL:
>= 0 - <= 40
Mortality:
1 in 10 rabbits (10% mortality)

Table 1 Dosing schedule

Animal Number and Sex

Body Weight (g) at Day

Dosage level

g/kg

Dose

ml (Total)

1

8

15

WAD

001m

2.46kg

2.52kg

2.58kg

 

2.00 g/kg

5.29

002m

2.38kg

2.50kg

2.40kg

 

2.00 g/kg

5.12

003m

2.74kg

2.49kg

2.57kg

 

2.00 g/kg

5.89

004m

2.72kg

2.73kg

2.86kg

 

2.00 g/kg

5.85

005m

2.87kg

2.93kg

3.10kg

 

2.00 g/kg

6.17

006f

2.86kg

2.34kg

2.60kg

 

2.00 g/kg

6.15

007f

2.14kg

2.21kg

2.50kg

 

2.00 g/kg

4.60

008f

2.52kg

2.35kg

2.68kg

 

2.00 g/kg

5.42

009f

2.60kg

2.61kg

-

2.26kg

2.00 g/kg

5.59

010f

3.05kg

2.95kg

2.98kg

 

2.00 g/kg

6.56

WAD = weight after death

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The dermal LD50 is greater than 2000 mg/kg. Since one death is observed at 2000 mg/kg this warrants classification in category 5 according to GHS criteria (table 3.1.1 note g-ii).
Executive summary:

Results:

Dose level

g/kg

No. Rabbits Dosed

No. of Death on Study Day

Cumulative Mortality

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

2.0

10

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

1/10

Percent mortality = 10%

95% Confidence Interval = 0-40%

The above data indicate that the dermal LD50 is greater than 2.0 g/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
one K2 study us available

Additional information

The dermal LD50 is greater than 2000 mg/kg.

Justification for classification or non-classification

Two acute oral toxicity studies are available in which animals were dosed up to 10 g/kg bw. The lowest LD50 from these studies is 4270 mg/kg bw. This results in no classification according to CLP. The dermal LD50 is greater than 2000 mg/kg. This results in no classification according to CLP.