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Toxicological information

Acute Toxicity: oral

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
additive
Test material form:
liquid
Details on test material:
FDRL Test Article ID: 81-0558
Sponsor Test Article ID: TA-54M75; tert-amyl peroxypivalate 75% in odorless mineral spirit
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

Test animals

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.

Administration / exposure

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.

Results and discussion

Effect levels
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"

Any other information on results incl. tables

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).

Applicant's summary and conclusion

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