tert-pentyl peroxypivalate

Acute Toxicity: oral

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

Test material information

Constituent 1

Reference substance name:

tert-pentyl peroxypivalate

EC Number:

249-530-6

EC Name:

tert-pentyl peroxypivalate

Cas Number:

29240-17-3

Molecular formula:

C10H20O3

IUPAC Name:

tert-pentyl peroxypivalate

additive 1

Reference substance name:

Hydrocarbons, C4, 1,3-butadiene-free, polymd., triisobutylene fraction, hydrogenated

EC Number:

297-629-8

EC Name:

Hydrocarbons, C4, 1,3-butadiene-free, polymd., triisobutylene fraction, hydrogenated

Cas Number:

93685-81-5

Molecular formula:

not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)

IUPAC Name:

isododecane

Test material form:

liquid

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:

4 270 mg/kg bw

Based on:

test mat.

95% CL:

>= 3.85 - <= 5.18

Remarks on result:

other: 4.27 g/kg bw

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:

other: 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