tert-butyl 3-oxobutanoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from Authoritative database

Data source

Reference

Reference 1

Reference Type:

other: Authoritative database

Title:

Acute oral toxicity study of test chemical was performed in rodents.

Author:

U.S. National Library of Medicine

Year:

2018

Bibliographic source:

Chemidplus Database,U.S. National Library of Medicine,2018

Reference 2

Reference Type:

secondary source

Title:

Acute oral toxicity study of test chemical was performed in rodents.

Author:

NTRL

Year:

1997

Bibliographic source:

NTRL REPORT,1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Principles of method if other than guideline:

Acute oral toxicity study of test chemical was performed in rodents.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

tert-butyl acetate

Cas Number:

540-88-6

Molecular formula:

C6H12O2

IUPAC Name:

tert-butyl acetate

Details on test material:

- Name of test material (IUPAC name): tert-butyl acetate- Common name: 1,1-Dimethyl acetate- Molecular formula: C6H12O2- Molecular weight: 116.1588 g/mol- Smiles notation: C(OC(C)=O)(C)(C)C- InChl: 1S/C6H12O2/c1-5(7)8-6(2,3)4/h1-4H3- Substance type: Organic

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Details on test animalTEST ANIMALS- Source: Ace Animals, Boyertown, PA- Age at study initiation: healthy male and healthy, non-pregnant and nulliparous female Wistar albino rats were taken. The animals were bom the weeks of 4/22 through 5/27/97.- Weight at study initiation: 265-296 grams : males 201-280 grams : females- Diet (e.g. ad libitum): Fresh Purina Rat Chow (Diet #5012) was freely available except for 16-20 hours prior to dosing- Water (e.g. ad libitum): Water was freely available at all times.- Acclimation period: a quarantine period of at least one weekENVIRONMENTAL CONDITIONS- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycleIN-LIFE DATES: From: 07/18/97 To: 08/01/97

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

no data

Doses:

2000,5000,7000 mg/kg bw

No. of animals per sex per dose:

Total:30 rats2000 mg/kg bw: 5 male and 5 female5000 mg/kg bw: 5 male and 5 female7000 mg/kg bw: 5 male and 5 female

Control animals:

not specified

Details on study design:

Details on study design:- Duration of observation period following administration: 14 days- Frequency of observations and weighing: In Vivo - Animals were observed 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for mortality. Body weights were recorded immediately pretest, weekly, at death and at termination in the survivors.Post Mortem - All animals were examined for gross pathology. Abnormal tissues were preserved in 10%buffered formalin for possible future microscopic examination.- Necropsy of survivors performed: yes- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

The LD50 and 95% Confidence Limits were calculated by the method of Litchfield J.T. Jr., &F. Wilcoxon JPET96:99.

Results and discussion

Preliminary study:

Five healthy male and five healthy female Wistar albino rats were dosed orally with tert-butyl acetate at 5000 mg/kg of body weight. Since mortality occurred at this level, additional groups were dosed at 2000,5000 and 7000 mg/kg bw.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

4 100 mg/kg bw

Based on:

test mat.

95% CL:

3 185 - 5 277

Remarks on result:

other: 50% mortality was observed

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

4 750 mg/kg bw

Based on:

test mat.

95% CL:

3 848 - 5 864

Remarks on result:

other: 50% mortality was observed

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 500 mg/kg bw

Based on:

test mat.

95% CL:

3 783 - 5 353

Remarks on result:

other: 50% mortality was observed

Mortality:

50% mortality was observed

Clinical signs:

other: Predeath physical signs included ataxia, flaccid muscle tone, lethargy, dyspnea, loss of righting reflex, prostration, piloerection, tremors and coma. Physical signs in the surviving animals of the 2000 and 5000 mg/kg groups included ataxia, flaccid muscl

Gross pathology:

Necropsy findings in the animals which died during the study included abnormalities of the lungs, spleen, kidneys, liver, stomach, intestines, as well as wetness and red & brown staining of the nose/mouth area. Necropsy findings in the animals which survived the study were normal.

Other findings:

no data

Any other information on results incl. tables

 

Table:Mortality response to the three oral dose levels was:

Dose mg/kg	# Treated M/F	# Dead M/F
2000	5/5	0/0
5000	5/5	4/2
7000	5/5	5/5

 

Table: TOXICITY CODE

B = Lethargy

C = Flaccid

E = Ataxia

F = Piloerection

G = Prostrate

H = coma

K = Negative righting reflex

M = Dyspnea

0 = Tremors

S = Chromorhinorrhea

V = Bloated abdomen

Z = Dead

Table : Systemic Observations

Dose level: 2000 mg/kg bw

TIME PERIODS	ANIMAL # / SEX
	11-M	12-M	13-M	14-M	15-M	16-F	17-F	18-F	19-F	20-F
Hours 1		B,E	B,E			B	B	B	B	B,E
Hours 2	B,E				B	B,E	B,E	B,E
Hours 4						B	B,E	B
Day 1					S
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15

 

No entry Indicates animal appeared normal at that observation period. Systemic observation code is on page preceding systemic observation tables.

 

Table: Systemic Observations (continued)

Dose level: 5000 mg/kg bw

TIME PERIODS	ANIMAL # / SEX
	1-M	2-M	3-M	4-M	5-M	6-F	7-F	8-F	9-F	10-F
Hours 1	B,E	B,E	B,E,G	B,E	B,E	B,E,G	B,E	B,E,C	B,E	B,E,G
Hours 2	B,E,G	B,E,G	B,E,G	B,E,G	B,E,G	B,E,G	B,E	B,E,C,G	B,E,G	B,E,G
Hours 4	B	B,E	B	B,E,Z (213 g)	B	B	Z	B,E,C,G	B,E,G
Day 1	Z^(272 g)	V	Z^(307 g)		Z^(275 g)	B,E		Z^(215 g)	C,F
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15

No entry Indicates animal appeared normal at that observation period. Systemic observation code Is on page preceding systemic observation tables.

 

Table 2: Systemic Observations (continued)

Dose level:7000 mg/kg bw

TIME PERIODS	ANIMAL # / SEX
	21-M	22-M	23-M	24-M	25-M	26-F	27-F	28-F	29-F	30-F
Hours 1	C,G,M	C,E	B,E	Z	B,E	Z	C,G	C,G	C,M,G	C,G
Hours 2	Z	C,G,K	B,E		B,E,O		Z	C,G	Z	Z
Hours 4		C,E,F	Z		H,M			Z
Day 1		Z^(258 g)			Z^(269 g)
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15

 

 

Table: Necropsy Observations

Dose level: 2000 mg/kg bw

OBSERVATION          Death/Sacrifice	11  M S	12  M S	13  M S	14 M S	15 M S	16 F S	17 F S	18 F S	19  F S	20 F S
Normal	X	X	X	X	X	X	X	X	X	X

CODES: S = sacrifice

X= observed

 

Table 3: Necropsy Observations (continued)

Dose Level: 5000 mg/kg

OBSERVATION          Death/Sacrifice	1  M D	2  M S	3  M D	4 M D	5 M D	6 F S	7 F D	8 F D	9  F S	10 F S
Normal		X				X			X	X
Nose/mouth - stained red							1
Nose/mouth - stained brown					1
Nose/mouth - wet							1
Lungs - darker than normal	2		2	2	2		2	2
Lungs - red areas	2		1	2	2		2	2
Liver - pale areas			2		2			1
Liver - darker than normal	1		1	2			2	1
Kidney - pale areas on left one	1		2		1			1
Stomach - red					2
Stomach· distended with gas			3
Stomach - pale	2							2
Intestines - red areas	1		1	1	2			2
Intestines - distended with mucus			2		1			1
Intestines - pale	2		1	1	1		3	2
Spleen - pale			2					1

CODES: D=death

S = sacrifice

X= observed

1=slight or scattered

2= moderate or few

3= pronounced or many

 

 

Table 3: Necropsy Observations (continued)

Dose Level: 7000 mg/kg

OBSERVATION          Death/Sacrifice	21  M D	22  M D	23  M D	24 M D	25 M D	26 F D	27 F D	28 F D	29  F D	30 F D
Nose/mouth - wet				1		1	1	1		1
Lungs - darker than normal	1	2	2	2	2	2	1	2	2	2
Lungs - red areas	1	3	1	2	3	1		2	2	1
Liver - darker than normal	1		1	2	1	1	1	1	1	1
Stomach - red	1		2	2		1	1		2	1
Stomach· distended with gas	1	1	1	1	1	1	2	1	1	1
Stomach –lining pale					2			2
Intestines - red areas	1	2		1	2	1	1	1
Intestines - distended with mucus	1	1	1	1	1	1	2	1	2	2
Intestines - pale			2		2	1		2	1	2

CODES: D = death

1= slight or scattered

2= moderate or low

3= pronounced or many

 

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Conclusions:

The lethal concentration (LD50) value for acute oral toxicity test was considered to be 4100 mg/kg bw in males;4750 mg/kg bw in females and 4500 mg/kg bw in both sex,when male and female wistar albino rats were treated with test chemical orally via gavage according to Health Effects Testing Guidelines, 40 CFR Part 798.1175.

Executive summary:

Acute oral toxicity study was performed in male and female wistar albino rats using test chemical via gavage according to Health Effects Testing Guidelines, 40 CFR Part 798.1175.50% mortality was observed at dose 4100 mg/kg bw in males,4750 mg/kg bw in females and 4500 mg/kg bw for both sex.Predeath physical signs included ataxia, flaccid muscle tone, lethargy, dyspnea, loss of righting reflex, prostration, piloerection, tremors and coma. Physical signs in the surviving animals of the 2000 and 5000 mg/kg groups included ataxia, flaccid muscle tone, lethargy, bloated abdomen, piloerection, chromorhinorrhea and assumption of a prostrate position. Body weight changes in the surviving animals in the 2000 and 5000 mg/kg groups were normal. Necropsy findings in the animals which died during the study included abnormalities of the lungs, spleen, kidneys, liver, stomach, intestines, as well as wetness and red & brown staining of the nose/mouth area. Necropsy findings in the animals which survived the study were normal.Hence,LD50 value was considered to be 4100;4750 and 4500 mg/kg bw,when rats were treated with test chemical orally via gavage.