2,3-epoxybutane

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented study report which meets basic scientific principles

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1961

Report date:

1961

Materials and methods

Principles of method if other than guideline:

Four groups of 8 Guinea pigs per sex were exposed to 400 and 800 ppm (1.18 mg/l air and 2.38 mg/l air) for 7 hours daily on 135 to 141 days over a period of 198 days.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,3-epoxybutane

EC Number:

221-877-8

EC Name:

2,3-epoxybutane

Cas Number:

3266-23-7

Molecular formula:

C4H8O

IUPAC Name:

2,3-dimethyloxirane

Details on test material:

- Name of test material (as cited in study report): Butylene oxide (varable components)
- Molecular formula (if other than submission substance): C4H8O
- Physical state: liquid, clear
- Composition of test material, percentage of components: 1-butylene oxide (70-90 +/- 3%), 2-butylene oxide (5-15 +/-3%), isobutylene oxide (2-10 +/- 3%), trace contaminents

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: in wire mesh bottom cages
- Diet (e.g. ad libitum): commercial chow plus cabbage; ad libitum except during exposure
- Water (e.g. ad libitum): water; ad libitum except during exposure

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

other: no data

Remarks on MMAD:

MMAD / GSD: no data

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: sheat-metal chamber (ca. 1760 l)
- System of generating particulates/aerosols: required amounts of substance was metered into a vapourizing flask where it was mixed with air and then evenly distributed throughout the exposure chamber by means of a large circulating fan

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

by method of Hollingsworth and Waling (1955)

Duration of treatment / exposure:

7 h/d, 135 - 141 days

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
400, 800 ppm
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
1.18, 2.34 mg/l air
Basis:
nominal conc.

No. of animals per sex per dose:

8

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: frequently

BODY WEIGHT: Yes
- Time schedule for examinations: every 5th week

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes: lung, heart, kidneys, live, spleen, testes

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY
- 800 ppm: nothing abnormal noted
- 400 ppm: nothing abnormal noted

BODY WEIGHT AND WEIGHT GAIN
- 800 ppm: depression of growth of males, significant depression of average final body weight of the males
- 400 ppm: after 12-15 weeks reduced growth of males, but not significant

HAEMATOLOGY
- 800 ppm: nothing abnormal noted
- 400 ppm: nothing abnormal noted

CLINICAL CHEMISTRY
- 800 ppm: nothing abnormal noted
- 400 ppm: nothing abnormal noted

ORGAN WEIGHTS
- 800 ppm: increase in lung weights of males and females, significant decrease in the average liver weight of females
- 400 ppm: nothing abnormal noted

HISTOPATHOLOGY:
- 800 ppm: nothing abnormal noted
- 400 ppm: nothing abnormal noted

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

400 ppm

Sex:

male/female

Basis for effect level:

other: decreased lung weights, body weights

2

Dose descriptor:

NOAEC

Effect level:

1.18 mg/L air

Sex:

male/female

Basis for effect level:

other: decreased lung weights, body weights

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Average final body weight and organ weight after 400 and 800 ppm exposure:

	Sex	Exposure	No. Animals	Body weight (g)	Organ weight in g/100 g body weight
					Lung	Heart	Liver	Kidney	Spleen	Testes
400 ppm	Male	control	7	966	0.73	0.27	2.84	0.6	0.12	0.42
		exposed	7	862*	0.7	0.27	3.17*	0.6	0.13	0.48
	Female	control	7	874	0.75	0.27	3.6	0.61	0.16	-
		exposed	8	813*	0.82	0.27	3.28	0.61	0.16	-
800 ppm	Male	control	8	934	0.65	0.28	3.08	0.5	0.12	0.43
		exposed	7	827*	0.83**	0.29	2.88	0.61	0.13	0.49
	Female	control	8	815	0.74	0.26	3.37	0.6	0.17	-
		exposed	7	782	1.04**	0.27	2.94*	0.59	0.15	-

*p<0.05; **p<0.01;***p<0.001