1,2-epoxybutane

Endpoint summary

Description of key information

In a study similar to OECD TG 401, an approximative oral LD50 value of about 913 mg/kg bw for male and female rats was reported.

In a study similar to OECD TG 403, rats inhaled the test material in a concentration of 6.3 mg/L as a vapour for 4 hours. No mortalities and no symptoms were observed. Thus, the LC50 was greater than 6.3 mg/L for 4 hours.

An acute dermal LD50 value of ca.1469 mg/kg bw was found for male rabbits.

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:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BASF SE
- Age at study initiation: no data
- Weight at study initiation: The mean body weight of male animals was 206 g, the mean body weight of female animals was 174 g

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

The test substance was given as an emulsion in 0.5% aqueous CMC solution.
Observation period: 7 resp. 14 days

Doses:

100, 464, 681, 1000, 1210, 1470, 1780, 2150, 4640, 10000 µL/kg

No. of animals per sex per dose:

5 and/or 10 (see mortality table)

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 resp. 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

no data

Key result

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

ca. 913 mg/kg bw

Remarks on result:

other: Calculated with density of 0.83 g/cm3

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

ca. 1 100 other: µL/kg

Remarks on result:

other: original value

Mortality:

yes (see table below)

Clinical signs:

other: slight apathy, partially staggering, dyspnoea, diarrheic feces, exsiccosis, abdominal and lateral position

Gross pathology:

acute heart dilatation (both sides), acute congestive hyperemia, intra-abdominal adhesions of the stomach, thickened wall of the forestomach, partially formation of diverticulum

Mortality:

Dose (µL/kg)	Concentration (%)	No. of animals	dead within
			1 hour	24 hours	48 hours	7 days	14 days
10000	35	5 males	0/5	5/5	5/5	5/5
		5 females	0/5	5/5	5/5	5/5
4640	35	5 males	0/5	5/5	5/5	5/5
		5 females	0/5	5/5	5/5	5/5
2150	30	10 males	0/10	10/10	10/10	10/10
		10 females	1/10	10/10	10/10	10/10
1780	15	5 males	0/5	5/5	5/5	5/5
		5 females	0/5	5/5	5/5	5/5
1470	15	10 males	0/10	10/10	10/10	10/10
		10 females	0/10	10/10	10/10	10/10
1210	15	5 males	0/5	2/5	2/5	2/5
		5 females	0/5	5/5	5/5	5/5
1000	15	5 males	0/5	1/5	1/5	1/5
		5 females	0/5	0/5	0/5	0/5
681	6	5 males	0/5	0/5	0/5	0/5
		5 females	0/5	0/5	0/5	0/5
464	6	5 males	0/5	0/5	0/5	0/5
		5 females	0/5	0/5	0/5	0/5
100	1.5	5 males	0/5	0/5	0/5	0/5	0/5
		5 females	0/5	0/5	0/5	0/5	0/5

Interpretation of results:

Category 4 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

913 mg/kg bw

Quality of whole database:

study similar to OECD 401

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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

dynamic inhalation method with analytical and nominal determination of the concentration.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA Sulzfeld, Germany
- Age at study initiation: no data
- Weight at study initiation: 185 +/- 15 g
- Housing: no data
- Diet: ad libitum, Standard diet
- Water: ad libitum
- Acclimation period: no data

Route of administration:

inhalation: vapour

Vehicle:

other: unchanged (no vehicle)

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of the animals were checked before starting of the study, after 7 days and at the end of the observation period. Clinical signs and mortality were checked daily.
- Necropsy of survivors performed: yes; After the 14-day observation period the animals were killed and a pathological-anatomical evaluation was done.

Statistics:

none

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 6.3 mg/L air (analytical)

Mortality:

none

Clinical signs:

other: no symptoms

Body weight:

No significant differences regarding body weight growth in comparison to the air control group (see table)

Gross pathology:

nothing abnormal detected

Absolute body weight growth:

Mean body weight	before starting		after 7 days		after 14 days
	males	females	males	females	males	females
Group 1
Body weight in g	185	178	219	190	258	206
No. of animals	10	10	10	10	10	10
Control
Body weight in g	178	180	219	190	254	210
No. of animals	10	10	10	10	10	10

 

Relative body weight growth:

Mean body weight	before starting		after 7 days		after 14 days
	males	females	males	females	males	females
Group 1
Body weight in g	0	0	34	12	73	28
No. of animals	10	10	10	10	10	10
Control
Body weight in g	0	0	41	10	76	30
No. of animals	10	10	10	10	10	10

 

 

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

6 300 mg/m³ air

Physical form:

inhalation: vapour

Quality of whole database:

study similar to OECD 403

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

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

Qualifier:

no guideline available

Principles of method if other than guideline:

In this study a rabbit received repeated exposures upon the abdomen to a 1% solution.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

not specified

Vehicle:

other: report states a 1% solution but doesn't identify the vehicle

Details on dermal exposure:

A rabbit received repeated exposures upon the abdomen to a 1% solution.

Duration of exposure:

no data

Doses:

1% solution

No. of animals per sex per dose:

no data

Control animals:

no

Dose descriptor:

LD50

Remarks on result:

not determinable because of methodological limitations

Butylene Oxide does not present a problem from skin absorption under ordinary handling conditions. However, prolonged exposure to relatively large areas of skin may result in the absorption of toxic amounts.

Interpretation of results:

study cannot be used for classification

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline available

Principles of method if other than guideline:

Range finding tests

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: 3 to 5 months of age
- Weight at study initiation: averaging 2.5 kg
- Housing: immobilized in a hood to prevent inhalation of vapor during the 24-hour skin contact period
- Diet: ad libitum, Rockland rabbit ration
- Water (e.g. ad libitum): no data
- Acclimation period: no data

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Male rabbits were immobilized in a hood to prevent inhalation of vapor during the 24-hour skin contact period. Thereafter, the polyethylene sheeting used to retain the dose in contact with the clipped skin of the trunk was removed and the animals were caged for the remainder of the 14-day observation period.

Duration of exposure:

24 hour

Doses:

1.25 or 2.5 mL/kg bw

No. of animals per sex per dose:

4/dose

Control animals:

no

Statistics:

The moving average method of calculating the LD50 was used.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1.77 mL/kg bw

Remarks on result:

other: ca. 1469 mg/kg bw (density 0.03 mg/cm3)

Mortality:

3/4 died at 2.5 mL /kg and 1/4 died at 1.25 mL/kg

Clinical signs:

other: The covered applications caused marked erythema and necrosis of the skin which healed with scab formation.

Gross pathology:

Lungs of victims sometimes had petechial hemorrhages, livers were pale or mottled, kidneys pale as were also the stomachs.

Interpretation of results:

Category 4 based on GHS criteria

Reference 3

Endpoint:

acute toxicity: dermal

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

Principles of method if other than guideline:

Draize test

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Type of coverage:

occlusive

Details on dermal exposure:

Observation period: 14 d

Duration of exposure:

24 h

No. of animals per sex per dose:

4

Control animals:

not specified

Statistics:

no data

Sex:

male

Dose descriptor:

LD50

Effect level:

> 1 500 - < 2 950 mg/kg bw

Interpretation of results:

Category 4 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

ca. 1 469 mg/kg bw

Quality of whole database:

WoE approach

Additional information

Acute oral

In the key study similar to OECD 401, an approximative oral LD50 value of about 913 mg/kg bw for male and female rats was reported. The substance was given via gavage as an emulsion in 0.5% aqueous CMC solution. Slight apathy, partially staggering, dyspnoea, diarrheic feces, exsiccosis, abdominal and lateral position were recorded (BASF SE, 1975).

In a supporting study, the substance was given orally (gavage) as a 10% solution in corn oil. Female rats were given doses of 1000 or 2000 mg/kg bw. No animal died in the low dose group; all animals died in the high dose group. Animals given 1 g/kg appeared normal during and after feeding and during a 2-week observation period. The LD50 was found to be > 1000- < 2000 mg/kg bw for female rats (Dow, 1965).

In another study the unchanged substance was tested. Male rats were dosed with the substance at levels differing by a factor of 2 in a geometric series. All animals died at 2 mL/kg and one animal died at 1 mL/kg. Clinical signs were not reported. The LD50 was found to be 1.3 mL/kg bw for male rats (Dow, 1958).

In a further study, the substance given in oral (gavage) doses of 0.63, 1 and 1.58 g/kg (10% in corn oil) resulted in an LD50 value for rats of > 2 and < 1.58 mg/kg bw. No mortalities were seen at 0.63 g/kg; all animals died at 1.58 g/kg; clinical signs were not reported (Dow, 1953).

Acute inhalation

In the key study similar to OECD TG 403, rats inhaled the test material in a concentration of 6.3 mg/L as a vapour for 4 hours. No mortalities and no symptoms were observed. Thus, the LC50 was greater than 6.3 mg/L for 4 hours (BASF SE, 1978).

In a supporting study, rats were exposed to an atmosphere saturated with the test substance (calculated around 660 mg/l or 200.000 ppm). Two rats died after 3-min exposure, all rats died at 10-min exposure. Clinical signs were irritation of the mucosa, dyspnoea and narcosis. Necropsy showed acute dilatation of the heart, congestive hyperemia and slight edema of the lung (BASF SE, 1975).

In a further study it was reported that the test substance has a very high vapour exposure. Rats survived a 6-minute exposure to saturated atmospheres at room temperature but failed to survive a 12-min exposure (Dow, 1965).

In another study (Dow, 1958), 8000 or 4000 ppm of the concentrated test substance vapour was tested up to 4 hours. The concentration of 8000 ppm (around 24 mg/l) was lethal for 6/6 rats within 4 hours; 1/6 rat died in the 4000 ppm (around 12 mg/l) concentration group.

In an older study (Dow, 1953) it was stated that butylene oxide presents a serious acute vapour inhalation hazard. Vapours in confined spaces may be dangerous even for single short exposure.

Acute dermal

For the endpoint acute dermal toxicity a WoE approach was applied.

An acute dermal LD50 value of 1.77 mL/kg bw (ca. 1469 mg/kg bw) was found for male rabbits. Unchanged 2-ethyloxirane was tested for 24 hours in doses of 1.25 or 2.5 mL/kg under occlusive conditions. The covered applications caused marked erythema of the skin which healed with scab formation. 3 of 4 rabbits died in the 2.5 mL/kg dose group and 1 of 4 rabbits died at the 1.25 mL/kg dose group (Dow, 1958).

The 1% solution of the test substance does not present a problem from skin absorption for rabbits under ordinary handling conditions. Prolonged exposure to relatively large areas of the skin may result in the absorption of toxic amounts. Further details are not given (Dow, 1953).

Smyth et al. (1962) found a dermal LD50 value of > 1500 - < 2950 mg/kg for male rabbits (24-hour occlusive). Further details are not given.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data the test item is classified for acute oral, dermal and inhalation toxicity Cat.4 (H302, H312, H332) according to Regulation (EC) No 1272/2008 (CLP). The substance is harmonized classified for acute oral, dermal and inhalation toxicity Cat.4 (H302, H312, H332) according to Annex VI of Regulation (EC) No 1272/2008.