Registration Dossier

Administrative data

Description of key information

There are no studies according to current guidelines available. But there are non-guideline studies on hand, which are adequately documented and considered to be of sufficient quality to allow an evaluation of this endpoint.

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:
1954
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well performed study, study performance before implementation of GLP, purity of test item not reported.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
not applicable
GLP compliance:
no
Test type:
standard acute method
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: raised at Mellon Institute of Industrial Research
- Age at study initiation: young adults
- Weight at study initiation: 90-120 grams
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Single exposure
Doses:
other
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- The tested chemicals were diluted with water, corn oil, or a 1 % solution of sodium 3,9-diethyl-6-tridecanol sulfate (Tergitol Penetrant 7) when
necessary to bring the volume given to one rat to between 1 and 10 ml. However, it is unknown which (if any) solvent and at which concentration was used in the case of dibutyl ether.
Statistics:
The most probable LD50 value and its fiducial range were estimated by the method of Thompson (1947) using the tables of Weil (1952).
Preliminary study:
not applicable
Sex:
male
Dose descriptor:
LD50
Effect level:
7 400 mg/kg bw
Based on:
test mat.
95% CL:
> 6 410 - < 8 530
Mortality:
no information available
Clinical signs:
no information available
Body weight:
no information available
Gross pathology:
no information available
Other findings:
no information available

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the acute oral LD50 of dibutyl ether is 7400 mg/kg body weight with 95% CL ranging between 6410 - 8530 mg/kg body weight and will not be classified.
Executive summary:

In this study, single dose oral toxicity for rats was estimated by intubation of dosages in a logarithmic series to groups of five male Carworth-Wistar rats (90 to 120 g), raised at the Mellon Institute of Industrial Research, University of Pittsburgh, USA. The tested chemicals were diluted with water, corn oil, or a 1 % solution of sodium 3,9-diethyl-6-tridecanol sulfate (Tergitol Penetrant 7) when necessary to bring the volume given to one rat to between 1 and 10 ml. However, it is unknown which (if any) solvent and at which concentration was used in the case of dibutyl ether. Fourteen days after dosing, mortality was considered complete. The most probable LD50 value and its fiducial range were estimated by the method of Thompson (1947) using the tables of Weil (1952). Clinical signs were not reported. Under the conditions of the study, the acute oral LD50 of dibutyl ether is 7400 mg/kg body weight with 95% CL ranging between 6410 - 8530 mg/kg body weight and will not be classified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
7 400 mg/kg bw

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
Study period:
1954
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well performed study, study performance before implementation of GLP, purity of test item not reported
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: raised at Mellon Institute of Industrial Research
- Age at study initiation: young adults
- Weight at study initiation: 90-120 grams
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
The stream was prepared by various styles of proportioning pumps. Nominal concentrations were recorded, not confirmed by analytical methods. Exposures were four hours long. Concentrations were in an essentially logarithmic series with a factor of two.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
other
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
Groups of six male Carworth-Wistar rats (90 to 120 g), raised at the Mellon Institute of Industrial Research, University of Pittsburgh, USA, were exposed to a flowing stream of known vapor concentrations of dibutyl ether. The stream was prepared by various styles of proportioning pumps. Nominal concentrations were recorded, not confirmed by analytical methods. Exposures were four hours long. Concentrations were in an essentially logarithmic series with a factor of two. The concentration yielding fractional mortality among six rats within 14 days was recorded. Clinical signs were not reported.
Statistics:
no information available
Preliminary study:
not applicable
Sex:
male
Dose descriptor:
other: approximate LC50
Effect level:
ca. 21 600 mg/m³ air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: approximately 4000 ppm
Mortality:
The 4-hour exposure to 4000 ppm dibutyl ether killed 2/6 rats within 14 days.
Clinical signs:
no information available
Body weight:
no information available
Gross pathology:
no information available
Other findings:
no information available

4000 ppm are at 25 °C and 1013 hPa equal to 21600 mg/m³.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The 4-hour exposure to 4000 ppm dibutyl ether killed 2/6 rats within 14 days. This substance is not classified for Acute toxicity
Executive summary:

In this study, groups of six male Carworth-Wistar rats (90 -120 grams) were exposed to a flowing stream of known vapour concentrations of dibutyl ether for 4 hours. Under the conditions of the study, the 4-hour exposure to 4000 ppm dibutyl ether killed 2/6 rats within 14 days and this substance is not classified for Acute toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
21 600 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1954
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well performed study, study performance before , implementation of GLP, purity of test item not reported.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Study conducted prior to guidelines but study conduct comparable to current OECD TG 402
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.5 -3.5 kg
Type of coverage:
occlusive
Vehicle:
other: no vehicle used
Details on dermal exposure:
The fur was closely clipped over the entire trunk, and the doses, retained beneath an impervious plastic film, the exposure area corresponded to about 1/10 of the body surface. After 24 hours of contact the film was removed.
Duration of exposure:
24 hours
Doses:
no information available
No. of animals per sex per dose:
4
Control animals:
no
Details on study design:
The acute dermal toxicity of dibutyl ether for rabbits was estimated by the technique of Draize et al. (1944), using groups of four male New Zealand giant albino rabbits weighing 2.5 to 3.5 kg. The fur was closely clipped over the entire trunk, and the doses, retained beneath an impervious plastic film, the exposed area corresponding to about 1/10 of the body surface. After 24 hours of contact the film was removed. Animals were observed for mortality fourteen days after dosing. Clinica;l signs were not reported.
Statistics:
The most probable LD50 value and its fiducial range were estimated by the method of Thompson (1947) using the tables of Weil (1952)
Preliminary study:
not applicable
Sex:
male
Dose descriptor:
LD50
Effect level:
10.08 mL/kg bw
Based on:
test mat.
95% CL:
4.41 - 23.04
Sex:
male
Dose descriptor:
LD50
Effect level:
7 741 mg/kg bw
Based on:
test mat.
95% CL:
3 387 - 17 695
Mortality:
no information available
Clinical signs:
no information available
Body weight:
no information available
Gross pathology:
no information available
Other findings:
no information available

Original values given by the authors in ml/kg bw: LD50 (95 % C.I.) 10.08 (4.41 - 23.04) ml/kg bw, which is equal to 7741 (3387 - 17695) mg/kg bw (density of dibutyl ether: 0.768 g/cm³).

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the LD50 of dibutyl ether was 10.8 ml/kg; which is equal to 7741 (3387 - 17695) mg/kg body weight to rabbits, therefore this substance is not classified.
Executive summary:

In this study, the acute dermal toxicity of dibutyl ether for rabbits was estimated by the technique of Draize et al. (1944), using groups of four male New Zealand giant albino rabbits weighing 2.5 to 3.5 kg. The fur was closely clipped over the entire trunk, and the doses, retained beneath an impervious plastic film, the exposed area corresponding to about 1/10 of the body surface. After 24 hours of contact the film was removed. Animals were observed for mortality for fourteen days after dosing. The most probable LD50 value and its fiducial range were estimated by the method of Thompson (1947) using the tables of Weil (1952). Clinical signs were not reported.

Under the conditions of the study, the LD50 of dibutyl ether was 10.8 ml/kg; which is equal to 7741 (3387 - 17695) mg/kg body weight to rabbits, therefore this substance is not classified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
7 741 mg/kg bw

Additional information

Inhalation

The 4-hour exposure to 21 600 mg dibutyl ether/m³ (4000 ppm) killed 2/6 rats within 14 days. This approximate 4-hour LC50 for dibutyl ether was determined in groups of six male Wistar rats. The rats were exposed to a flowing stream of dibutyl ether. Concentrations tested were in an essentially logarithmic series with a factor of two. Nominal concentrations not confirmed by analytical methods were tested and the concentration yielding fractional mortality within 14 days was published. Clinical signs were not reported (Smyth et al., 1954). In an inhalation hazard test, groups of six male Wistar rats were exposed between 30 minutes and 8 hours to highly enriched/saturated dibutyl ether vapor which was generated at room temperature. 30 Minutes was the longest exposure period which allowed all rats to survive 14 days. Clinical signs, as well as the exposure period that had killed half of the rats within 14 days, the concentration of dibutyl ether, and information as to whether the deaths were attributable to dibutyl ether or to asphyxia were not reported (Smyth et al., 1954). A single 6-hour exposure to 10 000 mg/m³ in a 7-day range finding study induced ataxia, piloerection and blepharospasm in male Wistar rats, but the chemical was apparently not narcotic. Because of these clear signs of toxicity immediately after the first exposure to 10 000 mg/m³, the top concentration level for male rats for the remainder of the 7-day range finding study was then reduced to 6500 mg/m³. The top concentration level for females, whose exposure started as scheduled one day later, was 6500 mg/m³ during the whole 7-day range-finding study. As clinical signs at 6500 mg/m³, only slight labored breathing after the first exposure in male and female Wistar rats (exposure day two for males and exposure day 1 for females), and, in females only, blepharospasm and sluggishness after the second and third exposures occurred (TNO, 2005).

Dermal

The dermal LD50value for dibutyl ether in male albinorabbits after a 14-day observation period was 7741 mg/kg bw (10.08 ml/kg bw). Clinical signs were not reported (Smyth et al., 1954).

Oral

An oral LD50-value of 7400 mg/kg bw was determined in male Wistar rats. Clinical signs were not reported (Smyth et al., 1954).

Studies in Humans

Inhalation

Volunteers were exposed in a gas cabinet to the substance for a period of 15 minutes. At 300 ppm (corresponding to 1599 mg/m³) the odor was not noticeable to the majority of subjects (Silverman, Schulte, and First, 1946).

Justification for classification or non-classification

Dibutyl ether is of low acute toxicity after inhalation (approximate 4-hour LC50rat: 21 600 mg/m³ (4000 ppm)), dermal (LD50rabbit: 7741 mg/kg bw (10.08 ml/kg bw)) and oral exposure (oral LD50rat: 7400 mg/kg bw). Dibutyl ether has no pronounced narcotic potential. The LD50 values are all high indicating a lack of acute toxicity. Therefore, the substance does not need to be classified and labelled for acute toxicity, according to the Regulation 1271/2008 and the Directive 67/548/EEC.