Registration Dossier

Administrative data

Description of key information

No studies are available for the registered substance 2,2-Dimethylbutane. Based on the read-across approach, information on n-hexane is used.

Key read across studies of C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane (Hine et al., 1970; Klimisch score=2) were identified to support each acute toxicity endpoint (oral, dermal, and inhalation) for this substance.

Acute toxicity oral LD50>16750 mg/kg in rats (OECD TG 401)

Acute toxicity dermal LD50>3350 mg/kg in rabbits (OECD TG 402)

Acute toxicity inhalation LC50>259354 mg/m3 in rats (OECD TG 403)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it is an acceptable well-documented publication which meets basic scientific principles.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
Pre-GLP study
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 150-300 g

Route of administration:
oral: gavage
Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 25 ml/kg
Doses:
up to 25 ml/kg
No. of animals per sex per dose:
6 males
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days

Statistics:
Litchfield and Wilcoxen.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 25 mL/kg bw
Remarks on result:
other: 16.75 g/kg
Mortality:
No mortality at doses up to 25 ml/kg (16.75 g/kg (density 0.67)).
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 for rats is > 25 mL/Kg.
Executive summary:

This study examined the oral toxicity of commercial hexane. 6 male rats were given doses of up to 25 mL/Kg of test substance by oral gavage. The animals were then observed for 14 days for mortality.

No mortality was observed at any of the doses. The oral LD50 is therefore > 25 mL/Kg (16.75 g/Kg; density of 0.67).

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it is an acceptable well-documented publication which meets basic scientific principles.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
Pre-GLP study
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 150-300 g

Route of administration:
oral: gavage
Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 25 ml/kg
Doses:
up to 25 ml/kg
No. of animals per sex per dose:
6 males
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days

Statistics:
Litchfield and Wilcoxen.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 25 mL/kg bw
Remarks on result:
other: 16.75 g/kg
Mortality:
No mortality at doses up to 25 ml/kg (16.75 g/kg (density 0.67)).
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 for rats is > 25 mL/Kg.
Executive summary:

This study examined the oral toxicity of commercial hexane. 6 male rats were given doses of up to 25 mL/Kg of test substance by oral gavage. The animals were then observed for 14 days for mortality.

No mortality was observed at any of the doses. The oral LD50 is therefore > 25 mL/Kg (16.75 g/Kg; density of 0.67).

Endpoint conclusion
Dose descriptor:
LD50
Value:
16 750 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it is an acceptable well-documented publication which meets basic scientific principles.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Remarks:
Pre-GLP study
Test type:
acute toxic class method
Species:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 150-300 g

Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 250 l
- Method of conditioning air: Sample was heated in a water bath at 77 degree F. Air was bubbled through the sample and entered the exposure chamber. For concentrations less than saturation, air flow was divided with part passing over the sample and part passing directly into the exposure chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: GLC

Duration of exposure:
4 h
Concentrations:
73,680 ppm (30-40% of saturation at 25 degree C)
81,800 ppm
No. of animals per sex per dose:
10 males
Details on study design:
- Duration of observation period following administration: at least 6 days
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
73 860 ppm
Exp. duration:
4 h
Remarks on result:
other: 259354 mg/m3
Mortality:
All deaths occurred during exposure, except one rat in the 81800 ppm group that died on day 6.
Clinical signs:
other: Surviving rats were uncoordinated, prostrate or comatose during exposure but recovered within a few hours of removal from the chamber. The rat that died on day 6 had convulsions during and after exposure.
Interpretation of results:
study cannot be used for classification
Conclusions:
The 4-hr LC50 for rats exposed by inhalation was 73,680 ppm.
Executive summary:

This study examined that acute inhalation toxicity of hexane to male rats. Groups of 10 male rats exposed to various large concentrations of hexane vapor for 4 hrs. Animals were then observed for clinical signs and mortality for at least the next 6 days.

Several animals died during the exposure period. Surviving animals experienced severe toxicological effects during the exposure. One animal experienced convulsions during and after exposure, and died on day 6 post-exposure. The LC50 was determined to be 73,680 ppm (259354 mg/m3). Due to the high concentration of the LC50, the test substance would not be classified as toxic by inhalation according to OECD GHS guidelines.

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it is an acceptable well-documented publication which meets basic scientific principles.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Remarks:
Pre-GLP study
Test type:
acute toxic class method
Species:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 150-300 g

Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 250 l
- Method of conditioning air: Sample was heated in a water bath at 77 degree F. Air was bubbled through the sample and entered the exposure chamber. For concentrations less than saturation, air flow was divided with part passing over the sample and part passing directly into the exposure chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: GLC

Duration of exposure:
4 h
Concentrations:
73,680 ppm (30-40% of saturation at 25 degree C)
81,800 ppm
No. of animals per sex per dose:
10 males
Details on study design:
- Duration of observation period following administration: at least 6 days
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
73 860 ppm
Exp. duration:
4 h
Remarks on result:
other: 259354 mg/m3
Mortality:
All deaths occurred during exposure, except one rat in the 81800 ppm group that died on day 6.
Clinical signs:
other: Surviving rats were uncoordinated, prostrate or comatose during exposure but recovered within a few hours of removal from the chamber. The rat that died on day 6 had convulsions during and after exposure.
Interpretation of results:
study cannot be used for classification
Conclusions:
The 4-hr LC50 for rats exposed by inhalation was 73,680 ppm.
Executive summary:

This study examined that acute inhalation toxicity of hexane to male rats. Groups of 10 male rats exposed to various large concentrations of hexane vapor for 4 hrs. Animals were then observed for clinical signs and mortality for at least the next 6 days.

Several animals died during the exposure period. Surviving animals experienced severe toxicological effects during the exposure. One animal experienced convulsions during and after exposure, and died on day 6 post-exposure. The LC50 was determined to be 73,680 ppm (259354 mg/m3). Due to the high concentration of the LC50, the test substance would not be classified as toxic by inhalation according to OECD GHS guidelines.

Endpoint conclusion
Dose descriptor:
LC50
Value:
259 354 mg/m³

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it is an acceptable well-documented publication which meets basic scientific principles.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
Pre-GLP study
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2-3 kg
Type of coverage:
occlusive
Details on dermal exposure:
TEST SITE
- Type of wrap if used: saran wrap sleeve


REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was wiped with damp towels
- Time after start of exposure: 4 hrs


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 ml/kg
Duration of exposure:
4 hrs
Doses:
up to 5.0 ml/kg
No. of animals per sex per dose:
3 males
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs
Statistics:
method of Litchfield and Wilcoxen
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 mL/kg bw
Remarks on result:
other: 3.35 g/kg
Mortality:
No mortality was observed.
Clinical signs:
Animals showed signs of discomfort and were uncoordinated at the end of the exposure period.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The 4-hr LD50 for dermal exposure in rabbits is > 5.0 mL/Kg bw (3.35 g/Kg).
Executive summary:

This study examined the dermal toxicity of the hexane. Doses of up to 5.0 mL/Kg of test substance was placed on the shaved skin of 3 male rabbits. The test area was then covered with a saran wrap sleeve for 4 hrs. After the exposure period, the test substance washed off, and the animals observed for toxicity and mortality over the next 14 days.

No animals died, however, they did show signs of discomfort and uncoordination after the exposure. The LD50 for dermal exposure is >5.0 mL/Kg (3.35 g/Kg). The test substance is not classified as toxic under EU GHS guidelines.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it is an acceptable well-documented publication which meets basic scientific principles.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
Pre-GLP study
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2-3 kg
Type of coverage:
occlusive
Details on dermal exposure:
TEST SITE
- Type of wrap if used: saran wrap sleeve


REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was wiped with damp towels
- Time after start of exposure: 4 hrs


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 ml/kg
Duration of exposure:
4 hrs
Doses:
up to 5.0 ml/kg
No. of animals per sex per dose:
3 males
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs
Statistics:
method of Litchfield and Wilcoxen
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 mL/kg bw
Remarks on result:
other: 3.35 g/kg
Mortality:
No mortality was observed.
Clinical signs:
Animals showed signs of discomfort and were uncoordinated at the end of the exposure period.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The 4-hr LD50 for dermal exposure in rabbits is > 5.0 mL/Kg bw (3.35 g/Kg).
Executive summary:

This study examined the dermal toxicity of the hexane. Doses of up to 5.0 mL/Kg of test substance was placed on the shaved skin of 3 male rabbits. The test area was then covered with a saran wrap sleeve for 4 hrs. After the exposure period, the test substance washed off, and the animals observed for toxicity and mortality over the next 14 days.

No animals died, however, they did show signs of discomfort and uncoordination after the exposure. The LD50 for dermal exposure is >5.0 mL/Kg (3.35 g/Kg). The test substance is not classified as toxic under EU GHS guidelines.

Endpoint conclusion
Dose descriptor:
LD50
Value:
3 350 mg/kg bw

Additional information

No studies are available for the registered substance 2,2-Dimethylbutane. Based on the read-across approach, information on n-hexane is used.

In a key read-across acute oral toxicity study of C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane (Hine et al., 1970; Klimisch score=2), 6 male rats were administered doses up to 25 ml/kg of commercial n-hexane by oral gavage, and observed for 14 days post-dosing. No mortality was observed at any of the doses. The oral LD50 is therefore > 25 ml/kg (16750 mg/kg; density of 0.67) which makes the test substance not classified under EU criteria.

In a key read-across acute inhalation toxicity study (Hine et al., 1970; Klimisch score=2), groups of 10 male rats were exposed to concentrations of C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane for 4 hours. Animals were then observed for clinical signs and mortality for at least 6 days post-exposure. Several animals died during the exposure period. Surviving animals experienced severe toxicological effects during the exposure. One animal experienced convulsions during and after exposure and died on day 6 post-exposure. The LC50 was determined to be 73,680 ppm (259354 mg/m3), and the test substance is therefore not classified under EU criteria.

In a key read-across acute dermal toxicity study of C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane (Hine et al., 1970; Klimisch score=2), 5.0 ml/kg was placed on the shaved skin of 3 male rabbits. The test area was then covered with a saran wrap sleeve for 4 hrs. After the exposure period, the test substance washed off, and the animals observed for toxicity and mortality over the next 14 days. No animals died; however, they did show signs of discomfort and uncoordination after the exposure. The LD50 for dermal exposure is > 5.0 ml/kg (3350 mg/kg). Therefore, the test substance is not classified under EU criteria.

Justification for classification or non-classification

Based on available read across data, 2,2 -dimethylbutane does not warrant classification for acute oral, inhalation, or dermal toxicity under the Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP).

On the basis of available read across physical and chemical property data (hydrocarbon fluid, viscosity ≤ 20.5 mm2/s), 2,2 -dimethylbutane is classified as a Category 1 aspiration hazard (H304) under the Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP).

 

Additionally, acute exposure may result in non-lethal narcotic effects and therefore, 2,2 -dimethylbutane is classified as STOT Single Exposure Category 3 (H336: narcosis) under the Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP).