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Administrative data

Description of key information

Skin Irritation

Not irritating to the skin

 

Ocular Irritation

Not irritating to eyes

 

Respiratory Irritation

No studies were located to indicate that 2-methylbutane is a respiratory irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1989-12-12 to 1990-02-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the full study protocol, was provided, including test materials and methods.
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
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Principles of method if other than guideline:
According to the McKee et al. article (1998; cross-reference to the same study), the Draize method was followed, and the study is compliant with more recent guidelines from the EU and the Organization for Economic Cooperation and Development (OECD).

Draize, J. 1959. The Appraisal of the Safety of Chemicals in Food, Drugs, and Cosmetics. Association of Food and Drug Officials of the United States, Austin, TX.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Products, Denver, Pennsylvania
- Age at study initiation: Approximately 12 weeks
- Weight at study initiation: Approximately 2 to 3 kg
- Housing: Individually housed in suspended stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 22 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 21°C
- Humidity (%): 40 to 60%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

IN-LIFE DATES: From: 1989-12-12 To: 1989-12-19
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:
4 hours
Observation period:
Dermal responses were evaluated 45 minutes, 24, 48, and 72 hours after patch removal and on day 7. Body weights were recorded on the day of dosing (day 0). Animals were sacrificed after day 7 observations via an intravenous administration of sodium pentobarbital solution and discarded without further examination.
Number of animals:
4 males and 2 females
Details on study design:
TEST SITE
The dorsal surface from the shoulder region to the lumbar region of each rabbit was shaved approximately 20 to 21 hours prior to administration. Elizabethan-type collars were placed around the rabbits' neck approximately one week prior to study initiation. Animals were then re-shaved as needed. At dosing, 0.5 mL of undiluted test material was placed under a gauze patch that was secured with tape. A semi-occlusive dressing was placed over the patch. After approximately 4 hours of exposure, the dressing, patch, and Elizabethan collars were removed and the site was washed.

REMOVAL OF TEST SUBSTANCE
Residual test material was removed from the test site by using reverse osmosis water and paper towels.

SCORING SYSTEM:
The Draize method of scoring was used to score edema and erythema and eschar formation. Edema and erythema and eschar formation were scored on a 5 point scale (0 to 4), with 0 being no effect and 4 being the most severe. Additional dermal observations were made and included: atonia, blanching, leathering skin, fissuring, desquamation, necrosis, exfoliation, and eschar.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 to 72 hours
Score:
0.67
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 to 72 hours
Score:
0.06
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
6
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
Based on the study results, the overall dermal irritation score was 0.67. Administration on n-pentane to rabbit skin resulted in limited and transient dermal irritation. Dermal responses were observed in 5 animals 45 minutes after application, 2 with well-defined erythema and 3 with very slight erythema. 24 hours after application, 1 animal exhibited well-defined erythema and 3 animals exhibited very slight erythema. At the 48- and 72-hour observation periods, one animal exhibited well-defined erythema. At study termination, animals were free of dermal irritation.



Other effects:
One animal exhibited the following clinical signs of toxicity: decreased food consumption, soft stool, small amount of stool, no stool, and emaciation.

 

Erythma and Edema Scores

45 minutes

24 hours

48 hours

72 hours

7 days

Erythma

Animal 1

0

0

0

0

0

Animal 2

1

1

0

0

0

Animal 3

2

2

2

2

0

Animal 4

2

1

0

0

0

Animal 5

1

1

0

0

0

Animal 6

1

0

0

0

0

Mean

1.17

0.83

0.33

0.33

0.00

 

Edema

Animal 1

0

0

0

0

0

Animal 2

0

0

0

0

0

Animal 3

2

1

0

0

0

Animal 4

0

0

0

0

0

Animal 5

0

0

0

0

0

Animal 6

0

0

0

0

0

Mean

0.33

0.17

0.00

0.00

0.00

Interpretation of results:
other: Not classified under EU DSD or CLP; not irritating.
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
According to the study authors, n-pentane was found to be mild irritant with a primary irritation index of 0.67. This classification was based on the descriptive ratings for skin irritation developed by Draize; however, based on mean erythema and oedema scores (0.5 and 0.06, respectively) over 72 hours (i.e., 24 to 72 hours), n-pentane would be considered non-irritating based on EU DSD or CLP guidelines.
Executive summary:

In a primary dermal irritation study, 4 male and 2 female New Zealand White rabbits were dermally exposed to 0.5 mL of n-pentane for 4 hours to dorsal surface from the shoulder region to the lumbar region of each rabbit. Animals then were observed for 7 days. Irritation was scored by the Draize method of scoring.

According to the study authors, n-pentane was found to be mild irritant with a primary irritation index of 0.67. The mean erythema score was 0.5 when averaged over 72 hours (i.e., 24 to 72 hours); the mean oedema score was 0.06 when averaged over 72 hours. n-Pentane would be considered non-irritating based on these mean erythema and oedema values under EU DSD or CLP guidelines.

This study received a Klimisch score of 1 and is classified as reliable without restriction because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the full study protocol, was provided, including test materials and methods. The study follows OECD guidelines 404. 

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1996-07-30 to 1996-08-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is classified as reliable without restriction because it is in compliance with OECD principles of GLP and the E.U. Council Decision on GLP.
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
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Protocol deviations were minor and were not expected to interfere with the overall study results. Test report did not provide rationale for in vivo testing. Test report did not provide analysis for the stability, identity, strength, purity, composition.
Qualifier:
according to guideline
Guideline:
other: EC Dangerous Substances Directive (67/548/EEC), Methods of Determination of Toxicity, Annex V, Part B.5
Deviations:
yes
Qualifier:
according to guideline
Guideline:
other: Animal Welfare Act (1966)
Qualifier:
according to guideline
Guideline:
other: Guide for the Care and Use of laboratory Animals (1985) DHHS
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: HPR Inc., Denver, Pennsylvania
- Age at study initiation: Approximately 12 to 13 weeks
- Weight at study initiation: 2.29 to 2.34 kg
- Housing: Each animal was kept in a separate suspended stainless steel and wire mesh cage with absorbent paper.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: lasted 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 21 °C
- Humidity (%): 40 to 60% relative humidity
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

IN-LIFE DATES: From: 1996-07-30 To: 1996-08-02
Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral eye on each animal served as the control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml



Duration of treatment / exposure:
Animals were exposed to 0.1 ml of the test material once over a 72-hour period.
Observation period (in vivo):
Observations were made at approximately 1, 24, 48, and 72 hours post-application.
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes of the 3 test animals remained unwashed.

SCORING SYSTEM: The Draize Standard Eye Irritation Grading Scale (Draize, 1959) was used for scoring. Animals were examined and scored using the naked eye begining at each 24 hour interval.

TOOL USED TO ASSESS SCORE: Two percent fluorescein dye was used under UV light to aid in examination and scoring.
Irritation parameter:
other: Redness
Basis:
mean
Time point:
other: 1 hour
Score:
2.33
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
other: Redness
Basis:
mean
Time point:
24 h
Score:
1.33
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
other: Redness
Basis:
mean
Time point:
48 h
Score:
0.33
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 hour
Score:
0.33
Max. score:
110
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
Some degree of occular irritation of the conjunctiva was observed in all three animals. Redness was observed in all animals at the 1 and 24 hour observation points. Only for rabbit number JEK361M did redness persisted through to the 48 hour timepoint; chemosis and discharge were also observed in this animal at the 1 hour interval. No irritation was observed for any other irritation parameter or time point for the remaining two animals. No conjunctival irritation was observed at 72 hours for any test organism. n-Pentane was observed to be fully reversible within 72 hours.
Other effects:
Clinical signs were not observed in any animal and all animals survived until study termination.

 

1 hour

24 hour

48 hour

72 hour

Redness

2.33

1.33

0.33

0.00

Chemosis

0.33

0.00

0.00

0.00

Iris

0.00

0.00

0.00

0.00

Opacity

0.00

0.00

0.00

0.00

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
Ocular exposure to 0.1 ml of n-pentane caused reversable irritation to the conjunctiva, but no iridial or corneal responses in any of the rabbits. Any sign of occular irritation was cleared in all test animals by the 72 hour interval.
Executive summary:

n-Pentane was tested for ocular irritation in 3 New Zealand White rabbits at a single 0.1 ml dose. Observations were made at 1, 24, 48, and 72 hours after application for indications of ocular irritation. Reactions were scored based on the Draize Standard Eye Irritation Grading Scale (Draize, 1959). N-pentane caused ocular irritation of the conjunctiva in all three test animals. All animals showed signs of redness at 1 hour and 24 hours after the installation. In only one animal did redness persist until the 48 hour observation period; this same animal was the only one to exhibit chemosis and discharge responses (at the 1 hour interval). All 3 animals were cleared of any ocular irritation at the 72 hour observation.

This study received a Klimish score of 1, reliable without restriction, because it is in compliance with OECD principles of GLP and the E.U. Council Decision on GLP.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Only human skin irritation data is available for 2-methylbutane. However, data in animals (skin and eye irritation) and humans (skin irritation) is available for structural analogue, pentane and presented in the dossier. This data is read across to 2-methylbutane based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Skin Irritation

 

Pentane

 

In a key primary dermal irritation study (ExxonMobil, 1990), 4 male and 2 female New Zealand White rabbits were dermally exposed to 0.5 mL of th n-pentane for 4 hours to dorsal surface from the shoulder region to the lumbar region of each rabbit. Animals then were observed for 7 days. Irritation was scored by the Draize method of scoring. According to the study authors, n-pentane was found to be mild irritant with a primary irritation index of 0.67. The mean erythema score was 0.5 when averaged over 72 hours (i.e., 24 to 72 hours); the mean oedema score was 0.06 when averaged over 72 hours. n-Pentane would be considered non-irritating based on these mean erythema and oedema values under EU CLP guidelines.

 

This study received a Klimisch score of 1 and is classified as reliable without restriction because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the full study protocol, was provided, including test materials and methods. The study follows OECD guidelines 404. 

With regard to the animal study on n-pentane, 4 male and 2 female New Zealand White rabbits were dermally exposed to 0.5 mL of n-pentane for 4 hours to dorsal surface from the shoulder region to the lumbar region of each rabbit (Trimmer, 1990). Animals were then observed for 7 days. Irritation was scored by the Draize method of scoring. The mean erythema and oedema score over 72 hours (0.5 and 0.06, respectively) are considered non-irritating based on EU guidelines.

Human Data

Pentane and 2-methylbutane

For the human studies, 30 human volunteers were dermally exposed to 2 -methylbutane or n-pentane for 24 hours, via a semi-occlusive patch. Thirty minutes after patch removal, the test sites were scored, and were scored again 24 hours after patch removal (Rue and Plaza, 1991). Test subjects remained under observation for a maximum of 4 hours after exposure. If the test material elicited severe reactions, the patches were removed. The average dermal irritation score for this test material was 0.27 on a scale from 0 to 7 for n-pentane. The average dermal irritation score for this test material was 0.33 on a scale from 0 to 7 for 2 -methylbutane. Therefore, both test substances were not likely to be irritating to humans.

Eye Irritation

 

Pentane

 

In a key ocular irrtiation study (ExxonMobil, 1996), the test material (n-Pentane0 was tested for ocular irritation in 3 New Zealand White rabbits at a single 0.1 mL dose. Observations were made at 1, 24, 48, and 72 hours after application for indications of ocular irritation. Reactions were scored based on the Draize Standard Eye Irritation Grading Scale (Draize, 1959). N-pentane caused ocular irritation of the conjunctiva in all three test animals. All animals showed signs of redness at 1 hour and 24 hours after the installation. In only one animal did redness persist until the 48 hour observation period; this same animal was the only one to exhibit chemosis and discharge responses (at the 1 hour interval). All 3 animals were cleared of any ocular irritation at the 72 hour observation.

 

This study received a Klimish score of 1, reliable without restriction, because it is in compliance with OECD principles of GLP and the E.U. Council Decision on GLP.

Respiratory Irritation

No studies were located to indicate that 2-methylbutane is a respiratory irritant.

Justification for classification or non-classification

Skin Irritation:

Based on the available substance specific and read across data, 2-methylbutane does not meet the criteria for classification for skin Irritation under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP). 2-methylbutane is, however, classified under EU CLP as EUH066 (Repeated exposure may cause skin dryness or cracking).

 

Ocular Irritation:

Based on available read across data, 2-methylbutane does not meet the criteria for classification as ocular irritants under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Respiratory Irritation:

There are no studies that warrant classification as a respiratory irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).