2,2,3-trimethylbutane

Endpoint summary

Description of key information

Skin Irritation

Irritating to the skin

 

Ocular Irritation

Not irritating to eyes

 

Respiratory Irritation

Not irritating to the respiratory tract

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

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:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Cunicole de Val de Selle, Prouzel, France
- Weight at study initiation: average weight: 2.4 ± 0.05 kg
- Housing: individually housed; polystyrene cages with feeding bottles and troughs
- Diet: Lapins entretien référence 112 C (U.A.R., Villemoisson-sur-Orge, France); ad libitum during the study
- Water: filtered drinking water; ad libitum during the study
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin areas of the test animals served as controls

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

15 days after application (at 1, 24, 48, 72 hours and thereafter daily)

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 6 square centimetre
- Type of wrap if used: gauze bandage and compress


SCORING SYSTEM: OECD Draize Scoring System

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

other: reversible on day 8, but dryness of the skin

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

other: reversible on day 9, but dryness of the skin

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritant / corrosive response data:

At 1 hour after exposure, erythema were observed for all three animals and edema for two of three animals.

Interpretation of results:

other: Irritating

Remarks:

Criteria used for interpretation of results: other: GHS (EU, 2007)

Conclusions:

The test substance was irritating to the skin according to the criteria of the EU and the GHS.

Executive summary:

The test substance was irritating to the skin according to the criteria of the EU and the GHS.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles, acceptable for assessment.

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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Exposure continued for 24 hours instead of 4 hours, no observations planned past 72 hours following initial application

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

yes

Remarks:

Exposure continued for 24 hours instead of 4 hours, no observations planned past 72 hours following initial application

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

not specified

Preparation of test site:

other: abraded and intact

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:

Single application for 24 hours

Observation period:

72 hours

Number of animals:

3 males, 3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no (24-hour exposure)
-Time after start of exposure: 24 hours


SCORING SYSTEM: OECD Draize

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: 24/48/72h's score not specified

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: 24/48/72h's score not specified

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: 24/48/72h's score not specified

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

other: 24/48/72h's score not specified

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

other: 24/48/72h's score not specified

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

other: 24/48/72h's score not specified

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: 24/48/72h's score not specified

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

other: 24/48/72h's score not specified

Irritation parameter:

other: Primary irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0.25

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: 24/48/72h's score not specified

Irritant / corrosive response data:

Very slight erythema (grade 1) noted on abraded sites of 3 of 6 rabbits and intact sites of 3 of 6 rabbits at 72 hours post application. No other dermal effects were noted in the study.

Other effects:

No effects.

Initial protocol did not include provision for observation until reversibility up until 14-day observation period. Even though complete reversibility was not observed it was anticipated as was observed with irritation in dermal LD50 study.

 

The test substance was irritating to the skin based on persistent irritation at study termination.

Interpretation of results:

other: Irritating

Remarks:

Criteria used for interpretation of results: other: CLP

Executive summary:

The test substance was irritating to the skin based on persistent irritation at study termination.

Reference 3

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:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

18 September 2000 - 26 July 2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions.

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:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products Inc. (formerly HRP), Denver, PA, USA
- Age at study initiation: approximately 15 - 16 weeks
- Weight at study initiation: 2.41 - 2.73 kg
- Housing: single housed during study; suspended stainless steel and wire mesh with absorbent paper below cages
- Diet (e.g. ad libitum): PMI Certified Rabbit Diet 5322; feed was analysed and not contaminated; the animals received new feed each day and the old feed, if any, was discarded. Availability of feed was checked at least once daily for all animals.
- Water (e.g. ad libitum): ad libitum, automatic watering system; water was analysed and not contaminated; availability of water was checked at least once daily for all animals
- Acclimation period: 22 days; animals were examined for viability at least once daily
- Other: animal identification by ear tags and corresponding cage identification


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8 - 22.2°C (64 - 72 degrees Fahrenheit)
- Humidity (%): 30 - 70 % relative humidity
- Photoperiod (hrs dark / hrs light): approx. 12 h light (06.00 - 18.00) and 12 h dark (18.00 - 06.00)

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

see observation period: The test substance was not washed out.

Observation period (in vivo):

1, 24, 48, 72 hours and 7 days

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize Standard Eye Irritation Grading Scale (Draize 1959: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Association of Food and Drug Officials of the US, vol. 49, pp. 2-56.

TOOL USED TO ASSESS SCORE: 2 % sodium fluorescein

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritant / corrosive response data:

Ocular instillation of the test substance elicited conjunctival responses in all animals. Iridic and corneal responses were not evident during the study. Conjunctival responses consisted of redness of Grade 2 in all animals and discharge of Grade 1 and Grade 2 for one animal each at the 1 hour evaluation. Discharge was not evident after the 1 hour evaluation but redness of Grade 1 was noted for 2 animals at the 24 and 48 hour evaluations. Redness of Grade 1 also was noted for all animals at 72 hour evaluation. Irritation was not evident at the Day 7 evaluation and the study was terminated.

Other effects:

All animals survived the study termination and were free of clincial signs during the study.

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: other: GHS (EU, 2007)

Conclusions:

Based on the study design the test substance, hydrocarbons, C7-C9, isoalkanes, is not irritating.

Executive summary:

Based on the study design the test substance, Hydrocarbons, C7-C9, isoalkanes, is not irritating.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles, acceptable for assessment.

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 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Observation day past 7 days post exposure not planned

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

Observation day past 7 days post exposure not planned

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animals served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 males, 3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes

SCORING SYSTEM: Draize scale for scoring ocular lesions

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: female rabbit

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effects

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effect

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effect

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effect

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effect

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritant / corrosive response data:

Conjunctival redness (grade 2) was noted in four rabbits at 1 hour post instillation and persisted in one rabbit to 24 hours. The redness reversed by 48 hours. No corneal opacity, iritis, conjunctival chemosis, or discharge was noted in any of the six rabbits.

Other effects:

No effects.

The initial protocol did not include provision for 21-day observation, but it was not necessary as all irritation reversed by 48 hours after instillation, which is acceptable per current protocols.

The test substance was not irritating to the eyes according to the criteria of the EU and the GHS.

Interpretation of results:

other: not irritating

Remarks:

Criteria used for interpretation of results: other: GHS, EU, 2007

Conclusions:

Based on the study design the test substance, 2,2,4-trimethylpentane, is not irritating.

Executive summary:

Based on the study design the test substance, 2,2,4 -trimethylpentane, is not irritating.

Reference 3

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 adverse effect observed (not irritating)

Additional information

No irritation data is available for 2,2,3-Trimethylbutane. However, irritation data is available for structural analogues, Hydrocarbons, C7-C9, isoalkanes (skin and eye irritation) and 2,2,4-trimethylpentane (skin, eye, and respiratory irritation) and presented in the dossier. This data is read across to 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

 

Hydrocarbons, C7-C9, isoalkanes

The skin irritation potential of hydrocarbons, C7-C9, isoalkanes was determined according to OECD 404 (Total Solvants, 2000). The test substance was applied to the intact skin of rabbits for 4 hours under semiocclusive conditions. After removal of the test substance, no edema, but well-defined to moderate erythema were noted in all three animals. Irritating effects were reversible within 9 days. Under the test conditions, the test substance was irritating to the skin.

2,2,4-trimethylpentane

 

In a primary skin irritation study (Chevron Phillips Chemicals, 1982), 2,2,4 -trimethylpentane was applied to the intact skin of rabbits for 24 hours. At 72 hours post application, very slight erythema (grade 1) were observed in 3 of 6 rabbits. No other dermal effects were noted in the study. Based on persistent irritation at premature study termination (reversibility was not seen 72 hours after application), 2,2,4 -trimethylpentane was considered to be skin irritating.

 

Eye Irritation

 

Hydrocarbons, C7-C9, isoalkanes

The eye irritation potential of hydrocarbons, C7-C9, isoalkanes was determined by instillation of 0.1 mL of the test material into the conjunctival sac of 3 rabbits (ExxonMobil, 2004). Ocular reactions were examined and scored 1, 24, 48, 72 hours after application. At the 1 hour evaluation, conjunctival redness (grade 2) was observed in all animals. Conjunctival redness (grade 0-1) was also noted in all animals at the 72 hour evaluation. All redness was reversible within 7 days. No corneal opacity, iritis or conjunctival chemosis was noted in any of the 3 rabbits.

 

Two further studies, performed according to OECD 404, showed that no ocular irritation in any animal at any time point could be observed for hydrocarbons, C7-C9, isoalkanes (both studies from ExxonMobil, 1997a,b).

 

In another study of ExxonMobil (1962c) conducted similar to OECD 405, at 1 hour after administration, 4 of 6 animals showed slight erythema which completely subsided by the 4 hour observation. The remaining 2 animals showed slight or moderate erythema, slight oedema, and slight discharge. These irritating effects were fully reversible within 72 hours after administration. Under the test conditions, hydrocarbons, C7-C9, isoalkanes was not irritating to the eyes.

2,2,4-trimethylpentane

 

The eye irritation potential of 2,2,4 -trimethylpentane was determined by instillation of 0.1 mL of the test material into the conjunctival sac of rabbits with subsequent washing (Chevron Phillips Chemicals, 1982). Conjunctival redness (grade 2) was noted in 4 of 6 rabbits at 1 hour post instillation and persisted in one rabbit to 24 hours. The redness reversed by 48 hours. No corneal opacity, iritis, conjunctival chemosis, or discharge was noted in any of the 6 rabbits.

 

In another primary eye irritation study (Chevron Phillips Chemicals, 1982), the treated eyes of all animals remained unwashed. Conjunctival redness (grade 2) was noted in 3 of 6 rabbits at 1 hour post instillation and persisted in two rabbits to 24 hours. All redness reversed by 48 hours. No corneal opacity, iritis, conjunctival chemosis, or discharge was noted in any of the 6 rabbits.

 

Respiratory Irritation

 

2,2,4-trimethylpentane

 

In a study examining respiratory tract irritancy (Chevron Phillips Chemicals, 1982), exposure to 2,2,4-trimethylpentane at a nominal concentration of 33.52 mg/L of air did elicit an apparent response from the animals upon exposure, however, it did not appear to produce upper airway irritancy in the mice.

Justification for classification or non-classification

Skin Irritation:

Based on available read across data, 2,2,3-Trimethylbutane meets the criteria for classification as a skin irritant (Skin Irrit. 2; H315; causes skin irritation) under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Ocular Irritation:

Based on available read across data, 2,2,3-Trimethylbutane does not meet the criteria for classification as an ocular irritant under the new Regulation (EC) 1272/2008 on classification, labelling 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, labelling and packaging of substances and mixtures (CLP).