Registration Dossier

Administrative data

Description of key information

2,4,4-trimethylpentene (purity>95%) does not cause irritation to skin or eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Froxfield SPF Rabbits, Broadway Farm, Froxfield, Hampshire, England
- Age at study initiation: Approximately 3 months
- Weight at study initiation: 2.23-2.52 kg
- Housing: Individually housed in suspended stainless steel cages
- Diet: Standard pelleted rabbit diet (STANRAB (P) SQC - Special Diets Services Ltd., Witham, Essex, England) ad libitum
- Water: Tap water ad libitum
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature: 18-25°C
- Humidity: 40-68%
- Air changes: at least 10/hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 28 May 1996 To: 12 June 1996
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
Amount(s) applied: 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
16 days
Number of animals:
3
Details on study design:
TEST SITE
- Day prior to application, the dorsum between the limb girdles was clipped
- Two areas 6 cm x 6 cm on either side of dorsum were marked
- Area of exposure: 3 cm x 2 cm on left dorsum
- Type of wrap: gauze patch (3 cm x 2 cm) held in place by strips of Blenderm. Pads of cotton wool and elasticated bandage used to protect patches and ensure good contact between skin and test substance
- Control site: 3 cm x 2 cm on right dorsum was covered by similar semi-occlusive dressing but otherwise remained untreated

REMOVAL OF TEST SUBSTANCE
- Washing: skin sites gently washed with warm water and dried with paper tissues
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize, 1959
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours after removal of dressings
Score:
1.6
Max. score:
2
Reversibility:
fully reversible within: 13 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritant / corrosive response data:
Very slight/ well defined erythema, spreading beyond test site, was present during first 7-10 days after application. Eschar formation was apparent in all animals 24 hours after dressing removal, resolving in one rabbit at 48 hours and in others by day 7. Exfoliation was evident at all test sites during the 2nd week and was still present in one animal at termination on day 16.

 Skin irritation scores according to the Draize scheme

Time

Erythema (Test/Control sites)

Oedema (Test/Control sites)

 Animal number

837

847

766

837

847

766

after 1 hour

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

after 24 hours

2*s/ 0

2*s/ 0

2*s/ 0

0 / 0

0 / 0

0 / 0

after 48 hours

1*/ 0

1*s/ 0

2*s/ 0

0 / 0

0 / 0

0 / 0

after 72 hours

1*/ 0

1*s/ 0

2*s/ 0

0 / 0

0 / 0

0 / 0

mean scores 24-72h

1.3

1.3

2

0

0

0

Overall mean score (24-72 h)

1.6

0

*   lesion spread beyond test site

s    eschar formation

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Mean values for erythema and oedema (at 24, 48 and 72 hours after application) did not equal or exceed EU limit values. Therefore, 2,4,4-trimethylpentene does not require classification for skin irritation.
Executive summary:

Skin irritation was assessed in a group of New Zealand white rabbits by applying 0.5 mL undiluted 2,4,4-trimethylpentene to the shaved skin under a semi-occlusive dressing for 4 hours. Very slight/ well defined erythema, spreading beyond test site, was present during first 7-10 days after application. Eschar formation was apparent in all animals 24 hours after dressing removal, resolving in one rabbit at 48 hours and in others by day 7. Exfoliation was evident at all test sites during the 2nd week and was still present in one animal at termination on day 16. Mean values for erythema and oedema (at 24, 48 and 72 hours after application) did not equal or exceed EU limit values. Therefore, 2,4,4-trimethylpentene does not require classification for skin irritation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: Froxfield SPF Rabbits, Broadway Farm, Froxfield, Hampshire, England
- Age at study initiation: Approximately 5 months
- Weight at study initiation: 2330-2510 g
- Housing: Individually housed in suspended stainless steel cages
- Diet: Standard pelleted rabbit diet (STANRAB (P) SQC - Special Diets Services Ltd., Witham, Essex, England) ad libitum
- Water: Tap water ad libitum
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature: 18-25°C
- Humidity: 40-68%
- Air changes: at least 10/hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 24 June 1996 To: 2 July 1996
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Single instillation into the conjunctival sac
Observation period (in vivo):
Observed constantly for several minutes immediately after instillation. At least twice during first hour after instillation and at least twice daily thereafter.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: As described in the regulatory guidelines and in addition: assessment of initial pain on a 0-5 scale, eye discharge on a 0-4 scale and area of cornea affected by lesions (if any) on a 0-4 scale

TOOL USED TO ASSESS SCORE: ophthalmoscope or pencil beam torch
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.86
Max. score:
3
Reversibility:
fully reversible within: 8 days in 2 rabbits
Remarks on result:
other: reversible in 72 h in 1 rabbit
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
Instillation caused slight initial pain in one animal but there was no initial pain response in the other 2 animals.
Injection of the conjunctival blood vessels was present in each animal during the first 72 hours after instillation and iritis was present in one animal at the 1 hour assessment only. All signs of eye irritation had resolved by day 8.

Eye irritation scores according to the Draize scheme

Time

Cornea

Iris

Conjunctiva

 

 

 

 

Redness

Chemosis

 Animal number

703

716

717

703

716

717

703

716

717

703

716

717

after 1 hour

0

0

0

1

0

0

1

1

1

0

0

0

after 24 hours

0

0

0

0

0

0

1

1

1

0

0

0

after 48 hours

0

0

0

0

0

0

1

1

1

0

0

0

after 72 hours

0

0

0

0

0

0

1

1

0

0

0

0

mean scores 24-72h

0

0

0

0

0

0

1

1

0.6

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
2,4,4-trimethylpentene is not classified as "irritant to the eye" according to the EU classification scheme.
Executive summary:

Eye irritation was assessed in a group of New Zealand white rabbits. 0.1 ml undiluted 2,4,4-trimethylpentene was instilled in the conjunctival sac and animals were observed for up to 8 days. Instillation caused slight initial pain in one animal but there was no initial pain response in the other 2 animals. Injection of the conjunctival blood vessels was present in each animal during the first 72 hours after instillation and iritis was present in one animal at the 1 hour assessment only. All signs of eye irritation had resolved by day 8. The mean values for ocular lesions at 24, 48 and 72 hours after instillation did not equal or exceed the EU limit values for classification of 2,4,4-trimethylpentene as "irritant to the eye".

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Guideline skin and eye irritation studies on 2,4,4 -trimethylpentene (>95% purity) have concluded that the material does not cause irritation to skin or eyes (HLS, 1996c; HLS, 1996d). Studies on diisobutylene (purity about 85%) have concluded that this material was moderately irritating to skin but was very slightly irritating to the eye (WIL, 2005a; WIL, 2005b).


Justification for selection of skin irritation / corrosion endpoint:
Available information indicates that this substance is not a skin irritant

Justification for selection of eye irritation endpoint:
Available information indicates that this substance is not an eye irritant

Justification for classification or non-classification

On the basis that the material of interest is 2,4,4 -trimethylpentene of purity >95%, the results of guideline skin and eye irritation studies indicate the substance does not warrant classification.