Registration Dossier

Administrative data

Description of key information

Based on assessment of the available data for 2-methylbut-2-ene (2M2B) should be considered as mildly irritating to skin and non-irritating to eyes.  The respiratory tract irritation potential of 2M2B is not known, as no data are available for this endpoint. 

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, available as unpublished report, near guideline study, minor restrictions in design and/or reporting but otherwise adequate for assessment
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Shell Toxicology Laboratory, Breeding Unit, Tunstall, UK
- Age at study initiation: 4-6 months
- Weight at study initiation: 2982-4208 g males, 3930-4915 g males
- Housing: Individually in hanging stainless steel cages with all mesh floors and tops and half mesh fronts (58 x 43 x 43 cm)
- Diet: SG1 with vitamin C supplement (Grain Harvesters Ltd.) ad libitum
- Water: Filtered public water ad libitum.
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 16-19 °C

IN-LIFE DATES: From: 7 May 1980 To: 18 July 1980
Type of coverage:
occlusive
Preparation of test site:
other: closely shorn. One site abraded and one site 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:
24 hours
Observation period:
7 days
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
- Area of exposure: 2cm x 2 cm
- Type of wrap if used: 2 cm x 2 cm lint patch, occluded by an impervious polythene sheet held in place with elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not washed
- Time after start of exposure: Dressings removed after 24 hours

SCORING SYSTEM: Graded scale of 0-4 for both erythema and oedema
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.8
Remarks on result:
other: non-abraded skin sites only
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.6
Remarks on result:
other: non-abraded skin sites only
Irritation parameter:
other: Primary irritation score (according to Draize)
Basis:
mean
Score:
1.79
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: mildly irritating to skin (grade 4)
Irritant / corrosive response data:
Application sites at day 7 were dry and flaking.

Table1: Individual and mean skin irritation scores of 2-methyl-2-butene (non-abraded skin) according to the Draize scheme

Time

Erythema

Oedema

Animal number

1564F

1565F

1573F

1574M

1576M

1575M

1564F

1565F

1573F

1574M

1576M

1575M

after 24 hours

1

1

0.5

1

0

0

1

0.5

0.5

1

0

0

after 48 hours

1.5

2

0.5

1

0

0

1

1

0.5

1

0

0

after 72 hours

1.5

2

1

1

0

0

1

1

1

1

0

0

mean score 24-72 h

0.8

0.6

after 7 days

2

2

1

2

0

0

1

1

1

2

0

0

 

Table2: Individual and mean skin irritation scores of 2-methyl-2-butene (abraded skin) according to the Draize scheme

Time

Erythema

Oedema

Animal number

4915

3930

4155

4208

4030

3074

4915

3930

4155

4208

4030

3074

after 24 hours

1

1

1

2

1

0.5

1

0.5

0.5

1

0.5

0

after 48 hours

1.5

2

1.5

2

1

0.5

1

1

0.5

1

0.5

0

after 72 hours

2

2

2

2

1

0.5

1

1

0.5

1

0.5

0

mean score 24-72 h

1.4

0.6

after 7 days

2

2

2

2

1

0.5

1

1

1

2

0

0

 

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
2-methyl-2-butene was mildly irritating to rabbit skin (grade 4).
Executive summary:
2-methyl-2-butene was mildly irritating to rabbit skin (grade 4).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, available as unpublished report, near guideline study, minor restrictions in design and/or reporting but otherwise adequate for assessment
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Shell Toxicology Laboratory, Breeding Unit, Tunstall, UK
- Age at study initiation: 4-6 months
- Weight at study initiation: 2982-4208 g males, 3930-4915 g males
- Housing: Individually in hanging stainless steel cages with all mesh floors and tops and half mesh fronts (58 x 43 x 43 cm)
- Diet: SG1 with vitamin C supplement (Grain Harvesters Ltd) ad libitum.
- Water: Filtered public water ad libitum.
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 16-19 °C

IN-LIFE DATES: From: 7 May 1980 To: 18 July 1980
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.2 mL
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: Initial pain scored on a 1-6 scale. Eye irritation scored according to the Draize scale. Mean total scores transcribed to a grade and descriptive rating using a modification of the Kay and Calandra technique.

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 hour, 1, 2, 3 and 7 days
Score:
0.5
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 hour, 1, 2, 3 and 7 days
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1 hour, 1, 2, 3 and 7 days
Score:
0

Immediately following instillation into the eye, all rabbits showed signs of moderate initial pain (grade 4).

Table 1: Eye irritation scores of 2-methyl-2-butene according to the Draize scheme 

Time (hours)

Cornea

Iris

Conjunctiva

Redness

Chemosis

1

1

2

3

4

5

6

1

2

3

4

5

6

1

2

3

4

5

6

1

2

3

4

5

6

24

0

0

0

0

0

0

0

0

0

0

0

0

0.5

0

0

0

0

0.5

0

0

0

0

0

0

48

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

72

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

mean 24-72

0

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
2-methyl-2-butene was non irritant to the rabbit eye.
Executive summary:

Instillation of 2-methyl-2-butene into the eye resulted in a moderate initial pain response (grade 4) in all animals. The mean total scores for the responses of the conjunctiva, cornea and iris at 1 hour, 1, 2, 3 and 7 days were calculated and were. 0.5, 0, 0, 0 and 0 respectively.

 

2-Methyl-2-butene may be described as non irritating to rabbit eyes.

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

Respiratory irritation

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

Additional information

Skin Irritation

Studies in Animals

An occlusive patch test based on the method of Draize (1975) was used to assess the primary skin irritation induced by 2M2B applied neat. The mean erythema and oedema scores for abraded and non-abraded skin were 0.8 and 0.6 i.e. <2 and <1 respectively. The primary irritation score calculated according to the method of Draize was 1.79.

On this basis 2M2B may be regarded as being mildly irritating to rabbit skin. The erythema and oedema scores at 7 days were higher than those at 72 hours but at 7 days all the skin patches were beginning to dry out and flake. It is possible the animals scratching these areas was a contributory factor, resulting in the slightly higher erythema scores (SRC, 1980).

Studies in Humans

No human information available

Eye Irritation

Studies in Animals

The method of Draize (1963) was used to assess the eye irritancy of 2M2B in New Zealand White rabbits. Instillation of 2M2B into the eye resulted in a moderate initial pain response (grade 4) in all animals. Mean total scores for the responses of the conjunctiva, cornea and iris were 0.5, 0 and 0 (i.e. all ≤0.5) and based on these results, 2M2B should be considered as non-irritating to rabbit eyes (SRC, 1980).

Studies in Humans

No human information available

Respiratory Tract Irritation

No studies on respiratory tract irritation have been conducted with 2M2B.  From the acute inhalation study and repeat dose study (HLS, 2003) there is no specific evidence of acute irritation effects warranting classification.

 


Justification for selection of skin irritation / corrosion endpoint:
Available data indicate the occurrence of mild persistent skin irritation

Justification for selection of eye irritation endpoint:
Available data indicate no potential to cause eye irritation

Effects on skin irritation/corrosion: slightly irritating

Justification for classification or non-classification

Based on assessment of the available data, 2M2B does not warrant classification as a respiratory tract or eye irritant under CLP. 

For skin irritation, all responses were below the threshold scores for classification however on the basis of criteria that inflammation of the skin is also significant if it persists in at least two animals (implied of 3, i.e. 4 of 6) at the end of the observation time, classification as category 2 (H315: causes skin irritation) may be warrented under CLP.