Registration Dossier

Diss Factsheets

Administrative data

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

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
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:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
0.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
other: Primary irritation score
Basis:
mean
Time point:
72 h
Score:
0.25
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: 24/48/72h data not specified
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: 24/48/72h data 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
Conclusions:
The test substance was irritating to the skin based on persistent irritation at study termination.
Executive summary:

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

Endpoint:
skin corrosion: 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

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
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, Isooctane, is not irritating.
Executive summary:

Based on the study design the test substance, Isooctane, is not irritating.

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

Respiratory irritation data is available for Heptane. Skin and eye irritation data are available for structural analogue 2,2,4-trimethylpentane. 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

 

2,2,4-trimethylpentane

In a key primary skin irritation study (Chevron Phillips Chemicals, 1982), 2,2,4-trimethylpentane was applied to the intact skin of rabbits for 24 hours. Animals were observed for 72 hours and dermal responses were evaluated according to the Draize method of scoring. At 72 hours post application, very slight erythema (grade 1) was 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

 

2,2,4-trimethylpentane

In a key eye irritation study (Chevron Phillips Chemicals, 1982), 0.1 mL of 2,2,4-trimethylpentane was instilled into the conjunctival sac of rabbits with subsequent washing. Ocular damage was assessed and scored according to the Draize eye test. 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. Under the conditions of this study, 2,2,4-trimethylpentane was considered to be not irritating.

 

In a supporting eye irritation study of (Chevron Phillips Chemicals, 1982), 0.1 mL of 2,2,4-trimethylpentane was instilled into the conjunctival sac of rabbits. The treated eyes of all animals remained unwashed. Ocular damage was assessed and scored according to the Draize eye test. 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. Under the conditions of this study, 2,2,4-trimethylpentane was considered to be not irritating.

 

Respiratory Irritation

 

Heptane

The respiratory tract irritation potential of Normal-Heptane was investigated in mice after single exposure to 29.29 mg/mL followed by 81.9 mg/mL heptane separated by a 10 min exposure to room air only (Chevron Phillips Chemicals, 1982). This exposure regimen failed to produce respiratory irritancy in mice. measured as sensory irritation, e.g., increased respiration rate.

Justification for classification or non-classification

Skin Irritation:

Based on available read across data, Heptane 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, Heptane 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:

Based on available data, Heptane does not meet the criteria for classification as a respiratory irritant under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP).