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
Study period:
1989-12-13 to 1990-02-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report equivalent or similar to OECD guideline 404: 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
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
six test animals
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Denver, PA
- Age at study initiation: ca. 15 weeks
- Weight at study initiation: ca 2.0-3.0 kg
- Housing: individual
- Diet (e.g. ad libitum): restricted diet based on the recommendation of the supplier
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 37 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-70
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12


Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml

Duration of treatment / exposure:
ca. 4 hours
Observation period:
Dermal responses were evaluated approximately 45 minutes, 24, 48 and 72 hours following patch removal, and on Day 7.

Body weights were recorded on the day of dosing.
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: back
- Type of wrap if used: gauze patch which was secured with tape, patch was loosely held in contact with the skin by means of semi-occlusive dressing


REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed using reverse osmosis water and paper towels.
- Time after start of exposure: 4h


SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.56
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The mean erythema and edema scores for the test material were 1.56 and 0 respectively. Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

MRD-89-520 was administered  via semi-occlusive patch for four hours to six male rabbits to assess dermal irritation.  Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing and on Day 7 according to the Draize method of scoring. Dermal responses were observed in all animals.  At the 45 minute, 48 hour and 72 hour observations, three animals displayed well-defined erythema and three displayed very slight erythema.  Four animals were noted with well-defined erythema and two were noted with very slight erythema at the 24 hour observations.  At study termination (Day 7), four animals showed very slight erythema   No other dermal observations were noted during the study.  The mean erythema and edema scores for MRD-89-520 were 1.56 and 0 respectively.  Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

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 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

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:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report equivalent or similar to OECD guideline 405: 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
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products
- Age at study initiation: ca. 12 weeks
- Weight at study initiation: 2.14-2.49 kg
- Housing: individually
- Diet (e.g. ad libitum): Agway restricted feeding regimen
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-70
- Humidity (%): 40-60%
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 1991-05-09 To: 1997-05-21
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of each animal served as the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1ml

Duration of treatment / exposure:
The test material was instilled into the lower conjunctival sac of the right eye of each animal. The upper and lower lids were gently held together for approximately 1 second to prevent loss of the material. The treated eyes remained unwashed.
Observation period (in vivo):
Animals were observed for viability twice daily on Monday-Friday, and once daily on Saturday and Sunday. Observations of signs of ocular irritation were made 1, 24, 48, and 72 hours post-instillation and on Day 7.
Number of animals or in vitro replicates:
six males
Details on study design:

SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: 2% sodium fluorescein dye under UV light
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: average of six animals
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: average of six animals
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: average of six animals
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: average of six animals
Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The mean corneal opacity, iris lesion, conjunctivae redness, and chemosis scores for MRD-91-972 were all 0. Classification as an ocular irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

MRD-91-972 was administered to the right eye of six male rabbits to assess for ocular irritation. Ocular examinations occurred at 1h, 24h, 48h, 72h, and day 7 post instillation. Ocular damage was assessed and scored according to the Draize eye test. All animals survived the exposure. Ocular instillation of the test material elicited conjunctival irritation limited to redness noted in five of the six test animals at the 1 hour observation.  No other signs of ocular irritation were noted during the study.  The mean corneal opacity, iris lesion, conjunctivae redness, and chemosis scores for MRD-91-972 were 0, 0, 0, and 0 respectively. Classification as an ocular irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

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

A respiratory irritation study is available for Octane. No skin or eye irritation data is available for Octane, however; data is available for structural analogues 2,2,4-trimethylpentane and Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics. 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, C9-C11, isoalkanes, cyclics, <2% aromatics

In a key study (ExxonMobil, 1990), the test material (Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics) was administered via semi-occlusive patch for four hours to six male rabbits to assess dermal irritation.  Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing and on Day 7 according to the Draize method of scoring. Dermal responses were observed in all animals.  At the 45 minute, 48 hour and 72 hour observations, three animals displayed well-defined erythema and three displayed very slight erythema.  Four animals were noted with well-defined erythema and two were noted with very slight erythema at the 24 hour observations.  At study termination (Day 7), four animals showed very slight erythema   No other dermal observations were noted during the study.  The mean erythema and edema scores were 1.56 and 0 respectively. 

 

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

 

Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics

In a key study (ExxonMobil, 1991), the test material (Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics) was administered to the right eye of six male rabbits to assess for ocular irritation. Ocular examinations occurred at 1h, 24h, 48h, 72h, and day 7 post instillation. Ocular damage was assessed and scored according to the Draize eye test. All animals survived the exposure. Ocular instillation of the test material elicited conjunctival irritation limited to redness noted in five of the six test animals at the 1 hour observation.  No other signs of ocular irritation were noted during the study. The mean corneal opacity, iris lesion, conjunctivae redness, and chemosis scores were 0, 0, 0, and 0 respectively.

 

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 (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

 

Octane

In a supporting study (Chevron Phillips Chemicals, 1983), the respiratory tract irritation potential of Octane was examined in male CD-1 mice (4/dose) treated via inhalation. Mice received 2 treatments of 1 minute separated by a 10-minute non-treatment period in a head only exposure chamber of 24.88 or 100 mg/L of Octane. Plethysmographic respiratory patterns (shown to be indicative of irritation) were noted after exposure to room air (control), after the first 1-minute exposure and after the second 1-minute exposure. No graphic patterns indicative of respiratory pauses were evident throughout the exposures, therefore, Octane was not considered to be a respiratory irritant.

Justification for classification or non-classification

Skin Irritation:

Based on available read across data, skin irritating effects are expected from exposure to Octane. Therefore the substance is considered a skin irritant and classified as a Category 2 skin irritant.

 

Ocular Irritation:

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

Respiratory Irritation:

Based on available data, Octane 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).