Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, <2% aromatics

Endpoint summary

Description of key information

Skin Irritation

Not irritating to the skin

 

Ocular Irritation

Not irritating to eyes

 

Respiratory Irritation

No studies were located to indicate that Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, <2% aromatics are respiratory irritants.

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

Study period:

2000/4/12-2000/6/22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to OECD test 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:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Source:Harlan UK Ltd
Number of Animals: Three
Age at study initiation: Approximately 13 weeks
Weight at study initiation: 2.7-3.2 kg
Housing: Individually
Diet (e.g. ad libitum): Special Diet Service STANRAB SQC (pellets); ad libitum
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 22d

ENVIRONMENTAL CONDITIONS
Temperature (°C): 18-21
Humidity (%): 53-65%
Photoperiod (hrs dark / hrs light): 12/12
Monitored at least once a day

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Amount(s) applied (volume or weight): 0.5 ml
Concentration (if solution): neat

Duration of treatment / exposure:

Test material was administered to the clipped backs as a single dose introduced under a gauze patch (secured with non-irritating tape) and held in contact with the skin by means of a semi-occlusive dressing for 4 hours. Residual test material was then removed.

Observation period:

24, 48, and 72h post application and once per day until Day 14

Number of animals:

Three females

Details on study design:

SCORING SYSTEM: Draize scale for dermal irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

ca. 2

Max. score:

2

Reversibility:

fully reversible within: 13 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

ca. 1.7

Max. score:

2

Reversibility:

fully reversible within: 13 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

ca. 2

Max. score:

2

Reversibility:

fully reversible within: 13 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.9

Max. score:

2

Reversibility:

fully reversible within: 13 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

ca. 1.3

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

2

Reversibility:

fully reversible

Irritant / corrosive response data:

Topical application of Petrepar 134 (50/50) elicited dermal responses in all animals. Well defined erythema and slight edema followed exposure and was resolved by day 13.

Interpretation of results:

other: R38 under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations. Not classified under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The average erythema score (24,48, and 72 hours) was 1.9, with 2 out of 3 animals having a mean (24-72 hour) erythema score of 2.0. The average edema score (24,48, and 72 hours) was 1.1. Based on the individual animal dermal irritation scores, the test substance warrants classification of the test material as a skin irritant (R38) under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations. 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).

Executive summary:

In this study, 3 rabbits were subjected to a 4h dermal (shaved) exposure of 0.5 ml of Petrepar 134 (50/50) via a semi-occluded patch. Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing and once a day for a total of 14 days according to the Draize method of scoring. Topical application of Petrepar 134 (50/50) elicited dermal responses in all animals. Well defined erythema and slight oedema followed exposure and was resolved by day 13. The average erythema score (24,48, and 72 hours) was 1.9, with 2 out of 3 animals having a mean (24-72 hour) erythema score of 2.0. The average edema score (24,48, and 72 hours) was 1.1. Based on the individual animal dermal irritation scores, the test substance warrants classification of the test material as a skin irritant (R38) under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations. 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).

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

1997/04/27- 1997/07/23

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 animals

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd
- Age at study initiation: adult
- Housing: individually
- Diet (e.g. ad libitum): Special Diets Services
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-19
- Humidity (%): 50-53
- 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:

4 hours

Observation period:

Dermal responses were evaluated approximately 60 minutes, 24, 48, and 72 hours following patch removal.

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: dorsal surface from the shoulder region to the lumbar region
- % coverage: N/A
- Type of wrap if used: under a gauze patch secured with tape, the patch was loosely held in contact with the skin by means of a semi-occlusive dressing


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


SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0.55

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: based on scores of three animals

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.66

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter	Basis	Time Point	Score	Reversibility
erythema score	animal #1	24 hours	1	Fully reversible by 72 hours
erythema score	animal #2	24 hours	1	Fully reversible by 72 hours
erythema score	animal #3	24 hours	1	Fully reversible by 72 hours
erythema score	animal #1	48 hours	1	Fully reversible by 72 hours
erythema score	animal #2	48 hours	1	Fully reversible by 72 hours
erythema score	animal #3	48 hours	0	Fully reversible by 72 hours
erythema score	animal #1	72 hours	0	Fully reversible by 72 hours
erythema score	animal #2	72 hours	0	Fully reversible by 72 hours
erythema score	animal #3	72 hours	0	Fully reversible by 72 hours
erythema score	mean	24 hour mean	1	Fully reversible by 72 hours
erythema score	mean	48 hour mean	0.66	Fully reversible by 72 hours
erythema score	mean	72 hour mean	0	Fully reversible by 72 hours
erythema score	mean	24-72 hour mean	0.55	Fully reversible by 72 hours
edema score	animal #1	24 hours	2	Fully reversible by 72 hours
edema score	animal #2	24 hours	1	Fully reversible by 72 hours
edema score	animal #3	24 hours	1	Fully reversible by 72 hours
edema score	animal #1	48 hours	1	Fully reversible by 72 hours
edema score	animal #2	48 hours	1	Fully reversible by 72 hours
edema score	animal #3	48 hours	0	Fully reversible by 72 hours
edema score	animal #1	72 hours	0	Fully reversible by 72 hours
edema score	animal #2	72 hours	0	Fully reversible by 72 hours
edema score	animal #3	72 hours	0	Fully reversible by 72 hours
edema score	mean	24 hour mean	1.3	Fully reversible by 72 hours
edema score	mean	48 hour mean	0.66	Fully reversible by 72 hours
edema score	mean	72 hour mean	0	Fully reversible by 72 hours
edema score	mean	24-72 hour mean	0.66	Fully reversible by 72 hours

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 0.55 and 0.66 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:

The test material was administered  via semi-occlusive patch for four hours to three rabbits (3 female) to assess dermal irritation  Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing according to the Draize method of scoring.  Application of the test material elicited responses in all animals.  Erythema scores decreased as the study progressed.  Effects continued to subside until all animals were free of adverse clinical signs by study termination (Day 7).   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.

Reference 3

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.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

1990/02/09

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 animals

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd
- Age at study initiation: 12 weeks
- Housing: individually
- Diet (e.g. ad libitum): restricted
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 22 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:

4 hours

Observation period:

Dermal responses were evaluated approximately 60 minutes, 24, 48, and 72 hours following patch removal and on day 7.

Number of animals:

1 male; 5 females

Details on study design:

TEST SITE
- Area of exposure: dorsal surface from the shoulder region to the lumbar region
- % coverage: N/A
- Type of wrap if used: under a gauze patch secured with tape, the patch was loosely held in contact with the skin by means of a semi-occlusive dressing


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


SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.05

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter	Basis	Time Point	Score	Reversibility
erythema score	animal #1	60 min	2	Fully reversible by day 7
erythema score	animal #2	60 min	2	Fully reversible by day 7
erythema score	animal #3	60 min	1	Fully reversible by day 7
erythema score	animal #4	60 min	2	Fully reversible by day 7
erythema score	animal #5	60 min	2	Fully reversible by day 7
erythema score	animal #6	60 min	2	Fully reversible by day 7
erythema score	animal #1	24 hours	2	Fully reversible by day 7
erythema score	animal #2	24 hours	1	Fully reversible by day 7
erythema score	animal #3	24 hours	1	Fully reversible by day 7
erythema score	animal #4	24 hours	2	Fully reversible by day 7
erythema score	animal #5	24 hours	2	Fully reversible by day 7
erythema score	animal #6	24 hours	2	Fully reversible by day 7
erythema score	animal #1	48 hours	1	Fully reversible by day 7
erythema score	animal #2	48 hours	1	Fully reversible by day 7
erythema score	animal #3	48 hours	0	Fully reversible by day 7
erythema score	animal #4	48 hours	1	Fully reversible by day 7
erythema score	animal #5	48 hours	1	Fully reversible by day 7
erythema score	animal #6	48 hours	1	Fully reversible by day 7
erythema score	animal #1	72 hours	1	Fully reversible by day 7
erythema score	animal #2	72 hours	0	Fully reversible by day 7
erythema score	animal #3	72 hours	0	Fully reversible by day 7
erythema score	animal #4	72 hours	1	Fully reversible by day 7
erythema score	animal #5	72 hours	1	Fully reversible by day 7
erythema score	animal #6	72 hours	1	Fully reversible by day 7
erythema score	mean	24 hour mean	1.67	Fully reversible by day 7
erythema score	mean	48 hour mean	0.83	Fully reversible by day 7
erythema score	mean	72 hour mean	0.66	Fully reversible by day 7
erythema score	mean	24-72 hour mean	1.05	Fully reversible by day 7
edema score	animal #1	60 min	0
edema score	animal #2	60 min	0
edema score	animal #3	60 min	0
edema score	animal #4	60 min	0
edema score	animal #5	60 min	0
edema score	animal #6	60 min	0
edema score	animal #1	24 hours	0
edema score	animal #2	24 hours	0
edema score	animal #3	24 hours	0
edema score	animal #4	24 hours	0
edema score	animal #5	24 hours	0
edema score	animal #6	24 hours	0
edema score	animal #1	48 hours	0
edema score	animal #2	48 hours	0
edema score	animal #3	48 hours	0
edema score	animal #4	48 hours	0
edema score	animal #5	48 hours	0
edema score	animal #6	48 hours	0
edema score	animal #1	72 hours	0
edema score	animal #2	72 hours	0
edema score	animal #3	72 hours	0
edema score	animal #4	72 hours	0
edema score	animal #5	72 hours	0
edema score	animal #6	72 hours	0
edema score	mean	24 hour mean	0
edema score	mean	48 hour mean	0
edema score	mean	72 hour mean	0
edema score	mean	24-72 hour mean	0

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The mean erythema and edema scores for MRD-89-521 were 1.0 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-89-521 was administered  via semi-occlusive patch for four hours to six rabbits (1 male; 5 female) 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.  Application of the test material elicited responses in all animals.  At the 60 minute observation, five animals were noted with well-defined erythema and one animal was noted with very slight erythema.  Erythema scores decreased as the study progressed with four animals displaying well-defined erythema and two animals with very slight erythema at the 24 hour observation.  Effects continued to subside until all animals were free of adverse clinical signs by study termination (Day 7).  The mean erythema and edema scores for MRD-89-521 were 1.0 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 conclusion

Endpoint conclusion:

no adverse effect observed (not 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:

2000/03/08

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:

according 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: Harlan UK Ltd
- Age at study initiation: 13 weeks
- Weight at study initiation: 2.7 - 3.2 kg
- Housing: individual
- Diet (e.g. ad libitum): Special Diet Services STANRAB SQC pellet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 25 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 -23
- Humidity (%): 36-45
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: contralateral eye

Amount / concentration applied:

0.1mL

Duration of treatment / exposure:

The eyelids were gently held together for one second before releasing.

Observation period (in vivo):

1, 24, 48, and 72 hours post-treatment

Number of animals or in vitro replicates:

3

Details on study design:

Test material was applied to the eyes and the eyelids were gently held together for one second before releasing. Irritation and toxicity were monitored at 1, 24, 48, and 72 hours post-treatment. Irritation was scored according to the Draize methodology.

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

No corneal damage or iridial inflammation was observed. Hyperaemia of blood vessels of the conjuctivae was seen in all animals. Ocular reactions had resolved in all instances by one day after instillation.

Irritation parameter	Basis	Time Point	Score
conjuctivae score	animal #1	24 hours	0
conjuctivae score	animal #2	24 hours	0
conjuctivae score	animal #3	24 hours	0
conjuctivae score	animal #1	48 hours	0
conjuctivae score	animal #2	48 hours	0
conjuctivae score	animal #3	48 hours	0
conjuctivae score	animal #1	72 hours	0
conjuctivae score	animal #2	72 hours	0
conjuctivae score	animal #3	72 hours	0
conjuctivae score	mean	24 hour mean	0
conjuctivae score	mean	48 hour mean	0
conjuctivae score	mean	72 hour mean	0
conjuctivae score	mean	24-72 hour mean	0
chemosis score	animal #1	24 hours	0
chemosis score	animal #2	24 hours	0
chemosis score	animal #3	24 hours	0
chemosis score	animal #1	48 hours	0
chemosis score	animal #2	48 hours	0
chemosis score	animal #3	48 hours	0
chemosis score	animal #1	72 hours	0
chemosis score	animal #2	72 hours	0
chemosis score	animal #3	72 hours	0
chemosis score	mean	24 hour mean	0
chemosis score	mean	48 hour mean	0
chemosis score	mean	72 hour mean	0
chemosis score	mean	24-72 hour mean	0
cornea score	mean	24-72 hour mean	0
iris score	mean	24-72 hour mean	0

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The mean conjunctivae, chemosis, iris, and cornea scores for the Petrepar 134 (60/40) were 0.0, 0.0, 0.0, and 0.0 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.

Executive summary:

Petrepar 134 (60/40) (0.1 mL, neat) was administered to the right eye of three rabbits to assess occular irritation. Irritation and toxicity were monitored at 1, 24, 48, and 72 hours post-treatment. Irritation was scored according to the Draize methodology. No corneal damage or iridial inflammation was observed. Hyperaemia of blood vessels of the conjuctivae was seen in all animals. Ocular reactions had resolved in all instances by one day after instillation. The mean conjunctivae, chemosis, iris, and cornea scores for the Petrepar 134 (60/40) were 0.0, 0.0, 0.0, and 0.0 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.

Reference 2

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 conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There is no skin or eye irritation data available for Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics <2% aromatics. However, data is available for structural analogues, Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C11-C14, n-alkanes, <2% aromatics; Hydrocarbons, C12-C16, n-alkanes, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics; and Isohexadecane. This data is read across to Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, <2% aromatics 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.

Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics

In a key skin irritation study (Cepsa Quimica, 2000), 3 rabbits were subjected to a 4h dermal (shaved) exposure of 0.5 ml of test material (Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics) (50/50) via a semi-occluded patch. Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing and once a day for a total of 14 days according to the Draize method of scoring. Topical application of the test material (50/50) elicited dermal responses in all animals. Well defined erythema and slight oedema followed exposure and was resolved by day 13. The average erythema score (24,48, and 72 hours) was 1.9, with 2 out of 3 animals having a mean (24-72 hour) erythema score of 2.0. The average edema score (24,48, and 72 hours) was 1.1. Based on the individual animal dermal irritation scores, 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).

 

In a second key skin irritation study (Petrochem Carless, 1997), the test material (Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics) was administered  via semi-occlusive patch for four hours to three rabbits (3 female) to assess dermal irritation. Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing according to the Draize method of scoring. Application of the test material elicited responses in all animals. Erythema scores decreased as the study progressed. Effects continued to subside until all animals were free of adverse clinical signs by study termination (Day 7). 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).

 

In a supporting study (ExxonMobil, 1968), the test material (Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics) was administered via occlusive dermal patch on the skin of 100 human (female) test subjects for 48 hours. The test material was administered via semi-occlusive dermal patch on the skin of 25 human (female) test subjects for 48 hours. Clinical observations were made immediately after the patch was removed, 15 minutes, and 24 hours after post-application. In general minimal erythema was observed at the test site, with little to no noted edema. This study should be used for supporting purposes only due to the prolonged 48 hour exposure. Based on the minimal erythema displayed by the test subjects the test material was deemed to be a minimal dermal irritant.  

 

Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics

In a primary dermal irritation study (ExxonMobil, 1995) conducted according to OECD Guideline 404, six young adult male New Zealand White rabbits were dermally exposed to 0.5 mL of Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics. Test sites were covered with a semi-occlusive dressing for 4 hours. The skin reactions were assessed at 1, 24, 48 and 72 hours after removal of the dressing. The mean score was calculated across 3 scoring times for all animals at 24, 48 and 72 hours after patch removal. The mean scores over 24, 48 and 72 hours were 0.0 for erythema and for oedema.

Hydrocarbons, C12 -C16, n-alkanes, isoalkanes, cyclics, <2% aromatics

In a key study (ExxonMobil, 1995), the test substance (Hydrocarbons, C12 -C16, n-alkanes, isoalkanes, cyclics, <2% aromatics) was administered via semi-occlusive patch for four hours to six rabbits (1 male; 5 female) 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. Application of the test material elicited responses in all animals. At the 60 minute observation, five animals were noted with well-defined erythema and one animal was noted with very slight erythema. Erythema scores decreased as the study progressed with four animals displaying well-defined erythema and two animals with very slight erythema at the 24 hour observation. Effects continued to subside until all animals were free of adverse clinical signs by study termination (Day 7). The mean erythema and edema scores for MRD-89-521 were 1.0 and 0 respectively. 

Isohexadecane

In a clinical test including 15 human volunteers (Hill Top Research, 1994), isohexadecane was applied undiluted on upper arm in occlusive consitions (patch) for 24 h. Skin reactions were scored 30 min and 24 h after removal of the patch.

Mild signs of irritation were observed in only 3 volunteers and only slight signs of irritation in 8 volunteers in worse conditions (24-h exposure, occlusive conditions), leading to the conclusion that isohexadecane is not irritant for human skin.

In a supporting study (INEOS, 1980), the skin irritating properties of the substance isohexadecane was assessed in White Vienna rabbits (3 animals of both sexes). The test substance was applied on a wipe put in contact with the shaved skin under semi-occlusive dressing for 24 hours. At the end of exposure, skin reactions were recorded both at 24 hours (patch removal) and 48 hours after the end of exposure (i.e. 72 -hour time observation) according to the Draize scale. Complete observation time was 14 days.

Moreover, the behavior, general state and food consumption were also observed. Body weight was measured every day. There was a very slight erythema (score 1) in two rabbits at patch removal (observation time = 24h). At the 72-hour observation, no erythema was observed in all 6 animals. No oedema was noted in any animal at any observation time.

No systemic effect was observed following exposure to Isohexadecane. Behavior, general state, fur, food consumption and body weight development were normal.

 

Ocular 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.

Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics

In a key ocular irritation study (Cepsa Quimica, 2000), the test material (Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics; 60/40) (0.1 mL, neat) was administered to the right eye of three rabbits to assess ocular irritation. Irritation and toxicity were monitored at 1, 24, 48, and 72 hours post-treatment. Irritation was scored according to the Draize methodology. No corneal damage or iridial inflammation was observed. Hyperaemia of blood vessels of the conjunctivae was seen in all animals. Ocular reactions had resolved in all instances by one day after instillation. The mean conjunctivae, chemosis, iris, and cornea scores for the test material (60/40) were 0.0, 0.0, 0.0, and 0.0 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).

 

Isohexadecane

In a supporting study (INEOS, 1980), the irritant potential of the substance Isohexadecane was assessed by applying 0.1 mL of the test substance in the conjunctival sac of the left eye of 6 male Himalayan rabbits. After application the animals lid were kept closed for 1 second. The right eye was used as control and received 0.1 mL of physiological NaCl solution. The eyes were examined and the changes were graded according to a numerical scale at 15 min, 1, 24, 48 and 72 hours after dosing. No conjunctival chemosis, corneal and iridal lesion were observed throughout the observation period. Slight redness of the conjunctivae was observed in all animals at 1 hour but only in one animal by the 24 hours after instillation. At 48-hour observation period, no redness was observed in any rabbit. Hence, the mean individual score for redness was 0.33-0.0-0.0.

 

Respiratory Irritation

 

No studies were located to indicate that Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, <2% aromatics are respiratory irritants.

Justification for classification or non-classification

Skin Irritation:

Based on available read across data, Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics <2% aromatics do not meet the criteria for classification for 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, Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics <2% aromatics do not meet the criteria for classification as ocular irritants under the new Regulation (EC) 1272/2008 on classification, labeling 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, labeling and packaging of substances and mixtures (CLP).