Hydrocarbons, C4, 1,3-butadiene-free, polymd., tetraisobutylene fraction, hydrogenated

Endpoint summary

Description of key information

Skin Irritation

Irritating to the skin

Ocular Irritation

Not irritating to eyes

Respiratory Irritation a

No studies were located to indicate that Hydrocarbon, C4, 1,3-butadiene-free, polymd,, tetraisobutylylene fraction, hydrogenated is a respiratory irritant.

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:

experimental study

Adequacy of study:

key study

Study period:

2000/10/12-2000/10/18

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:Covance Research Products Inc.
Number of Animals: Three males
Age at study initiation: Approximately 13 weeks
Weight at study initiation: 2.7-3.2 kg
Housing: Individually
Diet (e.g. ad libitum): PMI Cert. Rabbit Diet; limited
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 8d

ENVIRONMENTAL CONDITIONS
Temperature (°F): 64 to 72
Humidity (%): 30 to 70%
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 males

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: 14 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

ca. 2.3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

ca. 2.7

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

ca. 1.3

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

ca. 1.3

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

ca. 1.7

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:

All animals survived to study termination, were free of adverse clinical signs, and displayed normal body weight patterns during the test period.

Topical application of the test substance to the skin of rabbits elicited dermal irritation in all animals during the study. Erythema and edema were observed in all animals.

Erythema started as Grade 2 erythema in all animals at the 60-minute evaluation and remained the same at the 24-hour evaluation. Erythema increased slightly at the 48- hour evaluation when two animals displayed Grade 2 erythema and one animal displayed Grade 3 erythema. Erythema reached its maximum severity at the 72- hour evaluation when one animal displayed Grade 2 erythema and two animals displayed Grade 3 erythema. Erythema subsided after the 72-hour evaluation and on Days 7 and 10 all animals displayed Grade 1 erythema. At the Day 14 evaluation one animal displayed Grade 1 erythema.

Edema was first noted and was most severe at the 60-minute evaluation. Grade 2 edema was noted for all animals at this interval. Edema decreased slightly at the 24 and 48-hour evaluations when Grade 1 edema was noted in two animals and Grade 2 edema was noted in one animal. Edema increased slightly at the 72-hour evaluation when one animal displayed Grade 1 edema and two animals displayed Grade 2 edema. At the Day 7 evaluation Grade 1 edema was displayed by two animals and Grade 3 edema was displayed for one animal. After the Day 7 evaluation edema subsided. One animal displayed Grade 2 edema at Day 10 and one animal displayed Grade 1 edema at Day 14.
Supplemental dermal observations, which included desquamation and cracking, were noted on Days 7 and 10. Desquamation was noted for all animals at both intervals and cracking was noted for one animal on Day 7.

Interpretation of results:

other: Irritating

Remarks:

R38 Criteria used for interpretation of results: EU

Conclusions:

The average erythema score (24, 48, and 72 hours) was 2.33. The average edema score (24, 48, and 72 hours) was 1.1. The test material would be classified as a Category 2 dermal irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP). The test material would be classified as an R38 dermal irritant under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

In this study, 3 rabbits were subjected to a 4h dermal (shaved) exposure of 0.5 ml of MRD-00-710 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 MRD-00-710 elicited dermal responses in all animals. Well defined erythema and slight odema followed exposure.  The average erythema score (24, 48, and 72 hours) was 2.33.  The average edema score (24, 48, and 72 hours) was 1.1.  The test material would be classified as a Category 2 dermal irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP). The test material would be classified as an R38 dermal irritant under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997/10/08-1997/10/19

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: Elevage Cunicole de Val de Selle
Number of Animals: Three males
Age at study initiation: Approximately 13 weeks
Weight at study initiation: 2.6 +/-0.1 kg
Housing: Individually
Diet (e.g. ad libitum): 112 C pelleted diet
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 8d

ENVIRONMENTAL CONDITIONS
Temperature (°C): 15-21
Humidity (%): 30 to 70%
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 males

Details on study design:

SCORING SYSTEM: Draize scale for dermal irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

ca. 1.3

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

ca. 1.3

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

ca. 2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.53

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

A very slight or well-defined erythema was observed in all animals from day 1 up to day 9 or 10. A slight oedema was noted in two animals on day 1 only. Dryness of the skin was recorded in all animals from day 4or 5 up to day 1 or 11. Mean scores over 24, 48 and 72 hours for each animal were 1.3, 1.3 and 2.0 for erythema and 0.0, 0.0 and 0.0 for oedema.

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

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:

In this study, 3 rabbits were subjected to a 4h dermal (shaved) exposure of 0.5 ml of ECOLANE 90 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.  A very slight or well-defined erythema was observed in all animals from day 1 up to day 9 or 10. A slight oedema was noted in two animals on day 1 only. Dryness of the skin was recorded in all animals from day 4 or 5 up to day l or 11.  Mean scores over 24, 48 and 72 hours for each animal were 1.3, 1.3 and 2.0 for erythema and 0.0, 0.0 and 0.0 for oedema.  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 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

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

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. Only slight signs of irritation were observed in the rabbits.

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 Sample V 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:

Sample V (0.1 mL, neat) was administered to the right eye of three rabbits to assess for 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. Only slight signs of irritation were observed in the rabbits. The mean conjunctivae, chemosis, iris, and cornea scores for sample V 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 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 study available

Additional information

There is no data available for Hydrocarbon, C4, 1,3-butadiene-free, polymd,, tetraisobutylylene fraction, hydrogenated. However, data is available for structural analogues, Hydrocarbons, C10-C12, isoalkanes, <2% aromatics, and isohexadecane. 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, C10-C12, isoalkanes, <2% aromatics

In a key study (Exxonmobil Corp., 2004), 3 rabbits were subjected to a 4 hour dermal (shaved) exposure of 0.5 ml of Hydrocarbons, C10-C12, isoalkanes, <2% aromatics 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 elicited dermal responses in all animals. Well defined erythema and slight odema followed exposure.  The average erythema score (24, 48, and 72 hours) was 2.33.  The average edema score (24, 48, and 72 hours) was 1.1. 

In another key study (TOTAL Fuides, 1998), 3 rabbits were subjected to a 4 h dermal (shaved) exposure of 0.5 ml of Hydrocarbons, C10-C12, isoalkanes, <2% aromatics 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.  A very slight or well-defined erythema was observed in all animals from day 1 up to day 9 or 10. A slight oedema was noted in two animals on day 1 only. Dryness of the skin was recorded in all animals from day 4 or 5 up to day l or 11.  Mean scores over 24, 48 and 72 hours for each animal were 1.3, 1.3 and 2.0 for erythema and 0.0, 0.0 and 0.0 for oedema. 

In a supporting study (Exxonmobil Corp, 1991), fifteen human volunteers received one application of the test material (Hydrocarbons, C10-C12, isoalkanes, <2% aromatics) under semi-occlusive conditions. The sample remained in contact with the skin for 24 hours and was removed by the laboratory staff. Sites were graded approximately thirty minutes after patch removal, and again 24 hours after the initial patch removal. Under the conditions of this test, the test material was considered an irritant.

Isohexadecane

In a supporting study (Hill Top Research, Inc., 1994), a clinical test including 15 human volunteers was conducted and isohexadecane applied undiluted on upper arm in occlusive conditions (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 an irritant for the human skin.

In another supporting study (INEOS, 1980), the skin irritating properties of 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. Under these test conditions, the substance was not classified as a skin irritant according to CLP Regulation 1272/2008.

 

Ocular Irritation

Hydrocarbons, C10-C12, isoalkanes, <2% aromatics

In a key study (TOTAL Solvants, 1998), the test material (0.1 mL, neat) was administered to the right eye of three rabbits to assess for 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. Only slight signs of irritation were observed in the rabbits. The mean conjunctivae, chemosis, iris, and cornea scores 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 iridial 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. Isohexadecane is not classified as eye irritant according to CLP Regulation 1272/2008.

Respiratory Irritation

No studies were located to indicate that Hydrocarbon, C4, 1,3-butadiene-free, polymd,, tetraisobutylylene fraction, hydrogenatedi s a respiratory irritant.

Justification for classification or non-classification

Skin Irritation:

Based on available read across data, Hydrocarbon, C4, 1,3-butadiene-free, polymd,, tetraisobutylylene fraction, hydrogenated does 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, Hydrocarbon, C4, 1,3-butadiene-free, polymd,, tetraisobutylylene fraction, hydrogenated does 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).