Hydrocarbons, C9-C10, 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, C9-C10, n-alkanes, isoalkanes, cyclics, <2% aromatics 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:

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 2

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:

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:

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.

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 skin or eye irritation data available for Hydrocarbons, C9-C10, n-alkanes, isoalkanes, cyclics <2% aromatics. However, data is available for structural analogues, Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics, Hydrocarbons, C9-C11, n-alkanes, isoalkanes, cyclics, <2% aromatics, Hydrocarbons, C14-C19, isoalkanes, cyclics, <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, 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, C9-C11, n-alkanes, isoalkanes, cyclics, < 2% aromatics

In a supporting study (TOTAL, 1991), the test material (Hydrocarbons, C9-C11, n-alkanes, isoalkanes, cyclics, < 2% aromatics) was administered via semi-occlusive patch for four hours to 3 male rabbits to assess dermal irritation  Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing and once daily for 11 days according to the Draize method of scoring. After 24 hours and up until Day 5 post exposure, animals exhibited moderate erythema (grade 4).  By day 6, one animal had very light erythema while 2 animals exhibited well-defined erythema.   Erythema gradually lessened until all animals were free of adverse clinical signs at Day 8. Edema was not noted at any observation time during the study.  The mean erythema and edema scores for the test material were 2.67 and 0 respectively.  This finding warrants classification of the test material as a Category 2 dermal irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

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.

 

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. Under these test conditions, the substance Isohexadecane is not classified as a skin irritant according to annex VI of the Directive 67/548/EEC and CLP Regulation 1272/2008.

 

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.

 

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. Isohexadecane is not classified as eye irritant according to Annex VI of the Directive 67/548/EEC and CLP Regulation 1272/2008.

 

Respiratory Irritation

 

No studies were located to indicate that Hydrocarbons, C9-C10, n-alkanes, isoalkanes, cyclics, <2% aromatics is a respiratory irritant.

Justification for classification or non-classification

Skin Irritation:

Based on the weight of evidence from available read across data, Hydrocarbons, C9-C10, n-alkanes, isoalkanes, cyclics <2% aromatics 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, Hydrocarbons, C9-C10, n-alkanes, isoalkanes, cyclics <2% aromatics does not meet the criteria for classification as an ocular irritant 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).