Registration Dossier

Administrative data

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, C14-C20 (even numbered), n-alkanes, isoalkanes, <2% aromatics is a respiratory irritant.

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:
experimental study
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 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

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
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 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 Hydrocarbons, C14-C20 (even numbered), n-alkanes, isoalkanes, <2% aromatics. However, data is available for structural analogues, Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics, Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics, isohexadecane, and Hydrocarbons, C16-C20, n-alkanes, 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 skin irritation study (ExxonMobil, 1990), the test material, 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).

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

In a supporting study (ExxonMobil, 1995), conducted according to OECD guideline N°404, six young adult male New Zealand White rabbits were dermally exposed to 0.5 mL of the test material. 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. Based on the criteria provided under CLP Regulation 1272/2008, the test material is not considered as irritating to the rabbit skin.

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.

Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics

In a primary dermal irritation study (ExxonMobil, 1991a), conducted as similar to OECD guideline 404 in compliance with GLP, six young adult female New Zealand White rabbits were dermally exposed to 0.5 mL of the test material (Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics). Test sites were covered with a semi-occlusive dressing for 4 hours. The skin reactions were assessed at 45 minutes, 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. Based upon the CLP Regulation 1272/2008, the test material is not considered as irritating to the rabbit skin.

 

In another primary dermal irritation study according to OECD guideline 404 (ExxonMobil, 1991b), young adult New Zealand White rabbits (3 males + 3 females) were dermally exposed to 0.5 mL of the test material (Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics). Test sites were covered with a semi-occlusive dressing for 4 hours. Dermal responses were evaluated at 45 min, 24, 48, and 72 hours post-dosing according to the Draize method of scoring. Very slight erythema was observed at 45 min in 3 animals, all symptoms reversed by 24 hours. Edema was not noted in any of the animals. The individual mean score for erythema/eschar and oedema for each of the 3 animals was 0. Based upon the CLP Regulation 1272/2008, the test material is not considered as irritating to the rabbit skin.

 

Ocular Irritation

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

In a key ocular irritation study (ExxonMobil, 1991), the test material 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 the test material 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).

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 Hydrocarbons, C14-C20 (even numbered), n-alkanes, isoalkanes, <2% aromatics is a respiratory irritant.

Justification for classification or non-classification

Skin Irritation:

Based on available read across data, Hydrocarbons, C14-C20 (even numbered), n-alkanes, isoalkanes, <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, C14-C20 (even numbered), n-alkanes, isoalkanes, <2% aromatics 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 warrent classification as a respiratory irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).