Registration Dossier

Administrative data

Description of key information

Skin irritation: A reliable (Klimisch 1) GLP compliant study with alkenes, C11-12, hydroformylation products, distillation residues in NZW rabbits was conducted according to EPA OPPTS 870.2500 (Acute Dermal Irritation). Following a 4 hour semi-occlusive exposure the test item was found to be not-irritating to skin (according to EU criteria).
Eye Irritation: A reliable (Klimisch 1) GLP compliant eye irritation study was conducted with alkenes, C11-12, hydroformylation products, distillation residues. The study was conducted in NZW rabbits according to EPA OPPTS 870.2400 (Acute Eye Irritation). The test item in this instance was reported to be not-irritating to eyes (according to EU criteria).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study, well documented
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
yes
Remarks:
Temperature and humidity were outside protocol range but did not affect study outcome.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Nichols Rabbitry Inc., Lumberton, TX, USA
- Age at study initiation: approx. 3 month
- Weight at study initiation: 2.15 - 2.55 kg
- Housing: in suspended, wire-bottomed, stainless steel cages, 1 animal per cage
- Diet (e.g. ad libitum): Lab Rabbit Diet #5321 (PMI Feeds Inc.), approx. 8 oz. per day
- Water (e.g. ad libitum): Municipal water ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 (outside protocol range)
- Humidity (%): 22 - 68 (outside protocol range)
- Air changes (per hr): 10 - 12
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 2010-02-16 To: 2010-02-26
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: the contralateral intact side of the trunk served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after patch removal
Number of animals:
3 (2 male, 1 female)
Details on study design:
TEST SITE
- Area of exposure: 8 x 8 cm hair-free clipped area on the dorsal trunk
- % coverage: not mentioned
- Type of wrap if used: The test site was covered with a 4 ply, 2.5 x 2.5 cm surgical gauze patch, secured in place with a strip of non-irritating adhesive tape. The entire trunk of each animal was loosely wrapped with a semi-permeable dressing (othopedic stockinette) wich was secured on both edges with strips of tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with room temperature tap water and a clean cloth to remove as much residual test substance as possible
- Time after start of exposure: 4 hours


SCORING SYSTEM: according to Draize, John H., Woodward, Geoffrey, and Calvery, H.O., Methods for the Study of Irriation and Toxicity of Substances Applied Topically to the Skin and Mucous Menbranes, J.Pham & Ther. 82, 377 (1944)
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
8
Irritant / corrosive response data:
AVERAGE SCORE
- Erythema: 0
- Edema: 0
REVERSIBILITY: not applicable
Other effects:
No other signs of skin irritation were recorded. One animal was found dead on Day 1 of the study; no irritation had been observed at 1 hour after dosing, and the death was not considered related to the administration of the test substance. A replacement animal was dosed following a quarantine period and used for calculations and determinations in the study.

Table #1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

60 min

0/0/0

 0/0/0

24 h

 0/0/0

 0/0/0

48 h

 0/0/0

 0/0/0

72 h

 0/0/0

 0/0/0

Average 24h, 48h, 72h

 0

 0

Reversibility*)

 -

 -

Average time (unit) for reversion

 -

 -

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Erythema and edema were not observed at any time throughout the study. No other signs of irritation were observed during the study. The primary irritation index of 0.0 of a possible 8.0 was obtained from the observations at 24, 48 and 72 hours, and was used to give the test substance Alkenes, C11-12, hydroformylation products, distn. residues (CAS No.: 90622-27-8) a descriptive rating of non-irritant.
Executive summary:

A primary dermal irritation study was conducted in three albino rabbits using test substance Alkenes, C11 -12, hydroformylation products, distn. residues (CAS No: 90622 -27 -8). There was one intact test site per animal. Each test site was treated with 0.5 mL of the undiluted test substance and covered with a semi-permeable dressing. The test substance was maintained in contact with the skin for 4 hours. Observations for dermal irritation and defects were made at 1, 24, 48 and 72 hours after removal of the dressings. Erythema and edema were not observed at any time throughout the study. No other signs of irritation were observed during the study. One animal was found dead on Day 1 of the study; the death was not considered related to the administration of the test substance. A replacement animal was dosed. Based on the Primary Irritation Index (PII) of 0.0, the test substance was rated non-irritating.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
yes
Remarks:
Humdidity was outside protocol range but did not affect study outcome.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Nichols Rabbitry Inc., Lumberton, TX, USA
- Age at study initiation: approx. 3 month
- Weight at study initiation: 2.03 - 2.20 kg
- Housing: in suspended, wire-bottomed, stainless steel cages, 1 animal per cage
- Diet (e.g. ad libitum): Lab Rabbit Diet #5321 (PMI Feeds Inc.), approx. 8 oz. per day
- Water (e.g. ad libitum): Municipal water ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 24-46 (outside protocol range)
- Air changes (per hr): 10 - 12
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 2010-02-15 To: 2010-02-18
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as comparative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48 and 72 hours after test substance administration
Number of animals or in vitro replicates:
3 (1 male, 2 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): all treated eyes were washed out with room temperature deionized water for one minute
- Time after start of exposure: immediately after recording the 24-hour observation


SCORING SYSTEM:
according to Draize, John H., Woodward, Geoffrey, and Calvery, Herbert O., Journal of Pharmacol. Exp. Ther., 82, 377-390 (1944)


TOOL USED TO ASSESS SCORE: The treated eyes of all animals were examined without magnification under white room lighting provided by daylight-type fluorescent ceiling fixtures, and an additional source of white light affixed to the examination table or using a handheld flashlight.
After the 24-hour observation the corneas of all treated eyes were examined with a fluorescein sodium ophthalmic solution. A finoff ocular transilluminator with cobalt blue filter was utilized to enhance visualization of fluorescein staining.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0.11
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0.44
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
see table below
Other effects:
none

Table #1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

+/0/0

 1/0/0

 1/1/1

 1/1/1

24 h

 0/0/0

 1/0/0

 1/1/1

 1/1/0

48 h

 0/0/0

 0/0/0

 1/1/1

 1/1/0

72 h

 0/0/0

 0/0/0

 0/0/0

 0/0/0

Average 24h, 48h, 72h

 0

 0.11

 0.67

 0.44

Area effected

 1

 

 

 

Reversibility*)

 -

 c.

 c.

 c.

Average time (unit) for reversion

 -

 48 h

 72 h

 72 h

 + = slight dulling of normal luster

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the maximum average irritation score of 10.3, obtained 1 hour after treatment, the test substance was rated minimally irritating. Fluorescein staining did not occur in any of the eyes.
Executive summary:

An acute eye irritation study was conducted on three albino rabbits using test substance Alkenes, C11 -12, hydroformylation products, distn. residues (CAS No: 90622 -27 -8). 0.1 mL of the test substance was placed into the conjunctival sac of the right eye of each animal selected for testing. All treated eyes were washed with room temperature deionized water for one minute immediately after recording the 24-hour observation. There were no positive effects exhibited in any eyes at 48 hours after treatment. Non-positive irritation was clear by 72 hours, and the test substance was rated minimally irritating.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin Irritation

A primary dermal irritation study was conducted in three albino rabbits using test substance Alkenes, C11 -12, hydroformylation products, distillation residues (CAS No: 90622 -27 -8). There was one intact test site per animal. Each test site was treated with 0.5 mL of the undiluted test substance and covered with a semi-permeable dressing. The test substance was maintained in contact with the skin for 4 hours. Observations for dermal irritation and defects were made at 1, 24, 48 and 72 hours after removal of the dressings. Erythema and edema were not observed at any time throughout the study. No other signs of irritation were observed during the study. One animal was found dead on Day 1 of the study; the death was not considered related to the administration of the test substance. A replacement animal was dosed. The test item was found to be non-irritating to skin (according to EU criteria).

Eye Irritation

An acute eye irritation study was conducted on three albino rabbits using test substance alkenes, C11 -12, hydroformylation products, distillation residues (CAS No: 90622 -27 -8). 0.1 mL of the test substance was placed into the conjunctival sac of the right eye of each animal selected for testing. All treated eyes were washed with room temperature deionized water for one minute immediately after recording the 24-hour observation. There were no positive effects exhibited in any eyes at 48 hours after treatment. Non-positive irritation was clear by 72 hours. According to EU criteria the test item in this instance was reported to be non-irritating to eyes.

Justification for classification or non-classification

These findings do not warrant the classification of alkenes, C11 -12, hydroformylation products, distillation residues (CAS No: 90622 -27 -8) as skin or ocular irritants under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.