Registration Dossier

Skin Irritation:

The findings reveled persistent atonia and desquamation with some necrosis or eschar. Part of the irritation seen was associated with trapping of liquid under the occlusive binder at a point where the binder was bound to the animal. These areas of intimate contact and pressure gave rise to some of the reported necrosis and eschar. Also the chemical showed good dose relations for intensity and duration. Therefore, the test chemical was considered as moderately irritating to the clipped and intact abdominal skin of albino rabbits.

Eye Irritation:

The median score was 4, 0 and 0 at 24 hours, 27 hours and day 7 respectively. Also the chemical caused little irritation in most of the animals, but persistent corneal opacity in one rabbit. Thus on the basis of scores and observed effects the test chemical was considered as moderately irritating to the rabbits’ eye.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journal

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The dermal irritation study of the test chemical was conducted on clipped and intact abdominal skin of albino rabbits.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report):Tridecanol (C-13)
- Molecular formula :C13H28O
- Molecular weight :200.37 g/mole
- Substance type:Solid
- Physical state:Organic

Species:

rabbit

Strain:

other: Albino

Details on test animals or test system and environmental conditions:

- Housing: The animals were housed individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Type of coverage:

occlusive

Preparation of test site:

other: clipped and intact abdominal skin

Vehicle:

unchanged (no vehicle)

Remarks:

No data

Controls:

yes

Amount / concentration applied:

0.1 ml of undiluted test chemical

Duration of treatment / exposure:

24 hours

Observation period:

7 days

Number of animals:

4

Details on study design:

TEST SITE
Area of exposure: closely clipped, intact abdominal skin
% coverage: No data
Type of wrap if used: Occlusive binding of dental damming

REMOVAL OF TEST SUBSTANCE
Washing (if done): After the exposure, the binding was removed, and the remaining material, if any, was cleaned from the skin
Time after start of exposure: 24 hours

SCORING SYSTEM:
Grading scale is slight-moderate-marked and severe

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

no data

Remarks on result:

probability of moderate irritation

Irritant / corrosive response data:

The chemical caused persistent atonia and desquamation with some necrosis or eschar.

Other effects:

Part of the irritation seen was associated with trapping of liquid under the occlusive binder at a point where the binder was bound to the animal. These areas of intimate contact and pressure gave rise to some of the reported necrosis and eschar. Dermal irritation for tridecyl alcohol showed good dose relations for intensity and duration.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The findings reveled persistent atonia and desquamation with some necrosis or eschar. Part of the irritation seen was associated with trapping of liquid under the occlusive binder at a point where the binder was bound to the animal. These areas of intimate contact and pressure gave rise to some of the reported necrosis and eschar.Also the chemical showed good dose relations for intensity and duration.
Therefore, the test chemical was considered as moderately irritating to the clipped and intact abdominal skin of albino rabbits.

Executive summary:

The dermal irritation study of the test chemical was conducted on clipped and intact abdominal skin of albino rabbits.

The test chemical was applied full-strength to the closely clipped, intact abdominal skin of albino rabbits in groups of four. The exposed area was covered with an occlusive binding of dental damming for 24 hours. After the exposure, the binding was removed, and the remaining material, if any, was cleaned from the skin. The animals were housed individually with feed and water freely available. No mechanical restraints were used.

Observations for dermal irritation were made on a daily basis. Gross necropsies were performed at the end of the experiments.Grading scale was slight-moderate-marked and severe.

The findings reveled persistent atonia and desquamation with some necrosis or eschar. Part of the irritation seen was associated with trapping of liquid under the occlusive binder at a point where the binder was bound to the animal. These areas of intimate contact and pressure gave rise to some of the reported necrosis and eschar.Also the chemical showed good dose relations for intensity and duration.

Therefore, the test chemical was considered as moderately irritating to the clipped and intact abdominal skin of albino rabbits.

Endpoint conclusion:

adverse effect observed (irritating)

Reference

Endpoint:: eye irritation: in vivo
Type of information:: experimental study
Adequacy of study:: key study
Reliability:: 2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:: data from handbook or collection of data
Justification for type of information:: Data from peer review journals
Qualifier:: according to guideline
Guideline:: other: as mentioned below
Principles of method if other than guideline:: An ocular irritation study of the test chemical was condcuted on six rabbits to assess its eye irritation potential.
GLP compliance:: not specified
Specific details on test material used for the study:: - Name of test material: tridecan-1-ol
- Molecular formula: C13H28 O
- Molecular weight: 200.37 g/mole
- Substance type: Solid
- Physical state: Organic
Species:: rabbit
Strain:: not specified
Details on test animals or tissues and environmental conditions:: No data
Vehicle:: unchanged (no vehicle)
Controls:: yes
Amount / concentration applied:: 0.1 ml of undiluted alcohol
Duration of treatment / exposure:: 7 days
Observation period (in vivo):: at 1, 4, and 24 hours and at 2, 3, 4, and 7 days
Number of animals or in vitro replicates:: Six
Details on study design:: TEST SITE
Area of exposure: conjuctival sac of left eye
% coverage: No data
Type of wrap if used: no wrap used

REMOVAL OF TEST SUBSTANCE
Washing (if done): no washing performed
Time after start of exposure: not applicable

SCORING SYSTEM: Grading scale is slight-moderate-marked and severe.
Signs of irritation exposure were graded and scored according to the method of Draize.
Irritation parameter:: overall irritation score
Basis:: mean
Time point:: 24 h
Score:: 4
Reversibility:: not specified
Remarks on result:: positive indication of irritation
Irritation parameter:: overall irritation score
Basis:: mean
Time point:: 72 h
Score:: 0
Reversibility:: not specified
Remarks on result:: other: Little irritation and persistent corneal opacity was observed.
Irritation parameter:: overall irritation score
Basis:: mean
Time point:: 7 d
Score:: 0
Reversibility:: not specified
Remarks on result:: other: Little irritation and persistent corneal opacity was observed.
Other effects:: Little irritation and persistent corneal opacity was observed.
Interpretation of results:: Category 2 (irritating to eyes) based on GHS criteria
Conclusions:: The median score was 4, 0 and 0 at 24 hours, 27 hours and day 7 respectively. Also the chemical caused little irritation in most of the animals, but persistent corneal opacity in one rabbit. Thus on the basis of scores and observed effects the test chemical was considered as moderately irritating to the rabbits’ eye.
Executive summary:: An ocular irritation study of the test chemical was conducted on six rabbits to assess its eye irritation potential. A single application of 0.1 ml of undiluted alcohol was made into the conjunctival sac of the left eye of each of six rabbits. The untreated eye served as the control. The treated eye was closed for 30 seconds and eyes were not washed. Observations for irritancy and possible systemic toxicity were made at 1, 4, and 24 hours and at 2, 3, 4, and 7 days. Where positive effects persisted, observations were continued initially and at termination the eyes were examined following instillation of 2 % sodium fluorescein solution to detect any corneal lesions if not otherwise visible. Signs of irritation exposure were graded and scored according to the method of Draize. The median score was 4, 0 and 0 at 24 hours, 27 hours and day 7 respectively. Also the chemical caused little irritation in most of the animals, but persistent corneal opacity in one rabbit. Thus on the basis of scores and observed effects the test chemical was considered as moderately irritating to the rabbits’ eye.

Endpoint conclusion:

adverse effect observed (irritating)

Endpoint conclusion:

no study available

Skin Irritation:

Various studies have been summarized to determine the level of dermal irritation/ corrosion caused by test chemical in living organisms. These studies include in vivo experimental results on rabbits and humans for the test chemicals.

The dermal irritation study of the test chemical was conducted on clipped and intact abdominal skin of albino rabbits.

The test chemical was applied full-strength to the closely clipped, intact abdominal skin of albino rabbits in groups of four. The exposed area was covered with an occlusive binding of dental damming for 24 hours. After the exposure, the binding was removed, and the remaining material, if any, was cleaned from the skin. The animals were housed individually with feed and water freely available. No mechanical restraints were used. Observations for dermal irritation were made on a daily basis. Gross necropsies were performed at the end of the experiments. Grading scale was slight-moderate-marked and severe. The findings reveled persistent atonia and desquamation with some necrosis or eschar. Part of the irritation seen was associated with trapping of liquid under the occlusive binder at a point where the binder was bound to the animal. These areas of intimate contact and pressure gave rise to some of the reported necrosis and eschar. Also the chemical showed good dose relations for intensity and duration.

Therefore, the test chemical was considered as moderately irritating to the clipped and intact abdominal skin of albino rabbits.

This is supported by the acute toxicity study carried out to estimate the dermal irritation potential of the test chemical in albino rabbits. About 0.01 ml of undiluted sample or of solutions in water, propylene glycol, or acetone was applied on the on the clipped skin of each of five albino rabbits within 24 hours under uncovered application. The skin reaction was recorded in a 10-grade ordinal series and was based upon the severest reaction that development. Grade 1 indicates no irritation and Grade 2 the least visible capillary injection from the undiluted chemical. Grade 6 indicates necrosis when undiluted and Grade 10 indicates necrosis from a 0.01% solution.

Primary Irritation score after 24 hours for the test chemical was Grade 4. Therefore the test chemical was considered as irritating to the skin.

These results are supported by another skin irritation study conducted on the dorsal surface of theCD® (SD) hrBi hairless rat by using Hill top chamber.

The intimate contact of the chambers on the skin was ensured by the application of a waterproof tape (Johnson and Johnson, Inc., NJ, USA). The Hill top chamber was removed after 3 h, and the treatment area was gently wiped with Kimwipes to remove the residual liquid on the skin surface.

The skin irritation (erythema) was evaluated by visual scoring using a modified method of Draize et al. (1944). The scores were given from 0 to 4 depending on the degree of erythema as follows: no erythema-0, slight erythema (barely perceptible- light pink)-1, moderate erythema (dark pink)-2, moderate to severe erythema (light red)-3, severe erythema (extreme redness)-4.

Results showed lower permeation enhancement effect but caused greater skin irritation after 72 and 96 hours at a score of 1.0. Therefore, the test chemical was considered to be skin irritant to CD® (SD) hrBi hair less rat.

The above results are further supported by an irritation study performed on Himalayan white-spotted guinea pigs to assess the irritation potential of the test chemical. 0.025ml of undiluted test chemical was applied to an area measuring 2cm2 previously marked with a circular stamp on the clipped flanks in of 6 to 8 animals under non-occlusive condition.

Skin reactions were evaluated after 24 hours of application. The test chemical caused mild erythema in at least 25 percent of the animals of the group concerned at concentration of 3%.

Therefore the test chemical was considered to be irritating to skin.

These results are also supported by another dermal irritation conducted for other test chemical.

The test chemical was applied full-strength to the closely clipped, intact abdominal skin of albino rabbits in groups of four. The exposed area was covered with an occlusive binding of dental damming for 24 hours. After the exposure, the binding was removed, and the remaining material, if any, was cleaned from the skin. The animals were housed individually with feed and water freely available. No mechanical restraints were used.

Observations for dermal irritation were made on a daily basis. Gross necropsies were performed at the end of the experiments. Grading scale was slight-moderate-marked and severe.

The findings reveled persistent atonia and desquamation with some necrosis or eschar. Part of the irritation seen was associated with trapping of liquid under the occlusive binder at a point where the binder was bound to the animal. These areas of intimate contact and pressure gave rise to some of the reported necrosis and eschar. Also the chemical showed good dose relations for intensity and duration.

Therefore the test chemical was considered as moderately irritating to the clipped and intact abdominal skin of albino rabbits.

Available studies for the test chemical indicate a strong possibility that it may cause moderate to severe irritation to skin.

Hence the test chemical can be considered to be irritating to skin. Comparing the above annotations with the criteria of CLP regulation, the test chemical can be classified under the category “Category 2”.

Eye Irritation

Various studies have been summarized to determine the level of dermal irritation/ corrosion caused by test chemical in living organisms. These studies include in vivo experimental results on rabbits and humans for the test chemicals.

An ocular irritation study of the test chemical was conducted on six rabbits to assess its eye irritation potential.

A single application of 0.1 ml of undiluted alcohol was made into the conjunctival sac of the left eye of each of six rabbits. The untreated eye served as the control. The treated eye was closed for 30 seconds and eyes were not washed. Observations for irritancy and possible systemic toxicity were made at 1, 4, and 24 hours and at 2, 3, 4, and 7 days. Where positive effects persisted, observations were continued initially and at termination the eyes were examined following instillation of 2 % sodium fluorescein solution to detect any corneal lesions if not otherwise visible. Signs of irritation exposure were graded and scored according to the method of Draize.

The median score was 4, 0 and 0 at 24 hours, 27 hours and day 7 respectively. Also the chemical caused little irritation in most of the animals, but persistent corneal opacity in one rabbit. Thus on the basis of scores and observed effects the test chemical was considered as moderately irritating to the rabbits’ eye.

This is supported by the acute toxicity study carried out to estimate the ocular toxicity of the test chemical in rabbits.

Eye injury in rabbits was recorded in a 10- grade ordinal series and was based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical. Grade 1 indicated at most a very small area of necrosis resulting from 0.5 ml of undiluted chemical in the eye. Grade 5 indicated a so-called severe burn from 0.005 ml, and Grade 10 indicated a severe burn from 0.5 ml of a 1% solution in water or propylene glycol.

The Irritation score for the test chemical was Grade 2. Therefore the test chemical was considered as slightly irritating to the rabbits’ eye.

These results are supported by an ocular irritation study performed to determine the corneal injuries caused by the chemical to rabbit eyes. The albino rabbit eyes were selected on the basis of absence of grossly visible staining by a 5-percent aqueous solution of fluorescein sodium, flushed with distilled water 20 seconds after application. After a two-hour interval to allow the eye to return to normal, 0.005 ml. of the undiluted material was applied to the center of the cornea while the lids are retracted. About one minute later, the lids were released.

This procedure was necessary to prevent the removal of a portion of the dose by the very efficient wiping system of the lids before intimate contact has been made with the eye. Eighteen to 24 hours later, the eye was examined in strong diffuse daylight, and then stained with fluorescein, and the injury scored.

The chemical caused corneal injuries of Grade 3(out of grade 10). Therefore, the test chemical was considered as irritating to the eyes of albino rabbits.

The above results are further supported by another ocular irritation study performed on six rabbits to assess the irritation potential of the other test chemical. A single application of 0.1 ml of undiluted alcohol was made into the conjunctival sac of the left eye of each of six rabbits. The untreated eye served as the control. The treated eye was closed for 30 seconds and eyes were not washed. Observations for irritancy and possible systemic toxicity were made at 1, 4, and 24 hours and at 2, 3, 4, and 7 days. Where positive effects persisted, observations were continued initially and at termination the eyes were examined following instillation of 2 % sodium fluorescein solution to detect any corneal lesions if not otherwise visible. Signs of irritation exposure were graded and scored according to the method of Draize.

The median scores were 28, 11 and 0 at 24 hours, 27 hours and day 7 respectively. Also the test chemical caused corneal sloughing or pitting. Thus on the basis of observed effects scores, the test chemical was considered to be severely irritating to the rabbits’ eye.

Available studies for the test chemical indicate a strong possibility that it may cause moderate to severe irritation to eyes.

Hence the test chemical can be considered to be irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, the test chemical can be classified under the category “Category 2”.

Available studies for the test chemical indicate a strong possibility that it may cause moderate to severe irritation to skin and eyes.

Hence, the test chemical can be considered to be irritating to eyes and skin. It can be further classified under the category “Category 2” as per CLP regulation.

Alcohol	Irritation	Median Score
Alcohol	Irritation	24 hr	72 hr	7 days
Tridecyl alcohol	Moderate	4	0	0