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Administrative data

Description of key information

Skin Irritation:

The pilot study group of 5 volunteers and remaining 23 volunteers completed the assay without any reactions. Therefore, it was reported that the test chemical was not a primary skin irritant.

Eye Irritation:

As seen by the results, instillation of the test chemical did not produce any corneal opacity or iris congestion. However, an intense conjunctival irritation did occur, involving chemosis and discharge. On the seventh day of discharge, the treated eyes were normal. Therefore, the test chemical can be considered to be not irritating to rabbit eyes.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental reports following standard procedures
Qualifier:
according to guideline
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Evaluation of the irritating and sensitizing potentials of the test chemical in humans.
GLP compliance:
not specified
Species:
human
Strain:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: the age of the volunteers lies between 24 - 56
A total of 28 volunteers were randomly selected for the study. Of these 28 human subjects, 15 were male and 13 were female.
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
other: 10% w/v alcohol
Controls:
not specified
Amount / concentration applied:
0.5 ml (the test sample was made up as a 10% (w/v) solution in alcohol)
Duration of treatment / exposure:
24 hours
Observation period:
24 hours
Number of animals:
Pilot study: 5 volunteers
Main study: 23 volunteers
Details on study design:
All applications were made as closed patches which were subsequently secured by overlying strips of firmly secured adhesive tape. These closed patches covered 0.5 ml of diluted test sample.The patches were applied on the arms of the human subjects.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The pilot study group of 5 volunteers and remaining 23 volunteers completed the assay without any reaction
Other effects:
No data available
Interpretation of results:
other: not irritating
Conclusions:
The pilot study group of 5 volunteers and remaining 23 volunteers completed the assay without any reactions. Therefore, it was reported that the test chemical was not a primary skin irritant.
Executive summary:

The objective of the assay was to study the irritating and sensitizing potentials of the test sample when applied to humans as a 10% solution in alcohol.

A total of 28 volunteers were randomly selected for the study. Of these 28 human subjects, 15 were male and 12 were female. The test sample was made up as a 10% (w/v) solution in alcohol. Immediately upon receiving the test sample, patches were applied to five of the volunteers as a preliminary check for primary irritation. Since no reactions were found in the 5 volunteers after 24 hours. The remaining individuals also had their arms patched. All applications were made as closed patches which were subsequently secured by overlying strips of firmly secured adhesive tape. These closed patches covered 0.5 of diluted test sample. The patches were applied on the arms of the human subjects. The pilot study group of 5 volunteers and remaining 23 volunteers completed the assay without any reactions. Therefore, it was reported that the test chemical was not a primary skin irritant.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
data is from experimental reports following standard procedures
Qualifier:
according to guideline
Guideline:
other: as mentioned below
Principles of method if other than guideline:
To determine the ocular irritation potential of the test chemical im rabbits.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data available
Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye acted as control
Amount / concentration applied:
0.1 ml of the test sample was instilled into the right eye of the rabbits
Duration of treatment / exposure:
7 days
Observation period (in vivo):
The rabbits were examined every 24 hours for four days and then again on the 7th day.
Duration of post- treatment incubation (in vitro):
No data available
Number of animals or in vitro replicates:
3 healthy, normal albino rabbits were used for the study.
Details on study design:
Scoring System: The scorings were made according to the Draize scale for scoring of ocular lesions.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
80
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
10
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
7 d
Score:
14
Max. score:
20
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Remarks:
The score is the mean of conjunctivae redness, chemosis and conjunctivae discharge.
Irritant / corrosive response data:
The score is the mean of conjunctivae redness, chemosis and conjunctivae discharge.
Other effects:
No data available

Results of the Individual animals after instillation of the test chemical

Rabbit 1

Area of the eye involved

Results

1 day

2 days

3 days

4 days

7 days

Cornea

 

 

 

 

 

A. Opacity

0

0

0

0

0

B. Area of cornea involved

0

0

0

0

0

Total = A*B*5 (maximum = 80)

0*0*5 = 0

Iris

 

 

 

 

 

A. Values

0

0

0

0

0

Total = A*5 (maximum = 10)

0*5=0

Conjunctivae

 

 

 

 

 

A. Redness

3

2

2

2

0

B. Chemosis

2

2

1

1

0

C. Discharge

2

1

1

0

0

Score = (A+B+C)*2 (maximum = 20)

(3+2+2)*2 = 14

Rabbit 2

Area of the eye involved

Results

1 day

2 days

3 days

4 days

7 days

Cornea

 

 

 

 

 

A. Opacity

0

0

0

0

0

B. Area of cornea involved

0

0

0

0

0

Total = A*B*5 (maximum = 80)

0*0*5 = 0

Iris

 

 

 

 

 

A. Values

0

0

0

0

0

Total = A*5 (maximum = 10)

0*5=0

Conjunctivae

 

 

 

 

 

A. Redness

3

2

2

2

0

B. Chemosis

2

2

1

1

0

C. Discharge

2

1

0

0

0

Score = (A+B+C)*2 (maximum = 20)

(3+2+2)*2 = 14

 

Rabbit 3

Area of the eye involved

Results

1 day

2 days

3 days

4 days

7 days

Cornea

 

 

 

 

 

A. Opacity

0

0

0

0

0

B. Area of cornea involved

0

0

0

0

0

Total = A*B*5 (maximum = 80)

0*0*5 = 0

Iris

 

 

 

 

 

A. Values

0

0

0

0

0

Total = A*5 (maximum = 10)

0*5=0

Conjunctivae

 

 

 

 

 

A. Redness

3

2

2

2

0

B. Chemosis

2

2

1

1

0

C. Discharge

2

1

1

0

0

Score = (A+B+C)*2 (maximum = 20)

(3+2+2)*2 = 14

Interpretation of results:
other: not irritating
Conclusions:
Instillation of the test chemical did not produce any corneal opacity or iris congestion, while an intense conjunctival irritation occurred involving chemosis and discharge.On the seventh day of discharge the treated eyes were normal. Based on these observations,the test chemical can be considered to be not irritating to rabbit eyes.

Executive summary:

In an eye irritation study, the toxic effects of the test chemical was investigated to see if it produced any irritation when instilled into eyes of rabbits. 0.1 ml of the test sample was instilled into the right eye of 3 healthy, normal albino rabbits. The rabbits were examined every 24 hours for four days and then again on the 7th day. The left eye acted as control. The scorings were made according to the Draize scale for scoring of ocular lesions. As seen by the results, instillation of the test chemical did not produce any corneal opacity or iris congestion. However, an intense conjunctival irritation did occur, involving chemosis and discharge. On the seventh day of discharge, the treated eyes were normal. Therefore, the test chemical can be considered to be not irritating to rabbit eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

Various studies have been summarized to determine the degree of dermal irritation caused by the test chemical in living organisms. These results include in vivo experimental data in humans as well as rabbits. The results are summarized below:

The objective of the assay was to study the irritating and sensitizing potentials of the test sample when applied to humans as a 10% solution in alcohol.

A total of 28 volunteers were randomly selected for the study. Of these 28 human subjects, 15 were male and 12 were female. The test sample was made up as a 10% (w/v) solution in alcohol. Immediately upon receiving the test sample, patches were applied to five of the volunteers as a preliminary check for primary irritation. Since no reactions were found in the 5 volunteers after 24 hours. The remaining individuals also had their arms patched. All applications were made as closed patches which were subsequently secured by overlying strips of firmly secured adhesive tape. These closed patches covered 0.5 of diluted test sample. The patches were applied on the arms of the human subjects. The pilot study group of 5 volunteers and remaining 23 volunteers completed the assay without any reactions. Therefore, it was reported that the test chemical was not a primary skin irritant.

This is supported by the results of other study whose procedure was an adaptation of the repeated insult patch test procedure suggested by Dr. Draize and described in the "Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics", published by the Association of Food and Drug Officials of the United States of America. The subjects were furnished by churches, Parent - Teachers Associations and similar organizations in suburban areas around Cincinnati. The test was initiated on 43 subjects, of whom only 37 completed the assay.

Initially ten subjects were started on each sample. If no untoward results were observed upon completion of the test with these, enough additional subjects were added to bring the total to about 40 subjects. The test patch was a one-inch square of Webril (absorbent non woven cotton fabric) affixed to the center of a 1*3 inch strip of adhesive elastic bandage material .The test bandages were specially prepared by Duke Laboratories, Inc. Immediately before application to each subject, 0.5 ml of the test sample was added to Webril swatch and the bandage was then placed on the subjects upper arm. Six to nine different samples were tested simultaneously on each group of subjects, and the order in which they were applied was rotated from one subject to the next. The subjects removed the bandages 24 hours after application. The reactions of each subject were scored.

Under the conditions of the study, the test chemical caused little or no primary irritation in the subjects. Hence it can be considered that test chemical was not irritating to human skin in the Repeated Insult Patch test.

These results are supported by a study performed according to Annex V of EEC directive 79/831 to assess the irritation potential of the test chemical. 4 female New Zealand white albino rabbits were used for the study.

0.5 ml aliquot of neat test chemical was applied to a 2.5 cm2 of surgical lint, which was then applied to the left flank, which had been clipped free of hair, and was held in place by an Elastoplast® elastic adhesive bandage. Patches were removed after 4 h of treatment and the skin sites were cleansed by gentle swabbing with cotton wool soaked in warm water. Reactions were assessed at 24, 48, 72 h after patch removal.

No significant irritation was reported. Irritation observed at 24, 48 and 72 hours had an average erythema and edema scores of 1.4, 1.5 respectively

Based on the scores and observations, the test chemical was considered to be not irritating to rabbit skin.

These results are also supported the results of a modified dermal primary irritation (MDPI) test conducted to determine the level of irritation caused by the test chemical. 12 human(2 males and 10 females) volunteers were used for the study. The test chemical was allowed to volatilize for at least 15 min but no longer than 40 min prior to application. 0.3 ml aliquot of test chemical at 60% was applied under occlusion to the back of each volunteer. Each volunteer received two, 24 h applications. Reactions were scored at patch removal and 24 after patch removal.

No irritation was observed at patch removal and 24 hours after patch removal.

Hence, the test chemical was considered to be not irritating to human skin.

In a primary skin irritation test conducted in rabbits, 5% in DEP or neat test chemical was applied to abraded and intact rabbit skin. Untreated skin on the same rabbit served as a control. Reactions were read at 24 and 72 h and were scored by the method of Draize. Following application of neat alpha-iso-methyl-ionone, well-defined erythema was observed on abraded and intact rabbit skin at 24 h. Very slight to well-defined erythema was still present at 72 h. There was very slight to well-defined edema in 2/3 rabbits at 24 h, which disappeared by 72 h. Application of 5% test chemical on the other hand showed no evidence of erythema or edema at 24 or 72 h. Hence, it is considered that the test chemical does not induce an irritating effect and should be regarded as a non-irritating chemical.

The above results are further supported by a study in which Skin irritation was evaluated during the induction phase of a human repeated insult patch test (HRIPT) in 106 volunteers (26 males and 80 females).

0.3 ml aliquot of test chemical at 60% in 3:1 DEP:EtOH, was applied under occlusion to the back of each volunteer. A series of nine, 24 h applications were made over a 3-week period. Reactions were read at patch removal. One subject out of 106 volunteers showed evidence of irritation. Hence, the test chemical was considered to be non-irritating since irritation was observed in only one single subject.

These results are also lent support by a dermal 90-day sub-chronic toxicity study conducted on Sprague-Dawley rats where the irritation potential was also evaluated.

1% test chemical in phenyl ethyl alcohol at a dose of 10 mg/kg was applied to the clipped backs of 5 male and 5 female Sprague-Dawley rats. All rats were observed daily for skin reactions.

No dermal reactions were observed in all the treated animals through out the study. Hence, the test chemical was considered to be not irritating to skin.

Available studies for the test chemical indicate a very strong possibility that the test chemical lacks the potential to cause irritation to skin.

Hence, the test chemical can be considered to be not irritating to skin. It can be further classified under the category “Not Classified” as per CLP regulation.

Eye Irritation

Various studies have been summarized to determine the extent of ocular damage caused by the test chemical in living organisms. These results include in vivo experimental data in rabbits. The results are summarized below:

In an eye irritation study, the toxic effects of the test chemical were investigated to see if it produced any irritation when instilled into eyes of rabbits. 0.1 ml of the test sample was instilled into the right eye of 3 healthy, normal albino rabbits. The rabbits were examined every 24 hours for four days and then again on the 7th day. The left eye acted as control. The scorings were made according to the Draize scale for scoring of ocular lesions. As seen by the results, instillation of the test chemical did not produce any corneal opacity or iris congestion. However, an intense conjunctival irritation did occur, involving chemosis and discharge. On the seventh day of discharge, the treated eyes were normal. Therefore, the test chemical can be considered to be not irritating to rabbit eyes.

This is supported by the results of an eye irritation study performed on 3 healthy rabbits to assess the irritation potential of the test chemical.

A 0.1 ml aliquot of 12.5% the test chemical was instilled into the right eye of three normal, healthy albino rabbits. The untreated left eye of each animal served as its own control. Both eyes were examined every 24 h for 4 days and again on day 7. Scoring was done according to the Draize scale of ocular lesions. As seen by the results, instillation of test chemical did not cause any corneal opacity or iris congestion. However, intense conjunctival irritation with chemosis and discharge was observed in all three rabbits on days 1–4. All eyes were normal by day 7. Thus, the test chemical was considered to be non-irritant to rabbit eyes.

Available studies for the test chemical indicate a very strong possibility that the test chemical lacks the potential to cause irritation to eyes.

Hence, the test chemical can be considered to be not irritating to eyes. It can be further classified under the category “Not Classified” as per CLP regulation.

Justification for classification or non-classification

Available studies for the test chemical indicate a very strong possibility that the test chemical lacks the potential to cause irritation to eyes and skin.

Hence, the test chemical can be considered to be not irritating to eyes and skin. It can be further classified under the category “Not Classified” as per CLP regulation.