Registration Dossier

Administrative data

Description of key information

Skin Irritation:

The Primary Irritation Index (PII) for the test chemical after 14 days of observation was 0.0. Also the test chemical did not produce any clinical signs of toxicity throughout the examination period of 14 days.

Hence, under the test conditions, the test chemical can be concluded to be not irritating to New Zealand White rabbit skin.

Eye Irritation:

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.00, 0.00; 0.00, 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, 0.00, respectively. Hence under the experimental test conditions, the test chemical can be considered as “Non Irritant” to New Zealand White female 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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
data is from experimental reports
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
To assess the dermal irritation parameter of the test chemical in accordance with OECD 404
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Sex: Female
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 2 kg+ 200g
- Housing:animals were housed individually in stainless steel cages provided with steel mesh bottom and facilities for food and water
- Diet (e.g. ad libitum): Pelleted feed supplied by Pranav Agro
- Water (e.g. ad libitum):Community tap water kept in glass bottles, ad libitum
- Acclimation period: The healthy rabbits selected for study were acclimatized to laboratory conditions one week prior to testing
- Identification: By cage tag and corresponding color body marking

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25 degC
- Humidity (%): relative humidity - 40-60%
- Air changes (per hr): Air conditioned rooms with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5gm
Duration of treatment / exposure:
4 hours
Observation period:
24,48 and 72 hours after patch removal till 14days
Number of animals:
3- [1- initial test; 2- confirmatory test]
Details on study design:
TEST SITE
- Area of exposure: 6 sq.cm of the dorsal area of the trunk
- % coverage: 6 sq.cm
- Type of wrap if used: impervious dressing with an adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: the patches were removed and the site of application was cleaned with lukewarm water after patch removal

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : The treated sites were examined and scored at 60 minutes, 24,48 and 72 hours after application.

SCORING SYSTEM:
- Method of calculation: Draize method
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test compound didnot produce any signs of irritation through out the observation period
Other effects:
The test compound did not produce any clinical signs of toxicity through out the study.

TABLE - 1

INDIVIDUAL ANIMAL DERMAL IRRITATION SCORES

Rabbit No.

Sex

INTACT SKIN

3 Min.

4 Hours

24 Hours

48 Hours

72 Hours

14 days

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

01

F

0

0

0

0

0

0

0

0

0

0

0

0

02

F

-

-

0

0

0

0

0

0

0

0

0

0

03

F

-

-

0

0

0

0

0

0

0

0

0

0

Total

0

0

0

0

0

0

0

0

0

0

0

0

Mean

0

0

0

0

0

0

0

0

0

0

0

0

Grand Total

0.00

Dermal Irritation Index: 0.0/4 = 0.0

CLINICAL SIGNS

 

SEX

ANIMAL NO.

Time (Min.)

Time (Hours)

Time (Day)

3

1

4

24

48

72

14

 

FEMALE

 

01

N

N

N

N

N

N

N

02

N

N

N

N

N

N

N

03

N

N

N

N

N

N

N

 

N: No Clinical Signs

C: Clinical Signs Observed

Interpretation of results:
other: not irritating
Conclusions:
The Primary Irritation Index (PII) for the test chemical after 14 days of observation was 0.0. Also the test chemical did not produce any clinical signs of toxicity throughout the examination period of 14 days.
Hence, under the test conditions,the test chemical can be concluded to be not irritating to New Zealand White rabbit skin.
Executive summary:

A dermal irritation study was conducted on New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of the test chemical. 3 female New Zealand White rabbits were used for the study. The animals were prepared 24 hrs prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric

clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 0.5 gm of the test compound was applied on a small area 6 square cms of the intact test site. Each site of application was covered with an impervious dressing which was secured with an adhesive tape. The animals were housed individually and restrained by the use of plastic collars. After patch removal [4 hours later] the unabsorbed test chemical was removed and the test site was washed with lukewarm water. The intact skin site of application was observed for erythema and edema at 1, 24,48 and 72 hours till 14 days after application and scored according to Draize method.

The Primary Irritation Index (PII) for the test chemical after 14 days of observation was 0.0. Also the test chemical did not produce any clinical signs of toxicity throughout the examination period of 14 days.

Hence, under the test conditions,the test chemical can be concluded  to be not irritating to New Zealand White rabbit skin.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
data is from experimental reports
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
To assess the eye irritation potential of the test chemical according OECD 405 Guidelines
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: Female
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 2 kg+ 200g
- Housing:animals were housed individually in stainless steel cages provided with steel mesh bottom and facilities for food and water
- Diet (e.g. ad libitum): Pelleted feed supplied by Pranav Agro
- Water (e.g. ad libitum):Community tap water kept in glass bottles, ad libitum
- Acclimation period: The healthy rabbits selected for study were acclimatized to laboratory conditions one week prior to testing
- Identification: By cage tag and corresponding color body marking

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25 degC
- Humidity (%): relative humidity - 40-60%
- Air changes (per hr): Air conditioned rooms with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 gm
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
1,24,48 and 72 hours after test substance application
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
3- [Initial test =1; and confirmatory tes = 2]
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: The eyes of the test animal were washed

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: The examination of the reactions were facilatated by use of biomicroscope and hand slit lamp.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
110
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
0.1gm of the test chemical when applied to the eyes of New Zealand White rabbits did not produce any lesions such as pannus, staining through out the observation period of 72 hours.
Other effects:
There were no other signs observed through out the observation period of 21 days.

TABLE- 1     GRADING OF OCULAR LESIONS

 

S.NO/

SEX

 

OBSERVATION

Score

Total

Total Score

1/F

 

1 hr

24hrs

48 hrs

72 hrs

Cornea

A.       Opacity-Degree of Density

0

0

0

0

0

 

0×0×5=0

B.       Area of Cornea Involved

0

0

0

0

0

Iris

A.       Values

0

0

0

0

0

0×5=0

Conjunctivae

A.       Redness

1

0

0

0

0

 

0+0 +0×5=0

B.       Chemosis

0

0

0

0

0

C.       Discharge 

0

0

0

0

0

2/F

Cornea

A.       Opacity-Degree of Density

0

0

0

0

0

 

0×0×5=0

B.       Area of Cornea Involved

0

0

0

0

0

Iris

A.       Values

0

0

0

0

0

0×5=0.0

Conjunctivae

A.       Redness

1

0

0

0

0

 

0+0 +0×5=0

B.       Chemosis

0

0

0

0

0

C.       Discharge 

0

0

0

0

0

3/F

Cornea

A.       Opacity-Degree of Density

0

0

0

0

0

 

0×0×5=0.0

B.       Area of Cornea Involved

0

0

0

0

0

Iris

A.       Values

0

0

0

0

0

0×5=0.0

Conjunctivae

A.       Redness

1

0

0

0

0

 

0+0 +0×5=0

B.       Chemosis

0

0

0

0

0

C.       Discharge 

1

1

0

0

2

Grand total

0

Mean

0

Eye Irritation Scoring Index

0

 

Interpretation of results:
other: not irritating
Conclusions:
0.1gm of the test chemical when applied to the eyes of New Zealand White rabbits did not produce any lesions such as pannus, staining through out the observation period of 72 hours. The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.00, 0.00; 0.00, 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, 0.00, respectively. Hence under the experimental test conditions, the test chemical can be considered as “Non Irritant” to New Zealand White female rabbit eyes.
Executive summary:

Acute Eye Irritation/Corrosion Study of test chemical in Rabbits was performed as per OECD guideline no. 405.

3 female New Zealand White Rabbits free from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment.

The test compound in the amount of 0.1 gm was applied as such and then placed in the conjunctival sac of one eye of each animal after gentle pulling the lower eye lid away from the eye ball. The eye lids were then gently held together for about one second to prevent the loss of the material. The other eyes which remains untreated, served as control. The eyes of the test animal were not washed for at least 24 hours following instillation of the test compound. After 24 hours, eyes were washed gently with the luke warm water. The eye was observed at 1, 24, 48 and 72 hours after test item instillation.

In the initial test, 0.1 ml of test item was applied into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions till 24 hour observation hence a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 0.1 ml of test item was instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control. There were no other signs observed through out the observation period of 21 days.

 The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.00, 0.00; 0.00, 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, 0.00, respectively. Hence under the experimental test conditions, the test chemical can be considered as “Non Irritant” to New Zealand White female 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

A dermal irritation study was conducted on New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of the test chemical. 3 female New Zealand White rabbits were used for the study. The animals were prepared 24 hrs prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric

clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 0.5 gm of the test compound was applied on a small area 6 square cms of the intact test site. Each site of application was covered with an impervious dressing which was secured with an adhesive tape. The animals were housed individually and restrained by the use of plastic collars. After patch removal [4 hours later] the unabsorbed test chemical was removed and the test site was washed with lukewarm water. The intact skin site of application was observed for erythema and edema at 1, 24,48 and 72 hours till 14 days after application and scored according to Draize method.

 

The Primary Irritation Index (PII) for the test chemical after 14 days of observation was 0.0. Also the test chemical did not produce any clinical signs of toxicity throughout the examination period of 14 days.

Hence, under the test conditions, the test chemical can be concluded to be not irritating to New Zealand White rabbit skin.

Eye Irritation

 

Acute Eye Irritation/Corrosion Study of test chemical in Rabbits was performed as per OECD guideline no. 405.

3 female New Zealand White Rabbits free from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment.

The test compound in the amount of 0.1 gm was applied as such and then placed in the conjunctival sac of one eye of each animal after gentle pulling the lower eye lid away from the eye ball. The eye lids were then gently held together for about one second to prevent the loss of the material. The other eyes which remains untreated, served as control. The eyes of the test animal were not washed for at least 24 hours following instillation of the test compound. After 24 hours, eyes were washed gently with the luke warm water. The eye was observed at 1, 24, 48 and 72 hours after test item instillation.

In the initial test, 0.1 ml of test item was applied into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions till 24 hour observation hence a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 0.1 ml of test item was instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control. There were no other signs observed through out the observation period of 21 days.

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.00, 0.00; 0.00, 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, 0.00, respectively. Hence under the experimental test conditions, the test chemical can be considered as “Non Irritant” to New Zealand White female rabbit eyes. 

Justification for classification or non-classification

Available results from the Guideline studies indicate a very strong possibility that the test chemical lacks the potential to cause any 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.