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Description of key information

Skin Irritation:

Acute Dermal Irritation/corrosion Study of test chemical in Rabbits, was performed as per OECD guideline No. 404. The test compound in the amount of 0.5 gm did not produce any skin reaction as well as clinical signs of toxicity throughout the observation period of 72 hours after patch removal. However, there was no corrosivity of the test compound was observed during the entire observation period of 14 days. The dermal irritation index of New Zealand white rabbits is calculated as 0.00 and test compound can be classified under "Not Classified".

 

 

Eye Irritation:

Acute Eye Irritation/Corrosion Study of Test chemical in Rabbits, was performed as per OECD guideline No. 405. The. In the confirmatory test, the test compound when applied to the conjunctival sac of the animals produced some conjunctival blood vessels hyperemic upto 24 hours. There were no other signs observed throughout the observation period of 21 days. Based on above findings, it can be concluded that the test compound is practically non-irritant when applied in the amount of 0.1 gm in the conjunctival sac of the rabbits and test compound can be classified under "Not Classified".

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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
To evaluate the dermal irritation potential of the test chemical in New Zealand white rabbits
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
-Source : In-bred
-Age : 10 to 12 weeks
-Body weight range :1.80kg±200gm
-Identification : By cage tag and corresponding colour body marking.
-Acclimatization : The healthy rabbits selected for study was acclimatized to standard laboratory condition for one week in experimental room under Veterinary examination.
-Randomization : After acclimatization and Veterinary examination three females were randomly selected.
-Accommodation : Animals were housed individually in stainless steel cages provided with stainless steel mesh bottom and facilities for food and water bottle.
-Diet : Pelleted feed
-Water : Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles, ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22-25 deg.C
- Humidity (%): 40-60%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12 hours artificial fluorescent light and 12 hours dark.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 gm of test compound
Duration of treatment / exposure:
4 hrs.
Observation period:
14 days
Number of animals:
Three female rabbits
Details on study design:
Details on study design
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage:approx 6 square cm
- Type of wrap if used: impervious dressing
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: after patch removal, the site of application was cleaned with luke warm
water
OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : 1, 24,48 and 72 hours
SCORING SYSTEM: The intact skin site of application was observed for erythema and edema and scored according to Draize method
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Skin reaction:
The test compound when applied at the dose level of 0.5 gm on shaven back skin (approximately 6 cm2) of rabbit produced Mild Erythema the site of application of test compound after four hour patch removal upto 48 hours.
Other effects:
Clinical signs:
The test compound applied on the shaven back skin of rabbit at the dose level of 0.5 gm did not produce any clinical signs of toxicity throughout the examination period of 14 days.

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:
not irritating
Conclusions:
The dermal irritation index of the test chemical in New Zealand white rabbits was calculated as 0.00 and test compound can be classified under "Not Classified".
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.

In the initial test one healthy rabbit of body weight 1.80kg±200gm kg was selected for the study after acclimatization. The test compound in the amount of 0.5 gm was applied at the different sites on the shaven back skin of animal. The hairs of back sides were removed (approximately 6 cm2) one day earlier before the treatment. The test substance in the amount of 0.5 gm was applied to a small area (approximately 6 cm2) of skin and covered with a gauze patch, which was held in place with non-irritating tape. The first patch was applied on the shaven back skin of rabbit and removed after three minutes. No serious reaction was observed at the site of application. The second patch was applied on the different shaven back side and removed after one hour. There were no signs of skin reaction observed at this site of application. Finally, a third patch was applied at a different site and was removed after four hour. . There were no signs of skin reaction observed at the site of application. Finally, the animal was observed for 14 days, for any irritation and corrosion.

Because no corrosive effect observed in the initial test, a confirmatory test was done in order to confirm the irritant or negative response of the test substance by using two additional animals. In the confirmatory test the test compound in the amount of 0.5 gm was applied on the shaven back skin of two animals, each with one patch, for an exposure period of four hours. After four hours the patch was removed and the skin reactions were graded according to Draize’s method.

The test compound in the amount of 0.5 gm did not produce any skin reaction as well as clinical signs of toxicity throughout the observation period of 72 hours after patch removal. However, there was no corrosivity of the test compound was observed during the entire observation period of 14 days. The dermal irritation index of New Zealand white rabbits is calculated as 0.00 and test compound can be classified under "Not Classified".

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:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
To evaluate the acute eye irritation index of the test chemical in New Zealand White rabbit.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
-Source : In-bred
-Age : 10 to 12 weeks
-Body weight range :1.80kg±200gm
-Identification : By cage tag and corresponding colour body marking.
-Acclimatization : The healthy rabbits selected for study was acclimatized to standard laboratory condition for one week in experimental room under Veterinary examination.
-Randomization : After acclimatization and Veterinary examination three females were randomly selected.
-Accommodation : Animals were housed individually in stainless steel cages provided with stainless steel mesh bottom and facilities for food and water bottle.
-Diet : Pelleted feed
-Water : Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles, ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22-25 deg.C
- Humidity (%): 40-60%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12 hours artificial fluorescent light and 12 hours dark.
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
A dose of 0.1gm of test substance was applied into the one eye of the rabbits. The other eye, which remains untreated, served as a control.
Duration of treatment / exposure:
24 hours
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
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not washed
SCORING SYSTEM:Scale of weighted scores for grading the severity of ocular lesions developed by //Draize et al
TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: hand-slit lamp
Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. After recording the observations at 24 hours, the eyes were further examined with the aid of fluorescein.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test compound when applied to the eye of New Zealand white rabbit at the dose level of 0.1 gm did not produced any lesions such as pannus, staining throughout the observation period of 72 hours. However some blood vessels of conjunctiva were observed hyperemic at 1 to 24th hour after the application of test substance.
Other effects:
The test compound applied in conjunctival sac of rabbits did not show any observable clinical signs throughout the observation period of 21 days.

GRADING OF OCULAR LESIONS

 

S.NO

SEX

OBSERVATION

Score

Total score

1

F

1 hour

24hours

48 hours

72 hours

Cornea

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae

1

0

0

0

1

Chemosis

0

0

0

0

0

2

F

Cornea

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae

1

0

0

0

1

Chemosis

0

0

0

0

0

3.

F

Cornea

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae

1

0

0

0

1

Chemosis

0

0

0

0

0

Grand total

3

Total mean

1

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test compound when applied to the eye of New Zealand white rabbit at the dose level of 0.1 gm did not produced any lesions such as pannus, staining throughout the observation period of 72 hours. However some blood vessels of conjunctiva were observed hyperemic at 1 to 24th hour after the application of test substance.The test compound Sodium saccharin applied in conjunctival sac of rabbits did not show any observable clinical signs throughout the observation period of 21 days.
Based on above findings, it can be concluded that the test compound was non-irritating when applied in the amount of 0.1 gm in the conjunctival sac of the rabbits under test condition.
Executive summary:

The acute eye irritation study of the test chemical was conducted in New Zealand White Rabbit as per the OECD- 405 Guideline. 3 female young adult New Zealand White rabbits were used for the study.

 

One healthy rabbit of body weight 1.80kg±200gm was selected for study after acclimatization. Both eyes of rabbits were examined for any abnormal discharge such as eye irritation, ocular defects or pre-existing corneal injury from eye 24 hours prior to application of test compound. The test compound was applied in the conjunctival sac of rabbit after gently pulling the lower lid away from the eyeball at the dose rate of0.1gm.The lids were then gently held for about one second in order to prevent loss of the material. The other eye which remain untreated, served as a control. The acute irritation to eye conjunctiva, cornea and iris was evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reaction (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animal was observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weight before and during the study was observed.

The test compound when applied to conjunctival sac of rabbit in the amount of 0.1gm produces some conjunctiva blood vessels hyperemic upto 24 hours.

The result obtained from the initial test was confirmed in additional two animal of same sex and same dose level

In the confirmatory test the test compound was applied in the amount of 0.1 gm in the conjunctival sac of two more rabbits after gently pulling the lower lid away from the eyeball. The other eye which remain untreated, served as a control. The acute irritation to eye conjunctiva, cornea and iris was evaluated at 1, 24, 48 and 72 hoursafter the treatment. The grades of ocular reaction (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weight before and during the study was observed.

In the confirmatory test, the test compound when applied to the conjunctival sac of the animals produced some conjunctival blood vessels hyperemic upto 24 hours. There were no other signs observed throughout the observation period of 21 days.

Based on above findings, it can be concluded that the test compound is practically non-irritant when applied in the amount of 0.1 gm in the conjunctival sac of the rabbits.

Respiratory irritation

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

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.

In the initial test one healthy rabbit of body weight 1.80kg±200gm kg was selected for the study after acclimatization. The test compound in the amount of 0.5 gm was applied at the different sites on the shaven back skin of animal. The hairs of back sides were removed (approximately 6 cm2) one day earlier before the treatment. The test substance in the amount of 0.5 gm was applied to a small area (approximately 6 cm2) of skin and covered with a gauze patch, which was held in place with non-irritating tape. The first patch was applied on the shaven back skin of rabbit and removed after three minutes. No serious reaction was observed at the site of application. The second patch was applied on the different shaven back side and removed after one hour. There were no signs of skin reaction observed at this site of application. Finally, a third patch was applied at a different site and was removed after four hour. . There were no signs of skin reaction observed at the site of application. Finally, the animal was observed for 14 days, for any irritation and corrosion.

Because no corrosive effect observed in the initial test, a confirmatory test was done in order to confirm the irritant or negative response of the test substance by using two additional animals. In the confirmatory test the test compound in the amount of 0.5 gm was applied on the shaven back skin of two animals, each with one patch, for an exposure period of four hours. After four hours the patch was removed and the skin reactions were graded according to Draize’s method.

The test compound in the amount of 0.5 gm did not produce any skin reaction as well as clinical signs of toxicity throughout the observation period of 72 hours after patch removal. However, there was no corrosivity of the test compound was observed during the entire observation period of 14 days. The dermal irritation index of New Zealand white rabbits is calculated as 0.00 and test compound can be classified under "Not Classified".

 

Eye irritation

 

The acute eye irritation study of the test chemical was conducted in New Zealand White Rabbit as per the OECD- 405 Guideline. 3 female young adult New Zealand White rabbits were used for the study.

 

One healthy rabbit of body weight 1.80kg±200gm was selected for study after acclimatization. Both eyes of rabbits were examined for any abnormal discharge such as eye irritation, ocular defects or pre-existing corneal injury from eye 24 hours prior to application of test compound. The test compound was applied in the conjunctival sac of rabbit after gently pulling the lower lid away from the eyeball at the dose rate of0.1gm.The lids were then gently held for about one second in order to prevent loss of the material. The other eye which remain untreated, served as a control. The acute irritation to eye conjunctiva, cornea and iris was evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reaction (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animal was observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weight before and during the study was observed.

The test compound when applied to conjunctival sac of rabbit in the amount of 0.1gm produces some conjunctiva blood vessels hyperemic upto 24 hours.

The result obtained from the initial test was confirmed in additional two animal of same sex and same dose level

In the confirmatory test the test compound was applied in the amount of 0.1 gm in the conjunctival sac of two more rabbits after gently pulling the lower lid away from the eyeball. The other eye which remain untreated, served as a control. The acute irritation to eye conjunctiva, cornea and iris was evaluated at 1, 24, 48 and 72 hoursafter the treatment. The grades of ocular reaction (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weight before and during the study was observed.

In the confirmatory test, the test compound when applied to the conjunctival sac of the animals produced some conjunctival blood vessels hyperemic upto 24 hours. There were no other signs observed throughout the observation period of 21 days.

Based on above findings, it can be concluded that the test compound is practically non-irritant when applied in the amount of 0.1 gm in the conjunctival sac of the rabbits.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical was observed in experimental studies. The results obtained from these studies indicate that the chemical is not likely to cause skin and eye irritation. Hence the test chemical can be classified under the category “Not Classified” for skin and eye as per CLP.