Hydrogen tetrasodium bis[2-[[6-[[4-chloro-6-[3-sulphoanilino]-1,3,5-triazin-2-yl]amino]-1-hydroxy-3-sulpho-2-naphthyl]azo]benzoato(4-)]chromate(5-)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Experimental data from various test chemicals

Justification for type of information:

Data for the target chemical is summarized based on data from various test chemicals

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study report

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

The acute eye irritation study of test chemical was conducted in New Zealand White Rabbits as per the OECD- 405 Guideline

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Details on test animals:
- Age: 10 to 12 weeks
- Sex: Female
- Body weight range: 2.0kg ±200g
- Housing: Rabbit was housed in stainless steel cages provided with stainless steel mesh bottom and facilities for food and water bottle.
- Diet:Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi, India
- Water:Community tap water passed through ‘Aqua Guard on line water filter’ was kept in bottles, ad libitum.
- Acclimatization: The rabbit was acclimatized to standard laboratory condition for 24 hours in experimental room before study.

ENVIRONMENTAL CONDITIONS
- Temperature:temperature between 22-250C
- Humidity (%):relative humidity 40-60%
- Air changes (per hr):Air conditioned room 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.


HUSBANDRY
Environmental conditions :Air conditioned rooms with 10-15 air changes per hour, temperature between 19-25 0C, relative humidity 30-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
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 supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi, India
Water : Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles,mad-libitum

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100mg (0.1g)

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

The eyes were examined at 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 female rabbits

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:

72 h

Score:

0

Reversibility:

not specified

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 0.1gm did not produce any lesions such as pannus, staining throughout the observation period of 72 hours.

Other effects:

The test compound applied in conjunctival sac of rabbits did not show any observable clinical signs of eye irritation throughout 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
	Conjunctivae	A.       Redness	1	0	0	0	1	0+0+0×5=5
		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
	Conjunctivae	A.       Redness	1	0	0	0	1	0+0+0×5=5
		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
		B.       Area of Cornea Involved	0	0	0	0	0
	Iris	A.       Values	0	0	0	0	0	0
	Conjunctivae	A.       Redness	1	0	0	0	1	0+0+0×5=5
		B.       Chemosis	0	0	0	0	0
		C.       Discharge	0	0	0	0	0
Grand total								0.00
Mean								0.00
Eye Irritation Scoring index								0.00

Interpretation of results:

other: not irritating

Conclusions:

The overall irritation index of the test chemical was 0.0 after 72 hours. Also the test chemical did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, the test chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

Executive summary:

An ocular irritation study was conducted on New Zealand white rabbits in accordance with OECD 405 to assess the irritation parameter of the test chemical. Three female New Zealand White rabbits were used for the study. In the initial test, One healthy rabbit of body weight 2.11 kg was selected for study after acclimatization. Both eyes of rabbit 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. 0.1 gm of the test chemical was applied by gently pulling the eye lids into the conjunctival sac of the rabbit.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 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 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 0.1 gm did not produce any eye irritation or any eye discharge. Furthermore, no other clinical signs were recorded after application of test compound such as cage side activity, pain etc. The result obtained from the initial test was confirmed in additional two animal (body weight ranges 200±gm) of same sex and same dose level. 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. The overall irritation index of Test chemical was 0.0 after 72 hours. Also test chemical did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, the test chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

Cross-reference 2

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source

Principles of method if other than guideline:

The eye irritation study was conducted to evaluate the irritating effects of administration of Acid Orange 7 to eye of rabbits.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

No data

Observation period (in vivo):

No data

Duration of post- treatment incubation (in vitro):

No data

Number of animals or in vitro replicates:

3 males

Details on study design:

No data

Irritation parameter:

overall irritation score

Basis:

mean

Reversibility:

not specified

Remarks on result:

other: no irritation effects was observed to eye of rabbits.

Irritant / corrosive response data:

No data

Other effects:

No data

Interpretation of results:

not irritating

Conclusions:

The test chemical did not induce ocular irritation in the eyes of 3 male rabbits. Hence the test chemical is likely to be "Non irritating"

Executive summary:

Ocular irritation study was performed to determine the toxic nature of the test chemical. The study was performed by administering 100 mg of the test chemical to 3 male rabbits. Based on the reported results, the test chemical did not induce ocular irritation in the eyes of 3 male rabbits. Hence the test chemical is likely to be "Non irritating".

Data source

Reference

Reference Type:

publication

Title:

WoE of occular irritation study for CAS no

Author:

Sustainability Support Services (Europe) AB

Year:

2019

Bibliographic source:

WoE report, Sustainability Support Services (Europe) AB, 2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

WoE for the target chemical is summarized based on experimental data from various test chemicals

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen tetrasodium bis[2-[[6-[[4-chloro-6-[3-sulphoanilino]-1,3,5-triazin-2-yl]amino]-1-hydroxy-3-sulpho-2-naphthyl]azo]benzoato(4-)]chromate(5-)

EC Number:

277-492-0

EC Name:

Hydrogen tetrasodium bis[2-[[6-[[4-chloro-6-[3-sulphoanilino]-1,3,5-triazin-2-yl]amino]-1-hydroxy-3-sulpho-2-naphthyl]azo]benzoato(4-)]chromate(5-)

Cas Number:

73507-17-2

Molecular formula:

C52H28Cl2CrN14O18S44Na

IUPAC Name:

Hydrogen tetrasodium bis[2-[[6-[[4-chloro-6-[3-sulphoanilino]-1,3,5-triazin-2-yl]amino]-1-hydroxy-3-sulpho-2-naphthyl]azo]benzoato(4-)]chromate(5-)

Details on test material:

- Name of the test chemical: Hydrogen tetrasodium bis[2-[[6-[[4-chloro-6-[3-sulphoanilino]-1,3,5-triazin-2-yl]amino]-1-hydroxy-3-sulpho-2-naphthyl]azo]benzoato(4-)]chromate(5-)
- Molecular formula: C52H28Cl2CrN14O18S4.H.4Na
- Molecular weight: 2693.61 g/mol
- Substance type: Organic

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

3. Not specified

Details on test animals or tissues and environmental conditions:

2. Details on test animals:
- Age: 10 to 12 weeks
- Sex: Female
- Body weight range: 2.0kg ±200g
- Housing: Rabbit was housed in stainless steel cages provided with stainless steel mesh bottom and facilities for food and water bottle.
- Diet:Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi, India
- Water:Community tap water passed through ‘Aqua Guard on line water filter’ was kept in bottles, ad libitum.
- Acclimatization: The rabbit was acclimatized to standard laboratory condition for 24 hours in experimental room before study.

ENVIRONMENTAL CONDITIONS
- Temperature:temperature between 22-250C
- Humidity (%):relative humidity 40-60%
- Air changes (per hr):Air conditioned room 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.


HUSBANDRY
Environmental conditions :Air conditioned rooms with 10-15 air changes per hour, temperature between 19-25 0C, relative humidity 30-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
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 supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi, India
Water : Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles,ad-libitum

3. No data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100mg (0.1g)

Duration of treatment / exposure:

2. 24 hours
3. No data

Observation period (in vivo):

2. The eyes were examined at 1, 24, 48 and 72 hours after test substance application
3. No data

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

2. 3 female rabbits
3. No data

Details on study design:

2. 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.

3. No data

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

2

Results 2

Irritation parameter:

overall irritation score

Basis:

mean

Remarks on result:

no indication of irritation

Remarks:

3

Irritant / corrosive response data:

2. The test compound when applied to the eye of New Zealand white rabbit at the dose level of 0.1gm did not produce any lesions such as pannus, staining throughout the observation period of 72 hours.

Other effects:

2. The test compound applied in conjunctival sac of rabbits did not show any observable clinical signs of eye irritation throughout the observation period of 21 days.

Applicant's summary and conclusion

Interpretation of results:

other: not irritating

Conclusions:

The test chemical did not induce ocular irritation in the eyes of rabbits. Hence the test che mical is likely to be "Non irritating" to rabbit eyes.

Executive summary:

Data available for the various test chemicals was reviewed to determine the toxic nature of the test chemical. The studies are as mentioned below:

An ocular irritation study was conducted on New Zealand white rabbits in accordance with OECD 405 to assess the irritation parameter of the test chemical. Three female New Zealand White rabbits were used for the study. In the initial test, One healthy rabbit of body weight 2.11 kg was selected for study after acclimatization. Both eyes of rabbit 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. 0.1 gm of the test chemical was applied by gently pulling the eye lids into the conjunctival sac of the rabbit.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 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 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 0.1 gm did not produce any eye irritation or any eye discharge. Furthermore, no other clinical signs were recorded after application of test compound such as cage side activity, pain etc. The result obtained from the initial test was confirmed in additional two animal (body weight ranges 200±gm) of same sex and same dose level. 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. The overall irritation index of Test chemical was 0.0 after 72 hours. Also test chemical did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, the test chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

Ocular irritation study was performed to determine the toxic nature of the test chemical. The study was performed by administering 100 mg of the test chemical to 3 male rabbits. Based on the reported results, the test chemical did not induce ocular irritation in the eyes of 3 male rabbits. Hence the test chemical is likely to be "Non irritating".

Based on the data available and applying the weight of evidence approach, the test chemical did not induce ocular irritation in the eyes of rabbits. Hence the test che mical is likely to be "Non irritating" to rabbit eyes.