C.I. Solvent Blue 79

Endpoint summary

Description of key information

Skin irritation

Based on the predicted data for the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone and different supporting studies for its structurally and functionally similar read chemical, skin irritation potential of the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone has been determined. The studies are as mentioned below:

 

According to Danish QSAR database , the skin irritation effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) . Based on estimation, no skin irritation reactions were observed in rabbits. Therefore, the chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) was considered to be not irritating.

 

The above result was supported by the skin irritation studies of two read across chemicals performed as per OECD Guidelines 404 in three female New Zealand White rabbits and complying with the GLP procedures. In each study, three 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 ml of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application and the responses were scored according to Draize method. The Primary Irritation Index (PII) for test chemical after 14 days of observation was 0.0 for both the chemicals. Also test chemicals did not produce any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions, test chemicals can be concluded to be not irritating to New Zealand White rabbit skin.

 

Thus on the basis of the predicted data for the test chemical and supporting experimental studies of the structurally and functionally similar read across chemical and applying the weight of evidence approach, the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0),it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Eye irritation

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0). The studies are as mentioned below:

 

 

The experimental study was conducted for the structurally similar read across substance in three female New Zealand White rabbits as per OECD Guidelines 405 and complying to the GLP procedures. About 0.1g of the undiluted test chemical was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (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 weights before and during the study was observed. The overall irritation index of test chemical was 0.0 after 72 hours. Also did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, the chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

 

The above result was further supported by another experimental study conducted for another similar read across chemical. The study was followed by the same method as per mentioned in above study according to OECD test guideline 405 in New Zealand White rabbits. 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, test chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

 

Based on the above summarized studies for target chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “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:

read-across from supporting substance (structural analogue or surrogate)

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 of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

WoE report is based on 5 skin irritation studies as- WoE-2 ,WoE-3 , WoE-4, WoE-5 and WoE-6.
Skin irritation study of test chemical was conducted on rats and rabbits to assess its skin irritating effects.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone
- Substance type : Organic
- Physical state : Solid

Species:

rabbit

Strain:

other: 1-3. Not specified 4-5.New Zealand White

Details on test animals or test system and environmental conditions:

1-3. Not specified
4.Details on test animals
Age: 10 to 12 weeks
Sex:Female
Body weight range: 1.90kg±200g
Identification : By cage tag and corresponding colour body marking
Housing: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
Water:Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles, ad libitum
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.

Details on environmental conditions:
- Temperature (°C): temperature between 22-25 deg C
- 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.

5.Details on test animals
Age: 10 to 12 weeks
Sex:Female
Body weight range: 0.80kg±200g
Identification : By cage tag and corresponding colour body marking
Housing: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
Water:Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles, ad libitum
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.

Details on environmental conditions:
- Temperature (°C): temperature between 22-25 deg C
- 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:

other: 1-3. Not specified 4-5.occlusive

Preparation of test site:

other: 1-3. Not specified 4-5.clipped

Vehicle:

other: 1-3. Not specified 4-5.unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

1-3.Not specified
4-5.0.5ml

Duration of treatment / exposure:

1-3.Not specified
4-5.4 hours

Observation period:

1-3.Not specified
4-5.60 min., 24, 48 and 72 hours after application.

Number of animals:

1-3.Not specified
4-5.3 female rabbits

Details on study design:

1-3.Not specified

4-5.TEST SITE
- Area of exposure: dorsal area of trunk
- % coverage: small area (approximately 6 cm2)
- Type of wrap if used: impervious dressing which was secured in position with adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure:after patch removal the test site was washed with lukewarm water

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application.

SCORING SYSTEM:
- Method of calculation:The intact skin site of application of each animal was observed for signs of erythema and oedema and the responses were scored following Draize’s method

Irritation parameter:

other: 1-3.overall irritation score

Basis:

mean

Time point:

other: Not specified

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

other: 4-5.primary dermal irritation index (PDII)

Basis:

mean

Time point:

14 d

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation was observed.

Interpretation of results:

other: not irritating

Conclusions:

The test material Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) was considered to be not irritating to the skin of rabbits.

Executive summary:

Based on the predicted data for the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone and different supporting studies for its structurally and functionally similar read chemical, skin irritation potential of the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone has been determined. The studies are as mentioned below:

 

According to Danish QSAR database , the skin irritation effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) . Based on estimation, no skin irritation reactions were observed in rabbits. Therefore, the chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) was considered to be not irritating.

 

The above result was supported by the skin irritation studies of two read across chemicals performed as per OECD Guidelines 404 in three female New Zealand White rabbits and complying with the GLP procedures. In each study, three 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 ml of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application and the responses were scored according to Draize method. The Primary Irritation Index (PII) for test chemical after 14 days of observation was 0.0 for both the chemicals. Also test chemicals did not produce any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions, test chemicals can be concluded to be not irritating to New Zealand White rabbit skin.

 

Thus on the basis of the predicted data for the test chemical and supporting experimental studies of the structurally and functionally similar read across chemical and applying the weight of evidence approach, the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0),it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “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:

read-across from supporting substance (structural analogue or surrogate)

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 of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

WoE report is based on 2 eye irritation studies as- WoE-2 and WoE-3.
An eye irritation study of test chemical was conducted on rats and rabbits to assess its eye irritating effects.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone
- Substance type : Organic
- Physical state : Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

1.Details on test animals:
-Age: 10 to 12 weeks
-Sex:Female
- Body weight range: 2.0kg ± 200 g
- 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.

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.

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 ml undiluted test chemical

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 0.1 ml 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 throughout the observation period of 21 days.

1.

TABLE-    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

2.

TABLE-      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 test material Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) was considered to be Not irritating to the eyes of rabbits.

Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0). The studies are as mentioned below:

 

 

The experimental study was conducted for the structurally similar read across substance in three female New Zealand White rabbits as per OECD Guidelines 405 and complying to the GLP procedures. About 0.1g of the undiluted test chemical was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (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 weights before and during the study was observed. The overall irritation index of test chemical was 0.0 after 72 hours. Also did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, the chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

 

The above result was further supported by another experimental study conducted for another similar read across chemical. The study was followed by the same method as per mentioned in above study according to OECD test guideline 405 in New Zealand White rabbits. 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, test chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

 

Based on the above summarized studies for target chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Based on the predicted data for the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone and different supporting studies for its structurally and functionally similar read chemical, skin irritation potential of the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone has been determined. The studies are as mentioned below:

 

According to Danish QSAR database , the skin irritation effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) . Based on estimation, no skin irritation reactions were observed in rabbits. Therefore, the chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) was considered to be not irritating.

 

The above result was supported by the skin irritation studies of two read across chemicals performed as per OECD Guidelines 404 in three female New Zealand White rabbits and complying with the GLP procedures. In each study, three 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 ml of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application and the responses were scored according to Draize method. The Primary Irritation Index (PII) for test chemical after 14 days of observation was 0.0 for both the chemicals. Also test chemicals did not produce any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions, test chemicals can be concluded to be not irritating to New Zealand White rabbit skin.

 

Thus on the basis of the predicted data for the test chemical and supporting experimental studies of the structurally and functionally similar read across chemical and applying the weight of evidence approach, the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0),it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Eye irritation

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0). The studies are as mentioned below:

 

 

The experimental study was conducted for the structurally similar read across substance in three female New Zealand White rabbits as per OECD Guidelines 405 and complying to the GLP procedures. About 0.1g of the undiluted test chemical was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (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 weights before and during the study was observed. The overall irritation index of test chemical was 0.0 after 72 hours. Also did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, the chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

 

The above result was further supported by another experimental study conducted for another similar read across chemical. The study was followed by the same method as per mentioned in above study according to OECD test guideline 405 in New Zealand White rabbits. 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, test chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

 

Based on the above summarized studies for target chemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

On the basis of the predicted data for the test chemical and supporting experimental studies of the structurally and functionally similar read across chemical and applying the weight of evidence approach, ,it can be concluded that the testchemical Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (EC No: 911-358-0) is unlikely to cause skin and eye irritation and hence considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified” for skin and eye as per CLP.