2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar-heptyl ar',ar''-Me derivs.

Endpoint summary

Description of key information

Reliable skin irritation (in vivo) and eye irritation (in vivo) studies using rabbits are available

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

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study methodology was equivalent or similar to OECD 404 and in accordance with the Principles of Good Laboratory Practice (GLP)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Not Applicable

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
-Source: New York State Rabbit Development, Hartwick, N.Y.
-Weight at Initiation: Approximately 2-4kg
-Identification: Ear tag, Cage tab
-Housing: Individually housed in wire mesh bottom cages
-Diet: HIH Animal Feed A, certified feed, ad libitum. Supplied fresh daily.
-Water: Tap wate, ad libitum.
-Quarantine: Minimum of 5 days

ENVIRONMENTAL CONDITIONS
-Temperature: as per "Guide for the care and use of Laboratory Animals"
-Humidity: as per "Guide for the care and use of Laboratory Animals"
-Air Changes (per hour): 12-15 air changes/hour
-Photoperiod (hrs dark/hrs light): 12 hours light/dark cycle

Type of coverage:

occlusive

Preparation of test site:

other: intact and abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml of Automate Red B nonvolatile

Duration of treatment / exposure:

Four hours post-dose, the occlusive binders and patches were removed. The exposure sites were gently wiped with clean gauze to remove as much non-absorbed test article as possible.

Observation period:

One-half hour after unwrapping, the exposure sites were examined and scored separately for both erythema and edema on a graded scale of 0 to 4 in accordance with the method of Draize. The exposure sites were again examined and scored at 48, 72 and 96 hours.

Number of animals:

6 rabbits

Details on study design:

Animals will be weighted and the weights recorded prior to the initiation of the study. Approximately 24 hours prior to dosing, the fur shall be clipped from the back and flanks of each animal. Just prior to application of the test article the right dorsal side of each animal will be abraded with the point of a 22 guage clean hypodermic needle. The abrasions will penetrate the stratum corneum but will not be deep enough to disturb the dermis or cause bleeding. The test article will be applied to each of the to sites per animal, one on abraded skin and the other on intact skin. All sites will have an area of one square inch. If necessary, a glass rod will be used to evenly distribute the test article. Each test site shall be occluded with a one square inch gauze patch, two single layers thick, held on with masking tape and the area subsequently secured by a nonabsorbant binder according to FDRL's Standard Operating Procedures. The binders will be left on the animals for 4 hours follwoing application of the test article. At that time, the binders will be removed and the test areas gently wiped using a soft clean gauze. Skin sites will be examined at 30-60 minutes, and then at 24, 48, and 72 hours after patch removal. Erythema and edema will be scored individually and evaluated according to the method of Draize, 1965.

Irritation parameter:

erythema score

Remarks:

6 rabbits

Basis:

mean

Remarks:

0.0

Time point:

other: 24.5, 48, 72, and 96 hours

Score:

0

Max. score:

4

Remarks on result:

other: Results for intact skin

Irritation parameter:

edema score

Remarks:

6 rabbits

Basis:

mean

Remarks:

0.0

Time point:

other: 24.5, 48, 72, and 96 hours

Score:

0

Max. score:

4

Remarks on result:

other: Results for intact skin

Irritation parameter:

erythema score

Remarks:

6 rabbits

Basis:

mean

Remarks:

0.0

Time point:

other: 24.5, 48, 72 and 96 hours

Score:

0

Max. score:

4

Remarks on result:

other: Results for abraded skin

Irritation parameter:

edema score

Remarks:

6 rabbits

Basis:

mean

Remarks:

0.0

Time point:

other: 24.5, 48, 72 and 96 hours

Score:

0

Max. score:

4

Remarks on result:

other: Results for abraded skin

Irritant / corrosive response data:

non-irritating

Other effects:

None

Based on the individual animal mean score for the 24.5, 48 and 72 hr time-point for each parameter (Erythema and Eschar Formation and Edema Formation) on intact skin, this material would not be classified under EU regulations.

			Rabbit Number
Parameter scored	Exposure Time (hours)	Skin	1116	1117	1118	1119	1121	1122
Erythema and Eschar Formation	24.5	Intact	0	0	0	0	0	0
	48	Intact	0	0	0	0	0	0
	72	Intact	0	0	0	0	0	0
Mean score for 24.5, 48 and 72 h time-point			0	0	0	0	0	0
(A)Erythema and Eschar Sub-total					0	0	0	0
Edema Formation	24.5	Intact	0	0	0	0	0	0
	48	Intact	0	0	0	0	0	0
	72	Intact	0	0	0	0	0	0
Mean score for 24.5, 48 and 72 h time-point			0	0	0	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the test material is non-irritating.

Executive summary:

The skin irritation potential of the test material was evaluated in 6 New Zealand rabbits. A single dermal application of 0.5 ml of undiluted test material was applied to the abraded and intact skin of the rabbits under an occlusive wrap. Four hours post-dose, the occlusive binders and patches were removed. The exposure sites were gently wiped with clean gauze to remove as much non-absorbed test article as possible. One-half hour after unwrapping, the exposure sites were examined and scored separately for both erythema and edema on a graded scale of 0 to 4 in accordance with the method of Draize. The exposure sites were again examined and scored at 48, 72 and 96 hours. Based on the results of the study, the test material is considered to be non-irritating.

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

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study methodology followed was equivalent or similar to OECD TG 405 and in accordance with the Principles of Good Laboratory Practice (GLP)

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test Animals:
-Source: New York State Rabbit Development, Hartwick, N.Y.
-Weight at study initiation: Approximately 2-4kg
-Housing: Individually housed in wire mesh bottom cages
-Food: NIH Animal feed A, ad libitum
-Water: Tap water, ad libitum
-Acclimation period: minimum of 5 days

Environmental Conditions
-Temperature (C): as per "Guide for the Care and Use of Laboratory Animals"
-Humidity (%): as per "Guide for the Care and Use of Laboratory Animals"
-Air Changes (per hr): 12-15 air changes/hour
-Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye for each animal served as untreated control.

Amount / concentration applied:

A volume of 0.1 ml instilled in the everted lower lid of one eye of each animal. The other eye served as the untreated control.

Duration of treatment / exposure:

The lids of the treated eyes of the animals were held closed for one second following instillation and were not irrigated. The animal was then returned to it's cage.

Observation period (in vivo):

Observations for eye irritation were made at 1, 24, 48, and 72 hours and again at 7 days after application of the test article.

Number of animals or in vitro replicates:

6

Details on study design:

Method:
Animals wiil be weighed and weights recorded prior to the initiation of the study.
Approximately 24 hours prior to test initiation, the eyes of each rabbit were examined with sodium fluorescein and an ultraviolet lamp. Only those
rabbits whose eyes were free of irritation and corneal lesions were used.
A volume of 0.1 ml was instilled in one eye of each rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test article was deposited. The lids were then held together for one second after which the animal was returned to its cage. The treated eyes were not irrigated.
With the untreated eye serving as a control, the eyes were examined using fluorescein dye procedures and the grade of ocular reaction for each animal was recorded at 1, 24, 48 and 72 hours and again at 7 days using the Draize Scale for Scoring Ocular Lesions. If injury persisted the eyes were further examined and scored every 3 days for 13 days or until all signs of reversible irritation subsided.

Test Article Classification:
The mean eye irritation score and the standard deviation of the mean were determined for each observation period. The greatest mean score observed was used to assign the test article an ocular irritation rating in accordance with the classification system of Draize.

Irritation parameter:

cornea opacity score

Basis:

other: Mean score for all animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

other: Mean score for all animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

other: Mean score for all animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

other: Mean score for all animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

See results section.

Individual Rabbit Eye Irritation Scores

			Reading
Rabbit Number	Item	Tissue	1 hr	24 hr	48 hr	72 hr	Day 7
0906NW	A	Cornea Opacity	0	0	0	0	0
	B	Cornea Area	0	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0	0
	C	Iris	0	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0	0
	D	Conjunctiva Redness	0	0	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0	0
	F	Conjunctiva Discharge	0	0	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	0	0	0	0	0
		Totals Added= (1+2+3)	0	0	0	0	0
0874NW	A	Cornea Opacity	0	0	0	0	0
	B	Cornea Area	0	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0	0
	C	Iris	0	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0	0
	D	Conjunctiva Redness	0	0	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0	0
	F	Conjunctiva Discharge	0	0	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	0	0	0	0	0
		Totals Added= (1+2+3)	0	0	0	0	0
0875NW	A	Cornea Opacity	0	0	0	0	0
	B	Cornea Area	0	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0	0
	C	Iris	0	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0	0
	D	Conjunctiva Redness	0	0	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0	0
	F	Conjunctiva Discharge	0	0	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	0	0	0	0	0
		Totals Added= (1+2+3)	0	0	0	0	0
0877NW	A	Cornea Opacity	0	0	0	0	0
	B	Cornea Area	0	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0	0
	C	Iris	0	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0	0
	D	Conjunctiva Redness	0	0	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0	0
	F	Conjunctiva Discharge	0	0	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	0	0	0	0	0
		Totals Added= (1+2+3)	0	0	0	0	0
0878NW	A	Cornea Opacity	0	0	0	0	0
	B	Cornea Area	0	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0	0
	C	Iris	0	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0	0
	D	Conjunctiva Redness	0	0	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0	0
	F	Conjunctiva Discharge	0	0	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	0	0	0	0	0
		Totals Added= (1+2+3)	0	0	0	0	0
0799NW	A	Cornea Opacity	0	0	0	0	0
	B	Cornea Area	0	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0	0
	C	Iris	0	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0	0
	D	Conjunctiva Redness	0	0	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0	0
	F	Conjunctiva Discharge	0	0	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	0	0	0	0	0
		Totals Added= (1+2+3)	0	0	0	0	0

 

Initial Body Weights:

Animal Number              Initial Body Weight (kg)

82 -0906 M                            2.70

82 -0874 M                            2.85

82 -0875 M                            2.87

82 -0877 M                            2.83

82 -0878 M                            2.94

82 -0799 M                            2.75

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the test material is not considered corrosive to the eyes of rabbits.

Executive summary:

The eye irritation potential of the test material was evaluated in 6 New Zealand White rabbits. Animal body weights were recorded prior to the initiation of the study. Approximately 24 hours prior to test initiation, the eyes of each rabbit were examined with sodium fluorescein and an ultraviolet lamp. Only those rabbits whose eyes were free of irritation and corneal lesions were used. A volume of 0.1 ml was instilled in one eye of each rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test article was deposited. The lids were then held together for one second after which the animal was returned to its cage. The treated eyes were not irrigated. With the untreated eye serving as a control, the eyes were examined using fluorescein dye procedures and the grade of ocular reaction for each animal was recorded at 1, 24, 48 and 72 hours and again at 7 days using the Draize Scale for Scoring Ocular Lesions. Under the conditions of the study, The test material is not considered corrosive to the eyes of rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

The skin irritation potential of Automate Red B Nonvolatile was evaluated in 6 New Zealand rabbits. A single dermal application of 0.5 ml of undiluted test material was applied to the abraded and intact skin of the rabbits under an occlusive wrap. Four hours post-dose, the occlusive binders and patches were removed. The exposure sites were gently wiped with clean gauze to remove as much non-absorbed test article as possible. One-half hour after unwrapping, the exposure sites were examined and scored separately for both erythema and edema on a graded scale of 0 to 4 in accordance with the method of Draize. The exposure sites were again examined and scored at 48, 72 and 96 hours. Based on the results of the study, the test material is considered to be non-irritating.

Eye Irritation:

The eye irritation potential of Automate Red B Nonvolatile was evaluated in 6 New Zealand White rabbits. Animal body weights were recorded prior to the initiation of the study. Approximately 24 hours prior to test initiation, the eyes of each rabbit were examined with sodium fluorescein and an ultraviolet lamp. Only those rabbits whose eyes were free of irritation and corneal lesions were used. A volume of 0.1 ml was instilled in one eye of each rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test article was deposited. The lids were then held together for one second after which the animal was returned to its cage. The treated eyes were not irrigated. With the untreated eye serving as a control, the eyes were examined using fluorescein dye procedures and the grade of ocular reaction for each animal was recorded at 1, 24, 48 and 72 hours and again at 7 days using the Draize Scale for Scoring Ocular Lesions. Under the conditions of the study, Automate Red B Nonvolatile is not considered corrosive to the eyes of rabbits.

Justification for classification or non-classification

Not classified for skin or eye irritation