Reaction products of 7-amino-4-hydroxynaphthalene-2-sulfonic acid reacted with 2-((1,3,5-triazin-2-yl)amino)ethan-1-ol, coupled with diazotised 3-amino-4-hydroxybenzenesulfonic acid, subsequently coupled with diazotised 2-amino-5-methoxybenzenesulfonic acid, chelated with copper, sodium salt

Eye irritation

Some information in this page has been claimed confidential.

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-05-19 to 1991-05-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Details on test material:

Direct Red 83:1

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

New Zealand White rabbit (Safepharm Definitive Protocol Number TX 3077)
Source: (David Percival Ltd. Moston, Sandbach, Cheshire, U.K.)
Identification: Numbering
Husbandry: Individually housed in suspended metal cages.
-free access to food to mains drinking water and food.
3 animals (only with a healthy intact epidermis were selected for the study)
2.96 – 3.1 kg
Approx. 12 – 16 weeks old
Minimum of acclimatisation period 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C
- RELATIVE Humidity (%): 50-66%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: 1991-05-13 to 1991-05-21

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Single application to non- irrigated to both eyes of the rabbits
Immediately before the start of the test
One rabbit initially tested: 0.1 mL of test material, approx. 98 mg

Duration of treatment / exposure:

Assessment of ocular damage/irritation was made approx. 1 h and 24, 48 and 72 h following the treatment.

Observation period (in vivo):

Additional observation on day 7 to assess reversibility of ocular effects.

Number of animals or in vitro replicates:

3

Details on study design:

- Time after start of exposure: 1 hour and 24, 48 and 72 hours following treatment

SCORING SYSTEM:
To classify ocular irritancy potential: modified version of system described by Kay J.H. and Calandra J.C., J. Soc. Cosmet. Chem., 1962 13 281-289
Results interpreted according to Commission Directive 83/467/EEC
TOOL USED TO ASSESS SCORE: fluorescein
Confirmation of corneal opacity was made by examination of the eye under ultra-violet illumination using sodium fluorescein B.P

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

cornea opacity

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Remarks:

cornea opacity

Basis:

animal: 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

iris score

Basis:

animal: 1, 2

Time point:

24/48/72 h

Score:

>= 0 - <= 0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Remarks:

at 24 h, the evaluation was impaired due to the heavy staining due to the test substance

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

conjunctivae score

Remarks:

Conjunctival redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 1.33 - <= 2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 6

Irritation parameter:

conjunctivae score

Remarks:

Conjunctival redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.6

Max. score:

3

Reversibility:

fully reversible within: 7 d

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Remarks:

Conjunctival redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

chemosis score

Remarks:

Conjunctival chemonis

Basis:

animal: 1, 2

Time point:

24/48/72 h

Score:

1.6

Max. score:

4

Reversibility:

fully reversible within: 7 d

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

chemosis score

Remarks:

Conjunctival chemonis

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

See results and discussions

Other effects:

None

Any other information on results incl. tables

Individual scores and individual total scores for ocular irritation

 

Rabbit No and Sex (bodyweight kg)	IPR = 3 183 male (2,96)					IPR = 0 173 Male ^+ (3,02)					IPR = 0 167 Female  ^+ (3.10)
Time after treatment	1 h	24 h	48 h	72 h	7 d	1 h	24 h	48 h	72 h	7 d	1 h	24 h	48 h	72 h	7 d
Cornea E = Degree of Opacity F = Area of Opacity	0^FS	1^FS	0	0	0	0^FS	0^FS	0	0	0	0^FS	0	0	0	0
	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Score (ExF)x5	0	5	0	0	0	0	0	0	0	0	0	0	0	0	0
IRIS D	?s<1	?s<1	0	0	0	?s<1	?s<1	0	0	0	?s<1	0	0	0	0
Score (D x 5)	0 or 5	0 or 5	0	0	0	0 or 5	0 or 5	0	0	0	0 or 5	0	0	0	0
Conjunctiveae A = Redness B = Chemosis C = Discharge	?s	?s	2^s	2^s	0^s	?s	2^s	2^s	1^s	0^s	?s	1	0	0	0
	2	2	1	1	0	2	2	1	1	0	2	1	0	0	0
	3^Re	2^Re	1^Re	0^Re	0^Re	3^Re	1^Re	0^Re	0^Re	0^Re	3^Re	0^Re	0^Re	0^Re	0^Re
Score (A + B + C) x 2	10 - 16	8 - 14	8	6	0	10 - 16	10	6	4	0	10 – 16	4	0	0	0
Total score	10 - 32	13 - 24	8	6	0	10 - 21	10 - 15	6	4	0	10 - 21	4	0	0	0

Individual total scores and group mean scores for ocular irritation at different times of observation:

 

Rabbit Number and Sex	1 h	24 h	48 h	72 h	7 d
183 m	10 – 21	13 – 24	8	6	0
173 m	10 – 21	10 - 15	6	4	0
167 f	10 – 21	4	0	0	0
Group Total	30 – 63	27 – 43	14	10	0
Group mean score	10 – 21 1 hour	9,0 – 14.3 24 hours	4.7 48 hours	3.3 72 hours	0 7 days

 

Individual and mean scores for cornea, iris and conjunctivae required for EEC labelling Regulations

 

Rabbit Number, sex, bodyweight	Time after treatment	Corneal opacity	Iridial inflammation	Conjunctival redness	Conjuntival Chemosis
183 m (2.96)	24 hours	1	<=1	?s	2
	48 hours	0	0	2	1
	72 hours	0	0	2	1
Total		1	<=1	4-7	4
Mean		0.3	<=0.3	1.3-2.3	1.3
173 m (3.02)	24 hours	0	<1	2	2
	48 hours	0	0	2	1
	72 hours	0	0	1	1
Total		0	<1	5	4
Mean		0.0	<=0.3	1.7	1.3
167 f (3.10)	24 hours	0	0	1	1
	48 hours	0	0	0	0
	72 hours	0	0	0	0
Total		0	0	1	1
Mean		0.0	0.0	0.3	0.3

 Produced moderate conjunctival irritation. Diffuse corneal opacity was confined to one treated eye. All treated eyes appeared normal seven days after treatment.

 

 

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material did not produce positive criteria in any rabbit according to the CLP labeling regulation and was classified as non-irritant. No symbol and risk phrase are therefore required.

Executive summary:

In an eye irritation/corrosion study, 98 mg of Direct Red 83:1 was administered once to the non-irrigated right eye of three rabbits. In each case the untreated eyes served as a control.

The aim of this study was to assess the irritancy potential of the test substance after a single administration to the rabbit eye.

A single application of the test substance to the non-irrigated eye of three rabbits produced a transient slight to moderate conjunctival irritation. Diffuse corneal opacity was confined to one treated eye. All treated eyes appeared normal seven days after treatment.

Diffuse corneal opacity was confined to one treated eye at the 24-hour observation. No other adverse corneal effects were noted. Corneal opacity was confirmed using sodium fluorescein B.P. in all treated eyes one hour after treatment and in two treated eyes at the 24-hour observation.

Red-coloured staining precluded accurate evaluation of iridial inflammation in all treated eyes one hour after treatment and in two treated eyes at the 24-hour observation. The reaction were considered to be less than or equal to grade 1.

Red coloured standing prevented accurate evaluation of conjunctival redness in all treated eyes one hour after treatment and in one treated eye in the 24-hour observation.

Conjunctival chemosis and discharge were noted in all treated eyes one hour after treatment with slight or moderate conjunctival chemosis and discharge in one treated eye at the 24-hour observation. Minimal or moderate conjunctival reddening was noted in two treated eyes at the 24-hour observation with minimal conjuctival reddening at the 48 and 72-hour observations. Moderate conjunctival reddenind was noted in one treated eye at the 48 hour observation with minimal conjunctival reddening at the 72 -hour observation. Residual test material was noted around all treated eyes during the study.

Direct Red 83:1 did not produce positive criteria in any rabbit according to the CLP labeling regulation and was classified as non-irritant. No symbol and risk phrase are required.