Multi constituent substance

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to OECD guideline 405 in compliance to GLP.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Reference 2

Reference Type:

other: Published secondary source

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Multi constituent substance

EC Number:

916-604-0

IUPAC Name:

Multi constituent substance

Details on test material:

Test substance : Basic Brown 17 (COLIPA number B007)
Batch number : NDKS 1944
Methylsulphate anion : 8.2%
Chloride ion : 3.6%
Water : 6.0%
Basic Red 118 : 2.4%
Purity : 96.3% (HPLC)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

45 mg

Duration of treatment / exposure:

Each animal was treated by instillation of the test substance in the conjunctival sac of one eye. The substance remained in permanent contact with the eyes until treatment of the eyes with 2% fluorescein 24 hours after test item instillation.

Observation period (in vivo):

All eyes were examined and scored 1, 24, 48, 72 hours and 7 days after instillation of the test substance.

Number of animals or in vitro replicates:

Three

Details on study design:

Treatment
Each animal was treated by instillation of 45mg (~0.1 mL) of the test substance in the conjunctival sac of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

Observations
Mortality/viability : Twice daily
Toxicity : At least once daily
Body weight : Day of treatment (prior to instillation) and at termination
Irritation : The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded. The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores were recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean 24-72 hours

Score:

0

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean 24-72 hours

Score:

0

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: mean 24-72 hours

Score:

0

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean 24-72 hours

Score:

0

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: mean 24-72 hours

Score:

0.3

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: mean 24-72 hours

Score:

0

Results 7

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

other: mean 24-72 hours

Score:

1.7

Results 8

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

other: mean 24-72 hours

Score:

2

Results 9

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

other: mean 24-72 hours

Score:

1.7

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean 24-72 hours

Score:

0.3

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean 24-72 hours

Score:

1

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean 24-72 hours

Score:

0.3

Irritant / corrosive response data:

Instillation of the test item resulted in effects on the iris in two animals and on the conjunctivae in all animals. Iridial irritation grade 1 was observed and had resolved within 24 or 72 hours. The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 7 days in all animals. No corneal opacity was observed. Treatment of the eyes with 2% fluorescein 24 hours after test item instillation revealed no corneal epithelial damage. There was no evidence of ocular corrosion. Remnants of the test substance were present in the eye 1 hour after instillation. Remnants were prsent on the outside of the eyelids 24 and 48 hours after instillation in one animal. Yellow-brown staining of the fur on the head and paws, caused by the test substance, was noted during the observation period. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Individual eye Irritation Scores

Time after Dosing	Cornea Opacity Score	Iris Score	Conjunctivae (Redness) Score	Chemosis Score	Discharge	Comments
Animal 1
1 hour	0	1	2	1	2	e, h, b
24 hours	0	0	2	1	1	e, c
48 hours	0	0	2	0	0	e, c
72 hours	0	0	1	0	0	e
7 days	0	0	0	0	0	e
Animal 2
1 hour	0	1	2	2	2	e, h, b
24 hours	0	0	2	2	1	e
48 hours	0	1	2	1	1	e
72 hours	0	0	2	0	0	e
7 days	0	0	0	0	0	e
Animal 3
1 hour	0	0	1	2	2	e, h, b
24 hours	0	0	2	1	2	e
48 hours	0	0	2	0	1	e
72 hours	0	0	1	0	0	e
7 days	0	0	0	0	0	e

Comments

b : Remnants of the test substance in the eye

c : Remnants of the test substance on the outside of the eyelids

e : Yellow-brown staining of the head and paws by the test substance

h : No scoring of the lower eyelids was possible because of yellow-brown staining

No ulceration or opacity of cornea observed for all animals at all observation times

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item is not irritating to the rabbit eye.

Executive summary:

The study was performed according to OECD guideline 405, EU method B.5, US EPA OPPTS 870.2400. Single samples of approximately 45mg of Basic Brown 17 (~0.1 mL) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7 days after instillation. Instillation of the test substance resulted in effects on the iris in two animals and on the conjunctivae in all animals. Iridial irritation grade 1 was observed and had resolved within 24 or 72 hours. The irritation of the conjunctivae consisted of redness, chemosis and disharge and had completely resolved within 7 days in all animals. Remnants of the test substance were present in the eye 1 hour after instillation. Remnants were also present on the outside of the eyelids 24 and 48 hours after instillation in one animal. Yellow-brown staining of the fur on the head and paws, caused by the test substance, was noted during the observation period. Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC) Basic Brown 17 does not have to be classified and has no obligatory labelling requirement for eye irritation.