Disodium 1-amino-4-[[3-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]-2-methyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Dec 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

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:

Disodium 1-amino-4-[[3-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]-2-methyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

EC Number:

276-374-6

EC Name:

Disodium 1-amino-4-[[3-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]-2-methyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Cas Number:

72139-17-4

Molecular formula:

C25H16ClF2N5O8S2.2Na

IUPAC Name:

disodium 1-amino-4-({3-[(5-chloro-2,6-difluoropyrimidin-4-yl)amino]-2-methyl-5-sulfophenyl}amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate

Test material form:

solid: particulate/powder

Details on test material:

Reactive Blue 114

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Lippischen Versuchstierzucht, Hagemann GmbH & Co. KG, 4923 Extertal 1
- Weight at study initiation: 2.6 kg (mean)
- Housing: one animal per cage
- Diet (e.g. ad libitum): ad libitum ("mümmel z" (ssniff / Soest))
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 40
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

single treatment, 100 µL of the test item was placed into the lower lid ofthe right eye of each animal. The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated and served as a control.

Observation period (in vivo):

1, 24, 48, 72, 96 h and 8 d

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM: according to Draize (see Table 1 in box "Any other information on material and methods")

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

no indication of irritation

Remarks:

partly blue staining of cornea area

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.77

Max. score:

3

Reversibility:

fully reversible within: 72 h

Remarks on result:

probability of weak irritation

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.77

Max. score:

4

Reversibility:

fully reversible within: 8 d

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

All symptoms were fully reversible within 8 days. Cornea scores could only be obtained for a few time points due to blue staining of the eye. For individual results see Table 2 in box "Any other information on results icl. tables"

Any other information on results incl. tables

Table 2: Individual results of the eye irritation test

Animal number	Endpoint	Draize score
		1 h	24 h	48 h	72 h	8 d	mean (24/48/72 h)
1	Cornea	x	x	x	0	0	x
	Iris	0	0	0	0	0	0.0
	Conjuntivae	x	1	1	0	0	0.7
	Chemosis	2	2	1	1	0	1.3
2	Cornea	x	x	x	x	0	x
	Iris	0	0	0	0	0	0.0
	Conjuntivae	2	1	1	0	0	0.7
	Chemosis	2	1	0	0	0	0.3
3	Cornea	x	x	0	0	0	x
	Iris	0	0	0	0	0	0.0
	Conjuntivae	x	1	1	1	0	1.0
	Chemosis	2	1	1	1	0	1.0

x: not scored/calculated, due to strong blue staininig of the eye

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute eye irritation/corrosion study conducted according to OECD 405, the test substance causes no serious irritant effects on the rabbit eye. Only slight effects in the conjunctivae were observed at 24 and 48 h but fully reversible within 72 h. Initially found slight chemosis effects were fully reversible within 8 d.

Executive summary:

In a primary eye irritation study conducted according to OECD 405, 0.1 mL of the undiluted test item was instilled into the conjunctival sac of one eye of 3 male New Zealand White rabbits. The untreated eye served as control. No washing was performed after instillation. Animals were then observed for 8 days. Eyes were examined at 1, 24, 48, and 72 and 192 hours after instillation. Irritation was scored by the method of Draize. Animals showed only weak signs of irritation during the first 72 h of the observation period. Determination of the cornea score was only partly possible due to blue staining of the treated eyes. All symptoms were fully reversible within 8 days. 

In this study, the test material is not an eye irritant and therefore does not warrant for classification according to CLP criteria.