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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 August 1998 to 11 September 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to EU & OECD test guidance in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Details on test material:
Name: T-9601
Certificate of analysis: NB 203 dated November 16, 1998
Purity: 94.7 % (m/m) ± 0.5 %
Appearance: red powder
Melting point: 155°C-160°C
Solubility: <0.5 g/l in water
Batch number: Hl-295
Date of production: May 29, 1998
Date of receiving: July 20, 1998
Date of expiry: May 2001
Storage conditions: darkness at approximately 5°C in a refrigerator

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species: New Zealand albino rabbit
Origin: Charles River Deutschland GmbH
Number of animals: 3
Body weight at start of the study: 3.1 -3.8 kg
Animal maintenance: in fully air-conditioned rooms in separate cages arranged in a battery
Room temperature: 20 ± 3eC
Relative humidity: 50 ± 20 %
Lighting time: 12 hours daily
Acclimatisation: 1 week under study conditions
Food: ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
Water: water from automatic water dispensers, ad libitum
Animal identification: numbered ear tags

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Dose levels: 100 mg per eye, applied neat.
Duration of treatment / exposure:
24 hours duration
Observation period (in vivo):
Initially 72 hours extended to 7 days
Number of animals or in vitro replicates:
3
Details on study design:
About 24 hours before the start of the study the test eyes of all animals were examined under UV light for corneal lesions after instillation of one drop of a 0.01 % fluorescein-sodium solution. Only animals without ocular abnormalities were used for the study.

100 mg T-9601 was administered once to the conjunctival sac of the left eye of three rabbits. The untreated eyes served in each case as a control.

24 hours after administration and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution took place, the treated eyes were washed out thoroughly with isotonic saline at approx. 37 °C.

The eyes were examined 1, 24, 48 and 72 hours after administration of the test substance. At 24 and 72 hours as well as after 7, 14 days, the eyes were also examined for corneal lesions under UV light after instillation of one drop of a 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically. All other changes or toxic effects were recorded. Since effects were still present in the eyes after 72 hours, further examinations were carried out after 7 days.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
other: overall 24, 48 & 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
other: overall 24, 48 & 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
animal #1
Time point:
other: overall 24, 48 & 72 hours
Score:
1.67
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
other: overall 24, 48 & 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
other: overall 24, 48 & 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
other: overall 24, 48 & 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
animal #2
Time point:
other: overall 24, 48 & 72 hours
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
other: overall 24, 48 & 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
other: overall 24, 48 & 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
other: overall 24, 48 & 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
animal #3
Time point:
other: overall 24, 48 & 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
other: overall 24, 48 & 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
7 days after application the irritations observed were all reversible.
Other effects:
From one hour up to 3 days after application the conjunctiva of the animal showed definitely injected blood vessels up to deeper crimson red colours and slight swellings up to swelling with partial eversion of lids. The irritations were attended by clear coloured eye discharge.

Any other information on results incl. tables

Generalised Results By Animal – Animals Against Parameters – Multiple Times

Activity : - Eye Irritation Results

Study: 98.0575 – T-9601 – Eye Irritation Test in Rabbits

Group Sex

Animal Number

Day Number

Time Slot

Bodyweight g

Treated Eye

Control Eye normal

Duration Treatment

Initial Pain Reaction

Eye Irrigated

Fl.ceine staining

Opacity Grade

Opacity Area

Iris

Redness

Chemosis

Discharge

1f

57

1

Treatment

3480

Left

Yes

24 hour

None

 

 

 

 

 

 

 

 

 

1 hour after treatment

 

 

Yes

 

 

No

 

0

0

0

1

2

2

2

24 hours after treatment

 

 

Yes

 

 

Yes

0

0

0

0

2

2

1

3

48 hours after treatment

 

 

Yes

 

 

No

 

0

0

0

2

1

0

4

72 hours after treatment

 

 

Yes

 

 

Yes

0

0

0

0

1

0

0

8

7 days after treatment

 

 

Yes

 

 

Yes

0

0

0

0

0

0

0

607

1

Treatment

3180

Left

Yes

24 hour

None

 

 

 

 

 

 

 

 

 

1 hour after treatment

 

 

Yes

 

 

No

 

0

0

0

2

2

2

2

24 hours after treatment

 

 

Yes

 

 

Yes

0

0

0

0

2

0

0

3

48 hours after treatment

 

 

Yes

 

 

No

 

0

0

0

0

0

0

4

72 hours after treatment

 

 

Yes

 

 

Yes

0

0

0

0

0

0

0

681

1

Treatment

3770

Left

Yes

24 hour

None

 

 

 

 

 

 

 

 

 

1 hour after treatment

 

 

Yes

 

 

No

 

0

0

0

2

1

1

2

24 hours after treatment

 

 

Yes

 

 

Yes

0

0

0

0

1

0

0

3

48 hours after treatment

 

 

Yes

 

 

No

 

0

0

0

0

0

0

4

72 hours after treatment

 

 

Yes

 

 

Yes

0

0

0

0

0

0

0

Nominal Dose: Group 1 – 0.1g

 

Clinical Observation – Clinical Signs by Animal

Study: 98.0575 – T-9601 – Eye Irritation Test in Rabbits

Day numbers relative to Start Date

Group Sex

Animal Number

Clinical Signs

1

2

3

4

8

1 hour p. appl.

24 hours p. appl.

48 hours p. appl.

72 hours p. appl.

7 days p. appl.

1f

57

No Abnormalities Detected

X

-

X

X

X

 

Eye discharge serous

M

S

-

-

-

607

No Abnormalities Detected

-

X

X

X

-

 

Eye discharge serious

M

-

-

-

-

681

No Abnormalities Detected

-

X

X

X

-

 

Eye discharge serious

S

-

-

-

-

X = Present  S = slight  M = Moderate

Nominal Dose: Group 1 – 0.1g

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Testing of T-9601 for primary eye irritation in the rabbit showed, that the substance is not irritating to eye.
Executive summary:

Testing for primary irritation in the rabbit eye provides information on ocular lesions after a single administration of the test substance to the conjunctival sac of the eye and serves as a basis for classification and labelling.

 

The present study was conducted in compliance with EEC-Guideline B.5."Acute Toxicity Eye Irritation" of the Directive 92/69/EEC: Commission Directive of July 31,1992 adapting to technical progress for the seventeenth time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packag­ing and labelling of dangerous substances and OECD Guidelines for Testing of Chemicals, 405 „Acute Eye Irritation / Corrosion", updated guideline, adopted: February 24, 1987.This study was conducted in compliance with the Principles of Good Laboratory Practice (GLP).

 

From one hour up to 3 days after application the conjunctiva of the animal showed definitely injected blood vessels up to deeper crimson red colours and slight swellings up to swelling with partial eversion of lids. The irritations were attended by clear coloured eye discharge.

7 days after application the irritations were reversible.

 

Based on the individual scores after 24, 48 and 72 hours, the following mean values were calculated:

 

Opacity of cornea

All animals

0.00

Iris

All animals

0.00

Animal 57

0.00

Animal 57

0.00

Animal 607

0.00

Animal 607

0.00

Animal 681

0.00

Animal 681

0.00

Redness of conjunctiva

All animals

0.89

Chemosis of conjunctiva

All animals

0.33

Animal 57

1.67

Animal 67

1.00

Animal 607

0.67

Animal 607

0.00

Animal 681

0.33

Animal 681

0.00

 

Testing of T-9601 for primary eye irritation in the rabbit showed, that the substance is not irritating to eye.