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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:
01 - 13 Apr 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The in vivo test is performed according to Novartis internal Tiered Testing Strategy as a regular set of tests for all substances during the development of the project. (TRD Development Manual Chapter C.26 requirements.)
The Novartis Pharma Data Set (NPDS) has been put in place many years before the REACh regulation was released and we have, since then, systematically acquired data for all substances (RM, IM, DS, reagents, etc.) on behalf of TRD and PCS, for internal and external classification purposes.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 2017
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 2012
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
adopted in 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
adopted in 1998
Qualifier:
according to
Guideline:
other: JMAFF Guidelines
Version / remarks:
adopted in 2000
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L’Arbresle, France
- Age at study initiation: approx. 32 - 33 weeks
- Weight at study initiation: 4230 - 4478 g
- Housing: individual, in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm), animals were provided with shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) except when interrupted by study procedures/activities
- Diet: Pelleted diet for rabbits (Global Diet 2030 Teklad®, Mucedola, Milanese, Italy) once daily throughout the study and in addition hay (TecniLab-BMI BV, Someren, The Netherlands) was available during the study period
- Water: Municipal tap-water, ad libitum (analyses were performed)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24 (mean = 20)
- Humidity (%): 40 to 70 (mean = 61 - 62)
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: approx. 81.8 mg; approx. 0.1 mL

Duration of treatment / exposure:
1 h
Observation period (in vivo):
14 days
Reading timepoints: 1, 24, 48 and 72 h and for 1 animal (sentinel) 7 days after instillation of the test substance
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Yes, the treated eye was rinsed with approximately 50 mL tepid tap water
- Time after start of exposure: after the 1 h observation

SCORING SYSTEM: Draize method

TOOL USED TO ASSESS SCORE: Fluorescein for evidence of corneal damage

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0.9
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
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
Irritant / corrosive response data:
The corneal injury consisted epithelial damage and slight dulling of the normal luster of the cornea. The corneal injury resolved within 24 h in one animal and within 72 h in the other two animal, in the third animal no corneal injury was noted.The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 7 days in one animal and within 72 h in the other two animals. No iridial irritation was observed. There was no evidence of ocular corrosion.
Other effects:
- Clinical observations/ mortaliity: No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1: Individual Eye Irritation Scores

Animal No.

Time after

dosing

Cornea

Iris

Conjunctivae

Comments

Opacity

Area

Fluor area

(%) (b)

 Redness

Chemosis

Discharge

1 (a)

1 h

0

1

-

0

2

1

2

c, d

24 h

0

0

0

0

2

1

1

-

48 h

0

0

-

0

1

0

0

-

72 h

0

0

-

0

0

0

0

-

7 days

0

0

-

0

0

0

0

-

Mean
(24, 48, 72 h)

0.0

-

-

0.0

1.0

0.3

-

-

2

1 h

0

1

-

0

2

1

1

c, d

24 h

0

0

15

0

2

1

1

d

48 h

0

0

-

0

1

0

0

-

72 h

0

0

0

0

0

0

0

-

Mean
(24, 48, 72 h)

0

-

-

0.0

1.0

0.3

-

-

3

1 h

0

0

-

0

2

1

1

c

24 h

0

0

0

0

1

1

1

-

48 h

0

0

-

0

1

0

0

-

72 h

0

0

-

0

0

0

0

-

Mean
(24, 48, 72 h)

0.0

-

-

0.0

0.7

0.3

-

-

Mean (24, 48, 72 h)
of 3 animals

0.0

-

-

0.0

0.9

0.3

-

-

a = sentinel

b = green staining after fluorescein treatment (percentage of total corneal area)

c = remnants of the test substance in the eye

d = slight dulling of the normal luster of the cornea

Applicant's summary and conclusion

Interpretation of results:
other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified

An in vivo eye irritation study according to OECD Guideline 405 in rabbits was performed with the test substance. The observed effects on the cornea and conjunctivae were reversible within the observation period.