1-(3-chloropyridin-2-yl)-N-[4-cyano-2-methyl-6-(methylcarbamoyl)phenyl]-3-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 - 28 May 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 2012

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

adopted in 1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted in 2008

GLP compliance:

yes (incl. QA statement)

Remarks:

GYEMSZI National Institute for Quality- and Organizational Development in Healthcare and Medicines, Budapest, Hungary

Test material

Test material information

Constituent 1

Reference substance name:

1-(3-chloropyridin-2-yl)-N-[4-cyano-2-methyl-6-(methylcarbamoyl)phenyl]-3-{[5-(trifluoromethyl)-2H-1,2,3,4-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide

EC Number:

810-161-6

Cas Number:

1229654-66-3

Molecular formula:

C22 H16 Cl F3 N10 O2

IUPAC Name:

1-(3-chloropyridin-2-yl)-N-[4-cyano-2-methyl-6-(methylcarbamoyl)phenyl]-3-{[5-(trifluoromethyl)-2H-1,2,3,4-tetrazol-2-yl]methyl}-1H-pyrazole-5-carboxamide

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: S&K-LAP Kft., Kartal, Hungary
- Age at study initiation: 10 - 11 weeks
- Weight at study initiation: 2765 - 2803 g
- Housing: individual in AAALAC approved metal wire rabbit cages
- Diet: diet for rabbits (Agribands Europe Hungary PLC, Karcag, Hungary), ad libitum
- Water: municipal tap water, ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.1 - 20.1
- Humidity (%): 40 - 75
- Air changes (per hr): 15 - 20
- 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: 0.1 g

Duration of treatment / exposure:

1 h

Observation period (in vivo):

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The treated eye was rinsed with physiological saline solution.
- Time after start of exposure: 1 h

SCORING SYSTEM: Draize scoring system and OECD 405

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 6

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 7

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Results 8

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Other effects:

- Lesions and clinical observations: There were no mortalities and no clinical signs of systemic toxicity observed during the study. The general state and behaviour of animals were normal throughout the study period.
- Ophthalmoscopic findings: Fluorescein staining was negative in all animals during the observation period.
- Other observations: Discharge was noted 1 h post application in 3/3 males but was reversible within 24 h. The body weight and body weight changes were considered to be normal with no indication of any treatment related effect.

Any other information on results incl. tables

Table 1 Individual mean scores

Animal number	Effects	24 h	48 h	72 h	Mean scores	Response	Reversible (days)
1	Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae Discharge	0 0 1 1 0	0 0 1 0 0	0 0 0 0 0	0.00 0.00 0.67 0.33 0.00	- - - - -	na na 3 2 1*
2	Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae Discharge	0 0 1 0 0	0 0 0 0 0	0 0 0 0 0	0.00 0.00 0.33 0.00 0.00	- - - - -	na na 2 1* 1*
3	Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae Discharge	0 0 1 0 0	0 0 0 0 0	0 0 0 0 0	0.00 0.00 0.33 0.00 0.00	- - - - -	na na 2 1* 1*

-- = negative, na = not applicable, * = in respect of the result 1 h post application

Applicant's summary and conclusion

Interpretation of results:

other: CLP/GHS criteria not met; no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

CLP: not classified