1H-Imidazole-5-methanol, 2-butyl-4-chloro-1-[[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 27 august 2012 to 6 september 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 405) and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

[2-butyl-4-chloro-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-imidazol-5-yl]methanol

EC Number:

601-329-8

Cas Number:

114798-26-4

Molecular formula:

C22H23ClN6O

IUPAC Name:

[2-butyl-4-chloro-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-imidazol-5-yl]methanol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): MK-0954 Free Acid
- Molecular formula (if other than submission substance): C22H23ClN6O
- Molecular weight (if other than submission substance): 422.91
- Structural formula attached as image file (if other than submission substance): see reference substance
- Physical state: white powder
- Analytical purity: not provided
- Lot/batch No.: not available
- Expiration date of the lot/batch: 24 april 2013
- Stability under storage conditions: stable
- Storage condition of test material: at room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Conditions
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

Accommodation
Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
Acclimatization period was at least 5 days before start of treatment under laboratory conditions.

Diet
Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period

Water
Free access to tap water.

Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures.
There were no findings that could interfere with the study.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

undiluted,
applied amount: approx. 0.1 ml volume or 65.6 - 66.0 mg

Duration of treatment / exposure:

Eyes unwashed

Observation period (in vivo):

Observation to 7 days in some cases

Number of animals or in vitro replicates:

3 male animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
-Washing: unwashed

SCORING SYSTEM:
after Draize, 1959

TOOL USED TO ASSESS SCORE: fluorescein (for 1-day reading)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean of data at 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean of data at 24, 48, 72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean of data at 24, 48, 72 h

Score:

1.1

Max. score:

3

Reversibility:

fully reversible within: 3 d for two animals and 7 days for one animal

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean of data at 24, 48, 72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 3 d for two animals and 7 d for one animal

Any other information on results incl. tables

					Cornea				Iris		Conjunctivae				Comments
Animal	Time after dosing				Opacity (0-4)	Area (0-4)	Fluor area (%)^2		(0-2)		Redness (0-3)	Chemosis (0-4)	Discharge (0-3)
330^1	1 hour				0	0	-		1		2	1	1		b
	24 hours				0	0	0		0		2	0	1		-
	48 hours				0	0	-		0		1	0	0		-
	72 hours				0	0	-		0		1	0	0		-
	7 days				0	0	-		0		0	0	0		-
329	1 hour				0	0	-		1		2	2	2		b
	24 hours				0	0	0		0		2	1	1		-
	48 hours				0	0	-		0		1	0	0		-
	72 hours				0	0	-		0		0	0	0		-
331	1 hour				0	0	-		1		2	2	1		b
	24 hours				0	0	0		0		2	1	1		-
	48 hours				0	0	-		0		1	0	0		-
	72 hours				0	0	-		0		0	0	0		-

¹ Sentinel, ² Green staining after fluorescein treatment (percentage of total corneal area)

Comments: b Remnants of the test substance in the eye

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

A reliable study, conducted according to OECD 405, and in compliance with GLP. Iridial irridial irritation grade 1 was observed in all animals. The study was terminated at 7 days, when the irritation of the conjunctivae completely resolved. Based on these results, the test substance does not need to be classified for eye irritation according to GHS.