Ethanol, 2-[(3-aminopyrazolo[1,5-a]pyridin-2-yl)oxy]-, hydrochloride (1:1)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 06 Mar.2006 to 09 Mar.2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: the test substance was applied diluted at 10%

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-({3-aminopyrazolo[1,5-a]pyridin-2-yl}oxy)ethan-1-ol hydrochloride

EC Number:

695-745-7

Cas Number:

1079221-49-0

Molecular formula:

C9 H11 N3 O2, ClH

IUPAC Name:

2-({3-aminopyrazolo[1,5-a]pyridin-2-yl}oxy)ethan-1-ol hydrochloride

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: CEGAV breeding establishment - Les Hautes Noës, Saint Mars d0Egrenne, 61350 Passais la Conception, France
- Age at study initiation: Between 12 and 16 weeks at the start of the experiment
- Weight at study initiation: Between 2.9 kg and 3.3 kg at the start of the experiment
- Housing: Animals were housed individually in cages of standard size. Excreta were removed by unrolling plasticised brown paper, previously placed under cages. These cages were placed in an airconditioned (17- 21 ° C) animal house kept at between 45 % and 65 % relative humidity (except during the cleaning slot) in which non-recycled filtered air is changed approximately ten times per hour. The artificial day/night cycle was 12 hours light and 12 hours darkness with light on at 7.30 a.m.
- Diet (e.g. ad libitum): SDS/DIETEX STANRAB (P) SQC feed was available ad libitum. The criteria for acceptable levels of contaminants were within the limits of the analytical specifications established by the diet manufacturer.
- Water (e.g. ad libitum): Drinking water was available ad libitum in polycarbonate feeder bottles with a stainless steel nipple. A specimen of water is sent every 6 months to the Laboratoire Départemental d'Analyse du Cher - 216 rue Louis Mallet, 18014 Bourges Cedex, France - for analysis. The criteria for acceptable levels of contaminants in the water supplied were within the limits of the analytical
- Acclimation period:For at least 5 days before the treatment, in the area where the experiment took place.

ENVIRONMENTAL CONDITIONS, see above

IN-LIFE DATES: period not clearly mentionned, but according to study plan probabaly at the end of the 72h observation period.

Test system

Vehicle:

water

Controls:

other: The non-treated right eye was used as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit) and Concentration (if solution): As required by the guideline, 0.1 mL of the test item diluted at 10% in sterile water was instilled

VEHICLE
- Amount(s) applied (volume or weight with unit): see above
- Concentration (if solution):/
- Lot/batch no. (if required):/
- Purity:/

Duration of treatment / exposure:

0.1 mL of the test item diluted at 10% in sterile water was introduced once only into the conjunctival sac of the left eye of each of the animals. The conjunctival sac was opened by gently pulling the lower lid away from the eyeball. Eyelids were held closed for approximately 1 second in order to avoid any loss of test item diluted at 10% in sterile water. The non-treated right eye was used as control. Following treatment, animals were kept for approximately one hour in a restraint cage, in order to prevent rubbing
of the eye.

Observation period (in vivo):

Lesions of the conjunctiva, iris and cornea were monitored by direct examination. One hour, 24 hours, 48 hours and 72 hours approximately after the instillation of the test item diluted at 10% in sterile water, all possible conjunctival, iris or corneal lesions were evaluated on the left eye of each animal.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done):No
- Time after start of exposure:/

SCORING SYSTEM: Ocular lesions were graded using the following scoring system in accordance with the OECD Guideline No. 405.
Calculation of ocular primary irritation indices: Mean indices were calculated from results obtained for each rabbit by direct examination at times 24 hours, 48 hours and 72 hours. The surface area of corneal opacity and the lacrimation were not taken into account in the calculation of mean index. For each parameter, mean of indices for each rabbit for the three times was noted (Mean index per parameter, per animal for the three times = Mi). The maximum theoretical score was 4 (chemosis), 3 (redness), 2 (iris lesions) and 4 (corneal lesions).

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: No, lesions of the conjunctiva, iris and cornea were monitored by direct examination

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 72H

Score:

0

Results 2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 72H

Score:

0

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 72H

Score:

0

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 72H

Score:

0

Irritant / corrosive response data:

The application of the test item did not induce colouring of the application site and did not interfere with grading of any eye lesion.
Any conjunctival, iris and corneal lesion was evaluated approximately one hour, 24 hours, 48 hours and 72 hours after instillation of test item diluted at 10% in sterile water.
No ocular reaction was observed during the study on the three animals treated up to the end of the exposure time (i.e. at time 72 hours).
Mean scores calculated for each animal over 24, 48 and 72 hours were 0, 0 and 0 for chemosis, for redness of the conjunctiva, for iris lesions, and for corneal opacity.

Any other information on results incl. tables

Body weight (individual values in Kg)

Treatment	Animal number	Day 1	Day 4
Test item diluted at 10%	20060073	2.943	2.968
	20060074	3.233	3.257
	20060075	3.160	3.191

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No ocular reaction was observed during the study on the three eyes of animals with the test susbtance applied at 10% in sterile water. Mean scores calculated for each animal over 24, 48 and 72 hours were 0, 0 and 0 for chemosis, for redness of the conjunctiva, for iris lesions, and for corneal opacity.
Under the experimental conditions adopted, the test item applied diluted at 10% in sterile water to rabbit eye was non-irritant.

Executive summary:

At the Sponsor's request, any irritant property and/or degree of corrosion of the test item diluted at 10% in sterile water was evaluated following a single ocular instillation in the rabbit in accordance with the General Requirements of O.E.C.D Guideline No. 405 (April 24, 2002) and method B5 of Commission Directive No. 92/69/EEC (July 31, 1992) adapting to technical progress for the 17th time Council Directive No. 67/548/EEC and subsequent amendments (GLP study, scored as validity 2 according to Klimisch criteria).

Three animals were used for the study. 0.1 mL of test item diluted at 10% in sterile water was introduced into the conjunctival sac of the left eye of each of the animals. The untreated right eye served as a control.

The application of the test item did not induce colouring of the application site and did not interfere with grading of any eye lesion.

Any conjunctival, iris and corneal lesion was evaluated approximately one hour, 24 hours, 48 hours and 72 hours after instillation of the test item diluted at 10% in sterile water.

No ocular reaction was observed during the study on the three animals treated up to the end of the exposure time (i.e. at time 72 hours). Mean scores calculated for each animal over 24, 48 and 72 hours were 0, 0 and 0 for chemosis, for redness of the conjunctiva, for iris lesions, and for corneal opacity.

Under the experimental conditions adopted, the test item applied diluted at 10% in sterile water to rabbit eye was non-irritant.