Reaction mass of N-[(5-methyl-1H-pyrazol-1-yl)methyl]acetamide AND N-[(3-methyl-1H-pyrazol-1-yl)methyl]acetamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-05-10 - 2007-06-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of N-[(5-methyl-1H-pyrazol-1-yl)methyl]acetamide AND N-[(3-methyl-1H-pyrazol-1-yl)methyl]acetamide

EC Number:

700-208-8

Molecular formula:

C7H11N3O

IUPAC Name:

Reaction mass of N-[(5-methyl-1H-pyrazol-1-yl)methyl]acetamide AND N-[(3-methyl-1H-pyrazol-1-yl)methyl]acetamide

Test material form:

solid: crystalline

Details on test material:

Chemical name: N-(3(5)-Methyl-1 H-pyrazol-1 -yl-methyl)-acetamid
Code of the sponsor: P 70/05 Formula: C7H11N3O
Description: white, amorphous solid
Purity: > 99 % (HPLC and NMR)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

The study room and cages were cleaned and disinfected before the animals arrived. During the study, the room and cages were cleaned at regular intervals.
The animals were housed individually.
Air conditioned: temperature: 18.5 - 22.5 °C, with a shortly rising on 24.5 °C,
relative humidity: 33 - 70 % artificial light was set to give a cycle of 12 hours light and 12 hours dark; the light phase was from 6.30 a.m. - 6.30 p.m.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml of the test item (approx. 51 mg)

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

The test was carried out with three male rabbits.
Both eyes of each animal were examined before testing. Two to three drops of a fluorescein sodium solution (0.5 % in deionised water) were instilled into the conjunctival sac and rinsed out again after 30 sec with deionised water. No ocular defects were observed in any of the animals.
A volume of 0.1 ml of the test item (approx. 51 mg) was instilled into the conjunctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then held together gently for approximately 1 second in order to prevent loss of the material. The other eye of the same animal, which remained untreated, served as control.
The treated eyes were carefully rinsed out with deionised water one hour after instillation because partly a lot of test item could be observed in the conjunctival sac.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.8

Max. score:

3

Reversibility:

fully reversible

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

The acute eye irritation/corrosion of N-(3(5)-Methyl-1H-pyrazoI-l-yl-methyl)-acetamid (P 70/05) was tested in three albino rabbits according to OECD Guideline 405 (Acute Eye Irritation / Corrosion). The test item was instilled as the original substance at a single dose of 0.1 ml to one of the eyes in each animal. The untreated eye was used as control.
The animals were examined for clinical signs and the eyes were examined for lesions of the conjunctivae, cornea and iris 60 minutes, 24, 48 and 72 hours and from day 4 till day 14 after instillation of the test item. The grades for ocular lesions were recorded in accordance with the guideline.
A single instillation of N-(3(5)-Methyl-lH-pyrazol-l-yl-methyl)-acetamid (P 70/05) into the conjunctival sac of three albino rabbits caused a damage of the epithelia of the cornea, slight effects to the iris, slight to moderate redness and swelling of the conjunctivae and a purulent secretion from the eye.
All effects were reversible within an observation period of 13 days. None of the animals died or showed clinical signs during the course of testing.
The alterations of the eyes after instillation of N-(3 (5)-Methyl-1 H-pyrazol-1 -yl-methyl)- acetamid (P 70/05) meet the criteria for classification as an eye irritant.

Executive summary:

The acute eye irritation/corrosion of N-(3(5)-Methyl-1H-pyrazoI-l-yl-methyl)-acetamid (P 70/05) was tested in three albino rabbits according to OECD Guideline 405 (Acute Eye Irritation / Corrosion). The test item was instilled as the original substance at a single dose of 0.1 ml to one of the eyes in each animal. The untreated eye was used as control.

The animals were examined for clinical signs and the eyes were examined for lesions of the conjunctivae, cornea and iris 60 minutes, 24, 48 and 72 hours and from day 4 till day 14 after instillation of the test item. The grades for ocular lesions were recorded in accordance with the guideline.

A single instillation of N-(3(5)-Methyl-lH-pyrazol-l-yl-methyl)-acetamid (P 70/05) into the conjunctival sac of three albino rabbits caused a damage of the epithelia of the cornea, slight effects to the iris, slight to moderate redness and swelling of the conjunctivae and a purulent secretion from the eye. All effects were reversible within an observation period of 13 days. None of the animals died or showed clinical signs during the course of testing. The alterations of the eyes after instillation of N-(3 (5)-Methyl-1 H-pyrazol-1 -yl-methyl)- acetamid (P 70/05) meet the criteria for classification as an eye irritant.