4-methyloxazole-5-carbonitrile

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according to OECD test guideline no. 405 (2002) and Commission Regulation (EC) No 440/2008, B.5.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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

Test material

Test material information

Constituent 1

Reference substance name:

4-methyloxazole-5-carbonitrile

EC Number:

213-709-7

EC Name:

4-methyloxazole-5-carbonitrile

Cas Number:

1003-52-7

Molecular formula:

C5H4N2O

IUPAC Name:

4-methyl-1,3-oxazole-5-carbonitrile

Details on test material:

Name of test item (as cited in the report): CMO
Physical state: liquid
Purity: 99.9% (m/m)
Batch Number: 485
CAS Number: 1003-52-7
Expiry Date: 04-Dec-2010
Storage Conditions: In the refrigerator (range of 5 ± 3 °C, provided by Harlan Laboratories Ltd.), light and humidity protected, under inert gas (nitrogen).

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kisslegg / Germany
- Age at treatment start: males: 16 weeks, females 16 and 24 weeks
- Weight at streatment start: male: 3349 g, females 2912 g and 3347 g
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet (e.g. ad libitum): Pelleted standard Kliba Nafag 3418 rodent maintenance diet (batch no. 05/10 provided by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) available ad libitum. Results of analyses for contaminants are archived at Harlan Laboratories Ltd.
- Water (e.g. ad libitum):Community tap water from Füllinsdorf ad libitum.
- Acclimation period: 26-Mar-2010 to 30-Mar-2010 (one female) and 26-Mar-2010 to 31-Mar-2010 (the male and the second female)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark


IN-LIFE DATES: From: 31-Mar-2010 To: 08-Apr-2010

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL/animal

Duration of treatment / exposure:

single instillation

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

1 male
2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
Washing (if done): no washing done


SCORING SYSTEM: according to the numerical scoring system listed in the Commission Regulation (EC) No 440/2008, B.5.
Data were summarized in tabular form, showing for each individual animal the irritation scores for the designated observation time, a description of the degree and nature of irritation, the presence of serious lesions and non-ocular effects. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values (with the exception of the sclerae) for each type of lesion.


TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic-lamp (Roth AG, 4153 Reinach / Switzerland)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

other: mean score for animal numbers 29, 30 and 31

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Remarks on result:

other: individual mean score: 0 -0 -0

Results 2

Irritation parameter:

iris score

Basis:

other: mean score for animal numbers 29, 30 and 31

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects observed

Remarks on result:

other: individual mean score: 0 -0 -0

Results 3

Irritation parameter:

conjunctivae score

Basis:

other: mean score for animal numbers 29, 30 and 31

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days after instillation

Remarks on result:

other: individual mean scores: 2.00 - 1.67 - 1.33

Results 4

Irritation parameter:

chemosis score

Basis:

other: mean score for animal numbers 29, 30 and 31

Time point:

24/48/72 h

Score:

2.11

Max. score:

4

Reversibility:

fully reversible within: 7 days after instillation

Remarks on result:

other: individual mean scores: 2.00 - 2.67 -1.67

Irritant / corrosive response data:

The test item did not induce significant or irreversible damage to the rabbit eye.

Other effects:

When assessable, slight to moderate reddening of the sclerae was noted at the 48-hour reading in the male (No. 29) and in one female (No. 31). The sclerae was slightly reddened at the 72-hour reading in all animals. No scleral reddening was observed in any animal 7 days after test item instillation. Slight to marked discharge was noted in all animals from the 1- to 48-hour readings, and persisted as slight up to the 72-hour reading. Nostaining produced by the test item was observed in the treated eyes.

Applicant's summary and conclusion

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labeling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and
amending Regulation (EC) No 1907/2006), CMO corresponds to Category 2 irritating to eyes with respect to eye irritation in rabbits.

Executive summary:

The primary eye irritation potential of CMO was investigated according to OECD test guideline no. 405 (2002). The test item was applied by instillation of 0.1 mL into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed

approximately 1, 24, 48 and 72 hours, as well as 7 days after test item instillation. The eyes were not washed following instillation of the test item.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris light reflex, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris light reflex were 0.00 for all three animals. The individual mean scores for the conjunctivae were 2.00, 1.67 and 1.33 for reddening and 2.00, 2.67 and 1.67 for chemosis, respectively.

The instillation of CMO into the eye resulted in slight to marked, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, ocular discharge and chemosis. These effects were reversible and were no longer evident 7 days after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or for the iris light reflex of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed.

Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labeling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006), CMO corresponds to Category 2 irritating to eyes with respect to eye irritation in rabbits.