Phenyl N-(4,6-dimethoxypyrimidin-2-yl)carbamate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

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:

Phenyl N-(4,6-dimethoxypyrimidin-2-yl)carbamate

EC Number:

406-600-2

EC Name:

Phenyl N-(4,6-dimethoxypyrimidin-2-yl)carbamate

Cas Number:

89392-03-0

Molecular formula:

C13H13N3O4

IUPAC Name:

phenyl N-(4,6-dimethoxypyrimidin-2-yl)carbamate

Test material form:

solid: crystalline

Details on test material:

- Identification: IN-E6758
- Description: Off white to light blue solid
- Batch: E52691-89-3-B22
- Purity: approx. 100%
- Expiry date: not indicated
- Storage: at room temperature in a cool place in the dark (avoid high temperatures)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: female
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: approx. 17 weeks
- Weight at study initiation: 2683 - 2967 grams
- Housing: individually in cages with perforated floors equipped with an automatic drinking system
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (lKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 g/d
- Water (e.g. ad libitum): Tap water
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 21°C
- Humidity: 55%
- Air changes: 15 air changes per hour
- Photoperiod: 12 hours artificial light

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

55 mg test item = equivalent to 0.1 ml

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

17 days

Number of animals or in vitro replicates:

3 animals

Details on study design:

The test substance (approx. 55 mg per animal) was instilled in the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was applied to both eyes of each animal to quantitatively examine the potential for corneal injury. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: overall 24, 48 and 72 hours

Score:

0

Max. score:

0

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: overall 24, 48 and 72 hours

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score 1 observed oe hour after treatment

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: overall 24, 48 and 72 hours

Score:

1.1

Max. score:

2

Reversibility:

fully reversible within: 17 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: overall 24, 48 and 72 hours

Score:

0.1

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Irritant / corrosive response data:

At 1 hour and 24 hours, conjunctival redness (maximum grade 1) and chemosis (maximum grade 2) and redness and chemosis of the eyelids or nictitating membrane (maximum grade 2) occurred in all the animals. An iris score of 1 was noted in one animal at 1 hour. At 72 hours, grade 1 redness of the scleral conjunctivae was observed in one animal.

Other effects:

No staining by the test substance was observed.

Any other information on results incl. tables

Following the 72- hour reading, observation was only carried out at 17 days.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item was found to be non-irritating to rabbit eyes.

Executive summary:

The study was performed according to EU-method B.5 on three New Zealand White rabbits. There were no effects observed in iris and cornea whereas slight to moderate irritant effects were noted in conjunctiva (Redness and chemiosis). However, based on the mean scores observed, the test substance can be considered as non-irritant to the rabbit eye.