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

Endpoint summary

Description of key information

The test item was tested in two GLP-studies for skin and irritation on rabbits for the purposes of a new substance notification in 1991. Both studies were performed with three rabbits of the New Zealand White species. In the skin irritation test, no irritating effects (score 0) were observed for erythema and oedema endpoints.
In the eye irritation study, slight to moderate irritation was noted in the conjunctiva (redness and chemosis), whereas no effects were observed in the cornea and iris of the treated animals. The observed effects were reversible within 24 hours up to 17 days after instillation of the test item.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin 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

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: female
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: approx. 12 weeks
- Weight at study initiation: 2140 - 2377 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

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

500 mg test item

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 animals

Details on study design:

TEST SITE
- Area of exposure: approx. 100 cm2

On test day 1, 0.5 gram of the moistened test substance was applied to the intact skin of the shaved area on one flank, using a Metalline patch (2x3 cm, Lohman, Neuwied, W.-Germany) mounted to Micropore tape (3M, St. Paul, U.S.A.). The contralateral flank was similarly prepared (but without test article and vehicle) to act as a procedural control. The dressing was wrapped around the abdomen and secured with an elastic bandage (Coban, 3M, st. Paul, U.S.A.). Four hours after the application, the dressing was removed and the remaining test article was removed using a tissue moistened with tap-water and subsequently a dry tissue.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: overall 24, 48 and 72 hours

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: overall 24, 48 and 72 hours

Score:

0

Max. score:

0

Irritant / corrosive response data:

No skin irritation was observed.

Other effects:

No staining of the treated skin by the test substance was observed.

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 skin.

Executive summary:

The study was performed according to EU-method B.4 on three New Zealand White rabbits. Neither erythema nor oedema were observed throughout the test (score 0), therefore, the test substance can be considered as non-irritant to rabbit skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

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

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.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: overall 24, 48 and 72 hours

Score:

0

Max. score:

0

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

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Guideline study; GLP; Klimisch 1

Justification for selection of eye irritation endpoint:
Guideline study; GLP; Klimisch 1

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Based on the data available the substance is not classified or labeled according to Directive 67/548/EEC (DSD) or Regulation 1272/2008/EC (CLP).