6-ethyl-5-fluoro-4(3H)-pyrimidone

Endpoint summary

Description of key information

Skin irritation:

A study was performed to assess the skin irritation potential of test item to the rabbit following the method described in EC B.4.

No reactions were observed following a single semi-occlusive application of test item to intact rabbit skin for four hours.

Eye irritation:

A study was performed to assess the eye irritation potential of test item to the rabbit following the method as described in EC B.5.

A single instillation of test item into the eye of the rabbit elicited corneal opacification and well-defined to moderate to severe conjunctival irritation. Responses had resolved in all instances by 14 days after instillation.

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:

From 1996-05-29 to 1996-06-1

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

OJ No. L383A, 29.12.92

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Batch No.: Chichibu Lot No. 950704
Purity: 95.7%

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Interfauna UK Ltd, Huntingdon, Cambridgeshire, England.
- Age at study initiation: approximately 11 to 14 weeks
- Weight at study initiation: 2.6 to 3.1 kg
- Housing: housed individually in metal cages with perforated floors
- Diet: A standard laboratory diet SDS Stanrab (P) Rabbit Diet, ad libitum
- Water: ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Ca 19 °C
- Humidity (%): 30-70 %
- Air changes (per hr): approximately 19 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 hours

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
A 0.5 g amount of the test substance was applied under a 25 mm x 25 mm gauze pad which had been moistened with 0.5 mL distilled water to one intact skin site on each animal.
Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with warm water (30 to 40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
- Clinical signs: daily
- Dermal responses: on Day 1 (ie approximately 60 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure).

SCORING SYSTEM:
- Method of calculation: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: for all three animal tested

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: for all three animal tested

Irritant / corrosive response data:

No dermal response to treatment was observed in any animal throughout the observation period.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Individual scores:

Animal No.	Erythema				Oedema
	24 h	48h	72 h	Mean	24 h	48h	72 h	Mean
1	0	0	0	0	0	0	0	0
2	0	0	0	0	0	0	0	0
3	0	0	0	0	0	0	0	0

 

Interpretation of results:

GHS criteria not met

Conclusions:

A single semi-occlusive application of test item to intact rabbit skin for four hours elicited no dermal irritation.

Executive summary:

A study was performed to assess the skin irritation potential of test item to the rabbit following the method described in EC B.4.

Three rabbits were each administered a single dermal dose of 0.5 g of the test substance and observed for four days.

No reactions were observed following a single semi-occlusive application of test item to intact rabbit skin for four hours.

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:

From 1996-06-03 to 1996-06-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

OJ No. L383A, 29.12.92

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Batch No.: Chichibu Lot No. 950704
Purity: 95.7%

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Interfauna UK Ltd, Huntingdon, Cambridgeshire, England.
- Age at study initiation: approximately 12 to 13 weeks
- Weight at study initiation: 2.8 to 3.0 kg
- Housing: housed individually in metal cages with perforated floors
- Diet: A standard laboratory diet SDS Stanrab (P) Rabbit Diet, ad libitum
- Water: ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Ca 19 °C
- Humidity (%): 30-70 %
- Air changes (per hr): approximately 19 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3

Details on study design:

TREATMENT PROCEDURE
One animal was treated in advance of the others, approximately 100 mg of the test substance, the weight occupying a volume of 0.1 mL, was placed into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated.

REMOVAL OF TEST SUBSTANCE
- Washing: Not done


SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: handheld light

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible within: 3 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible within: 3 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

Dulling of the normal lustre of the cornea was seen in two animals one hour after instillation. Corneal opacification developed in one of these animals.
No iridial inflammation was seen.
A diffuse crimson to beefy red colouration was seen in all three animals, accompanied in two rabbits by considerable swelling with partial eversion of the eyelids or with the eyelids about half closed.
The reactions gradually ameliorated and the eyes were normal 4, 7 or 14 days after instillation.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Individual scores:

Animal No.	Cornea opacity				Iris				Conjunctivae				Chemosis
	24 h	48h	72 h	Mean	24 h	48 h	72 h	Mean	24 h	48h	72 h	Mean	24 h	48h	72 h	Mean
1	0	0	0	0	0	0	0	0	2	2	1	1.67	2	1	1	1.33
2	0	0	0	0	0	0	0	0	2	1	1	1.33	1	1	0	0.67
3	1	1	0	0.67	0	0	0	0	3	3	2	2.67	2	1	1	1.33

Interpretation of results:

GHS criteria not met

Conclusions:

Instillation of test item into the rabbit eye elicited corneal opacification and well-defined to moderate conjunctival irritation.

Executive summary:

A study was performed to assess the eye irritation potential of test item to the rabbit following the method as described in EC B.5.

Three rabbits were each administered a single ocular dose of 100 mg of the test substance and observed for a maximum of 14 days after instillation.

A single instillation of test item into the eye of the rabbit elicited corneal opacification and well-defined to moderate to severe conjunctival irritation. Responses had resolved in all instances by 14 days after instillation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin irritation in vivo, EC B.4:

Mean scores of erythema/eschar and oedemas at 24, 48 and 72 hours were all 0 for three test sites after removal of the dressing.

According to Regulation (EC) No 1272/2008, section 3.2.2 and Table 3.2.2, this substance should not be classified for this endpoint.

 

Eye irritation in vivo: EC B.5:

Mean scores at approximately 24, 48, 72 hours after administration:

Cornea Opacity: 0, 0, 0.67

Iris:0, 0, 0

Conjunctival Redness: 1.67, 1.33, 2.67

Chemosis: 1.33, 0.67, 1.33

According to Regulation (EC) No 1272/2008, section 3.3.2 and table 3.3.2, this substance should not be classified for this endpoint.