4H-Pyrido[1,2-a]pyrimidin-4-one, 3-[2-[4-[(Z)-(2,4-difluorophenyl)(hydroxyimino)methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-09-24 to 1991-09-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline 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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-{4-[(Z)-(2,4-DIFLUOROPHENYL)(HYDROXYIMINO)METHYL]PIPERIDIN-1-YL}ETHYL)-2-METHYL-6,7,8,9-TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE

EC Number:

603-689-1

Cas Number:

132961-05-8

Molecular formula:

C23H28F2N4O2

IUPAC Name:

3-(2-{4-[(Z)-(2,4-DIFLUOROPHENYL)(HYDROXYIMINO)METHYL]PIPERIDIN-1-YL}ETHYL)-2-METHYL-6,7,8,9-TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Name of test material: T 1624
- Analytical purity: 99.8% (w/w) based on base titration, 101.6% (w/w) based on acid titration
- Lot/batch No.: BEA011
- Storage condition of test material: at room temperature in closed containers

Test animals

Species:

rabbit

Strain:

other: Cunistar-MDL albino rabbits

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: established stock-farm of Buyens, Lichtaart, Belgium
- Age at study initiation: adult
- Weight at study initiation: 2.290 - 2.600 kg
- Housing: Rabbits were housed in an air-conditioned room individually in numbered metallic cages. The cages consisted of stainless steel walls and a wire mesh bottom and front door. The cages were suspended in racks above stainless steel drains with scrapers and sink holes for the collection of faeces and urine.
- Diet: The food consisted of Huybrechts pelleted rabbit food administered in self-raising hoppers and fed ad libitum throughout the study.
- Water: free and continuous access to fresh tap-water via automatic drinking nipples, ad libitum
- Acclimation period: one week


ENVIRONMENTAL CONDITIONS: no data

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

other: adjacent areas of the untreated shaved skin serving as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 grams per rabbit
- Concentration (if solution): 50 mg/100 mg


VEHICLE
- Amount(s) applied: no data
- Concentration: no data
- Lot/batch no.: no data
- Purity: no data

Duration of treatment / exposure:

four hours

Observation period:

72 hours (3 days)

Number of animals:

three male rabbits

Details on study design:

TEST SITE
- Area of exposure: about 6 square cm on shaved area of the back
- % coverage: no data
- Type of wrap if used: occlusive patch

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test substance was removed with water, without altering the existing response or integrity of epidermis
- Time after start of exposure: four hours


SCORING SYSTEM:
Draize

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 animals

Time point:

other: 1h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: A score of 0 was observed for all animals and all timepoints.

Results 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 animals

Time point:

other: 1h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: A score of 0 was observed for all animals and all timepoints.

Results 3

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: A score of 0 was observed for all animals and all timepoints.

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: A score of 0 was observed for all animals and all timepoints.

Irritant / corrosive response data:

No irritation was observed in any of the three animals. The erythema and oedema scores at 1, 24, 48, and 72 hours were 0 in all animals.

Other effects:

Body weight remained normal in all rabbits during the 3-day observation period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

T 1624, when given to Cunistar-MDL albino rabbits at a single dose of 0.5 g/rabbit by dermal application, produced no dermal irritation. Therefore, the test item should be considered not to be classified.