4H-Pyrido[1,2-a]pyrimidin-4-one, 9-hydroxy-3-(2-hydroxyethyl)-2-methyl-

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-05-20 to 2003-06-10

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Internal lab method: SPL Standard Test Method 595.12.

Deviations:

not specified

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

not specified

Principles of method if other than guideline:

The study is performed according to SPL Standard Test Method. The assay determines the level of lymphocyte proliferation in lymph nodes draining the application site of the test material. Determination of lymphocyte proliferation is quantified by measuring the incorporation of radiolabelled thymidine in the dividing lymph node cells. The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node (dpm/node) and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).

GLP compliance:

no

Remarks:

The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report has not been audited by the QA unit. No formal claim of GLP compliance is made for this study.

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

9-hydroxy-3-(2-hydroxyethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

EC Number:

605-935-3

Cas Number:

181525-38-2

Molecular formula:

C11H12N2O3

IUPAC Name:

9-hydroxy-3-(2-hydroxyethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

No data

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/Ca

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS: no data

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

2.5%, 5% and 10% w/w

No. of animals per dose:

four/dose group

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: no data
- Irritation: no data
- Lymph node proliferation response: no data
- Other: Following a preliminary sighting test, no deaths or signs of systemic toxicity were observed at a concentration of 10%.


MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: Test-to-control ratio of Stimulation Index (SI) greater than 3.0 indicates a ‘positive’ result.


TREATMENT PREPARATION AND ADMINISTRATION:
- 50 uL of the test substance (25 uL per ear) as a solution in dimethyl formamide at concentrations of 2.5%, 5% and 10% w/w.
- A further group of four animals was treated with dimethyl formamide alone.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

see: any other information on results (here below)

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1.35

Test group / Remarks:

2.5% w/w

Results 2

Parameter:

SI

Value:

0.79

Test group / Remarks:

5% w/w group

Results 3

Parameter:

SI

Value:

1.43

Test group / Remarks:

10% w/w group

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA
No data

DETAILS ON STIMULATION INDEX CALCULATION
see results table

Any other information on results incl. tables

Positive Control Local Lymph Node Assay in the Mouse (2003)

	Start Date	Finish Date	Test Material	Concentration	Vehicle	Stimulation Index^a	Classification^b
	13/03/2003	19/03/2003	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	acetone/olive oil 4:1	2.8, 2.3, 5.5	Positive
	13/03/2003	19/03/2003	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	acetone/olive oil 4:1	2.0, 1.9, 6.8	Positive
	10/10/2003	16/10/2003	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	acetone/olive oil 4:1	1.76, 2.78, 5.06	Positive
	16/10/2003	22/10/2003	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	acetone/olive oil 4:1	1.49, 1.73, 5.26	Positive

a=        Ratio of test to control lymphocyte proliferation

b=        Stimulation index greater than 3.0 indicates a positive result

* =        Standard Test Method 595 (Pooled nodes)

·=        Standard Test Method 599 (Individual nodes)

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was considered to be a non-sensitiser under the conditions of the test and is therefore considered to be not classified.