6-hydroxy-1H-pyrimidin-4-one

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-08-21 to 1995-12-29

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

Buehler test

Justification for non-LLNA method:

Currently no LLNA study is available for assessment. The Guinea pig Buehler test has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.

Test material

Test material information

Constituent 1

Reference substance name:

6-hydroxy-1-H-pyrimidin-4-one

IUPAC Name:

6-hydroxy-1-H-pyrimidin-4-one

Constituent 2

Reference substance name:

6-hydroxy-1H-pyrimidin-4-one

EC Number:

214-772-3

EC Name:

6-hydroxy-1H-pyrimidin-4-one

Cas Number:

1193-24-4

Molecular formula:

C4H4N2O2

IUPAC Name:

6-hydroxypyrimidin-4(3H)-one

Details on test material:

- Substance type: pure active substance
- Physical state: solid, homogeneous brownish-yellow powder

- Impurities (identity and concentrations): water 1.78%

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Strain: Dunkin Hartley, Pirbright White HSD/Win:DH (SPF)
- Age at study initiation: young adult
- Weight at study initiation: 310 - 381 g
- Housing: conventional, up to 5 animals/Macrolon cage type IV
- Diet: ad libitum, Ssniff G 4 Alleindiaet fuer Meerschweinchen
- Water: communal drinking water ad libitum
- Acclimation period: > 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: 1995-08-21 To: 1995-12-29

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Remarks:

vaseline

Induction 2

Concentration / amount:

Pretest: 2.5, 10, 25, 50 % (w/w)
Induction phases I-III: 50 % (w/w)
Challenge: 50 % (w/w)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Remarks:

vaseline

Challenge 2

Concentration / amount:

Pretest: 2.5, 10, 25, 50 % (w/w)
Induction phases I-III: 50 % (w/w)
Challenge: 50 % (w/w)

No. of animals per dose:

Pretest: 3 animals
Main test: 20 animals
Determination of challenge concentration: 3 animals each, pretest and week 4
Control to main test: 10 animals

Details on study design:

RANGE FINDING TESTS:
Formulation of the solid test material: Concentrations of 10, 50, and 70% (w/w) of the finely ground powder in petrolatum (vaseline) were tested, and 50% was determined to be the highest concentration that ensured a good skin contact.
Tolerability: Application of the test substance in petrolatum (0.5 g of mixture, concentrations 2.5, 10, 25, 50 %) to the shaved flanks of 3 animals, (4 gauze patches per animal, area 2x2cm each), with occlusive dressing, for 6 hours. Recording of skin reactions at 30 and 54 hours after the start of the application.
Similar Range finder during the 4th week of the experiment, with 3 untreated animals, to account for changes in skin sensitivity due to increased weight and age.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: 1 group of 20 animals
- Control group: 10 animals
- Site: left flank
- Frequency of applications: days 0, 7, and 14
- Duration: 28 days
- Concentrations: 50% test substance in petrolatum, 0.5 g of the mixture

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6 hours
- Test groups: 1 group of 20 animals
- Control group: 10 animals
- Site: right flank, posterior
- Vehicle patch site: right flank, anterior
- Concentrations: 50% test substance in petrolatum, 0.5 g of the mixture
- Evaluation (hr after challenge): 30 and 54

OTHER:

Challenge controls:

10 animals exposed to the pure vehicle 3 times during the induction period, challenged in the same way as the exposure group (50% w/w test material in petrolatum)

Positive control substance(s):

yes

Remarks:

Strain sensitivity to 2-mercaptobenzothiazole tested 1995-06-22

Results and discussion

Positive control results:

Sensitivity test HS-95/MCPT of the guinea pig strain Dunkin Hartley, Pirbright White (DHPW), performed 1995-05-22 to 1995-06-22, with 2-mercaptobenzothiazole (50% in petrolatum) in a Buehler test: 40% (4/10) of the test animals exhibited erythema, 30% also edema of the challenge test region. The sensitivity of the strain is considered positive.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

30

Group:

test chemical

Dose level:

50% w/w

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 30.0. Group: test group. Dose level: 50% w/w. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Results 2

Reading:

2nd reading

Hours after challenge:

54

Group:

test chemical

Dose level:

50% w/w

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 54.0. Group: test group. Dose level: 50% w/w. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Results 3

Reading:

1st reading

Hours after challenge:

30

Group:

negative control

Dose level:

50% w/w

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 30.0. Group: negative control. Dose level: 50% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Results 4

Reading:

2nd reading

Hours after challenge:

54

Group:

negative control

Dose level:

50% w/w

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 54.0. Group: negative control. Dose level: 50% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Results 5

Reading:

1st reading

Group:

positive control

Dose level:

50% 2-mercaptobenzothiazole

No. with + reactions:

4

Total no. in group:

10

Clinical observations:

4/10 exhibited erythema, 3/10 also edema

Remarks on result:

positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

The substance is considered to be not sensitising. The study is considered to be relevant and reliable.