(S)-3-methyl-2-(2-oxotetrahydropyrimidine-1-yl)butyric acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jan 26 to Feb 18, 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: done under GLP and OECD method

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

84/449/EEC Part B Acute Toxicity

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study carried out in 1998

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

430-900-2

EC Name:

-

Cas Number:

192725-50-1

Molecular formula:

Hill formula: C9H16N2O3 CAS formula: C9H16N2O3

IUPAC Name:

3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanoic acid

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Crl:(HA)BR Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Inc, Portage, Michigan
- Age at study initiation: 2 - 3 weeks
- Weight at study initiation: 200 - 250gram
- Housing: Individual Stainless Steel ventilated cages
- Diet: Certified Guinea Pig Chow®
- Water: ad libitum
- Acclimation period: 5 days followed by an 7 day pretreatment period.

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72
- Humidity (%): Ambient
- Photoperiod (hrs dark / hrs light): 12hr daily light cycle

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: 0.2% HPMC for 1st induction: Petrolatum for 2nd induction and challenges.

Induction 2

Concentration / amount:

Concentration of test material at First Induction (Intradermal injection): 5% in 0.2% HPMC.
Concentration of test material at Second Induction (topical application): 55% in petrolatum
Concentration of test material used for challenge (topical applications): 55% in petrolatum

Challenge

Challenge 1

Route:

other: Topically

Vehicle:

other: 0.2% HPMC for 1st induction: Petrolatum for 2nd induction and challenges.

Challenge 2

Concentration / amount:

Concentration of test material at First Induction (Intradermal injection): 5% in 0.2% HPMC.
Concentration of test material at Second Induction (topical application): 55% in petrolatum
Concentration of test material used for challenge (topical applications): 55% in petrolatum

No. of animals per dose:

10 animals assigned to the negative control group.
20 animals assigned to treatment group.

Details on study design:

MAIN STUDY

An approximate 40 x 60mm area of dorsal skin on the scapular region was clipped free of hair prior to treatment

A. INDUCTION EXPOSURE
- No. of exposures: 2 - intadermal and topical
- Exposure period: 7 days for first induction and 14 days for second induction.
- Observations: 24hrs after the intradermal injections and once daily for 5 days. 24 and 48hrs after second induction.
- 0.05ml injection vol.
- Site for 2nd induction was pre-treared by massaging 0.3ml of 10% sodium dodecyl sulphate in water into the skin of animals in both groups on the day prior to topical inductionto illicit an inflammatory reaction.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: Day 21
- Exposure period: 24hr occlusive bandage
- Site: right flank
- Evaluation (hrs after challenge):24 and 48 hr after challenge.

Body weights were measuredc twice during the pretreatment period, on the day of the first and second induction, on the day of the challenge and on the final day of the observations

Challenge controls:

10 animals with 0.2% Hydroxypropyl methylcellulose for the 1st induction, petrolatum for the 2nd induction. Challenge: 55% Abbott-164220 in petrolatum.

Positive control substance(s):

not required

Remarks:

Sensitivity tested periodically with α-hexylcinnamaldehyde

Results and discussion

Positive control results:

n/a

In vivo (non-LLNA)

Results

Reading:

other: Challenge

Hours after challenge:

48

Group:

test chemical

Dose level:

55% in petrolatum

No. with + reactions:

0

Total no. in group:

19

Clinical observations:

No signs of irritation

Remarks on result:

other: Reading: other: Challenge. . Hours after challenge: 48.0. Group: test group. Dose level: 55% in petrolatum. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: No signs of irritation.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Abbott-164220 did not induce delayed contact hypersensitivity in guinea pigs in this study. Criteria used for interpretation of results: EU

Conclusions:

Abbott-164220 did not induce delayed contact hypersensitivity in guinea pigs in this study.