1,3-dihydro-5-methoxy-2H-benzimidazole-2-thione

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

Screening of fragrance materials for allergenicity in the guinea pig I. Comparison of four testing methods.

Author:

G. Klecak , H. Geleick , J. R. Frey

Year:

1977

Bibliographic source:

Journal of the Society of Cosmetic Chemists, Vol. 28, No. 2, 53-64; 1977

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mmentioned below

Principles of method if other than guideline:

Guinea pig maximisation test was conducted in Himalayan white-spotted guinea pigs (male and female) to determine the skin sensitization potential of test chemical.

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Currently no LLNA study is available for assessment. The guinea pig maximisation 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:

Vanillin

EC Number:

204-465-2

EC Name:

Vanillin

Cas Number:

121-33-5

Molecular formula:

C8H8O3

IUPAC Name:

1-butoxypropan-2-ol

Details on test material:

- Name of test material (as cited in study report): Vanillin
- Molecular formula: C8H8O3
- Molecular weight: 152.1482 g/mol
- Substance type: organic
- Physical state: Solid
-Smiles: c1(cc(ccc1O)C=O)OC
-InChI: 1S/C8H8O3/c1-11-8-4-6(5-9)2-3-7(8)10/h2-5,10H,1H3

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Himalayan white-spotted

Sex:

male/female

Details on test animals and environmental conditions:

- Source: Institute of Biomedical Research , Fullinsdrof Switzerland

- Weight at study initiation: 400-500g

- Diet (e.g. ad libitum): pelleted feed supplemented with green: Vegetables carrots and vitamin C in the drinking water, all available ad libitum.
- Water (e.g. ad libitum): ad libitum

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

other: Epicutaneous : petrolatum

Concentration / amount:

Intradermal Concentration:2 X 0.1 ml of a 5% solution of the compound tested, with 0.1 ml of a 5 % emulsion of the same compound in Freund's complete adjuvant (FCA) and with 0.1 ml of FCA alone.

Epicutaneous Concentration: 25%
Amount: 250 mg in petrolatum

Day(s)/duration:

10 days

Adequacy of induction:

not specified

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

Concentration: at a sub-irritant Concentration in petrolatum (25%)

Day(s)/duration:

48 hours

Adequacy of challenge:

not specified

No. of animals per dose:

6-8 guinea pigs

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE: intradermal
- No. of exposures: 2
- Exposure period: 7 days
- Test groups:6-8 guinea pigs
- Control group: 6-8 guinea pigs
- Site: intradermal
- Frequency of applications: no data
- Concentrations: 5% (0.1ml)

B. INDUCTION EXPOSURE: epicutaneous
- No. of exposures: 1
- Exposure period: 24 hours
- Test groups:6-8 guinea pigs
- Control group: 6-8 guinea pigs
- Site: clipped skin area of the neck
- Frequency of applications: no data
- Concentrations: 25% (250 mg)



B. CHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge: On day 21
- Exposure period: no data
- Test groups: 6-8 guinea pigs
- Control group: 6-8 guinea pigs
- Site: flank
- Concentrations: at a sub-irritant Concentration in petrolatum
- Evaluation (hr after challenge): 24 and 48 hours

Challenge controls:

yes concurrent vehicle used.

Results and discussion

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

At a sub-irritant Concentration in petrolatum (25%)

Total no. in group:

8

Clinical observations:

Positive results were observed in treated groups.

Remarks on result:

positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:

other: Sensitizing

Conclusions:

The test material was considered to be sensitizing on Himalayan white-spotted guinea pigs in Guinea pig maximisation.

Executive summary:

Guinea pig maximisation test was conducted in Himalayan white-spotted guinea pigs (male and female) to determine the skin sensitization potential of test chemical.

 

During induction, on day 0the animals were injected intradermally with 0.1 ml of a   5% solution of the compound tested, with 0.1 ml of a 5 % emulsion of the same compound in Freund's complete adjuvant (FCA) and with 0.1 ml of FCA alone. On day 8 the animals were induced epicutaneously with 250 mf of 25% test compound in dissolved in petrolatum on clipped skin area of the neck under occlusion for 2 days.

 

On day 21, animals were challenged with the compound at a subirritant concentration in petrolatum was applied to the flank for 24 h. The reactions were read 24 and 48 h after removing the patch.

 

Since the test chemical showed positive signs of contact sensitization during the observation period, it was considered to be sensitizing to the skin of Himalayan white-spotted guinea pigs.