Benzenemethanol, 3-hydroxy-.alpha.-[[methyl(phenylmethyl)amino]methyl]-, (.alpha.S)-

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

3-[(1S)-2-[benzyl(methyl)amino]-1-hydroxyethyl]phenol

Cas Number:

286426-31-1

Molecular formula:

C17 H20 O2

IUPAC Name:

3-[(1S)-2-[benzyl(methyl)amino]-1-hydroxyethyl]phenol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Physical state: solid
- Analytical purity: 99.7 %
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH; D-33178 Borchen
- Weight at study initiation: 302 - 312 g
- Housing: The animals were kept in groups in Terluran-cages on Altromin saw fiber bedding. Max. gruop size 10 animals.
- Diet : Feeding ad libitum Altromin 3112 maintenance diet for guinea pigs, rich in crude fiber, totally-pathogen-free-TPF
- Water : Free access to tap water ( drinking water, municipalresidue control, microbiol. controlled periodically )
- Acclimation period: adequate

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 45 - 65
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12:12 , light 6:30 -18:30

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

physiological saline

Induction 2

Concentration / amount:

500 mg ( industion first stage )
50 % ( induction second stage and challenge )

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Challenge 2

Concentration / amount:

500 mg ( industion first stage )
50 % ( induction second stage and challenge )

No. of animals per dose:

10 animals per dose

Details on study design:

RANGE FINDING TESTS: Three animals were topically treated with 10 % / 25 % / 50 % concentration of the test item. No signs of irritation and systemic toxicity were recorded after a contact period of 48 h after application on 50 % concentration.
Therefore a 50 % concentration was chosen for the topical induction and for the challenge as well.
For the first stage of the induction the highest concentration ( 5 % ) applicable as interdermal injection, was chosen.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Test groups: Prepared test item in Freund`s Adjuvant complete
- Control group: NaCl in Freund`s Adjuvant complete
- Site: shoulder region
- Duration: 0- 20 d


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 24 h
- Test groups: 1.0 ml test item ( 50 % ) / 1.0 ml CMC 1 %
- Control group: 1.0 ml test item ( 50 % ) / 1.0 ml CMC 1 %
- Site: left and right flank
- Evaluation (hr after challenge ) : 24,48, 72 h

Challenge controls:

5 female animals
1.0 ml test item / 50 % concentration

Positive control substance(s):

yes

Remarks:

Mercaptobenzothiazol

Results and discussion

Positive control results:

The recent reliability checks were performed in November 1999. The raw data and summary of the study are kept in the BSL archives (BSL Project ID 991298). The test was performed in accordance with BSL Standard Operating Procedures and was audited by the QA-unit.
Positiv control substance : Mercaptobenzothiazol, Purity >98 %, CAS No. 149-30-4, Lot 117H3487, Sigma Chemicals Co.

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50% test substance concentration

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no observation

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% test substance concentration. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no observation.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Considering the reported data of this sensitization test it can be stated that the test item L-Benzyladrianol Base caused no reaction identified as
sensitization.
According to the EEC criteria for classification (93/21/EEC) no labelling is necessary as the sensitization rate was below 30 %.

Executive summary:

During the induction phase the guinea pigs (10 test group, 5 control group all female, strains: Hsd Poc:DH ) were interdermally injected with 5 % L-Benzyladrianol Base and, after treatment with sodium laurly sulfate, topically treated with 50 % L-Benzyladrianol Base. After a latencyof 14 days - to allow a pontential reaction of the immune system - the animals were challenged with 50 % L-Benzyladrianol Base on the flank. The grade of skin reaction was compared to control animals, which were treated with 0.9 % NaCl or CMC 1 % during the induction phase and, duing challenges phasewith the test item, respectively.

The sensitization rate after application of L-Benzyladrianol Base was 0%. Under the conditions described the test item showed no sensitizing properties. Animals of the test group showed normal weight gain as compared to historical data and the of the control group.