Benzyl-N-(2-(2-methoxy-phenoxy)-ethyl)amine hydrochloride

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The studies were carried out in 2010.

Test material

Test material information

Constituent 1

Reference substance name:

Benzyl-N-(2-(2-methoxy-phenoxy)-ethyl)amine hydrochloride

EC Number:

428-290-8

EC Name:

Benzyl-N-(2-(2-methoxy-phenoxy)-ethyl)amine hydrochloride

Cas Number:

120606-08-8

Molecular formula:

C16H20ClNO2

IUPAC Name:

benzyl[2-(2-methoxyphenoxy)ethyl]amine hydrochloride

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Carvedilol 6th/a intermediate (BEG HCl = Benzylaminoethoxy-guaiacol hydrochloride)
- Physical state: white or almost white crystalline powder
- Lot/batch No.: S-3082/1
- Expiration date of the lot/batch: 02. 2002
- Storage condition of test material: dry and cool place

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: LAB-ÁLL Bt , Hunyadi street 7, Budapest, H-1174, Hungary
- Weight at study initiation: 339-388 g
- Housing: Macrolon cage, size III (42x42x19 cm), 2-3 animals / cage
- Bedding: Laboratory bedding
- Diet (e.g. ad libitum): ad libitum (PURISTAR standard diet for rabbits produced by AGRIBANDS Europe Hungary)
- Water (e.g. ad libitum): ad libitum, tap water for human consumption containing 50 mg / 100 mlAscorbic acid
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 / 12 hours

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: 1 % methylcellulose

Induction 2

Concentration / amount:

10 (w/v) % (test item in methyl cellulose (1%) for dermal treatment
5 (w/v) % (test item in methyl cellulose (1%) for challange treatment
0.1 % (in physiological saline and Freund's complete adjuvant ) for intradermal treatment

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: 1 % methylcellulose

Challenge 2

Concentration / amount:

10 (w/v) % (test item in methyl cellulose (1%) for dermal treatment
5 (w/v) % (test item in methyl cellulose (1%) for challange treatment
0.1 % (in physiological saline and Freund's complete adjuvant ) for intradermal treatment

No. of animals per dose:

2 animals/two concentrations (in one animals two concentrations were tested: one concentration in left side, and other concentrations in right side)
10 animals (in test groups)
5 animals (in control groups)

Details on study design:

RANGE FINDING TESTS:
Two dose levels were tested in the preliminari dose range finding study to specify the primary irritation by intradermal injection and three dose levels by dermal application. (0.1, 1 w/v % and 1, 5, 10 w/v %)


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: I. a row of three injections , six in all, on each side of animals twice (test and control animals)
II. a row of dermal treatment on the same animals after seven days
- Exposure period: II. 48 hours
- Test groups: 10 animals
- Control group: 5 animals
- Frequency of applications: dermal treatment: six days after injections; untreated 14 days prior to challenge
- Duration: 48 hours +14 days
- Concentrations: 0.1% and 10%


B. CHALLENGE EXPOSURE (performed as a dermal exposure - close patch test)
- Exposure period: 24 hours
- Test groups: 10
- Control group: 5
- Concentrations: 5 %
- Evaluation (hr after challenge): 24 and 48 hours

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.3%

No. with + reactions:

6

Total no. in group:

10

Clinical observations:

patchy, confluent erythema

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.3%

No. with + reactions:

6

Total no. in group:

10

Clinical observations:

patchy, confluent erythema

Any other information on results incl. tables

Positive response was observed in 10% of the test animlas after the challenge with the test item. At the same time, positive response in the control group could not be found.

Challenge with the test item elicited discrete erythema in one animal on the skin surface of previously sensitized guinea pigs. The mean of the score was 0.10 and 0.00 according to the 24th and 48th hour observations.

The observed skin reaction in case of one animal may be attributed to the primary irritation of the test item and the individual sensitivity of the animal.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

On the basis of the results of the present study, the test item was classified as no sensitizer.