(2S)-3-Methyl-2-[N-({2'-(1H-1,2,3,4-tetrazol-5-yl)-[1,1-biphenyl]-4-yl}methyl)pentanamido]alkanoic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18.09.1995 - 12.10.1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

no data on positive control group

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

yes

Remarks:

no data on positive control group

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

N-Pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-L-valine

EC Number:

604-045-2

Cas Number:

137862-53-4

Molecular formula:

C24 H29 N5 O3

IUPAC Name:

N-Pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-L-valine

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Pirbright White (Tif:DHP)

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited, Stein, Switzerland
- Weight at study initiation: 338 - 430 g
- Housing: Animals were housed individually in Macrolon cages (Type 3).
- Diet: standard guinea pig pellets (NAFAG, Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 18 Sep 1995
To: 12 Oct 1995

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: peanut oil, vaseline

Induction 2

Concentration / amount:

1% test substance in peanut oil (intradermal) and 50% test substance in vaseline (epicutaneous)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: peanut oil, vaseline

Challenge 2

Concentration / amount:

1% test substance in peanut oil (intradermal) and 50% test substance in vaseline (epicutaneous)

No. of animals per dose:

test group: 10 males and 10 females
control group: 5 males and 5 females

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single intradermal injection on Day 0 and 48 h epicutaneous treatment on Day 8
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/physiological saline
Injection 2: 1% of test substance in peanut oil
Injection 3: 1% of test substance in a 1:1 mixture (v/v) FCA/physiological saline

Epicutaneous: 50% of the test substance in vaseline

- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/physiological saline
Injection 2: peanut oil
Injection 3: a 1:1 mixture (v/v) FCA/physiological saline

Epicutaneous: vaseline

- Site: shoulder region (intradermal and epicutaneous, respectively)
- Frequency of applications: on Days 0 and 8
- Concentrations: intradermal 1%, epicutaneous 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 22
- Exposure period: 24 h
- Site: one flank
- Concentrations: 10%
- Evaluation (hr after challenge): 24 and 48 h

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

1% test substance in vaseline

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1% test substance in vaseline

No. with + reactions:

1

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1% test substance in vaseline. No with. + reactions: 1.0. Total no. in groups: 20.0.

Results 3

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

1% test substance in vaseline

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1% test substance in vaseline

No. with + reactions:

2

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1% test substance in vaseline. No with. + reactions: 2.0. Total no. in groups: 20.0.

Any other information on results incl. tables

After removal of the occlusive dressing on Day 10 after epidermal induction, irritation at the application site was seen in all 20 guinea pigs of the test group.

Epidermal challenge of 10 male and 10 female guinea pigs (test group) resulted in positive responses in 1 female after 24 h and in 2 females after 48 h, corresponding to a sensitisation rate of 10%. No skin reactions were recorded for control animals.

Body weights were not affected by treatment with the test substance.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified