L-Valine, N-(1-oxopentyl)-N-[[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-, phenylmethyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6.6.1994 - 27.6.1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetrazolyl-valinesteramid (3-methyl-2-{pentanoyl-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-amino}-butyric acid benzyl ester)

EC Number:

604-047-3

Cas Number:

137863-20-8

Molecular formula:

C31 H35 N5 O3

IUPAC Name:

Tetrazolyl-valinesteramid (3-methyl-2-{pentanoyl-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-amino}-butyric acid benzyl ester)

Test animals

Species:

rabbit

Strain:

other: Chbb:HM (SPF)

Details on test animals or test system and environmental conditions:

Rabbits Chbb:HM (SPF) from Dr. K. Thomae GmbH, Biberach (FRG) were used. Animals were utilized only if they were judged healthy on the basis of general
observations and body weight (performed predose).
Animals were assigned to the study using computer-generated random numbers.
Animal identification was by an individual number written with a waterproof marker on the ear.
The animals were acclimatized to laboratory conditions for 7 days. The initial age (at dosing) was 148 to 169 days. The initial weight range (at dosing) was 2309 to
2346 g.
Husbandry
The animals were housed individually in stainless steel cages in an air-conditioned room. The temperature was 20 ± 3 °c, and the relative humidity 30 to 70 %.
Artificial light was provided from 6 a.m. to 6 p.m.
Pelleted standard diet NAFAG No. 814 was freely available (NAFAG, 9202 Gossau, Switzerland). The diet is analyzed for composition and contaminants by
the manufacturer and analytical results are archived by the Animal Supply Office CIBA-GEIGY (batches are given in the raw data).
Tap water was freely available. The water is analyzed periodically by Industrielle Werke Basel (Basel City water supply plant) for compliance with Swiss drinking
water specifications.

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

other:

Controls:

other: not required, the untreated skin sites of each animal served as control

Amount / concentration applied:

Application volume: 0.5 g / animal
Amount of test article applied: 0.5 g / patch

Duration of treatment / exposure:

4 h

Observation period:

7 d
reading time points: 1, 24, 48 and 72 h and 7 d

Number of animals:

3

Details on study design:

The study was conducted according to the OECD guideline 404 (adopted l 7-Jul-92).
The rabbit is one of the recommended species for irritation testing.
The animals were observed for 7 days after dosing to see if there were any latent toxic effects.
Selection of dose levels was based on OECD guideline.
PBS 859 DS, batch P.Op. 1 / 94, was administered topically under occlusion for 4 hours to groups of 3 rabbits (russian) Chbb:HM (SPF)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

Spotts of slight erythema reactions were observed in two of 3 animals 24 and 48 hrs. after removing the bandages. In one animal the slight erythema reaction covered the whole application area when assessed 72 hrs. after removing the bandage. At the end of the observation period, scaling was observed in the two animals showing erythema reactions at the beginning of the observation period. No edema formation was observed during the whole observation period.

Any other information on results incl. tables

Mortality: No mortality was observed.

Clinical Signs: No systemic clinical signs were observed

Body Weight: No compound related effect was observed.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
The reactions observed are clearly lower than the criteria defined for the risk phrase of skin irritation of the EEC