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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June - Aug 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 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

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:

rat

Strain:

other: Tif:RAlf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Albino rats, Tif:RAlf (SPF). from CIBA-GEIGY Limited, Animal Production, 4332 Stein, Switzerland 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 different groups using computer-generated random numbers. Animal identification was by an individual number written, with a waterproof marker, on the tail.
The animals were acclimatized to laboratory conditions for at least 5 days. The initial age (at dosing) was 6 to 9 weeks. The initial weight range (at dosing) was
226.4 to 273.6 g.

The animals were housed individually, on sterilized softwood particle bedding (manufactured by Scierie des Eplatures, 2300 La Chaux-de-Fonds, Switzerland), in
Macrolon® cages (type III), which were kept in an air-conditioned room. The temperature was 22 ± 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. 890 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.
Tap water was freely available. The water is analyzed periodically by lndustrielle Werke Basel (Basel City water supply plant) for compliance with Swiss drinking
water specifications

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: Wetting agent: Sesame oil

Remarks:

the test article was only wet with sesame oil and no solution was made

Details on dermal exposure:

The test article was administered once, by topical administration under occlusion, for 24 hrs.
The administration was performed between 8:00 a.m. and 10:30 p.m.,- following overnight fasting.
Start dose selected: 2000 mg/kg

Duration of exposure:

24h

Doses:

2000 mg/kg

No. of animals per sex per dose:

The aim was to test the accepted limit dose of 2000 mg/kg. This dose was given first to a single female rat and additional animals were treated to complete a group of five male and five female rats.

Control animals:

no

Details on study design:

The study was conducted according to the OECD guideline No.: 402 (Adopted 24-Feb-87) modified such that clinical signs were used as an endpoint and that animals with severe signs were sacrified.
The rat was selected as a standard rodent species.
The aim was to test the accepted limit dose of 2000 mg/kg. This dose was given first to a single female rat and additional animals were treated to complete a group of five male and five female rats.
The animals were observed for 14 days after dosing to see if there were any latent toxic effects. Necropsy included investigation of major viscera.
Selection of dose levels was based on guidelines.
PBS 859 DS, batch P.Op.1/94, was administered once by topical application under occlusion for 24 hrs.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality was observed.

Clinical signs:

No systemic and no local clinical signs were observed.

Body weight:

The body weight gain was generally not influenced by the PBS 859 DS treatment. In most of the females, the weight was slightly reduced on day 4 after the occlusive application; the body weight increased again by day 9.

Gross pathology:

No macroscopic changes were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of treatment with a limit dose of 2000 mg/kg, no systemic or local effects were observed. PBS 859 DS is, therefore, non-toxic dermally at the limit dose of 2000 mg/kg.