Benzoic acid, 2-ethoxy-4-[2-[[(1S)-3-methyl-1-[2-(1-piperidinyl)phenyl]butyl]amino]-2-oxoethyl]-, ethyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 10-27, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-Ethoxy-4-{3-[(S)-3-methy-1-(2-piperidin-1-yl-phenyl)-butylamino]-2-oxo-propyl}-benzoic acid ethyl ester

EC Number:

604-604-0

Cas Number:

147770-06-7

Molecular formula:

C29 H40 N2 O4

IUPAC Name:

2-Ethoxy-4-{3-[(S)-3-methy-1-(2-piperidin-1-yl-phenyl)-butylamino]-2-oxo-propyl}-benzoic acid ethyl ester

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Hsd:Wistar rats (HsdBrl:WH,Full-Barrier), Sex: male and female, body
weight at the commencement of the study: female 149 - 167 g and male 150
- 167 g. 3 male and 3 female animals were used.
The animals were derived from a controlled full barrier maintained breeding
system (spf).
Source: Harlan Winkelmann GmbH, D-33178 Borchen.
According to Art. 9.2, No.7 of the German Act on Animal Welfare the animals
were bred for experimental purposes.
The animals were barrier maintained (semi-barrier) in air conditioned rooms
- Temperature: 22 ± 3° C
- Rel. humidity: 55 ± 10%
- Artificial light, lighting regime 12: 12 hours, light 6.00 - 18.00
- Air change: 10 x / hour
- Feeding ad libitum, Altromin 1324 maintenance diet for rats and mice,
totally-pathogen-free-TPF
- Free access to tap water ( drinking water, municipal residue control,
microbial. controlled periodically)
- The animals were individually kept in Macrolon cages on Altromin saw fiber
bedding
- Acclimatization period: 1 week

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2000 mg/kg: 3 males/3 females

Control animals:

no

Details on study design:

The starting dose was 2000 mg/kg body weight. Since no presence of compound-
related mortality of the animals was observed no further testing was
required.
Animals were observed for 14 days after dosing.
The animals were weighed prior to first application and once a week thereafter.

A careful clinical examination was made twice a day on the day of dosing
and once a day thereafter.
Cageside observations included changes in the skin and fur, eyes and mucous
membranes. Also respiratory, circulatory, autonomic and central nervous
systems and somatomotor activity and behaviour pattern were examined.
Particular attention was directed to observations of tremor, convulsions,
salivation, diarrhoea, lethargy, sleep and coma.
At the end of the observation period the animals were sacrified by an overdosage
of pentobarbital.
All animals were subjected to gross necropsy. All gross pathological changes
were recorded.

Individual reactions of each animal were recorded at each observation time.
Toxic response data were recorded by sex and dose level.
Nature, severity and duration of clinical observations were described.
Body weight changes were summarized in tabular form.
Necropsy findings were described.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The oral application of the test item in a dose of 2000 mg/kg BW caused no
compound related mortalities.

Clinical signs:

other: No clinical signs of toxicity were observed throughout the observation period.

Gross pathology:

Necropsy revealed an acute injection of blood vessels in all animals in the
abdominal region. This finding is due to euthanasia with an overdose of
pentobarbital injected intraperitoneally.

Applicant's summary and conclusion

Interpretation of results:

other: not classified acc. to CLP

Conclusions:

Considering the reported data of this toxicity test it can be stated that the test
item AGEE 623 AMIDESTER has no acute toxic characteristics.
The LD50 was determined to be > 2000 mg/kg BW.

Executive summary:

The test item AGEE 623 AMID ESTER was given in a dose of 2000 mg/kg
body weight to two groups of 3 male and 3 female rats (HsdBrl: WH Wistar)
in a single exposure via oral gavage.
A careful clinical examination was made once a day. At the end of the observation
period the animals were sacrificed and necropsy was carried out to
record gross pathological changes.
A maximum dosage of 2000 mg/kg BW according to the acute toxic class
method regime, caused no compound related mortality within 14 days p.
appl.. No clinical signs of toxicity were observed throughout the observation
period.
Therefore, according to OECD guideline 423, a sufficient estimation of the
acute oral toxicity of the test item AGEE 623 AMID ESTER is provided.