N-(1-benzylpiperidin-4-yl)-N-phenylpropionamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-05-04 to 2005-06-08

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Test substance purity was not reported.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

Test substance purity was not reported.

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-(1-benzylpiperidin-4-yl)-N-phenylpropionamide

EC Number:

216-014-7

EC Name:

N-(1-benzylpiperidin-4-yl)-N-phenylpropionamide

Cas Number:

1474-02-8

Molecular formula:

C21H26N2O

IUPAC Name:

N-(1-benzylpiperidin-4-yl)-N-phenylpropanamide

Details on test material:

- Name of test material (as cited in study report): T424
- Substance type: No data
- Physical state: Solid
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Lot/batch No.: RT000424G1A251
- Expiration date of the lot/batch: 2005-12-31
- Stability under test conditions: No data
- Storage condition of test material: at room temperature (range of 20 +-5°C), light protected
- Other: No data

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: RT000424G1A251, Janssen Pharmaceutica N.V.
- Expiration date of the lot/batch: 31-December-2001
- Purity: Unknown

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: Stable under storage conditions
- Solubility and stability of the test substance in the solvent/vehicle: Unknown

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd., Laboratory Animal Services, CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: 7-12 weeks
- Weight at study initiation: 173.4-193.8 g (prior to administration)
- Fasting period before study: 19 h (access to water was permitted)
- Housing: in groups of three in Makrolon type 4-cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 4/05 ad libitum. Results of analysis are archived at RCC Ltd.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analysis are archived at RCC Ltd.
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 22 +- 3
- Humidity (%): 30-70% (values above 70% during cleaning process possible)
- Air changes (per hr): air conditioned, 10-15 air changes per hour
- Photoperiod: 12 hrs dark / 12 hrs light
- Other: music during the daytime light period

IN-LIFE DATES: From: 2005-05-04 To: 2005-06-08

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL, 0.03 g/mL, or 0.005 g/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The vehicle was chosen after a solubility trial was performed before the study initiation date.
- Lot/batch no. (if required):11077124 104041
- Expiration date: 2006-02-28
- Description: Colorless viscous liquid
- Stability: Stable under storage conditions (20+-5 deg C), light protected

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

Doses:

2000 mg/kg (one group of 3 animals)
300 mg/kg (one group of 3 animals)
50 mg/kg (two groups of 3 animals/each)

No. of animals per sex per dose:

3 animals/treatment

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations mortality/viability: Daily during acclimation period. 0.5, 1, 2, 3 and 5 h after administration of test at day 1 and twice daily during days 2-15.
- Frequency of observations weighing: on test day 1 (prior to administration), 8 and 15
- Clinical signs: Daily during acclimation period. 0.5, 1, 2, 3 and 5 h after administration of test at day 1 and twice daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes

Statistics:

No statistical analyses were performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Mortality:

All animals died or were humanely sacraficed in treatment groups 300 mg/kg and 2000 mg/kg (3 animals per treatment). No mortalities occurred at 50 mg/kg.

Clinical signs:

Slightly ruffled fur and exophthalmos were observed in all animals treated with 2000 mg/kg. These animals also showed slight to marked convulsions 0.5-1h after administration. One of these three animals also showed slight salivation and ventral recumbency 1 h after adminstration. Exophthalmos and marked convulsions were observed in all 30 mg/kg animals at .5 hr. No clinical signs were observed in the six animals treated with 50 mg/kg during the course of the study.

Body weight:

The body weights were within the range commonly recorded for this strain and age.

Gross pathology:

Liquid contents were found in all three animals treated with 2000 mg/kg at their necropsy. Congested lungs, liquid content in the stomach, duodenum, jejunum and ileum, and prominent follicles in the spleen were seen in all 300 mg/kg-treated animals at their necropsy. One 50 mg/kg-treated animal showed congestion to the lungs, whereas no macroscopic findings were recorded in the remaining animals treated with 50 mg/kg at their necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of this study, the female rat oral LD50 of the test substance was 50 mg/kg bw < LD50(rat) < 300 mg/kg bw (three doses tested).
According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (including all amendments) and Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures (including all amendments) T00424 should be classified as: Toxic if swalled for acute toxicity by the oral route.