N-phenyl-N-piperidin-4-ylpropionamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-04-27 to 2005-08-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD guideline 423 (Acute Oral Toxicity-Acute Toxic Class Method) and EU method B.1.tris (Acute Oral Toxicity-Acute Toxic Class Method) without deviation.

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:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-phenyl-N-piperidin-4-ylpropionamide

EC Number:

216-543-3

EC Name:

N-phenyl-N-piperidin-4-ylpropionamide

Cas Number:

1609-66-1

Molecular formula:

C14H20N2O

IUPAC Name:

N-phenyl-N-piperidin-4-ylpropionamide

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study reports): JNJ-1594255-AAA (T000425)
- Physical state: solid (powder)
- Appearance: white

Specific details on test material used for the study:

- Name of test material (as cited in study report): T425
- Substance type: no data
- Physical state: solid
- Analytical purity: no data
- Impurities (identity and concentrations): unknown
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: 00454795
- Expiration date of the lot/batch: 2005-12-31
- Stability under test conditions: Stable under storage conditions. Stability of test substance dilutions
was unknown.
- Storage condition of test material: at room temperature (20 ± 5 deg C), light protected

Test animals

Species:

rat

Strain:

other: HanRcc:WIST (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC, Ltd., Laboratory Animal Services, CH-4414 Fűllinsdorf, Switzerland
- Age at study initiation: 11-13 weeks
- Weight at study initiation: 177-201 grams
- Fasting period before study: 17 to 20 hours (access to water was permitted)
- Housing: in groups of 3 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
- Water (e.g. ad libitum): community tap water from Fűllinsdorf ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 22 ± 3 deg C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL, 0.005 g/mL, or 0.03 g/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The vehicle was chosen after a solubility trial which was performed before the study initiation date.
- Lot/batch no. (if required): 1107712 24104041
- Purity: no data


MAXIMUM DOSE VOLUME APPLIED:
- 10 mL/kg


DOSAGE PREPARATION (if unusual):
- not applicable


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data

Doses:

2000, 50, and 300 mg/kg body weight

No. of animals per sex per dose:

There were two groups of 3 animals in each group per dose. Therefore, a total of 6 animals were used at each dose level.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/viability and clincial signs were observed daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3, and 5 hours after administration on test day 1 and twice daily during days 2-15. Body weights were obtained on test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Mortality:

One 2000 mg/kg treated animal had to be sacrificed in extremis for ethical reasons approximately 3.5 hours after the test substance application. All remaining 2000 mg/kg treated animals were found dead approximately 0.5, 2.5, 3 or 5 hours after treatment.

Clinical signs:

Slightly ruffled fur, hunched posture and slight sedation were observed in all 2000 mg/kg treated animals from the 0.5- to the 2- or 3-hour reading, respectively. Two animals screamed by hand touch between the 0.5- and the 2- or 3-hour reading and slight tremor was noted in three animals at the 2- and/or 3-hour reading. Poor coordination was also noted in two animals at the 0.5-hour reading.
Slightly ruffled fur, exophthalmos and corneal opacity was observed in three 50 mg/kg treated animals from the 3- to the 5-hour reading.
Slightly ruffed fur was noted in all 300 mg/kg treated animals from the 0.5- to the 5-hour reading and persisted in one animal up to test day 2 and in three animals up to test day 3. Slight sedation was also noted in three animals from the 0.5-or 1-hour reading to the 5-hour reading, and in the three remaining animals at the 2- and 3-hour reading. Hunched posture was noted in three animals at the 2-hour reading and persisted up to the 5-hour reading in two animals.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

Liquid contents were noted in the stomach of all animals treated at 2000 mg/kg at their unscheduled necropsy. Two 2000 mg/kg treated animals showed also congested lungs. Liquid contents (reddish) were also noted in the ileum and/or duodenum and jejunum of three 2000 mg/kg treated animals. Congested lungs were also noted in two 50 mg/kg treated animals at their scheduled necropsy. No macroscopic findings were recorded in the remaining animals treated at 50 and 300 mg/kg at their scheduled necropsy.

Other findings:

- Organ weights: no data
- Histopathology: no data
- Potential target organs: no data
- Other observations: no data

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The median lethal dose of the test substance after single oral administration to female rats, observed over a period of 14 days is: 300 mg/kg body weight < LD50 (rat) < 2000 mg/kg body weight.