N-phenyl-N-piperidin-4-ylpropionamide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2006-05-10 to 2006-06-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study performed according to OECD guideline 404 (Acute Dermal Irritation/Corrosion) and EU method B.4. (Acute Toxicity: Dermal Irritation/Corrosion) with one deviation: the test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm instead of 6 cm2 to guarantee a good contact and uniform distribution of the test substance on the skin. This deviation should not affect the reliability of this study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

The test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2).

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

The test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2).

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate from the Swiss GLP Monitoring Authorities

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:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Janssen Pharmaceutica N.V., 00454795
- Expiration date of the lot/batch: 31 December 2005
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle: stability not indicated by the Sponsor; solubility in water: 43 g/L and solubility in ethanol > 500 g/L
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
The solid test item was ground to produce a granular material immediately prior to testing

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan France, Zl Le Malcourlet, 03800 Gannat, France
- Age at study initiation: 15 weeks (males and females)
- Weight at study initiation: 2091 to 2362 grams for females, 2293 grams for male
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4642 were provided for gnawing.
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): community tap water from Fűllinsdorf, ad libitum
- Acclimation period: 2006-05-10 to 2006-05-14 (one female); 2006-05-10 to 2006-05-15 (one male and one female)


ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 17-23 deg C
- Humidity (%): 30-70%
- Air changes (per hr): approximately 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other:

Controls:

other: Untreated skin area was used as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g per animal
- Concentration (if solution): not applicable


VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable
- Concentration (if solution): not applicable
- Lot/batch no. (if required): not applicable
- Purity: not applicable

Duration of treatment / exposure:

4 hours

Observation period:

The skin reaction was assessed at approximately 1, 24, 48, and 72 hours after exposure (removal of the dressing, gauze patch and test substance).

Number of animals:

1 male and 2 females

Details on study design:

TEST SITE
- Area of exposure: left flank (approximately 100 cm2) was clippped. The gauze patch (4 cm x 4 cm) with the test substance was applied to the intact skin of the clipped area.
- % coverage: no data
- Type of wrap if used: The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the skin was flushed with lukewarm tap water to clean the application site.
- Time after start of exposure: 4 hours after the start of exposure


SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean score across 3 scoring times (24, 48 and 72 hour)

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean score across 3 scoring times (24, 48 and 72 hour)

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean score across 3 scoring times (24, 48 and 72 hour)

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

of the 3 animals

Time point:

other: mean score across 3 scoring times (24, 48 and 72 hour)

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The mean erythema/eschar score of the three animals was 0.33, 0.67 and 0.33, respectively and the mean oedema score was 0.00 for all animals.
All three animals showed a very slight to well-defined erythema at the 1-hour reading, which persisted as very slight until 24 hours after application in two animals, and until 48 hours after application in one animal.
No abnormal findings were observed on the treated skin of any animal 72 hours after treatment, the end of the observation time.
Neither alterations of the treated skin were observed, nor were corrosive effects evident on the skin.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. No staining produced by the test substance of the treated skin was observed. The body weights of all animals were considered to be within the normal range of variability.

Any other information on results incl. tables

Coloration:

No staining produced by the test item of the treated skin was observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was considered to be "not irritating" to rabbit skin under the conditions of this study.