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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2005-05-20 to 2005-06-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study (OECD-430) with detailed documentation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 430 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER))

Deviations:

no

GLP compliance:

not specified

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

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): JNJ-1594164-AAA (T000424)
- Physical state: solid (powder)
- Appearance: White powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: RT000424G1A251
- Expiration date of the lot/batch: 2005-12-31
- Purity test date: no data
- Purity: 100%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, protected from light
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final preparation of a solid: the solid test item was ground to produce a granular material immediately prior to testing.

In vitro test system

Test system:

isolated skin discs

Source species:

rat

Source strain:

Wistar

Details on animal used as source of test system:

SOURCE ANIMAL
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Sex:
- Age at study initiation (in days): 29 days
- Weight at study initiation:
- Housing: Single, in Makrolon type II cages, with wire mesh top (EHRET GmbH, D-79302 Emmendingen), granulated soft wood bedding (Harlan Winkelmann GmbH, D-33178 Borchen)
- Diet (e.g. ad libitum): pelleted standard diet, ad libitum (Harlan Winkelmann GmbH, D-33178 Borchen)
- Water (e.g. ad libitum): tap water, ad libitum (Gemeindewerke, D-64380 Rossdorf)
- Acclimation period: minimum 10 days. During this period the animals did not show signs of illness or altered behaviour.

ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 21+/- 3°C
- Humidity (%): 30-70
- Air changes (per hr): No data
- Photoperiod: 12 hrs dark / 12 hrs light (artifical light 6.00 a.m. - 6.00 p.m.)


IN-LIFE DATES: From: no data To: no data

Vehicle:

unchanged (no vehicle)

Details on test system:

SKIN DISC PREPARATION
- The dorsal flank hair was carefully removed. The animals were then washed by careful wiping, whilst submerging the area in antibiotic solution containing streptomycin and penicillin to inhibit bacterial growth. Animals were washed with antibiotics again three days after the first wash, and were used within 3 days.
- Procedure used: animals were anaesthetised with CO2 and subsequently decapitated. The dorsal skin of each animal was removed and stripped of excess fat by carefully peeling it away from the skin. The skin was placed over the end of a PTFE (polytetrafluoroethylene) tube, ensuring that the epidermal surface was in contact with the tube. A rubber 'O' ring was press-fitted over the end of the tube to hold the skin in place and excess tissue was trimmed away. The tube was supported by a spring clip inside a receptor chamber containing magnesium sulphate solution (154 mM).
- Quality control for skin discs: Electrical resistance obtained with two of the isolated skin discs was [complete, e.g. 10 kΩ]

TEMPERATURE USED FOR TEST SYSTEM
- no data

REMOVAL OF TEST MATERIAL AND CONTROLS
- Number of washing steps: test item was removed by washing with a jet of tap water at up to 30°C until no further material could be removed.

DYE BINDING METHOD
- Dye used in the dye-binding assay: Sulforhodamine B
- Spectrophotometer: no data
- Wavelength: 565 nm

NUMBER OF INDEPENDENT TESTING RUNS / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1

PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be corrosive to skin if the mean TER value is less than or equal to 5 kΩ, if verified by the dye binding assay.
- The test substance is considered to be non-corrosive to skin if the mean TER value obtained for the test item is greater than 5 kΩ.
- If the mean TER value obtained was greater than or equal to 5 kOhms than the corrosivity was required to be confirmed by the dye binding assay. If the dye binding content is greater than or equal to the the mean disc content of the positive control, then the test substance is truely corrosive. If the mean disc dye content is well below the mean disc content of the positive control , then the test substance is a false positve and therefore, non-corrosive.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.0594 g, 0.0681 g, 0.0552 g of the test item was applied per skin disc. 150 uL deionised water was added on top of the test substance and was evenly distributed by shaking of the tube.

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 150 µL

POSITIVE CONTROL
- Amount(s) applied (volume or weight with unit): 150 µL
- Concentration (if solution): 36% (~10 M)

Duration of treatment / exposure:

24 h

Number of replicates:

3 replicates per test group (test item, negative control and positive control)

Test system

Duration of treatment / exposure:

24

Results and discussion

In vitro

Results

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Remarks:

mean of 3

Run / experiment:

1

Value:

2.9

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

SD = 0.75

Other effects / acceptance of results:

Resistance (kOhm):
- Negative control (mean of 3 replicates): 11.0 +/- 0.21
- Positive control (mean of 3 replicates): 0.6 +/- 0.03

Impedance measurements of all three skin discs treated with the test item indicated a corrosive effect induced by the test substance. Nevertheless, the sulforhodamine content was well below the dye content of the positive control and only slightly above the negative control. Furthermore, the skin discs appeared macroscopically intact after treatment.

Any other information on results incl. tables

Table 1. Summary of the TER-results

Sample	Resistance (kOhm)	Mean	Standard deviation	Corrosive
Negative Control 1	12.8
Negative Control 2	9.9	11.0	0.21	No
Negative Control 3	10.2
Positive Control 1	0.6
Positive Control 2	0.5	0.6	0.03	Yes
Positive Control 3	0.6
T424 1	2.4
T424 2	2.5	2.9	0.75	Yes
T424 3	3.8

11.0 and 0.21 are the mean and the standard deviation values, respectively, of the three negative controls.

0.6 and 0.03 are the mean and the standard deviation values, respectively, of the three positive controls.

2.9 and 0.75 are the mean and the standard deviation values, respectively, of the test substance tested in three skin disc replicates.

Table 2. Summary of the Sulforhodamine B-results

Sample	Absorption 565 nm	Sulforhodamine B content (ug/disc)	Mean	Standard Deviation	Corrosive
Negative Control 1	0.06	10.6
Negative Control 2	0.069	12.6	17.0	9.39	No
Negative Control 3	0.138	27.8
Positive Control 1	0.490	105.2
Positive Control 2	0.747	161.8	131.8	28.44	Yes
Positive Control 3	0.595	128.3
T424 1	0.152	30.9
T424 2	0.202	41.9	32.8	8.31	No
T424 3	0.128	25.6

17.0 and 9.39 are the mean and the standard deviation values, respectively, of the three negative controls.

131.8 and 28.44 are the mean and the standard deviation values, respectively, of the three positive controls.

32.8 and 8.31 are the mean and the standard deviation values, respectively, of the test substance tested in three skin disc replicates.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

T424 is considered to be non-corrosive in the TER test.