1-benzyl-N-phenylpiperidin-4-amine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2006-07-10 to 2006-07-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD Guideline 404 "Acute Dermal Irritation/Corrosion" and Commission Directive 2004/73/EC, 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:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate from the Swiss GLP Monitoring Authority

Test material

Test material information

Constituent 1

Reference substance name:

1-benzyl-N-phenylpiperidin-4-amine

EC Number:

214-583-6

EC Name:

1-benzyl-N-phenylpiperidin-4-amine

Cas Number:

1155-56-2

Molecular formula:

C18H22N2

IUPAC Name:

1-benzyl-N-phenylpiperidin-4-amine

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): JNJ-1594008-AAA (T000293)
- 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: 00479757RT000293G1A401
- Expiration date of the lot/batch: 2011-01-15
- Purity: 100%
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (range of 20 +/- 5°C), light protected
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was weighed as delivered by the sponsor and then moistened with approximately 0.5 mL of purified water.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: young adult New Zealand White rabbits, SPF; Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst, The Netherlands
- Age at study initiation: 13 weeks (1 male) and 13-14 weeks (2 females)
- Weight at study initiation: 2763 g (male), 2639 - 2780 g (females)
- Housing: Standard Laboratory Conditions; individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided for gnawing.
- Diet: pelleted standard Provimi Kliba 3418 rabbit maintenance diet, ad libitum
- Water: community tap water from Füllinsdorf, ad libitum
- Acclimation period: from 2006-07-05 to 2006-07-09, under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12, automatically controlled light cycle. Music was played during the daytime light period.

IN-LIFE DATES: From: 2006-07-10 To: 2006-07-17

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated skin areas were used as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g (per animal)

Duration of treatment / exposure:

4 hours

Observation period:

7 days (observations made at 1, 24, 48 and 72 hours, as well as 7 days after exposure)

Number of animals:

3 (1 male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: The left flank was clipped with an electric clipper, exposing an area of approximately 100 cm² (10 cm x 10 cm). The test substance was applied under a 4 cm x 4 cm surgical gauze patch. The gauze patch 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.
- Other:

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at the time.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- The skin reaction was assessed at approximately 1, 24, 48 and 72 hours as well as 7 days after exposure (removal of the dressing, gauze patch and test item).

SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004, (see scoring table in "Any other information on materials and methods" section below).
- If evident, corrosive or staining properties of the test substance were described and recorded.
- 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. An animal is positive when the mean score is 2 or greater. The test is positive for irritation when at least 2 animals are positive for the same endpoint (erythema/eschar or oedema).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: male

Results 2

Irritation parameter:

erythema score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: female

Results 3

Irritation parameter:

erythema score

Remarks:

mean

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: female

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

of all three animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Irritation:
- The mean erythema/eschar score of the three animals was 0.00, 0.00 and 1.00, respectively and the mean oedema score was 0.00. The application of the test item to the skin resulted in very slight erythema in one animal from the 1- to the 72-hour reading.

Corrosion:
- Neither alterations of the treated skin were observed, nor were corrosive effects evident on the skin.

Other effects:

Viability/Mortality/Clinical signs
- No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

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

Body Weights:
- The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), T000293 is considered to be "not irritating" to rabbit skin.