1-benzhydrylpiperazine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-10-19 to 2006-11-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well-documented GLP compliant study, performed according to OECD test guideline 404 and EU Method B.4. No deviations were recorded that influenced the result of the study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

test item was put on a surgical gauze patch of approx 4x4 cm (instead of 6 cm²) to guarantee good contact

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

test item was put on a surgical gauze patch of approx 4x4 cm (instead of 6 cm²) to guarantee good contact

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1-benzhydrylpiperazine

EC Number:

212-667-7

EC Name:

1-benzhydrylpiperazine

Cas Number:

841-77-0

Molecular formula:

C17H20N2

IUPAC Name:

1-(DIPHENYLMETHYL)PIPERAZINE

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study reports): JNJ-130806-AAA (T000750)
- Physical state: solid (powder)
- Appearance: white to slight beige powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst/The Netherlands, Postbus 6174, NL-5960 AD Horst/The Netherlands
- Age at treatment: 14 weeks (male) and 11 weeks (females)
- Weight at study initiation: male: 2730 g and females 2511 and 2527 g
- Housing: standard laboratory conditions; individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no 77/05, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no 51/06) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water (e.g. ad libitum): community tap water from Füllinsdorf, ad libitum
- Acclimatization period: 2006-10-19 to 2006-10-23 (one female); 2006-10-19 to 2006-10-24 (one male and one female); under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): approximately 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 h light/ 12 h dark. Music was played during the daytime light period.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

purified water to moisten

Controls:

not required

Amount / concentration applied:

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

VEHICLE
- Concentration (if solution): 0.5 g was moistened with approximately 0.5 mL of purified water

Duration of treatment / exposure:

4 hours

Observation period:

7 days after treatment
Skin observation time points and termination:
The skin reaction was assessed at approximately 1, 24, 48 and 72 hours, as well as 7 days after exposure

Observations: viability/mortality and clinical signs: daily from acclimatization of the animals to the termination of test; body weights: at start of acclimatization, on the day of application and at termination of observation

Number of animals:

3 (1 male, 2 females)

Details on study design:

TEST SITE
- Area of exposure: left flank
- % coverage: no data
- Type of wrap if used: 0.5 g of T750 was placed on a surgical gauze patch (ca. 4cm x 4 cm). This gauze patch was applied to the intact skin of the clipped area. 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): flushed with lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: grading of skin reaction according to Commission Directive 2004/73/EC, April 29, 2004. 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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: male

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

erythema score

Basis:

animal: female

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 3

Irritation parameter:

erythema score

Basis:

animal: female

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Remarks:

7 days

Results 4

Irritation parameter:

edema score

Basis:

animal: all : 1 male and 2 females

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable - score 0

Irritant / corrosive response data:

A well-defined erythema was noted at the application site of two animals one hour after test item exposure whereas one animal expressed a very slight erythema at this reading. In addition, a very slight swelling was noted in two animals. A very slight erythema persisted up to the 48- or 72- hour reading in one and two animals, respectively. Scaling of the treated skin was observed in one animal 48 and 72 hours after the treatment.
No abnormal findings were observed on the treated skin of any animal 7 days 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:

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

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not induce significant or irreversible damage to the skin. T000750 is considered to be 'not irritating' to rabbit skin according to the referred classification criteria (Commission Directive 2001/59/EC of August 2001). Based on the criteria in the CLP Regulation, the test item should not be classified for skin irritation.