N-((3R,4R)-1-benzyl-4-alkylpiperidin-3-yl)-2-halogeno-N-alkyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 05 to 13 December 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study run to a method comparable with current guidelines and to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Details on test material:

Batch No.: E010005632 or 166-TNN-73
Purity: 98%

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands BV
- Age at study initiation: 12 weeks
- Weight at study initiation: 2355g, 2322g, 2447g
- Fasting period before study:
- 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 Fullinsdorf ad libitum.
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23°C
- Humidity (%): 30-70% (values above 70% during cleaning process possible)
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

IN-LIFE DATES: From: 05 December 2007 To: 13 December 2007

Test system

Type of coverage:

semiocclusive

Preparation of test site:

abraded

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/animal
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

one male and two females

Details on study design:

TEST SITE
- Area of exposure: 100 cm2 (10cm×10cm)
- % coverage:
- Type of wrap if used: The patch was covered with a semi-occlusive dressing which was wrapped around the abdomen and anchored with tap.

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

SCORING SYSTEM: Draize score system

Any other information of method:
Observations
Mortality/Viability: 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.
Clinical signs: Daily from acclimatization of the animals to the termination of test.
Skin Reaction: The skin reation was assessed at approximately 1, 24, 48 and 72 hours after exposure.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

0

Remarks on result:

other: The exposure period is 4 hours.

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

0

Remarks on result:

other: The exposure period is 4 hours.

Irritant / corrosive response data:

Irritation: 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 test item did not elicit any skin reactions at the application site of any animal at any of the observation time. The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

Corrosion: Neither alterlations of the treated skin were observed nor were corrosive effects evident on the skin.

Any other information on results incl. tables

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

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

Body Weights

Body weight in grams
Animal No.	Sex	First day of Acclimatization	Day of Treatment	Last Day of Observation
70	male	2128	2355	2536
71	female	2167	2322	2471
72	female	2304	2447	2547

Skin Irritation Scores-Individual Values

Animal Number	Sex	Evaluation Interval	Erythema	Oedema	Cumulative
					Score	Mean
70	M	1 hour	0	0	0.00	0.00
71	F		0	0	0.00
72	F		0	0	0.00
70	M	24 hours	0	0	0.00	0.00
71	F		0	0	0.00
72	F		0	0	0.00
70	M	48 hours	0	0	0.00	0.00
71	F		0	0	0.00
72	F		0	0	0.00
70	M	72 hours	0	0	0.00	0.00
71	F		0	0	0.00
72	F		0	0	0.00

   M: male; F: female

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance is considered to be “not irritating” to rabbit skin.