4-Pyrimidineethanol, 6-chloro-.alpha.-(2,4-difluorophenyl)-5-fluoro-.beta.-methyl-.alpha.-(1H-1,2,4-triazol-1-ylmethyl)-, hydrochloride (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 15 to 25 July 1998

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:

1998

Report date:

1998

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

Reference substance name:

3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride

EC Number:

928-729-8

Cas Number:

188416-20-8

Molecular formula:

C16H13ClF3N5O.HCl

IUPAC Name:

3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride

Details on test material:

Batch No.: 5ABJ002
Purity: 90%

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Obtained from Harlan UK Ltd
- Age at study initiation: Approximately 10 to 12 weeks.
- Weight at study initiation: 2.4 to 2.6 kg
- Housing: Test animals were housed individually in stainless steel cages with perforated floors.
- Diet (e.g. ad libitum): A standard laboratory rabbit diet (Special Diet Services STANRAB (P) SQC pellet)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: six days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 to 24
- Humidity (%): 34 - 59
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

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

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

Duration of treatment / exposure:

First animals: The test substance was applied to three treatment sites and the exposure period was varied between treatment sites (ie three minutes, 60 minutes and four hours).
The remaining two animals: Four hours exposure period.

Observation period:

10 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approximately 100mm*100mm
- % coverage:
- Type of wrap if used: Each treatment site was covered with "Elastoplast" elastic adhesive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treatment sites washed with warm water to remove any residual test substance.
- Time after start of exposure: three minutes, 60 minutes and four hours

SCORING SYSTEM:

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:

ca. 1.44

Max. score:

2

Reversibility:

fully reversible within: 9 days

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:

ca. 0.22

Max. score:

1

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: The exposure period is 4 hours

Irritant / corrosive response data:

No dermal respose to treatment was observed following the three minute exposure.
Well-defined erythema only was seen following the one hour exposure.
Well-defined erythema with or without very slight oedma was seen in all animals following the four hour exposure. These reactions were accompanied in one rabbit by desquamation of the stratumn corneum (characterised by dryness and sloughing of skin). Reactions had resolved in all animals by Day 7, 8 or 10.

Any other information on results incl. tables

There were no signs of toxicity or ill health in any rabbit during the observation period.

Animal No. & Sex	Exposure Time	E=Erythema O=Oedema	Day
			1	2	3	4	5	6	7	8	9	10
1011 Female*	3 Minutes	E O	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
	1 Hour	E O	0 0	2 0	2 0	1 0	1 0	1 0	1 0	0 0
	4 Hours	E O	2 0	2 0	2 0	1 0	1 0	1 0	1 0	0 0
1012 Female	4 Hours	E O	1 0	2 1	1 0	1 0	1 0	1 0	0 0
1013 Female	4 Hours	E O	1 0	2 1	1 0	1 0	1 0	1 0	1 0	1a 0	1a 0	0 0

* Screen animal

a Desquamation of the stratum corneum (characterised by dryness and sloughing of skin)

Applicant's summary and conclusion

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

A single semi-occlusive application of this substance to intact rabbit skin for up to four hours elicited well-defined dermal irritation.