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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 24 November 1997 to 18 May 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 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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:

- Analytical purity: 90%
- Lot/batch No.: 5ABJ002

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan U.K.Ltd., Bicester, Oxon, England
- Age at study initiation: eight to eleven weeks of age
- Weight at study initiation: 217 to 260 g
- Fasting period before study:
- Housing: Sub-Dividable Rodent Cage-Polished stainless steel 20cmhigh*39cmwide*39cmlong, no more than five animals of the same sex were accommodated in each cage.
- Diet : a standard laboratory rodent diet
- Water : ad libitum
- Acclimation period: a minimum period of six days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.5-21.5ºC
- Humidity (%): 42-60%
- Air changes (per hr):
- Photoperiod : 12 hours of artificial light (0700-1900hours) in 24-hour period

IN-LIFE DATES: From 1 to 15 July 1998

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: aqueous methylcellulose

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 50mm*50mm
- % coverage: 10% of the total body surface area
- Type of wrap if used: Covered with porous gauze held in place with a non irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed with warm water (30 to 40ºC )
- Time after start of exposure: at the end of 24 hours exposure period

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg bodyweight
- Concentration (if solution): a maximum practical concentration of 40% w/v in 1% w/v aqueous methylcellulose
- Constant volume or concentration used: no
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): 5ml/kg
- Concentration (if solution): 1% w/v aqueous methylcellulose
- Lot/batch no. (if required):
- Purity:

Duration of exposure:

24h

Doses:

2000mg/kg bodyweight

No. of animals per sex per dose:

a group of ten rats (five males and five females)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least twice daily for mortalities
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths

Clinical signs:

other: A well-defined dermal response (erythema/oedema Grades 1 to 3) was first evident in all rats following removal of the dressing with a similar response also apparent 48 hours after dosing. These signs were accompanied by localised reactions characterised

Gross pathology:

No abnormalities were recorded at the macroscopic examination Day 15.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute lethal dermal dose to rats of this substance was demonstrated to be greater than 2000mg/kg bodyweight.