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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 28 January to 11 February 1997
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:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
188416- 34-4
IUPAC Name:
188416- 34-4
Constituent 2
Reference substance name:
(2RS,3SR)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (1R)-10- camphorsulphonate
IUPAC Name:
(2RS,3SR)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (1R)-10- camphorsulphonate
Constituent 3
Reference substance name:
(2RS,3SR)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (1R)- 10-camphorsulphonate
IUPAC Name:
(2RS,3SR)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (1R)- 10-camphorsulphonate
Details on test material:
- Analytical purity: 96.5%
- Lot/batch No.: 5ABK-003

Test animals

Species:
rat
Strain:
Sprague-Dawley
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 ten weeks of age
- Weight at study initiation: 220 to 250 g
- Fasting period before study:
- Housing: They were housed individually in metal cages with wire mesh floors
- Diet: A standard laboratory rodent diet
- Water: ad libitum
- Acclimation period: A minimum period of five days prior to the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21ºC
- Humidity (%): 32-52% RH
- Air changes (per hr): Maintained at 10 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700-1900 hours) in 24-hour period

IN-LIFE DATES: From 28 January To 11 February 1997

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: aqueous methylcellulose
Details on dermal exposure:
TEST SITE
- Area of exposure: Approximately 50 mm * 50 mm
- % coverage: Approximately 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: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight
- Concentration (if solution): A maximum practical concentration of 66.67% w/v in 1% w/v aqueous methylcellulose
- Constant volume or concentration used: no


VEHICLE
- Amount(s) applied (volume or weight with unit): 3 ml/kg bodyweight
- Concentration (if solution): 1% w/v aqueous methylcellulose
- Lot/batch no. (if required):
- Purity:
Duration of exposure:
24h
Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
a group of ten rats (five males and five females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Once in the morning and again at the end of the experimental day (with the exception of Day 15-morning only)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, mortality

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths
Clinical signs:
There were no signs of systemic reaction to treatment.
Body weight:
Slightly low bodyweight gains were noted for two females (nos 7 and 8) on Day 8. All other rats were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No macroscopic abnormalities were observed for the animals killed on Day 15.
Other findings:
Dermal reactions:
Transient slight to well defined dermal irritation (Grade 1 or 2 erythema and oedema) was evident in two males and two females on removal of the dressings, resolving completely by Day 5. In addition, desquamation (characterised by dryness/sloughing/scaling and/or spot/scab formation) was noted in two females during the first week of the study only. No dermal response to treatment was observed in the remaining six animals throughout the study.

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 2000 mg/kg bodyweight.