Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 October 1997 - 13 November 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted according to OECD guideline 402 and EU Method B.3 (Acute Dermal Toxicity Test) without deviations and GLP practices. .

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Epyrrol
- Substance type: pure active substance
- Physical state: Powder, off white in color
- Composition of test material, percentage of components: Main component= 75%, other= 18%, other= 7%
- Lot/batch No.: GL-1291 K1
- Expiration date of the lot/batch: 24 September 1998
- Stability under test conditions: Not indicated
- Storage condition of test material: Stable at room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 9-10 weeks old
- Weight at study initiation: 298 g (male mean) and 226 g (female mean)
- Fasting period before study: Food was withheld overnight prior to dosing until approximately 3-4 hours after treatment of the test substance
- Housing: Group house of 3 animals per sex per cage in labelled polycarbonatge cages
- Diet (e.g. ad libitum): Standard pelleted laboratory diet (from Carfil Quality BVBA, Oud-Turnout, Belgium), Ad libitum
- Water (e.g. ad libitum): Tap-water, ad libitum
- Acclimation period: At least 5 days before the start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 deg C
- Humidity (%): 50%
- Air changes (per hr): 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Not documented in the report To: Not documented in the report

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and or flank
- % coverage: 10% of total body surface (25 cm3 for males and 18 cm3 for females (5X5 cm and 3.5X5 cm, respectively))
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressings were removed and residual test substance was removed using a tissue moistened with tap water.
- Time after start of exposure: 24 hours after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg
- Concentration (if solution): No data
- Constant volume or concentration used: yes
Duration of exposure:
Single dose
Doses:
2000 mg/kg (10ml/kg) body weight
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability observed twice daily; Body weight observed on Days 1, 8 and 15; Clinical signs observed periodically on Days 1 and once daily thereafter, until Day 15 (the time of onset, degree and duration were recorded and the symptoms graded according to fixed scales).
- Necropsy of survivors performed: Yes, at the end of the observation period, all animals were sacrificed by asphyxiation using a oxygen/carbon dioxide procedure.
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture was noted in one male, between days 5-7. Focal erythema, scales, and scabs on the back and/or flank were noted in the majority of animals from day 3-5 onwards. The animals had recoved from the symptoms between days 7 and 14, although scabs persisted in two males at termination.
Body weight:
Body weight gain during the observation period was within the range expected for rats used in this type of study.
Gross pathology:
No abnormalities were found in the animals at macroscopic post mortem examination.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 for rats treated with a single dermal application was established as exceeding 2000 mg/kg bw as no mortalities were observed.