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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 18, 2001 till August 14, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD guideline 402 (Acute Dermal Toxicity) under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identity: ZP-TIX 1014
Batch number: NW-01-028
Appearance: solid
Purity: >99%
Stable under storage conditions, i.e. at room temperature (17-23°C), away from direct sunlight
Expiry date: 30.12.2001
The test item consists of three components, which appear as three separate peaks in the HPLC chromatogramm.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Details on animals: Rat, HanBrl: WIST (SPF)
Source of rats: RCC Ltd (Füllingsdorf, Switzerland)
Sex: both
Number of animals per group: 5 male and 5 female
Age (when treated): male (10 weeks) female (13 weeks)
Acclimatization: Under laboratory conditions after health examination. Only healthy animals without visual signs of illness were used.
Conditions: Standard Laboratory Conditions
- Air-conditioned with 10-15 air changes per hour
- continously monitored environment with target ranges for temperature 22±3°C and for relative humidity between 30-70%
- 12 hours fluorescent light/12 hours dark (light period 6:00 and 18:00h)
- music during light period
Accommodation: In groups of five per sex in Makrolon type-4 cages with standardised softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz/Switzerland)
Diet: Pelleted standard Provimi Kliba 3433 (batch no. 72/01) rat maintenance diet available ad libitum.
Water: Community tap water from Itingen, Switzerland, available ad libitum.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
TEST SITE
Area of exposure: approximately 10% of the total body surface
Dressing: semi-occlusive dressing
Type of wrap if used: wrapped around the abdomen and fixed with an elastic adhesive bandage, no further data

REMOVAL OF TEST SUBSTANCE
Washing (if done): skin was flushed with lukewarm tap water
Time after start of exposure: 24h

TEST MATERIAL
Amount(s) applied (volume or weight with unit): 2000mg/kg b.w. in PEG 300
Concentration (if solution): 0.5 g/mL
Constant volume or concentration used: 4mL

VEHICLE
Identity: polyethylene glycol PEG 300
Lot/batch no. (if required): 412565/151301
Purity: no data

OTHER DETAILS:
One day before exposure the back of the animals were clipped exposing an area of approximately 10% of the total body surface. Only animal without injury or irritation on skin were used. The preparation of the test item was made shortly before dermal application. On test day 1 the test item was applied at a dose of 2000mg/kg b.w. and covered with a semi-occlusive dressing.The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

Duration of exposure:
24h
Doses:
2000mg/kg b.w.
No. of animals per sex per dose:
5 male and 5 female animal per dose
Control animals:
no
Details on study design:
Observation periode: 14 days
Frequency of observations and weighing:
- mortality: daily during acclimatization and at least one, two, three and approximatley five hours after test item administraion.
- body weights: pre administration (day 1), day 8 and 15
- clinical signs: daily during acclimatization and at least one, two, three and approximatley five hours after test item administraion (test day 1)
Necropsy of survivors performed: yes
Other examinations performed: all animals were examined macroscopically at necropsy and thereafter discarded
Test item preparation: Testitem was placed into a glass baker and the vehicle (PEG 300) was added and warmed up to approx. 50°C for 2 minutes.
A weight by volumen dilution was prepared. Homogeneity of the test item in the vehicle was maintained during treatment.
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occured during the study.
Clinical signs:
Scales and slight or moderate erythema maculate was noted in males at 2000mg/kg on test day 4 until test day 14. Scales and slight or moderate erythema maculate and in one case general erythema was note in the females at 2000mg/kg bw on test day 6 until test day 15.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of ZP-TIX 1014 after single dermal adminsitration to rats of both sexes observed over a period of 14 days was
LD50(rat) > 2000mg/kg bodyweight
Executive summary:

OECD Guideline 402 (Acute Dermal Toxicity) a group of five male and five female HanBrl: Wist (SPF) rats was treated with ZP_TIX 1014 at 2000 mg/kg bw by dermal application. The test item was diluted in polyethylen glycol (PEG 300) and a volumen of 4 mL (weight corrected concentration approximately 0.5g/mL) was dermal administered. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2 -15. Mortality/viability was recorded together with clinical signs in the same time intervals. Body weights were recorded an day 1 (prior administraion) and day 8 and 15. All animals were necropsied and examined macroscopically at the end of the study.

No deaths occured during the study.

Scales and slight or moderate erythema maculate was noted in males at 2000mg/kg on test day 4 until test day 14. Scales and slight or moderate erythema maculate and in one case general erythema was note in the females at 2000mg/kg bw on test day 6 until test day 15.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were observed at necropsy.