Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2005-10-12 to 2005-11-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

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 (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
- Name of test material (as cited in study report): TIC2782 (T002907)
- Substance type: White solid
- Physical state: solid
- Analytical purity: 99.9 %
- Purity test date: No data
- Lot/batch No.: 00467090 (= charge 05C0836)
- Expiration date of the lot/batch: 2006-05-04
- stability of test item dilution: unknown in PEG300
- Stability of test item: stable under storage conditions
- Storage condition of test material: At room temperature (range of 20 +/- 5 °C), light protected.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HanRcc:WIST (SPF) from RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf / Switzerland
- Age when treated: Males: 8 - 9 weeks; Females: 12 -13 weeks.
- Weight at first day of treatment: Males: 236.9 - 246.4; Females: 188.3 - 205.4g.
- Fasting period before study: unknown
- Housing: Standard laboratory conditions; during acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation.
- Diet: Ad libitum, pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet.
- Water: Ad libitum, community tap water from Füllinsdorf
- Acclimation period: at least 6 days, under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30- 70 (values above 70% during cleaning process possible)
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12
- Other: Music during the daytime light period.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
PEG300
Details on dermal exposure:
TEST SITE
- Area of exposure: backs of the animals
- % coverage: 10% of the total body surface
- Type of wrap if used: gauze patch which was applied to the intact skin with a syring and sovered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm tapwater and dried with disposable paper towels.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/kg
- Concentration (if solution): 0.5g/mL
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE (PEG300)
- Amount(s) applied (volume or weight with unit): 4 mL/kg
- Lot/batch no.: 1157790 51105271
- Purity: no data
- justification: the vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males, 5 females all 2000 mg/kg body weight (total 10 animals)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Moratilty / Viability: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 ours after adminstration on test day 1 (with the clinical signs) and twice daily during days 2-15. clinical signs: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 ours after adminstration on test day 1 and once daily during days 2-15. Body weights: on test days 1 (prior to administration), 8 and 15; other: local signs: Once dailing during days 2-15.
- Necropsy of survivors performed: yes. All animals were killed at the end of the observation period by Carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.
Statistics:
No statistical analysis were used.

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 occured during the study.
Clinical signs:
No systemic or local signs of toxicity were observed during the study period.
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:
GHS criteria not met
Conclusions:
The median lethal dose of TIC2782 (T002907) after single dermal administration to rats of both sexes, observed over a period of 14 days is: LD50 (rat): greater than 2000 mg/kg body weight. Therefore T002907 is not classified based on CLP regulation.