Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 1st, 2001 to August 22nd, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

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
Remarks:
in compliance with the Swiss Ordinance relating to GLP, adopted February 2nd, 2000 [RS 813.016.5] and based on the OECD Principles of GLP, as revised in 1997 and adopted November 26th, 1997 by decision of the OECD Council [C(97)186/Final]
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): T002113
- Substance type: powder
- Physical state: solid
- Analytical purity: 92.9 %
- Purity test date: no data
- Lot/batch No.: RT002113G3A231
- Expiration date of the lot/batch: 1-dec-2001
- Storage condition of test material: at room temperature (range of 20 +/- 3 °C), away from direct sunlight
- Stability of test item: stable under storage conditions
- Stability of test item in vehicle: 2 hours , the concentration, homogeneity, and stability of T002113 was determined (see further)

Test animals

Species:
rat
Strain:
other: HanBrl: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: 10 rats (5 males and 5 females), RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Füllinsdorf, Switzerland
- Age when treated: 9 weeks for males, 12 weeks for females
- Weight at study initiation: 224.0-245.5 g for males, 201.6-208.1 g for females
- Housing: during acclimatization in groups of 5 per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz, Switzerland) during treatment and observation.
- Diet (e.g. ad libitum): ad libitum, pelleted standard Provimi Kliba 3433, batch no. 72/01 rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst). Results of analyses for contaminants are archived at RCC Ltd, Itingen.
- Water (e.g. ad libitum): ad libitum, community tap water from Itingen. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.
- Acclimation period: 7 days, 1-aug to 7-aug-2001 (males and females) (under laboratory conditions)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs fluorescent light (light period between 6.00 and 18.00), music during light period

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: bi-distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure: the back of the animal
- % coverage: approximately 10 % of the total body surface
- Type of wrap if used: semi-occlusive dressing, the dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was flushed with lukewarm tap water and dried with disposable paper towels
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight in 4 ml/kg body weight
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 ml/kg body weight
Duration of exposure:
24 hrs
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
2 x 5 (5 males and 5 females)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and viability daily during acclimatization period and twice daily during days 1-15. Body weights on test days 1 (pre-administration), 8 and 15. Clinical signs daily during acclimatization and at least four times on test day 1 after the test item administration. Once daily during days 2-15.
- Necropsy of survivors performed: yes, at the end of the observation period all animals were sacrificed by intraperitoneal injection of NARCOREN (Rhone Merieux GmbH, 0-88471 Laupheim) at a dose of at least 2.0 ml/kg body weight (equivalent to at least 320 mg sodium pentobarbitone/kg body weight).
- All animals were examined macroscopically
Statistics:
No statistical analysis was 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 occurred 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 T002113 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