Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-03-01 to 2007-03-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

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)
Remarks:
: certificate issued by Swiss GLP monitoring authorities
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study reports): T002675, TIC876
- Physical state: liquid
- Appearance: colorless to yellowish liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Name of test material (as cited in study report): T002675 (TIC876)
- Physical state: liquid, colorless to yellowish
- Analytical purity: 97.76%
- Lot/batch No.: 603T-1
- Expiration date of the lot/batch: 2007-12-19

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (range of 20 +/- 5 °C), light protected
- Stability under test conditions: Unknown in PEG 300, is excluded from the statement of compliance

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). The formulation was prepared shortly before the application using a magnetic stirrer as homogenizer. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Test animals

Species:
rat
Strain:
other: HanRcc:WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd., Laboratory Animal Services CH-4414 Füllinsdorf / Switzerland
- Age when treated: 11 weeks (female); 8 weeks (male)
- Weight at study initiation (day of treatment): Males: 228.2-254.6 g; Females: 189.4-204.2g
- Fasting period before study: no data
- Housing: during the 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 (e.g. ad libitum): pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 80/06, ad libitum
- Water (e.g. ad libitum): community tap water from Füllinsdorf, ad libitum
- Acclimation period: 2007-03-01 to 2007-03-07


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


IN-LIFE DATES: From: 2007-03-08 To: 2007-03-22

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Details on dermal exposure:
TEST SITE
- Area of exposure: The backs of animals
- % coverage: approximately 10% of the total body surface was exposed.
- Type of wrap if used: the test item was applied at a dose of 2000 mg/kg bw evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The semi-occlusive 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 a disposable paper towel.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/kg bw
- Concentration (if solution): 0.5 g/mL

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 mL/kg bw
- Concentration (if solution): no data
- Lot/batch no. (if required): 130022563006152
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
one group with 5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded; all animals were examined for clinical signs at approximately .5, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15; local signs were noted once daily from test day 2 to 15; mortality/viability was recorded at approximately .5, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15;
- Body weights were recorded on day 1 (prior to administration) and on days 8 and 15.
- Necropsy of survivors performed: yes, all surviving animals were killed at the end of the observation period by carbon dioxide asphyxiation
- Other examinations performed: macroscopic examination, no organs or tissues were retained
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
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 (LD50) of the test substance after single dermal administration to rats of both sexes, observed over a period of 14 days was greater than 2000 mg/kg bw .