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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14-JUN-2006 to 07-JUL-2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP

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 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Description: Black sticky powder
Purity: Content of organic part (Na-salt): approx. 80 %;Oligomers: 13 %;Main component: approx. 53 %
Stability: Stable under storage conditions. Stable in water for 7 days.
Storage: At room temperature, desiccated and light protected.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Test System: Rat, HanRcc:WIST (SPF)
Number of animals per group: 3 females
Total number of animals: 6 females
Age at treatment: 12 weeks (females)
Identification: By unique cage number and corresponding color-coded spots on the tail. The animals were marked at acclimatization start.
Randomization: Selected by hand at time of delivery. No computer generated randomization program.
Acclimatization: Under laboratory conditions after health examination. Only healthy animals were used for the study.

Conditions
Standard Laboratory Conditions.
Air-conditioned with ranges for room temperature of 22 ± 3 °C and relative humidity 30-70 % and approximately 10-15 air changes per hour. 12 hours artificial fluorescent light/12 hours dark, music during the light period.
Accommodation: during acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding.
Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet (batch 001/06) ad libitum.
Water: Community tap water, ad libitum.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The animals received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight after being fasted for approximately 18 to 19 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.
The application volume was 10 mL/kg body weight.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6 females
Control animals:
not specified
Details on study design:
Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (purified water) at a concentration of 0.2 g/mL and administered at a volume dosage of 10 mL/kg.
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 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 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. All animals were necropsied and examined macroscopically. All animals survived until the end of the study period.
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Mild or moderate clinical signs of toxicity (ruffled fur, hunched posture, sedation) were noted in the animals on the day of dosing and a slightly ruffled fur persisted in two animals still on day 2. From day 3 on for the remaining observation period all animals were absent of clinical findings.
Clinical signs:
A ruffled fur was observed in all animals on the day of dosing starting 1, 2 or 3 hours after dosing and persisting up to the 5-hour reading. This symptom was graded moderate in two animals 2-5 or 3-5 hours after dosing and otherwise considered slight. A slightly ruffled fur was still present in two animals on day 2 of the study.

A hunched posture was observed in three animals on the day of dosing 0.5-5 or 2-5 hours after administration or at the 0.5-hour reading and again 2-5 hours after dosing, respectively.

In addition, three animals expressed sedation 3-5 hours after dosing. The sedation was graded moderate in one animal at the 3-hour observation and otherwise considered slight. From day 3 on up to the end of the 2-week observation period all animals remained absent of clinical findings.
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 recorded at necropsy

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (female rat, oral): greater than 2000 mg/kg body weight.
Executive summary:

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (purified water) at a concentration of 0.2 g/mL and administered at a volume dosage of 10 mL/kg.

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 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 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. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

Mild or moderate clinical signs of toxicity (ruffled fur, hunched posture, sedation) were noted in the animals on the day of dosing and a slightly ruffled fur persisted in two animals still on day 2. From day 3 on for the remaining observation period all animals were absent of clinical findings.

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

No macroscopic findings were recorded at necropsy.

Therefore, the LD50 of test item can be estimated to be greater than 2000 mg/kg bw, which indicates that test article shall not be classified according to CLP (Regulation EC No. 1272/2008).