Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January - February 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline and GLP compliant study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (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
Details on test material:
Physical State: solid
Expiry Date: 31.12.2009

Test animals

Species:
rat
Strain:
other: WISTAR RjHan : WI rats (Full-Barrier)
Sex:
female
Details on test animals and environmental conditions:
Source: Janvier, F-53940 Le Genest-Saint-Isle
Sex: female, non-pregnant, nulliparous
Number of animals: 3 per step
Age at the beginning of the study: 8 - 12 weeks old
Body weight at the beginning of the study: Animals no 1 – 3, step 1: 213 – 220 g; animals no 4 – 6, step 2: 209 – 238 g

Housing and Feeding Conditions:
- Semi-barrier in an air conditioned room
- Temperature: 22 ± 3 °C
- Relative humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice
- Free access to tap water, sulphur acidified to a pH value of approx. 2.8
(drinking water, municipal residue control, microbiologically controlled
at frequent intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone
cages on Altromin saw fiber bedding
- Certificates of food, water and bedding are filed at BSL Bioservice
- Adequate acclimatisation period of at least five days
The animals were derived from a controlled full barrier maintained breeding system (SPF). According to Art. 9.2, No.7 of the German Act on Animal Welfare the animals were bred for experimental purposes.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Carboxymethylcellulose 1% in water
Details on oral exposure:
The animals were marked for individual identification by tail painting. Prior to the administration a detailed clinical observation was made of all
animals. Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing. The test item was administered at a single dose by gavage using an intubation cannula.
The test item was administered at a dosing volume of 10 mL/kg body weight.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Six
Control animals:
no
Details on study design:
All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality. The animals were weighed on day 0 (prior to the administration) and on days 7 and 14. A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as the symptoms noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded. Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, letharg , sleep and coma. At the end of the observation period the animals were sacrificed by an overdosage of pentobarbital injected intraperitoneally (Narcoren®, manufacturer: Merial; batch no.: 185118; expiry date: November 2011) at the dosage of approx. 8 mL/kg bw. All animals were subjected to gross necropsy. All gross pathological changes were recorded. All of the animals were subjected to gross necropsy. All gross pathological changes were recorded.
Statistics:
not applicable

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occured.
Clinical signs:
No clinical signs were observed.
Body weight:
No changes in body weight occured.
Gross pathology:
No gross pathology findings were observed.
Other findings:
No other treatment-related findings were observed.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
No indication of toxicity was observed after application of a single oral dose of 2000 mg/kg bw. The test item is therefore considered to be of low acute oral toxicity.
Executive summary:

All animals survived a single bolus dose of 2000 mg/kg bw. No adverse signs were noted for clinical observations, body weight and gross pathology.