Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

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 animals

Species:
rat
Strain:
other: CD / Crl: CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: males approx. 6 weeks, females approx. 7 weeks
- Weight at study initiation: males 192-201 g, females 180-188 g
- Fasting period before study: feeding was discontinued approx. 16 hours before administration
- Housing: 2-3 animals/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 55% +/- 15%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17.03.2003 To: 10.04.2003

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: aqueous hydroxypropylmethylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL in 0.8% aqueous hydroxypropylmethylcellulose gel

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg b.w.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: before and immediately, at 5, 15, 30 and 60 min, as well as at 3, 6 and 24 hours and 14 days after administration
- Observations on mortality were made at least once daily; the time of death was recorded as precisely as possible
- Observations on clinical signs: changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system, somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Individual body weights were recorded before administration of the substance and thereafter in weekly intervals up to the end of the study, and at death; changes in weight were calculated and recorded
- Necropsy of survivors performed: yes
- Other examinations performed: gross examination of organs at necropsy ; all gross pathological changes were recorded; no histopathology was carried out as no macroscopical findings were noted at autopsy; autopsy and macroscopic inspection of animals which died prematurely were carried out as soon as possible after exitus

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
1 of 3 male and 1 of 3 female animals died prematurely within 24 hours after dosing.
Clinical signs:
Slightly to moderately reduced motility, slight to moderate ataxia, slight to moderate dyspnoea, ptosis.
Body weight:
The surviving animals gained the expected weight throughout the whole study period.
Gross pathology:
No macroscopical findings were noted at autopsy.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
In this acute oral toxicity study in the rat after 14 days a combined LD50 value of >2000 mg/kg bw was determined.