Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: HanRcc:WIST (SPF)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd., Switzerland
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 176.5-199.5
- Fasting period before study:
- Housing: Individually in Makrolon type-3 cages with wire mesh tops and standard softwood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: yes, but time period not specified in report

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/ml

- Justification for choice of vehicle: The vehicle was chosen after a non-solubility trial which was performed before the study initiation date. This formulation trial is excluded from the statement of compliance. The test item prepared in corn oil was well-soluble.

- Lot/batch no. (if required): 18787208


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were examined daily during the acclimation period and mortality; viability and clinical signs were recorded. All animals were examined for mortality/viability and clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once (twice for mortality/viability) daily during test days 2-15. Body weights were recorded on test day 1 (prior to removal of food), on test days 1 (prior to administration) 8 and 15. All animals were necropsied and examined macroscopically.

- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
dissolved
Mortality:
All animals survived until the end of the study period.
Clinical signs:
Slightly to moderately ruffled fur was noted in all animals from the 1- or 5- hour reading up to test day 2 or 3, with persisting in one animal through test day 7. Slight to marked sedation was recorded in all animals from the 2-, 3- or 5-hour observation up to 5 hours post-dose or test days 2 or 3. Two animals showed slightly poor coordination on test day 2 only, while two other animals showed slight to markedly or slightly to moderately poor coordination from 5 hours post-dose until test day 2. Hunched posture was observed in four animals at the 1-hour reading and persisted through the 5-hour evaluation in one animal and through test day 2 in three animals. Ventral recumbency was noted in one animal on test day 2.
Body weight:
The body weight of animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Other findings:
None reported.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
An LD50 value of >2000 mg/kg was determined in a reliable study conducted in compliance with GLP.