Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000-03-15 to 2000-04-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
1996-03-22
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed March 1999
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- State of aggregation: yellow green powder
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the original container, at room temperature (range of 20 ± 3 °C), away from direct sunlight

Test animals

Species:
rat
Strain:
other: HanIbm: WIST (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC ltd, Biotechnology & Animal Breeding Division, Wölferstrasse 4, CH-4414 Füllinsdorf / Switzerland
- Age: males: 8 - 10 weeks; females: 8 - 10 weeks
- Weight: males: 196.1 - 209.7 g; females: 164.9 - 171.9 g
- Fasting period before study: 18 (females) to 20 (males) hours, but with free access to water; food was provided again 2 (males) to 3 (females) hours after dosing
- Housing: groups of three in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet (ad libitum, except for the overnight fasting period prior to intubation): pelleted standard Kilba 3433, batch no. 43/99 rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst)
- Water (ad libitum): community tap water
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature: 22 - 24 °C
- Relative humidity: 31 - 56 %
- Air changes: 10 - 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
(PEG 300)
Details on oral exposure:
DOSAGE PREPARATION:
The test article was placed into a glass beaker on a tared Mettler PM 460 balance and the vehicle (polyethylene glycol, PEG 300) was added. A weight by volume dilution was prepared using a magnetic stirrer and an ultrasonic water bath as homogenizers. Homogeneity of the test article in the vehicle was maintained during the treatment.
The preparation was made shortly before each dosing.

MAXIMUM DOSE VOLUME APPLIED: 10 mL



Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 males / 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
mortality: one, two, trhee and five hours after test article administration on test day 1 and twice daily during days 2 - 15.
body weights: on test days 1 (pre-administration), 8 and 15
Clinical signs: each animal was examined for changes in appearance and behaviour four times during day 1, and once daily for suriving animals during days 2 -15. All abnormalities were recorded.
- Necropsy of survivors performed: yes, at the end of the observation period all animals were sacrificed and examined macroscopically. All abnormalities were recorded.
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
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
Slight dyspnea was observed in one male animal treated with 2000 mg/kg bw from 3 to 5 hours after the administration. No clinical signs were observed during the observation period in all other animals.
Body weight:
One female animal showed a slight loss of body weight (1.7 %) between test day 8 and 15. The body weight of the other animals was within the range commonly recorded for animals of 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:
LD50 (rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.