Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Adopted 22 March 1996
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
Of commission Directive 96/54/EC
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
1998
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
Batch no. 554-MC-67-5

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent , United Kingdom
- Age at study initiation:approx. 8-12 weeks old
- Weight at study initiation: males: 242– 256 g, females: 200 – 237 g

- Housing: Groups of three by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet and water: Free access to food (Rat and Mouse Expanded Diet No. 1, Speciel Diets Services Limited, UK) and drinking water except for an overnight fast before dosing and approx. 3-4 hours after dosing
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C
- Humidity (%): 49-70 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
Dose volume 10 ml/kg bw administered by gavage.
Doses:
2000 mg/kg bw; 200 mg/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 3 female rats
200 mg/kg bw: 3 female + 3 male rats
Control animals:
no
Details on study design:
2000 mg/kg bw was selected as starting dose based on available information and administered to three fasted female rats. Based on the results from this dose level further groups of fasted animals were treated with a dose level of 200 mg/kg bw. Dosing was performed sequentially.
Animals were observed ½, 1, 2 and 4 hours after dosing and then once daily for up to 14 days.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 500 - < 1 000 mg/kg bw
Based on:
test mat.
Mortality:
Two animals treated with 2000 mg/kg were found dead within two hours of dosing.
Clinical signs:
Signs of systematic toxicity noted in animals treated with 2000 mg/kg were hunched posture, lethargy, ataxia, decreased respiratory rate, laboured respiration, pilo-erection, prostration, clonic convulsions and splayed gait, lasting up to five daty after dosing.
Hunched posture was noted in females treated with 200 mg/kg only on the day of dosing.
Body weight:
Surviving amimals showed expected gains in bodyweight over the study period.
Gross pathology:
Abnormalities noted at necroscopy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys.
No abnormalities were noted at necrospopy of animals killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LD50 (rat, oral): 500-1000 mg/kg bodyweight