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:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: flakes
Details on test material:
The test substance has the appearance of beige flakes. It has been stored at rool temperature, in the dark.
The test solution have been prepared with porpylene glycol, formulations were prepared 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of mL/kg body weight.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Animals are 9 females, nulliparous and non-pregnant., young adult (8-10 weeks old).
the body variation did not exceed +/- 20% of thesex mean.
They were identified by earmark.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Doses:
2000 mg/kg bw
300 mg/kg bw
No. of animals per sex per dose:
3 animals for the dose of 2000 mg/kg
2 X 3 animals for the dose of 300 mg/kg
Control animals:
not specified
Details on study design:
The fisrt group was treated at a dose of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step.
The onset, duration and severuty of the signs of toxicity were taken into account for determination of the time interval between the dose groups.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 20 000 mg/kg bw
Mortality:
at 2000 mg/kg; 2 out of 3 animals were found dead or were sacirifed in extremis on days 2 and 3 respectively. The other animal at 2000 mg/kg, and all animals at 300 mg/kg survived up to scheduled necropsy.
Clinical signs:
At 2000 mg/kg :
- lethargy
- hunched/flat posture
- piloerection
- chromodacryorrhea
- uncoordinated movements
- ptosis
were noted among ALL animals.
The surviving animal at 2000 mg/kg had recovered from the symptoms by day 4.


At 300 mg/kg :
- hunched posture
- and/or uncoordinated movements
were noted among 3 animals on day 1.
Body weight:
The mean body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of ,ormal untreated animals (same age and strain).
The two animals at 2000 mg/kg that were found dead or were sacrified in extremis showed weight loss before death/sacrifice on days 2/3.
Gross pathology:
one animal, at 2000 mg/kg showed red-brown foci on the galndular mucosa of the stomach.
No mascroscopic abnormalities were found among the other animals at 2000 mg/kg or among any animal at 300 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information if swallowed Criteria used for interpretation of results: EU
Conclusions:
The LD 50 value of 852 IMIDE Brute (tetrahydrocyclopenta[c]pyrrole-1,3(2H,3aH)-dione) in Wistae rats was established to be within the range of 300-2000 mg/kg bodyweight.
According to the OECD423 Guideline, the LD50 cut-off value was considered to be 1000 mg/kg bodyweight.
According to the regulation EC n°1272/2008, this substance should be classified as category 4 and should be labelled as H302 : HARFULL IF SWALLOWED.