Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 June 2008 - 27 June 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(2001)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(2004)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
(2002)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material: B508
- Physical state: powder



Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 8 - 10 weeks old
- Weight at study initiation: 151-182 g
- Fasting period before study: food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages containing sterilized sawdust as bedding material and paper as cage-enrichment
- Diet (e.g. ad libitum): Free access to pelleted rodent diet
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: 21-23 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.3 - 21.4
- Humidity (%): 41 - 76
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): (10 mL/kg) b.w.
- Justification for choice of vehicle: The vehicle was selected based on trial formulations and on test substance data supplied by the sponsor.

MAXIMUM DOSE APPLIED: 2000 mg/kg b.w

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle.

CLASS METHOD
- Rationale for the selection of the starting dose: The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg bw. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
Doses:
2000 mg/kg b.w.
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 and weighing: mortality/viability- twice daily; body weights- days 1 (pre-administration), 8 and 15; Clinical signs- at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture was noted in all animals and had resolved within 2 or 4 hours post-treatment.

Blue staining on the back of two animals was observed during the observation period. This finding was considered related to staining properties of the test substance and of no toxicological significance.
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. The slight body weight loss of one individual in the second week post-treatment was considered not indicative of toxicity, based on the absence of any corroborative findings in this animal.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study with rats, performed according to OECD 423 guideline and GLP Principles, an LD50 >2000 mg/kg bw was determined.

According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Executive summary:

B508 was administered by oral gavage to two subsequent groups of three females Wistar rats at 2000 mg/kg bw according to OECD 423 guideline and GLP Principles.

No mortality occurred. Hunched posture was noted in all animals and had resolved within 2 or 4 hours post-treatment. No effect on body weight gain was observed. The oral LD50 of the test substance was established to exceed 2000 mg/kg bw.