Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 February - 23 February 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 423) and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

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
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 (as cited in study report): PD 283 XX
- Physical state: yellow powder
- Analytical purity: 97.6 % (HPLC)
- Analysis test date: 12 january 2006
- Purity to be retested: january 2007
- Lot/batch No.: V12TFA00072
- Storage condition of test material: 20°C

Test animals

Species:
rat
Strain:
other: Crl:WI (Han), SPF quality
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, via Biological Laboratory Services, Boehringer Ingelheim
- Age at study initiation: approximately 7 weeks
- Weight at study initiation: males 148 g to 157 g, females 126 g to 137 g
- Fasting period before study: Prior to administration, the rats were kept over night without food
- Housing:
- Diet (e.g. ad libitum): pelleted dry food, ad libitum
- Water (e.g. ad libitum): Municipal tap drinking water, ad libitum
- Acclimation period: 5- to 7-days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 45% - 75%
- Air changes (per hr): minimum of 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12 hours

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% aqueous hydroxyethylcellulose
Doses:
200, 2000 mg/kg

No. of animals per sex per dose:
3 femals / 200 mg/kg
3 males/ 3 femals 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice a day
- Necropsy of survivors performed: yes
- Other examinations performed: body weight

Results and discussion

Preliminary study:
JUSTIFICATION OF DOSE LEVELS:
In the absence of prior experience, 200 mg/kg body weight was chosen as the initial dose.
The second dose was selected based on the animals’ response to 200 mg/kg.
Effect levels
Sex:
male/female
Dose descriptor:
other: ALD (approximate lethal dose)
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed subsequent to a single oral administration of 200 mg/kg and 2000 mg/kg, respectively.
Clinical signs:
Piloerection was observed at both doses as the only clinical sign on day 1.
Body weight:
No effects on body weight was observed for both doses.
Gross pathology:
No necropsy findings were noted in females treated with 200 mg/kg and 2000 mg/kg, respectively, as well as in one male at the latter dose.
Following 2000 mg/kg, necropsy of two males revealed disseminated, dark red discolorations up to the size of a pin tip on the surface of the lungs.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, which was designed to evaluate in rats the acute toxicity
of PD 283 XX subsequent to a single oral administration by gavage, no mortality was seen
subsequent to oral administration of 200 mg/kg and 2000 mg/kg, respectively.
Thus, the approximate lethal dose (ALD) for PD 283 XX, is set above 2000 mg/kg for male and female rats.