Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 October to 6 December 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study in accordance with recognised test method

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: JMAF 12 Nousan, Notification 8147, November 2000
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): PF-00346643
- Substance type: pure substance
- Physical state: pale yellow oil
- Analytical purity: 88.9%
- Lot/batch No.: 115565-67-1
- Expiration date of the lot/batch: 31 January 2008
- Stability under test conditions: stable
- Storage condition of test material: in a refrigerator (2-8°C) in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
Single dosage, on Day 1, 300 mg/kg (0.316 ml/kg) body weight, 2000 mg/kg (2.11 ml/kg) body weight

Dose volume calculated as: dose level (g/kg) / density (g/ml)
No. of animals per sex per dose:
3
Control animals:
no

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000

Any other information on results incl. tables

No mortality occurred.

On day 1, hunched posture was noted in all animals and uncoordinated movements and piloerection were noted in the animals dosed at 200 mg/kg.

The 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.

No abnormalities were found at post mortem examination of the animals.

Applicant's summary and conclusion

Conclusions:
The oral LD50 value of PF-00346643 in Wistar rats was established to exceed 2000 mg/kg body weight

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