Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 03/09/2008 to 26/09/2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP study performed according to OECD guideline 423 and EEC method B.1 Tris.

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)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
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: particulate/powder
Details on test material:
- Name of test material (as cited in study reports): JNJ-39453193-AAA (T003063)
- Physical state: solid (powder)
- Appearance: white to almost white powder

Test animals

Species:
rat
Strain:
other: HanRcc: WIST(SPF)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, Wölferstrasse 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: 182.3 - 199.5 g
- Fasting period before study: approximately 17 to 17,5 hours (access to water was permitted)
- Housing: In groups of 3 in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): between 30-70%
- Air changes (per hr): 10 - 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark, music during the daytime light period

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Polyethylene glycol 300 (PEG 300)
Details on oral exposure:
VEHICLE
- Lot/batch no. : 1349048

The dose formulations were made shortly before each dosing occasion using a magnetic stirrer and a spatula as homogenizers. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume).

Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.
Doses:
2000 mg/kg
No. of animals per sex per dose:
2 groups of 3 females, one dose tested
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality / Viability: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Body weights: On test days 1 (prior to administration), 8 and 15.
Clinical signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on day 1. Once daily during days 2 - 15.
- Necropsy of survivors performed: yes: all animals were killed at the end of the observation period by carbon dioxide asphyxiation and discraded after macroscopic examinations were performed. No organs or tissues were retained.
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs were observed during the course of the study.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose of T003063 after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight.