Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-09-15 to 2010-10-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
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 report): JNJ-38940642-AAA (T003010)
- Physical state: solid
- Appearance: white powder

Test animals

Species:
rat
Strain:
other: CD (Crl:CD ‘SD’)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 204-244 g
- Fasting period before study: overnight prior to and approximately four hours after dosing (with the exception of animal B1 which was fed approximately three and a half hours after dosing).
- Housing: individually, in solid bottomed polycarbonate cages with a stainless steel mesh lid, barriered rodent facility kept at a positive pressure
- Diet (e.g. ad libitum): ad libitum, standard rodent diet (Rat and Mouse No. 1 Maintenance Diet)
- Water (e.g. ad libitum): ad libitum, potable water taken from the public supply via polycarbonate bottles fitted with sipper tubes
- Acclimation period: 5-7 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 40-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: 20-09-2011 To: 18-10-2011

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: PEG 400, 1.2 eq NaOH 10N and 0.3 eq HCl 12N
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 35, 110 and 300 mg/mL (max feasible concentration)
- Amount of vehicle (if gavage): 5 mL/kg
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

DOSAGE PREPARATION (if unusual): Formulations were stirred before and throughout the dosing procedure
Doses:
175, 550 and 1500 mg/kg
No. of animals per sex per dose:
1 female/group (175 mg/kg, 550 mg/kg)
3 females/group (1500 mg/kg)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- mortality: cages of rats were checked at least twice daily for any mortalities
- clinical observations: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only).
- The weight of each rat was recorded on Day 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes were calculated.
- Necropsy of survivors performed: yes. all animals were humanely killed on day 15 by carbon dioxide asphyxiation
- Other examinations performed: macroscopic examinations: cranial, thoracic and abdominal cavities.
Statistics:
No stastistical analysis was used.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 500 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
There were no clinical signs related to treatment throughout the study.
Body weight:
There were no compound related effects on body weights at any dose.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Any other information on results incl. tables

The 35 and 110 mg/mL test substance formulations used in this study were found to be within acceptable criteria of concentration verification.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute median lethal oral dose (LD50) of JNJ-38940642-AAA to rats was > 1500 mg/kg bodyweight. Based on this unbounded LD50 value, the test item is classified for acute toxicity category 4 according to the criteria of the CLP Regulation (EC)1272/2008 as a worst case scenario.