Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003-06-02 to 2003-006-25
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study followed OECD guideline 423 (Acute Oral Toxicity-Acute Toxic Class Method), however, the test substance is not adequately characterized and insufficient information is provided on the test animals.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
modified on 2001-12-17
Deviations:
yes
Remarks:
: 1) no characterization of the test material; 2) not sufficient data for the animals tested.
Principles of method if other than guideline:
Study is performed according to SPL Standard Method 520.01
GLP compliance:
no
Remarks:
The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report had not been audited by the QA Unit. No formal claim of GLP compliance was made for the study.
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: JNJ-1692405-AAC (T002006)
- Appearance: yellow powder
- Physical state: solid

Test animals

Species:
mouse
Strain:
CD-1
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 28-38 g
- Fasting period before study: Yes, no further data provided
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE: no data


MAXIMUM DOSE VOLUME APPLIED:
- no data


DOSAGE PREPARATION (if unusual):
- no data


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: advised in OECD-423 guideline
Doses:
300 mg/kg bw (two groups); 2000 mg/kg bw stepwise procedure
No. of animals per sex per dose:
3 females/group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and clinical signs were observed 30 minutes, 1, 2, and 4 hours after dosing, and daily for 14 days after dosing. Body weights were recorded on days 0, 7, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight, and macroscopic examinations.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 500 mg/kg bw
Mortality:
All animals treated at a dose level of 2000 mg/kg bw were found dead one or two hours after dosing. There were no deaths noted in animals treated at a dose level of 300 mg/kg bw.
Clinical signs:
The animals treated with 2000 mg/kg bw, had hunched posture, lethargy, ataxia, decreased respiratory rate, and laboured respiration. No clinical signs were observed in animals treated at 300 mg/kg bw.
Body weight:
The bodyweight was within the normal range of variability.
Gross pathology:
The animals treated with 300 mg/kg bw had no abnormalities observed during necropsy. At 2000 mg/kg dose level, haemorrhagic lungs, dark liver, dark kidneys, and haemorrhagic gastric mucosa were observed in all animals.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of the test substance in female CD-1 strain mouse was estimated to be in the range of 300-500 mg/kg bodyweight. The test substance was classified as harmful and the symbol "Xn" and risk phrase R 22 "Harmful if swallowed" are required according to EU labeling regulations Commission Directive 2001/59/EC. However, based on expert judgement it is concluded that since only 300 and 2000 mg/kg were tested in this study, it cannot be estimated that the LD50 will be situated in the range 300 - 500 mg/kg according to the guidelines.