Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Full study report required to assess reliability. Current document is limited to a single page summary of the study with no details related to methods, test guidelines or details of study findings. Since the numbers of animals used per group is unknown, it is not clear whether the high dose represents a limit dose eliciting limited mortality or a dose level that caused the death of all animals exposed - this requires calrification from the full study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Acute oral toxicity was determined in rats given the test material by single gavage administration at dose levels up to the limit dose of 2000 mg/kg bw and including 200 and 1000 mg/kg bw dose levels. The rats were observed for mortlaity, viability and clinical signs of reaction to treatment. An estimate of the median lethal dose was based on determination of the maximum non-lethal dose level
GLP compliance:
not specified
Test type:
other: maximum non-lethal dose
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
No additional details provided in the test report summary

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: no data

DOSAGE PREPARATION (if unusual): no data
Doses:
200, 1000 and 2000 mg/kg bw
No. of animals per sex per dose:
Five or five males and five females - REQUIRES CONFIRMATION FROM STUDY REPORT
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs. The study objective was to determine a non-lethal dose level and consequently mortality was the primary parameter of interest

Statistics:
No data. Not required for determination of a maximum non-lethal endpoint

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: One rat died after administration of 1000 mg/kg bw and two died after single oral administration of 2000 mg/kg bw
Mortality:
One rat died after administration of 1000 mg/kg bw and two died after single oral administration of 2000 mg/kg bw.
Clinical signs:
Adverse signs observed ante-mortem at 1000 or 2000 mg/kg bw included convulsions and collapse shortly before death.
Among the surviving rats signs of subdued behaviour, piloerection and ataxia were commonly observed
Body weight:
No data
Gross pathology:
No macroscopic abnormalities were observed during necropsy of decedents or rats surviving to termination on day 15.
Other findings:
The maximum non-lethal dose was found to be between the 200 and 1000 mg/kg bw levels administered in this study

Any other information on results incl. tables

No further information on results to report.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The maximum non-lethal dose was greater than 200 but less than 1000 mg/kg bw. Oral administration of the limit dose, 2000 mg/kg bw, resulted in two mortalities. If the group size was five males and five females then it can be concluded that the LD50 exceeds the limit dose level.
Executive summary:

The acute oral toxicity of Ro 31-9373/000 (PTH-Decahydroamide) was investigated in rats. The study objective was to determine the maximum non-lethal oral dose and to this end dose levels of 200, 1000 and 2000 mg/kg bw were administered to groups of rats. Two animals died following dosing at 2000 mg/kg bw and one rat died after 1000 mg/kg bw administration. Clinical signs noted ante-mortem included convulsions and collapse. No necropsy changes of toxicological significance were observed in the decedents. Clinical signs observed in the surviving rats included piloerection, ataxia and subdued behaviour. No necropsy findings were reported for the rats terminated on Day 15.

The maximum non-lethal dose was found to be between 200 and 1000 mg/kg bw following single oral administration of Ro 31 -9373/000 (PTH-Decahydroamide) to rats.

The median lethal dose (LD50) may exceed 2000 mg/kg bw but confirmation of the number of rats exposed, compared to number of mortalities is required, this information was not available in the summary of the study findings.