Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
None

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Principles of method if other than guideline:
None
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
None

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles River U.K. Ltd., Margate, kent, England.- Age at study initiation: 7 weeks old approximately- Weight at study initiation: 160 g - 197 g- Housing: HRC cage type 5 - cages with wire mesh floors - Diet (e.g. ad libitum): standard laboratory rodent diet (Biosure LAD 1) ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: 7 days prior to the start of the main studyENVIRONMENTAL CONDITIONS- Temperature (°C): 21°C - 23°C- Humidity (%): 44 %H- Air changes (per hr): 15 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hour period

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
None
Doses:
5000 mg / kg bodyweight
No. of animals per sex per dose:
10 (5 males & 5 females)
Control animals:
not specified
Details on study design:
Duration of observation period following administration: 14 days - Frequency of observations and weighing: day 1, 8 & 15- Necropsy of survivors performed: yes- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: macroscopic appearance eaxmined
Statistics:
None

Results and discussion

Preliminary study:
The results of the preliminary study indicated that the acute lethal dose to male and female rats of D-523 was greater than 2.5 g/kg bodyweight.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
There were no deaths following a single oral dose of D-523 at 5.0 g/kg bodyweight.
Clinical signs:
Signs of toxicity related to dose levels:Piloerection was noted in all rats within 5 minutes of dosing and throughout day 1. All animals showed the expected gains in bodyweight over the study period.
Body weight:
Slightly low bodyweight gains were recorded on Day 15 for one male and 4 females; these animlas achieved anticipated gains on Day 8. All other rats achieved anticipated bodyweight gains throughout the study.
Gross pathology:
Terminal autopsy revealed no macroscopic abnormalities for the majority of rats. Unilateral hydronephrosis was apparent for one male on Day 15. A slow incidence of this abnormality occurs spontaneously among untreated rats of the CD starin at this laboratory, the finding was not considered to be related to treatment.
Other findings:
None

Any other information on results incl. tables

INDIVIDUAL BODUWEIGHT CHANGES (g) OF RATS DOSED WITH D-523:

Sex Dose (g/kg) Animal number & ear mark Bodyweight gains (g) at
Week 1 Week 2
Male 5 1 RP 76 50
2LP 90 66
3RPLP 100 74
4RIRO 95 63
5LILO 90 56
Female 5 6RP 54 8
7LP 58 16
8RPLP 37 4
9RIRO 36 9
10LILO 61 1

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The results of the main study indicated that the acute lethal dose to male and female rats of FAT 40554 was greater than 5000 mg/kg bodyweight.
Executive summary:

The aim of this study was to determine the acute oral toxicity potency of FAT 40554 in rats after single administartion by oral gavage.

This experiment was performed according to the EU Method B.1 (Acute Toxicity (Oral))

The test was performed on rats (5 males and 5 females) per dose level, at one dose level: 5000 mg/kg.

The test material was dissolved in distilled water.

The observation period was 14 days or until all symptoms have disappeared, whichever lasts longer.

Mortality:

No mortality occured during the experiment.

Body weight:Normal weight gain.

Signs of toxicity: Piloerection was noted in all rats within 5 minutes of dosing and throughout day 1. All animals showed the expected gains in bodyweight over the study period.

Effects in organs: Terminal autopsy revealed no macroscopic abnormalities for the majority of rats. Unilateral hydronephrosis was apparent for one male on Day 15. A slow incidence of this abnormality occurs spontaneously among untreated rats of the CD starin at this laboratory, the finding was not considered to be related to treatment.

In conclusion, the median lethal dose is found to be greater than 5000 mg/kg bodyweight.