Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 November 2007 to 05 December 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD test guidelines in compliance with GLP and reported with a valid GLP certificate.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
Identification: DUSANTOX 86Batch number: 005/07Quality control protocol No 040707/A9Storage conditions: The test article was maintained in a dark package, in the room No. 252 (at room temperature) of the laboratory of toxicology. Application form was prepared closely prior application in laboratory 264. Long term storage: protected against sunlight. Stable: for 24 months.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species: RatsStrain: WistarWeight: 140 – 160gNumber and sex: 3 females, 3 males – use due to limit test.Source: Accredited Breeding Velaz Prague CZIdentification: The animals were housed individually in cages after application. They were marked by number placed on the cages.Husbandry:Housing: Animals were housed in cage on bedding in groups by 5 in room No. 132 of experimental animal house. After application they were house individually. Environment: Environmental controls for the animal room will be set to maintain 22 ± 2°C, a relative humidity of 55 ± 5%. The temperature and relative humidity of air will be registered and the records maintained in animal house. A minimum of 10 air changes/air, and artificial light regime 12h light/12h dark. The sanitation was made according to standard operation procedure. Food and water: A standard certified laboratory diet (supplier Top Dovo Dobrá Voda) was served ad libitum and unlimited supply of drinking water. The diet was routinely analysed by the manufacturer for nutritional components and environmental contaminants. Acclimatisation: 5 days before the beginning of treatment.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
Vehicle Article: Olivae oleum raffinatumBatch number: L706203 (G. Heess)Quality control protocol No 625/539/64/2007
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 females & 3 males
Control animals:
no
Details on study design:
Preparation of doses: Application dose 2000 mg/kg for animals was prepared shortly prior to administration. To precise weighed test article was gradually added vehicle. Doses administration manner: The test article was applied in a single dose using a stomach tube. It was administered in uniform volume 10 ml/kg body weight. Animals were fasted prior to dosing (food but not water were withheld overnight). Following the period of fasting the animals were weighed and the test article administered. After the test article was administered food had been withheld for a further 3-4 hours. Animals dosage: On the base of literature data we use dose 2000 mg/kg for limit test. We applied 3 females and three males by dose 2000 mg/kg. Subsequently, observations of effects and death were made. Clinical observations: Animals were observed individually after dosing at least once during the forst 30 minutes, periodically during the first 24 hours, with special attention given during the first 4 hours, and daily thereafter, for a total of 14 days. All observations were systematically recorded, with individual records being maintained for each animal. We used separate OECD Guidance Document for assessing of clinical signs and conditions associated with pain, suffering and impending death.Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Bodyweight: Individual bodyweights of animals were determined shortly before the test article was administered and weekly thereafter. Weight changes after first and second week after application were calculated and recorded. Pathology: All test animals were subjected to gross necropsy. All gross pathological changes were recorded for each animal. Animals to be sacrificed were anesthetised, extinguished and necropsied according to standard procedures, euthanasia and autopsy of animal.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died in either the first 4 hours or in the 14 days observation period.
Clinical signs:
None of the animals displayed any toxic symptoms either in the first 4 hours or in the 14 days observation period.
Body weight:
All of animals gain bodyweight after first either after second week after administration of test article. They reached bodyweight gains from 5 to 30g per week. None of animals displayed any pathological lesions.
Gross pathology:
Pathology findings not detailed in the study report.
Other findings:
No further findings specified.

Any other information on results incl. tables

Tab. 1

Sex: females     Dose: 2000 mg/kg

Animal no.

Weight [g]

Weight [g]

Weight

Weight [g]

Weight

Appl. Vol.

Response

Initial

After 1 week

Change [g]

After 2 weeks

Change [g]

ml

1

170

200

30

205

5

1.7

O

2

170

200

30

207

5

1.7

O

3

170

190

20

195

5

1.7

O

 

Tab. 2

Sex: males         Dose: 2000 mg/kg

Animal no.

Weight [g]

Weight [g]

Weight

Weight [g]

Weight

Appl. Vol.

Response

Initial

After 1 week

Change [g]

After 2 weeks

Change [g]

ml

4

240

265

25

290

25

2.4

O

5

220

250

30

270

20

2.2

O

6

210

240

30

265

25

2.1

O

 

Tab. 3

Sex: females     Dose: 2000 mg/kg

Animal no.

Signs of toxicity

Immediately

After 30 min.

After 1 hour

After 4 hours

1

w/s

w/s

w/s

w/s

2

w/s

w/s

w/s

w/s

3

w/s

w/s

w/s

w/s

 

Tab.4

Sex: males         Dose: 2000 mg/kg

Animal no.

Signs of toxicity

Immediately

After 30 min.

After 1 hour

After 4 hours

4

w/s

w/s

w/s

w/s

5

w/s

w/s

w/s

w/s

6

w/s

w/s

w/s

w/s

w/s – without symptoms

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The LD50 of DUSANTOX 86 after single oral application is above limit dose of 2000 mg/kg.
Executive summary:

The test article DUSANTOX 86 was applied to 3 rats females and 3 rats males in a single oral dose 2000 mg/kg. Dose 2000 mg/kg was selected for a limit test due to presupposed low toxicity. Subsequently, observations of effects and death were made. Death and/or any toxicity symptoms did not occur. The experiment determined that the LD50 is above limit dose of 2000 mg/kg and DUSANTOX 86 fulfils conditions of category 5 “Unclassified” according to GHS. There was no observed difference in sensitivity on tested article between sexes.

No classification is applicable.