Registration Dossier

Administrative data

Description of key information

Acute oral LD50 >2000 mg/kg.
Acute dermal LD50 >2000 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
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
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.
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.
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.

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 September 2007 to 29 November 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with draft OECD test guideline in compliance with GLP and reported with a valid GLP certificate. Klimish 2 reliability assigned due to the fact that the study is still a draft guideline and not formally accepted.
Qualifier:
according to
Guideline:
OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)
Deviations:
yes
Remarks:
males and females where used where the guideline only recommends use of females
Principles of method if other than guideline:
OECD Guidelines for the Testing of Chemicals are periodically reviewed in the light of scientific progress and animal welfare considerations. The original acute Dermal Toxicity Guideline TG 402 was adopted in 1987. Development of a dermal Fixed Dose Procedure (FDP) was considered appropriate, following adoption of the revised Oral FDP, OECD Guideline 420 and deletion of OECD Guideline 401 in December 2001. This FDP guideline will allow the use of a series of fixed doses for the determination of acute dermal toxicity in only one sex (usually females). This study utilises both males and females. This is not expected to impact on the findings of the study.
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
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 – we used only 3 females and 3 males because of low acute toxicity of test article we could use 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. 133 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.
Type of coverage:
semiocclusive
Vehicle:
olive oil
Details on dermal exposure:
Approximately 24 hours before dose application, fur was removed from the dorsal area of the trunk of the test animals by clipping and shaving. The test article was applied uniformly as much of the area was covered with as thin and uniforms a film as possible on over an area which was approximately 10% of a total body surface. Test article was held in contact with the skin with a porous gauze patch covered with nonpermeabile folio by means of a semi-occlusive dressing and non-irritating tape throughout a 24-hours exposure period. At the end of the exposure period residual test article was removed, using water, without altering the existing response or integrity of the epidermis.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
Animal dosage: On the base of literature data a dose level of 2000 mg/kg for a limit test was selected. This dose was applied to 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 first 30 minutes, periodically during the first 24 hours, with special attention given during the first 3 hours, and daily thereafter, for a total of 14 days. All observations were systematically recorded, with individual records being maintained for each animal. Clinical signs and conditions associated with pain, suffering and impending death are described in detail in a separate OECD Guidance Document. 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 (including those that died during the test) 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
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died in the first 4 hours or in the 14 days observation period.
Clinical signs:
None of the animals displayed any toxic symptoms in the first 4 hours or in the 14 days observation period.
Body weight:
In first week after application 1 female did not reach weight gain. Otherwise animals reached bodyweight gains from 10 to 40 g per week.
Gross pathology:
None of animals displayed any pathological lesions.
Other findings:
Well defined or slight erythema was observed at the site of application; this subsequently healed within the study period.

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

160

170

10

180

10

0.400

O

2

170

180

10

190

10

0.425

O

3

170

170

0

180

10

0.425

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

220

230

10

255

25

0.550

O

5

210

250

40

275

25

0.525

O

6

240

250

10

265

15

0.600

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

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 dermal 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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Oral

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.

Dermal

The test article DUSANTOX 86 was applied to 3 rats females and 3 rats males in a single dermal 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.


Justification for selection of acute toxicity – oral endpoint
Effect level determined using OECD guideline 423

Justification for selection of acute toxicity – inhalation endpoint
No data available. The substance is of low volatility and limited particle size, and is not utilised in exercises where dusts or aerosols could be generated. As a result, inhalation is not considered to be a primary route of exposure.

Justification for selection of acute toxicity – dermal endpoint
Effect level determined using OECD guideline 434.

Justification for classification or non-classification

The above studies have all been ranked reliability 1 or 2 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted to GLP but the dermal toxicity study is conducted to a draft OECD Guideline. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for acute effects is therefore required.