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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
08 - 23 August 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study performed according to OECD Guideline 423 with no deviation
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Justification for type of information:
Resinoid of Cistus ladaniferus (Cistaceae) obtained from labdanum gum by organic solvents extraction and Gum of Cistus ladaniferus (Cistaceae) obtained from stems and leaves by extraction with alkaline solution are extracted from the same botanical plant: Cistus ladaniferus (Cistaceae)
Reason / purpose:
read-across source
Preliminary study:
Not applicable
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: estimated from the flow chart from OECD Guideline 423 (Appendix 2d)
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical signs related to the administration of the test item were observed during the study.
Body weight:
The body weight evolution of the animals remained normal throughout the study.
Gross pathology:
The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the oral LD50 of the test substance is >2000 mg/kg bw in rats. In accordance with OECD Guideline 423, the LD50 cut-off of the test substance may be considered to be higher than 5000 mg/kg bw by oral route in the rat. Therefore it is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and according to the Globally Harmonised System of classification and labelling of chemicals (GHS). Therefore the registered substance is considered as non claissifed
Executive summary:

In an acute oral toxicity study performed according to the OECD Guideline 423 and in compliance with GLP, a single dose of 2000 mg/kg bw of the test substance solubilized in olive oil and heated during 5 minutes at ca. 50°C was given by oral gavage to a group of 6 female Sprague Dawley rats. Animals were then observed for mortality, clinical signs and body weight changes for 14 days, and were all sacrificed for macroscopic examinations.

No mortality occurred during the study. No clinical signs related to the administration of the test item were observed during the study The body weight evolution of the animals remained normal throughout the study. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Rat Oral LD50 >2000 mg/kg bw.

Under the test conditions, the oral LD50 of the test substance is >2000 mg/kg bw in rats. In accordance with OECD Guideline 423, the LD50 cut-off of the test substance may be considered to be higher than 5000 mg/kg bw by oral route in the rat. Therefore it is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and according to the Globally Harmonised System of classification and labelling of chemicals (GHS).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
dated 17 December, 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
27 April 2017
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Remarks:
brown to brown-red paste
Details on test material:
- Name (as cited in study report): LABDANUM RESINOID / F
- Storage condition of test material: room temperature, darkness, closed container

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER LABS, France
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 169-206 g
- Fasting period before study: overnight. Redistributed 4 hours after the test item administration.
- Housing: Animals were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet (e.g. ad libitum): Foodstuff (ENVIGO – 2016 Teklad Global 16% Protein Rodent Diet), ad libitum
- Water (e.g. ad libitum): Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25°C
- Humidity: 30-70%
- Air changes: at least 10/hour
- Photoperiod: 12 hours dark / 12 hours light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: ca. 2000 mg/10 mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Olive oil was chosen as it produced the most suitable formulation at the requested concentration.

DOSAGE PREPARATION: In the first and second step of the study, 2.0090 g and 2.0098 g of the test item were weighed and Olive oil was added to two 10 mL volumetric flasks. Just before the administration, the preparations were stirred by vortex then magnetically during 5 minutes at approximately 50°C to obtain thick brown solutions.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 female rats
Control animals:
no
Remarks:
Historical data
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality were recorded at 30 min, 1h, 3h, 4h, 24h, 48h after administration of the test item and continued daily during 14 days.. Animals were weighed on day D0 (just before administering the test item) and then on D2, D7, and D14.
- Necropsy of survivors performed: Yes; animals were euthanized with sodium pentobarbital (Dolethal®) on D14 and macroscopic observations were noted.
Statistics:
No data

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: estimated from the flow chart from OECD Guideline 423 (Appendix 2d)
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical signs related to the administration of the test item were observed during the study.
Body weight:
The body weight evolution of the animals remained normal throughout the study.
Gross pathology:
The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the oral LD50 of the test substance is >2000 mg/kg bw in rats. In accordance with OECD Guideline 423, the LD50 cut-off of the test substance may be considered to be higher than 5000 mg/kg bw by oral route in the rat. Therefore it is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and according to the Globally Harmonised System of classification and labelling of chemicals (GHS).
Executive summary:

In an acute oral toxicity study performed according to the OECD Guideline 423 and in compliance with GLP, a single dose of 2000 mg/kg bw of the test substance solubilized in olive oil and heated during 5 minutes at ca. 50°C was given by oral gavage to a group of 6 female Sprague Dawley rats. Animals were then observed for mortality, clinical signs and body weight changes for 14 days, and were all sacrificed for macroscopic examinations.

No mortality occurred during the study. No clinical signs related to the administration of the test item were observed during the study The body weight evolution of the animals remained normal throughout the study. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Rat Oral LD50 >2000 mg/kg bw.

Under the test conditions, the oral LD50 of the test substance is >2000 mg/kg bw in rats. In accordance with OECD Guideline 423, the LD50 cut-off of the test substance may be considered to be higher than 5000 mg/kg bw by oral route in the rat. Therefore it is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and according to the Globally Harmonised System of classification and labelling of chemicals (GHS).