Resinoid of Cistus ladaniferus (Cistaceae) obtained from labdanum gum by organic solvents extraction

Endpoint summary

Description of key information

Acute toxicity: oral: LD50 (Female) > 5000 mg/kg bw (OECD 423 in rats; K, rel.1).

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:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

dated 17 December, 2001

Deviations:

no

Qualifier:

according to guideline

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. QA statement)

Remarks:

27 April 2017

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system 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

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

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).

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The key study is GLP-compliant and of high quality

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Not required for an Annex VII dossier

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Not required for an Annex VII dossier

Additional information

Acute toxicity: oral

A key study was identified (Phycher, 2017, Rel.1). In this 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 (Female) >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.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity via Oral route:

Based on the available data the substance is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and to the Globally Harmonised System of classification and labelling of chemicals (GHS) as the oral LD50 is higher than 5000 mg/kg bw.

Acute toxicity via Dermal route:

No data was available.

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

Based on the available data, the classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

No data was available

Specific target organ toxicity: single exposure (Inhalation):

No data was available.