Resinoid of Boswellia Carterii (Burseraceae) obtained from exudate by ethanol extraction

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

18 July - 02 August 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

dated 17 December, 2001

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

Resinoid of Boswellia Carterii (Burseraceae) obtained from exudate by hexane extraction

EC Number:

947-035-6

Molecular formula:

Not applicable (UVCB)

IUPAC Name:

Resinoid of Boswellia Carterii (Burseraceae) obtained from exudate by hexane extraction

Test material form:

solid

Details on test material:

Physical state: clear dark yellow solid
Storage Conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

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 or 9 weeks
- Weight at study initiation: 194-211 g
- Fasting period before study: Food was removed on Day 1 and then 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), 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:

DMSO

Details on oral exposure:

DOSAGE PREPARATION:In the first and second step of the study, 2.0082 g and 2.0030 g of the test item were weighed and DMSO (Dimethyl sulfoxide) was added to two 10 mL volumetric flasks. Just before the administration, the preparations were stirred, magnetically during 10 minutes at 50°C and by vortex, to obtain yellow solutions.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 female rats

Control animals:

no

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 minutes, 1 hour, 3 hours, 4 hours, and then once daily for 14 days. Animals were weighed on Day 0 (just before administering the test item) and then on Day 2, Day 7 and Day 14.
- Necropsy of survivors performed: Yes; animals were euthanized with sodium pentobarbital on Day 14 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:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: An increase of salivation was noted in the first hours of the test in one animal (1/6). Then a decrease of spontaneous activity, muscles tones and righting reflex was noted 24 hours post dose associated with a noisy breathing. The animal recovered normal

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 >5000 mg/kg bw by oral route in the rat. Therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the Globally Harmonised System of classification and labelling of chemicals (GHS). No signal word or hazard statement is required.

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 in DMSO was given by oral gavage to a group of 6 female Wistar rats. Animals were then observed for mortality and clinical signs of toxicity for 14 days.

No mortality occurred during the study. An increase of salivation was noted in the first hours of the test in one animal (1/6). Then a decrease of spontaneous activity, muscles tones and righting reflex was noted 24 hours post dose associated with a noisy breathing. The animal recovered normal activity on day 3. No other signs of systemic toxicity were noted. The body weight evolution of the animals remained normal during the study. The macroscopic examination of the animals at the end of the study did not reveal any 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 >5000 mg/kg bw by oral route in the rat. Therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the Globally Harmonised System of classification and labelling of chemicals (GHS). No signal word or hazard statement is required.