Resinoid of Commiphora erythraea (Burseraceae) obtained from the gum by ethanol extraction

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 to 28 April 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD Guideline 420 without deviation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on 17 Jue 2015 / signed on 24 September 2015)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Resinoid of Commiphora erythraea (Burseraceae) obtained from the gum by ethanol extraction

EC Number:

944-533-5

Molecular formula:

not applicable (UVCB)

IUPAC Name:

Resinoid of Commiphora erythraea (Burseraceae) obtained from the gum by ethanol extraction

Test material form:

solid

Remarks:

Brown red paste

Details on test material:

- Storage condition of test material: Room temperature, in the dark

Specific details on test material used for the study:

- Purity test date: 15 October 2015
- Expiration date of the lot/batch: 23 July 2016

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan™:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Ltd.
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: ca. 8-12 weeks
- Weight at study initiation: The body weight variation did not exceed ±20% of the mean body weight at the start of treatment. 195 g for the animal tested at 300 mg/kg bw and 160-173 g for the animals tested at 2000 mg/kg bw.
- Fasting period before study: overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing.
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Animal room: The rate of air exchange was at least fifteen changes per hour. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 06 to 28 April 2016

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Dimethyl sulphoxide was used because the test item did not dissolve/suspend in distilled water or arachis oil BP.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test substance was formulated at concentrations of 30 and 200 mg/mL in the vehicle. The test item was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

1 female at 300 mg/kg bw
5 females at 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
Mortality: Cages of rats were checked at least twice daily for any mortalities.
Clinical signs: Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days.
- Frequency of weighing: Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

None

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.

Remarks on result:

other: no mortality was observed

Mortality:

There were no deaths during the study.

Clinical signs:

- No signs of systemic toxicity were noted during the observation period for any animals receiving 300 or 2000 mg/kg bw.

Body weight:

All animals showed expected gains in body weight over the observation period.

Gross pathology:

All animals were killed at Day 14. No abnormalities were noted at necropsy.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of the test substance in female Wistar strain rat is estimated to be greater than 2000 mg/kg bw.
Under the test condicitions, and according to the OECD TG 420 criteria, the LD50 cut-off value is considered to be greater than 5000 mg/kg bw, therefore it is not classified according to the Annex VI of the Regulation EC No. 1272/2008 (CLP).

Executive summary:

In an acute oral toxicity study performed according to OECD Guideline 420 and in compliance with GLP, following a sighting test at dose levels of 300 mg/kg body weight and 2000 mg/kg body weight, a further group of four fasted females Wistar rats was given a single oral dose of test item, as a solution in DMSO, at a dose level of 2000 mg/kg body weight. Animals were then observed for mortality, clinical signs and body weights for 14 days and were all sacrificed for macroscopic examination.

 

There were no deaths and no clinical signs during the study. All animals showed expected gains in body weight. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 14.

Oral LD50 (female) > 2000 mg/kg bw

Under the test condicitions, and according to the OECD TG 420 criteria, the LD50 cut-off value is considered to be greater than 5000 mg/kg bw, therefore it is not classified according to the Annex VI of the Regulation EC No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.