Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 October - 24 October 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

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)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Test item: Boswellia Papyrifera Oil
Other names: Frankincense Papyrifera Oil
Batch No.: FRP.17124.297.6989.0.T0
Content: 100% UVCB Substance
Physical state: Clear yellowish liquid
Storage conditions: Ambient temperature (10 °C to 30 °C), dry, in the dark
Expiry date: September 03, 2020
Certificate: Certificate of analysis dated September 05, 2018, Laboratory of Esseterre Bulgaria EOOD Distillery, Bulgaria

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 or 9 weeks
- Weight at study initiation: 179-209 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:
unchanged (no vehicle)
Details on oral exposure:
DOSAGE PREPARATION:In the first and second step of the study, the test item was administered by gavage under a volume of 2.28 mL/kg bw (corresponding to 2 g/kg bw, according to the calculated density), using a suitable graduated syringe fitted with an oesophageal metal canula.
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:
One mortality was noted in animals treated at the dose of 2000 mg/kg bw on Day 1.
Clinical signs:
The mortality was preceeded by a red liquid around the nose.
Before the necropsy, rigor mortis was noted.
In the surviving animals (5/6), 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 animal revealed a presence of food in rib cage. This mortality may be due to a gavage injury.
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. Therefore it is not classified according to the Regulation (EC) N° 1272-2008. 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 was given by oral gavage to a group of 6 female Sprague-Dawley rats. Animals were then observed for mortality and clinical signs of toxicity for 14 days.

One mortality was noted in animals treated at the dose of 2000 mg/kg bw on Day 1. The mortality was preceeded by a red liquid around the nose. Before the necropsy, rigor mortis was noted. In the surviving animals (5/6), 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 animal revealed a presence of food in rib cage. This mortality may be due to a gavage injury. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Under the test conditions, the oral LD50 of the test substance is >2000 mg/kg bw in rats. Therefore it is not classified according to the Regulation (EC) N° 1272-2008. No signal word or hazard statement is required.