Extract of Boswellia serrata (Burseraceae) obtained from exudate by solvent extraction

Endpoint summary

Description of key information

In an acute oral toxicity study in rats (OECD 420) , the oral LD50 was found to be higher than 2000 mg/kg bw. (GLP, 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:

02-17 May 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study performed according to OECD Guideline 420 with minor deviations: temperature and relative humidity were sometimes outside the optimum ranges

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

dated 17 December, 2001

Deviations:

yes

Remarks:

temperature and relative humidity were sometimes outside the optimum ranges

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

temperature and relative humidity were sometimes outside the optimum ranges

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

27 April 2017

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Used as supplied

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: 194 ± 6.9 g
- Fasting period before study: 1 day
- 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: 18-31°C
- Humidity: 26-70%
- Air changes: At least 10/hour
- Photoperiod: 12 hours dark / 12 hours light

Route of administration:

oral: gavage

Vehicle:

DMSO

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: Dimethyl Sulfoxide (DMSO) was chosen as it produced the most suitable formulation at the requested concentrations.

DOSAGE PREPARATION: In the first and second step of the study, 1.0012g and 2.0032 g of the test item were weighed and DMSO was added to a 5 mL volumetric flask and to a 10 mL volumetric flask respectively. Just before the administration, the preparations were stirred by vortex to obtain orange-yellow solutions. Each preparation was administered under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 female rats

Control animals:

other: 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 minutes, 1 hour, 3 hours, 4 hours, 24 hours, and then once daily for 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:

> 2 000 mg/kg bw

Based on:

test mat.

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, except for an increase in salivation noted in two animals (2/5) only at 30 minutes post-dose.

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 Regulation (EC) No. 1272/2008 on classification, labelling and packaging substances and mixtures, the test item does not have to be classified. No signal word or hazard statement is required.
In accordance with Globally Harmonised System of classification and labelling of chemicals (GHS), and in absence of information about the toxicity at the dose of 5000 mg/kg bw, it is impossible to say if the test item Boswellia serrata extract has to be classified in Category 5 with the signal word “Warning” and the hazard statement “H303 May be Harmful if swallowed” or does not have to be classified with no signal word or hazard statement required.

Executive summary:

In an acute oral toxicity study performed according to the OECD Guideline 420 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 5 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, except for an increase in salivation noted in two animals (2/5) only at 30 minutes post-dose. 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 Regulation (EC) No. 1272/2008 on classification, labelling and packaging substances and mixtures, the test item does not have to be classified. No signal word or hazard statement is required.

In accordance with Globally Harmonised System of classification and labelling of chemicals (GHS), the test item Boswellia serrata extract has to be classified in Category 5 with the signal word “Warning” and the hazard statement “H303 May be Harmful if swallowed” or does not have to be classified with no signal word or hazard statement required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP guideline study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In an acute oral toxicity study performed according to the OECD Guideline 420 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 5 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, except for an increase in salivation noted in two animals (2/5) only at 30 minutes post-dose. 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 Regulation (EC) No. 1272/2008 on classification, labelling and packaging substances and mixtures, the test item does not have to be classified. No signal word or hazard statement is required.

In accordance with Globally Harmonised System of classification and labelling of chemicals (GHS), the test item Boswellia serrata extract has to be classified either Category 5 with the signal word “Warning” and the hazard statement “H303 May be Harmful if swallowed” or does not have to be classified with no signal word or hazard statement required.

Justification for classification or non-classification

Harmonized classification:

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

Self-classification:

Acute toxicity via Oral route:

Based on the available information, the registered substance is:

-not classified according to the Regulation (EC) No. 1272/2008.

Acute toxicity via Dermal route: This information is not available

Acute toxicity via Inhalation: This information is not available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 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.

Specific target organ toxicity: single exposure (Dermal):This information is not available

Specific target organ toxicity: single exposure (Inhalation):This information is not available.

Based on the physical state of the substance, the registered substance is not classified for aspiration hazard.