Essential oil of Boswellia carterii (Burseraceae) obtained from gum by distillation

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 December 2017 - 12 January 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study performed according to OECD Guideline 402 without any deviation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

dated 24 February 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

dated 30 May 2008

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

27 April 2017

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene; 2,6,6-trimethylbicyclo[3.1.1]hept-2-ene

EC Number:

946-037-4

Molecular formula:

Not applicable (UVCB)

IUPAC Name:

1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene; 2,6,6-trimethylbicyclo[3.1.1]hept-2-ene

Test material form:

liquid

Details on test material:

- Description: Pale yellow to yellow mobile liquid
- Storage conditions: refrigerated (2 to 8ºC), in the dark. Not stable in light and air. Test item was flushed with nitrogen after each use.
- Special precautions The test item was not compatible with rubber and plastic

Specific details on test material used for the study:

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

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/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: 200-218 g
- Housing: On Day 1 of the study, animals were housed by group of 3 in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. During the treatment, the animals were kept in individual cages or by two.
- 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

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal area of the trunk (50 mm X 50 mm)
- % coverage: At least 10% of the body surface area
- Type of wrap if used: Animals from treated groups received the topical application of the test material under non occlusive porous gauze dressing (50 mm x 50 mm non-woven swab of 4-layer patch from MEDISTOCK) secured in position with a strip of surgical adhesive tape (50 mm wides hypoallergenic microporeTM adhesive tape from 3M).

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours
- Washing (if done): After removal of the gauze dressings, the treated area was rinsed with distilled water and liquid paraffin.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.30 mL/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

other: historical control

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality were recorded at 1 hour, 3 hours, 5 hours, and then once daily for 14 days. Animals were weighed on Day D0 (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.

Remarks on result:

other: erythema was noted in all animals at 24-hour post-dose and was totally reversible on Days 4 and 5

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No systemic clinical signs related to the administration of the test substance were observed.

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal any treatment-related changes.

Other findings:

Erythema was noted in all animals at 24-hour post-dose and was totally reversible on Days 4 and 5. Dryness of the skin and scab were noted in two treated animals (2/3) between Days 4 and 5.

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 dermal 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. As no mortality and no adverse clinical signs were observed at 2000 mg/kg bw, it is anticipated that the registered substance is also not classified according to the GHS. No signal word or hazard statement is required.

Executive summary:

In an acute dermal toxicity study performed according to the OECD Guideline 402 and in compliance with GLP, a single dose of 2000 mg/kg bw of the test substance was applied onto the intact skin of 3 female Sprague Dawley rats under occlusive conditions for 24 hours. Animals were then observed for mortality, dermal reactions, body weight changes and clinical signs of toxicity for 14 days.

No mortality occurred during the study. No systemic clinical signs related to the administration of the test substance were observed. Erythema was noted in all animals at 24-hour post-dose and was totally reversible on Days 4 and 5. Dryness of the skin and scab were noted in two treated animals (2/3) between Days 4 and 5. Body weight gain of the animals remained normal throughout the study. The macroscopic examination of the animals at the end of the study did not reveal any treatment-related changes.

Rat Dermal LD50 >2000 mg/kg bw.

Under the test conditions, the dermal 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. As no mortality and no adverse clinical signs were observed at 2000 mg/kg bw, it is anticipated that the registered substance is also not classified according to the GHS. No signal word or hazard statement is required.