Litsea cubeba, ext.

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Test was conducted according to methods similar to OECD guideline 402 and was performed pre-GLP. A concise description of the protocol is available and results are reported clearly.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

1

Reference substance name:

Essential oil obtained from the fruits of Litsea cubeba (Lour.) Pers. by distillation

EC Number:

943-438-6

Cas Number:

90063-59-5

IUPAC Name:

Essential oil obtained from the fruits of Litsea cubeba (Lour.) Pers. by distillation

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: Approximately 2 kg
- Housing: 2 animals per cage
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum

ENVIRONMENTAL CONDITIONS
-Temperature controlled room

Administration / exposure

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: Abdominal area (skin was abraded)
- Type of wrap if used: 2 single layers of gauze and impervious material

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hrs

Duration of exposure:

24 hrs

Doses:

1250, 2500, 5000 mg/kg bw

No. of animals per sex per dose:

Four animals per dose, with a total of 12 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: symptomatology, skin irritation

Statistics:

Not relevant

Results and discussion

Preliminary study:

Not relevant

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

4 800 mg/kg bw

Based on:

test mat.

95% CL:

2 400 - 9 600

Mortality:

Mortality was observed in two out of four animals in the highest dose (5000 mg/kg bw) on the third and sixth day, and in one out of four animals on the fourth day in the 2500 mg/kg dose group.

Clinical signs:

other: For the two lowest dose groups no clinical signs were noted, while in the highest doser group anorexia, ptosis and ataxia were noted in 2 animals (not specified whether these were the same animals). In all rabbits and at all doses marked redness and moder

Gross pathology:

Necropsy:
- 2500 mg/kg bw: evidence of extreme diarrhea, extreme dermal and subdermal irritation in 1 animal
- 5000 mg/kg bw: liver blotchy in 1 animal, subdermal irritation in 1 animal, no visible lesion in 1 animal

Other findings:

Not reported

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Remarks:

according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP)

Conclusions:

Under the conditions of this study, dermal application of Litsea Cubeba oil induced mortality at a dose of 2500 mg/kg bw (1/4 animals) and at a dose of 5000 mg/kg bw (2/4 animals). The LD50 is established at 4800 mg/kg bw (CI: 2400-9600) and therefore the substance does not need to be classified for acute dermal toxicity according to the criteria outlined in Annex I of 1272/2008/EC (CLP).

Executive summary:

Three dose levels of Litsea Cubeba oil (1250, 2500, 5000 mg/kg bw) were applied dermally to the skin of 12 rabbits (4 per group). The rabbits were observed for 14 days thereafter for mortality and symptomatology (skin irritation).

No mortality was observed in the lowest dose group. In the 2500 mg/kg bw group, mortality was observed in 1 out of 4 animals. In the 5000 mg/kg bw group 2 out of 4 animals died. At the highest dose level, anorexia was observed in 2 animals, ptosis in 2 animals and ataxia in 2 animals. At 2500 mg/kg bw evidence of extreme diarrhea, extreme dermal and subdermal irritation in 1 animal were observed. At 5000 mg/kg bw a blotchy liver was observed in 1 animal, subdermal irritation in 1 animal and no visible lesions were observed in 1 animal.

Based on the conditions of this study, the LD50 was established to be 4800 mg/kg bw (confidence interval of 2400-9600 mg/kg bw) and therefore the substance does not need to be classified for acute dermal toxicity according to the criteria outlined in Annex I of 1272/2008/EC (CLP).