Essential oil of Ylang Ylang III obtained from the flowers of Cananga odorata (Annonaceae) by steam distillation

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test was conducted according to methods similar to OECD guideline 401 (limit test) and was performed pre-GLP. A concise description of the protocol is available and results are reported clearly.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The full read across justification report is attached under "Attached justification".

05 February 2018 READ-ACROSS STUDY / YLANG YLANG III OIL - ACUTE ORAL TOXICITY I&B9W8768R001F0.2

1 Executive Summary
According to Annex VII, 8.5 of the REACh Regulation (EC) No 1907/2006, acute toxicity by the oral route is standard information required for the registration of substances manufactured or imported in quantities of one tonne per year or more. However, according to Annex XI, 1.5 of the REACH Regulation, Read-across and grouping approaches can be used to adapt the standard testing regime. This read-across study report follows notably the recommendations made by the European Chemicals Agency in its “Guidance on information requirements and chemical safety assessment Chapter R.6 – QSARs and grouping of chemicals” (ECHA, 2008) and in its document “Read-Across Assessment Framework (RAAF)” (ECHA, 2017).

A read-across approach appears appropriate to predict the endpoint “, Acute toxicity by the oral route” for the substance Ylang Ylang III oil because:

The source substance used in this read-across, Ylang Ylang Ext/ I/ II oil, gives rise to the highest concern regarding the acute toxicity endpoint, as the constituents with known acute oral toxicological potential (4-Methylanisole, Linalool, Benzyl acetate) add up to 1 – 44 % (w/w) in the source versus 0.3 - 7.4 % (w/w) in the target UVCB.
An acute oral toxicity study, according to OECD test guideline 401, is available for the substance Ylang Ylang Ext, which has a composition very similar to the target substance.


This report follows the RAAF method and so presents:
1) The hypothesis: analogue read-across approach, based on the similarity of the structures and the acute oral toxicity for these types of structures;
2) The scientific justifications (“Assessment Elements”) and their evaluation (“Assessment Options”); which demonstrate the confidence that can be put in this prediction.
3) The conclusions, usable for classification assessment or risk assessment, which are summarised hereafter.

Reason / purpose for cross-reference:

read-across source

Preliminary study:

Not relevant

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Coma and chromodacryorrhea were seen 24 hours post-treatment. These effects had disappeared 48 hours after treatment.

Gross pathology:

No effects were observed at necropsy

Interpretation of results:

other: Not classified

Remarks:

based on CLP criteria (Annex I of 1272/2008/EC)

Conclusions:

The oral LD50 value of Ylang Oil Extra in rats was established to be higher than 5000 mg/kg bw and was used for read-across to Ylang Ylang III oil. Based on this information, this substance does not need to be classified according to the classification criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Executive summary:

A single 5000 mg/kg bw dose of Ylang Oil Extra was administered by oral gavage to 10 male Wistar rats. The animals were observed for 14 days. No mortality was noted. Coma and chromodacryorrhea were observed 24 h post-treatment, effects that could no longer be detected 48 h after treatment. The oral LD50 value of Ylang Oil Extra in rats was established to be higher than 5000 mg/kg bw and was used for read-across to Ylang Ylang III oil. Based on this information, this substance does not need to be classified according to the classification criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1973

Report date:

1973

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ylang-ylang, ext.

EC Number:

281-092-1

EC Name:

Ylang-ylang, ext.

Cas Number:

83863-30-3

IUPAC Name:

Essential oil of Ylang Ylang Ext/I/II obtained from the flowers of Cananga odorata (Annonaceae) by steam distillation

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Ylang oil extra
- Purity: No data
- Lot/batch No.: confidential

Specific details on test material used for the study:

- Name of test material (as cited in study report): Ylang oil extra
- Purity: No data
- Lot/batch No.: confidential

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: approximately 200 g
- Fasting period before study: 16-18 hrs
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10 males

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

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Coma and chromodacryorrhea were seen 24 hours post-treatment. These effects had disappeard 48 hours after treatment.

Gross pathology:

No effects were observed during necropsy.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Remarks:

based on CLP criteria (Annex I of 1272/2008/EC)

Conclusions:

The oral LD50 value of Ylang Oil Extra in rats was established to be higher than 5000 mg/kg bw, under the conditions of this study. The substance therefore does not need to be classified according to the classification criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Executive summary:

A single 5000 mg/kg bw dose of Ylang Oil Extra was administered by oral gavage to 10 male Wistar rats. The animals were observed for 14 days. No mortality was noted. Coma and chromodacryorrhea were observed 24 hours post-treatment, effects that could no longer be detected 48 hours after treatment.The oral LD50 value for Ylang Oil Extra in rats was established as exceeding 5000 mg/kg body weight, under the conditions of this study. The substance therefore does not have to be classified according to the classification criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).