Registration Dossier

Administrative data

Description of key information

Acute oral toxicity (similar to OECD TG 401): LD50 > 5000 mg/kg bw (read-across from Ylang Ylang oil extra)

Acute dermal toxicity (similar to OECD TG 402): LD50 > 5000 mg/kg bw (read-across from Ylang Ylang oil extra)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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:
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:
Coma and chromodacryorrhea were seen 24 hours post-treatment. These effects had disappeared 48 hours after treatment.
Body weight:
No data available
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).

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.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
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
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals 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
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
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:
Coma and chromodacryorrhea were seen 24 hours post-treatment. These effects had disappeard 48 hours after treatment.
Body weight:
No data available.
Gross pathology:
No effects were observed during 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, 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).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
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".
23 April 2018 READ-ACROSS STUDY / YLANG YLANG III OIL / ACUTE DERMAL TOXICITY I&B9W8768R001F0.1


Executive Summary
According to Annex VII, 8.5 of the REACh Regulation (EC) No 1907/2006, acute toxicity by the dermal 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 dermal 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 toxicological potential (Benzyl acetate, Methyl benzoate, 4-Methylanisole) add up to 2.2 – 29% (w/w) in the source versus 0.3 – 2.6% (w/w) in the target UVCB.
An acute dermal toxicity study, according to OECD test guideline 402, 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 dermal 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:
read-across source
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
Skin irritation was observed in the rabbits: slight redness (1/10), moderate redness (1/10) and slight edema (3/10).
Body weight:
No data
Gross pathology:
No data
Interpretation of results:
other: Not classified
Remarks:
based on CLP criteria (Annex I of 1272/2008/EC)
Conclusions:
The acute dermal toxicity of Ylang Ylang III oil was read across from Ylang Ylang Oil Extra. The dermal LD50 value of Ylang Oil Extra in rabbits 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 for acute dermal toxicity according to the classification criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
Executive summary:

The acute dermal toxicity of Ylang Ylang III oil was read across from Ylang Ylang Oil Extra.

Ten rabbits were exposed to a single dose of 5000 mg/kg bw Ylang oil Extra. The animals were observed for 14 days. No mortality was noted. Skin irritation (slight and moderate redness, slight edema) was observed. The dermal LD50 value for Ylang oil Extra in rabbits was established as exceeding 5000 mg/kg body weight, under the conditions of this study. The substance therefore does not have to be classified for acute dermal toxicity according to the classification criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
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 information
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
No data

ENVIRONMENTAL CONDITIONS
No data
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
No data
Duration of exposure:
Single administration
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following exposure: 14 days
- Frequency of observations: Daily
- Necropsy of survivors performed: No
- Other examinations performed: Clinical signs
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
Skin irritation was observed in the rabbits: slight redness (1/10), moderate redness (1/10) and slight edema (3/10).
Body weight:
No data
Gross pathology:
No data
Interpretation of results:
other: Not classified
Remarks:
based on CLP criteria (Annex I of 1272/2008/EC)
Conclusions:
The dermal LD50 value of Ylang Oil Extra in rabbits 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 for acute dermal toxicity according to the classification criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
Executive summary:

Ten rabbits were exposed to a single dose of 5000 mg/kg bw Ylang oil Extra. The animals were observed for 14 days. No mortality was noted. Skin irritation (slight and moderate redness, slight edema) was observed. The dermal LD50 value for Ylang oil Extra in rabbits was established as exceeding 5000 mg/kg body weight, under the conditions of this study. This result was used for read-across to Ylang Ylang III oil.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute oral toxicity (read-across from Ylang Ylang oil extra)

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.

Acute dermal toxicity (read-across from Ylang Ylang oil extra)

Ten rabbits were exposed to a single dose of 5000 mg/kg bw Ylang oil Extra. The animals were observed for 14 days. No mortality was noted. Skin irritation (slight and moderate redness, slight edema) was observed. The dermal LD50 value for Ylang oil Extra in rabbits was established as exceeding 5000 mg/kg body weight, under the conditions of this study. This result was used for read-across to Ylang Ylang III oil.

Justification for classification or non-classification

Based on the available data, Ylang Ylang III oil does not need to be classified for acute oral or dermal toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).