Registration Dossier

Administrative data

Description of key information

Acute toxicity, oral: LD50 = 3320 mg/kg bw (WoE).
Acute toxicity, dermal: LD50 > 5000 mg/kg bw (Rel 2, K).
Acute toxicity: inhalation: waiver.

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:
experimental study
Adequacy of study:
weight of evidence
Study period:
1984
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Original reference in Japanese language; data from English abstract and table only
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Principles of method if other than guideline:
LD50 determination in mice following gavage administration.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
other: ddY
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 18.0-22.0 g
- Fasting period before study: 20 h
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 0.1 mL/10 g
Doses:
2200, 2900 , 3700, 4800 and 6200 mg/kg bw
No. of animals per sex per dose:
10 males/dose
Control animals:
no
Details on study design:
- Toxic symptoms and changes in the body weight gain of the surviving mice were observed and the number of death was recorded for 7 days.
Statistics:
- LD50 with 95 % confidence limits was calculated with use of Litchfield-Wilcoxon's method.
Preliminary study:
Not applicable
Sex:
male
Dose descriptor:
LD50
Effect level:
3 320 mg/kg bw
Based on:
test mat.
95% CL:
2 770 - 3 980
Mortality:
Mortalities: 10, 20, 70, 90 and 100 % at 2200, 2900 , 3700, 4800 and 6200 mg/kg bw, respectively
Clinical signs:
Restraint of growth was observed in each surviving mouse.
Body weight:
No data
Gross pathology:
No data
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 for eucalyptus oil is higher than 2000 mg/kg bw in mice therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).
Executive summary:

In an acute oral toxicity study, groups (10/dose) of male ddY mice were given a single oral dose of eucalyptus oil diluted in olive oil at 2200, 2900 , 3700, 4800 and 6200 mg/kg bw. Toxic symptoms and changes in the body weight gain of the surviving mice were observed and the number of death was recorded for 7 days.

Mortalities in male were 10, 20, 70, 90 and 100 % at 2200, 2900, 3700, 4800 and 6200 mg/kg bw, respectively. Restraint of growth was observed in each surviving mouse. The oral LD50 for eucalyptus oil was 3320 (2770-3980) mg/kg bw in male mice.

The oral LD50 for eucalyptus oil is higher than 2000 mg/kg bw in mice therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only short abstract available
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Principles of method if other than guideline:
LD50 determination in rats following gavage administration.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data, all rats came from the same litter
- Age at study initiation: no data
- Weight at study initiation: 100 g
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): Essentially consisted of oats, potato skins, bran and vegetables of all kinds, especially carrots. Then there were given appropriate doses vitamin D.
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
No data
Route of administration:
oral: gavage
Vehicle:
physiological saline
Details on oral exposure:
none
Doses:
no data
No. of animals per sex per dose:
5 per group
Control animals:
yes
Details on study design:
none
Statistics:
no data
Preliminary study:
Not applicable
Sex:
not specified
Dose descriptor:
LD50
Effect level:
4 440 mg/kg bw
Based on:
test mat.
Mortality:
No data
Clinical signs:
The animals near to death no longer feed themselves.
Body weight:
No data
Gross pathology:
No data
Other findings:
No data

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Oral LD50 = 4400 mg/kg bw.
Executive summary:

In an acute oral test, 5 rats per dose were administered a single oral dose of Eucalyptus oil diluted in physiological saline by gavage.

Oral LD50 = 4400 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 320 mg/kg bw
Quality of whole database:
Only basic data given in the two available studies, however results are consistent and were therefore considered sufficiently robust to cover this endpoint.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Only basic data given. However, the result was non-toxic at the dose level of 5000 mg/kg bw, which is 2.5 times more than the limit dose of the OECD 402. A repeat study is unlikely to show worse effects on mortality, therefore this study was considered sufficiently robust to cover this endpoint.

Additional information

Acute toxicity: oral

The two available studies were only poorly described but showed consistent results. Therefore a weight-of-evidence approach was followed for this endpoint. LD50 of 3320 mg/kg bw in mice and 4400 mg/kg bw in rats were reported by Oshumi and vonSkramlik, respectively. As a worst-case, the lowest LD50 value was selected as the key effect level for this endpoint.

Acute toxicity: dermal

A key study was identified (Moreno, 1973, rel.2). In this acute dermal toxicity study, rabbits were administered a single dermal dose of eucalyptus oil at 5000 mg/kg bw. No deaths and clinical signs of toxicity occurred during the observation period. Dermal reactions noted were slight redness (5/10 rabbits), moderate redness (3/10 rabbits) and moderate oedema (10/10 rabbits) at the site of application. The dermal LD50 for eucalyptus oil is higher than 5000 mg/kg bw in rabbits.


Justification for selection of acute toxicity – oral endpoint
No study was selected since a weight-of-evidence approach was followed to conclude on acute toxicity via oral route. As a worst-case, the lowest LD50 value was selected as the key effect level for this endpoint.

Justification for selection of acute toxicity – inhalation endpoint
In accordance with column 2 of REACH Annex VIII (§8.5), the acute toxicity by inhalation does not need to be conducted since the acute toxicity study is already provided for both the oral and the dermal route.

Justification for selection of acute toxicity – dermal endpoint
Only one study available

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP3.

Self-classification:

Acute toxicity via Oral route:

Based on the available information, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 2000 mg/kg bw

- not classified according to the Directive 67/548/EEC as the LD50 is greater than 2000 mg/kg bw.

Acute toxicity via Dermal route:

Based on the available information, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 5000 mg/kg bw

- not classified according to the Directive 67/548/EEC as the LD50 is greater than 5000 mg/kg bw.

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):

The classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single exposure, dermal 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 (dermal) for a Category 1 classification (C ≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw ≥ C > 1000 mg/kg bw). No classification is required.

Specific target organ toxicity: single exposure (Inhalation):

This information is not available.

However, based on its viscosity, the substance should be classified for aspiration hazard:

- H304, May be fatal if swallowed and enters airways according to the regulation (EC) No. 1272/2008

- Xn, R65, Harmful: may cause lung damage if swallowed according to the Directive 67/548/EEC.