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Description of key information

Acute oral toxicity: LD50 >5000 mg/kg bw (similar to OECD401)

Acute dermal toxicity: LD50 = 2480 mg/kg bw (similar to OECD402)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed according to a guideline similar to OECD401 and in accordance with GLP. Materials and methods and results are reported clearly.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
equivalent or similar to guideline
Guideline:
other: Hagan E.C., "Acute Toxicity", p17-25, 1975
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: licenced dealer, no details available
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: between 200 and 300 grams bodyweight
- Fasting period before study: 18 hours
- Housing: galvanized cages with indirect bedding
- Diet (e.g. ad libitum): growth and maintanance ration from commercial producer, ad libitum
- Water (e.g. ad libitum): ad libitium
- Acclimation period: at least 2 days prior to test initiation

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature controlled room
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ light cycle
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: no details available
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5 rats (male)
5 rats (female)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 1, 3, 9, 24 hours after treatment and daily thereafter for a total of 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: observed for signs of pharmacololgic activity and drug toxicity
Statistics:
Not relevant
Preliminary study:
Not relevant
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
24 hours after treatment, mortality was observed in two males and one female (30% mortality rate).
Gross pathology:
Internal organs on superficial examination appeared normal
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the oral LD50 value of Eucalyptus Citriodora oil in rats was established to be >5000 mg/kg body weight. The substance therefore does not need to be classified according to the classification criteria outlined in Annex VI of 67/548/EEC (DSD) and Annex I of 1272/2008/EC (CLP).
Executive summary:

An acute oral toxicity test was performed according to methods similar to OECD401 and under GLP conditions. A single 5000 mg/kg bw dose of eucalyptus citriodora oil was administered by oral gavage to 5 male and 5 female Wistar albino rats. The animals were observed for signs of pharmacologic activity, drug toxicity and mortality on 1, 3, 9, 24 hours after treatment and daily thereafter for a total of 14 days. Mortality was observed 24 hours after treatment in two males and one female. Internal organs on superficial examination appeared normal.

24 hours after treatment, mortality was observed in two males and one female (30% mortality rate). Based on these results, the oral LD50 value of Eucalyptus Citriodora oil in rats was established to be >5000 mg/kg body weight. Therefore the substance does not need to be classified in accordance with the criteria outlined in Annex VI of 67/548/EEC (DSD) and Annex I of 1272/2008/EC (CLP).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3 May - 15 June 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed according to methods similar to OECD guideline 402 and under GLP conditions. Test groups included only 3 animals of each sex and included animals with abraded skin.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
For each of four dose levels three male and three female rabbits were used and the skin of two males and one female was abraded
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: a suitably licensed dealer
- Age at study initiation: no data
- Weight at study initiation: 1.47 to 2.25 kg
- Fasting period before study: no data
- Housing: galvanized or stainless steel cages
- Diet: growth and maintenance ration from a commercial producer
- Water: ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: mid dorsal area of the trunk between the scapulae and pelvis
- % coverage: no data
- Type of wrap if used: impermeable plastic wrap fixed with adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the excess test article was gently wiped off
- Time after start of exposure: 24 hours

TEST MATERIAL
- Single dermal application (volumetric dosing).
Duration of exposure:
24 hours
Doses:
250, 1000, 2000, 3500 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation at 1, 3, 6, and 24 hours; once per day thereafter. Weighing on the day of dosing, after 14 days or upon death
- Necropsy of survivors performed: yes, animals sacrificed at the end of the 14 day observation period as well as non-survivors
- Other examinations performed: clinical signs
Preliminary study:
Successive dose levels were chosen on the basis of the mortality observed at previously performed test level.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 480 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 530 - < 4 002
Mortality:
250 mg/kg: none
1000 mg/kg: 1M
2000 mg/kg: 2M, 1F
3500 mg/kg: 2M, 1F
Clinical signs:
250 mg/kg: none
1000 mg/kg: none
2000 mg/kg after 24 hours: 1M, 1F slight depression, 1M severe depression
3500 mg/kg after 6 hours: 1M slight depression; after 24 hours: 1M; 1M, 2F slight depression
Body weight:
250 mg/kg: day 1: 1.60-1.80 kg, day 14: 2.06 - 2.27 kg
1000 mg/kg: day 1: 1.47 -2.25 kg, day 14: 1.4 (died) - 2.65 kg
2000 mg/kg: day 1: 1.87-2.13 kg, day 14: 1.82 (died) - 2.21 kg
3500 mg/kg: day 1: 1.84 - 2.19 kg, day 14 1.80 (died) - 2.15 kg
Gross pathology:
250 mg/kg: none
1000 mg/kg: : 2M, 3F blanched skin; 1M faeces loose, 1M liver and lungs discoulered, 2F scab formed over test site, sloughing
2000 mg/kg: 2M, 2 F blanched skin; 1 M 1 F skin slightly reddened and swollen, blanched; 1M kidneys pitted; 1F yellow-white liver lesions, 0.2 - 0.3 cm, firm; 2F scab formed over test site, sloughing
3500 mg/kg: 2M 1F skin slightly reddened and swollen, blanched; 1M, 2F scab formed over test site, sloughing

Draize scores:

- 250 mg/kg: all animals 1/1;

- 1000 mg/kg: 2/1, 0/0, 2/2, 1/1, 2/2, 2/1;

- 2000 mg/kg: 1/2, 1/2, 1/1, 1/1;

- 3500 mg/kg: 1/2, 1/1, 1/2

The LD50 can be considered as a 'worst-case' value since animals with abraded skin were included in the calculation. It is expected that the LD50 would have been higher when all animals would have been tested with intact skin.

Interpretation of results:
not classified
Remarks:
based on CLP criteria
Conclusions:
Under the conditions of this study, the acute dermal LD50 in rabbits was calculated to be 2480 mg/kg bw. Based on this result, the test substance does not need to be classified in accordance with the criteria outlined in CLP (1272/2008/EC).
Executive summary:

Acute dermal toxicity was tested in a test similar to OECD guideline 402. New Zealand white rabbits were acclimated for at least 6 days and dosed in groups of six (3M:3F) at 250, 1000, 2000 and 3500 mg/kg bw. The skin of half the animals (2M:1F) was abraded. Each animal received a single dermal application of the test substance. The test sites were occluded for 24 hours after which the wrap and remaining substance was removed. Animals were observed for clinical signs and mortality 1, 3, 6 and 24 hours after treatment and daily thereafter for a total of 14 days. All animals were subjected to gross necropsy.

Mortality was observed starting from the 1000 mg/kg bw dose group (1 animal). In the highest dose groups 3 animals of each group died. Clinical signs were only noted in the 2 highest dose groups and included slight and severe depression. Gross necropsy showed no effects in the lowest dose groups. From the 1000 mg/kg bw dose group effects on skin (blanching, reddening, swelling, scab formation) and some internal organs (liver and lungs discoloured, kidneys pitted, liver lesions) were observed.

Based on these results, the LD50 was calculated to be 2480 (CI: 1530 - 4020) mg/kg bw and therefore the test substance does not need to be classified in accordance with the criteria outlined in CLP (1272/2008/EC).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 480 mg/kg bw

Additional information

Acute oral toxicity Acute oral toxicity test was tested by administration of a single 5000 mg/kg bw dose of Eucalyptus Citriodora oil to 10 Wistar albino rats. Mortality was observed 24 hours after treatment in two males and one female (30% mortality rate). Internal organs appeared normal upon superficial examination. Based on these results, the oral LD50 value of Eucalyptus Citriodora oil in rats was established to be >5000 mg/kg body weight.

Acute dermal toxicity

New Zealand white rabbits were dosed in groups of six (3M:3F) at 250, 1000, 2000 and 3500 mg/kg bw. The skin of half the animals (2M:1F) was abraded. Mortality was observed starting from the 1000 mg/kg bw dose group (1 animal). In the highest dose groups 3 animals of each group died. Based on these results, the LD50 was calculated to be 2480 (CI: 1530 - 4020) mg/kg bw.

Justification for selection of acute toxicity – oral endpoint

The selected study is the key study for this endpoint.

Justification for selection of acute toxicity – dermal endpoint

The selected study is the key study for this endpoint.

Justification for classification or non-classification

Based on the available information, Eucalyptus Citriodora has shown to be non-toxic after oral exposure. Therefore, the substance does not need to be classified for Acute Oral Toxicity in accordance with the criteria outlined in Annex I of 1272/2008/EC (CLP/EU-GHS).

Based on the available information, Eucalyptus Citriodora has shown to be non-toxic in contact with skin. Therefore, the substance does not need to be classified for Acute Dermal Toxicity in accordance with the criteria outlined in Annex I of 1272/2008/EC (CLP/EU-GHS).

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