Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: LD50>5000 mg/kg bw (standard acute method, limit test)
Acute dermal toxicity: LD50>5000 mg/kg bw (standard acute method, limit test)

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:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
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.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substance Act (FHSA)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: Approx. 200 g
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Fasting period: 16-18 hrs
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
No data available
Doses:
5000 mg/kg
No. of animals per sex per dose:
10 rats (male)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily (and frequently on day of test)
- Necropsy of survivors performed: no
- Other examinations performed: symptomatology
Statistics:
Not relevant
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 observed
Clinical signs:
No effects observed
Body weight:
No data available
Gross pathology:
Not performed
Other findings:
Necropsy was not performed
Interpretation of results:
other:
Remarks:
CLP criteria not met
Conclusions:
The oral LD50 value of orange oil in rats was established as exceeding 5000 mg/kg body weight, under the conditions of this study. 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:

A single 5000 mg/kg bw dose of orange oil was administered by oral gavage to 10 male Wistar albino rats. The animals were observed for 14 days while food and water were available ad libitum. No mortality and no symptoms were noted. The oral LD50 value of orange oil 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 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
Quality of whole database:
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.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
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:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Test was conducted according to methods similar to OECD guideline 402 (limit test) and was performed pre-GLP. A concise description of the protocol is available and a table with results is included.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substance Act (FHSA)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: approx. 2 kg
- Housing: 2/cage
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum

ENVIRONMENTAL CONDITIONS
Temperature controlled room
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
TEST SITE
- Area of exposure: Adbominal 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 hours
Duration of exposure:
24 hours
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 rabbits (female)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs and skin irritation
Statistics:
Not relevant
Preliminary study:
Not relevant
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Moderate redness was noted in 10 out of 10 animals, slight edema in 3/10 and moderate edema in 5/10 animals
Mortality:
No mortality observed
Clinical signs:
No effects observed
Body weight:
No data on weight change reported
Gross pathology:
Not performed
Other findings:
Skin irritation: moderate redness was noted in 10 out of 10 animals, slight edema in 3/10 and moderate edema in 5/10 animals
Interpretation of results:
other:
Remarks:
CLP criteria not met
Conclusions:
Under the conditions of this study, dermal application of orange oil did not induce any mortality at a dose of 5000 mg/kg. Therefore, a LD50 of >5000 mg/kg was established and 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) and Annex VI of 67/548/EEC (DSD).
Executive summary:

A single dose of 5000 mg/kg orange oil was applied dermally to the abraded abdominal skin of 10 female New Zealand White rabbits. Skin was covered with 2 single layers of gauze and wrapped with impervious material for 24 hours. After 24 hours the wrapping was removed and the rabbits were cleansed. The rabbits were observed for 14 days thereafter for mortality and symptomatology (skin irritation).

Under the conditions of this study, dermal application of orange oil did not induce any mortality or clinical signs at a dose of 5000 mg/kg. Skin irritation was observed, as moderate redness was noted in 10 out of 10 animals, slight edema in 3/10 and moderate edema in 5/10 animals. In conclusion, a LD50 of >5000 mg/kg was established and 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) and Annex VI of 67/548/EEC (DSD).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Test was conducted according to methods similar to OECD guideline 402 (limit test) and was performed pre-GLP. A concise description of the protocol is available and a table with results is included.

Additional information

Acute oral toxicity was tested in a standard acute limit test, in which a single dose of orange oil (5000 mg/kg bw) was administered by oral gavage to 10 male Wistar rats. No mortality was observed up to 14 days after application, therefore the oral LD50 was established to be >5000 mg/kg bw.

Acute dermal toxicity was also tested in a standard acute limit test, in which 10 female New Zealand White rabbits were exposed to a single dose of orange oil (5000 mg/kg bw) dermally on the abraded abdominal skin. Based on the absence of mortality, a dermal LD50 >5000 mg/kg bw was established.

Justification for classification or non-classification

Based on the available information, orange oil has been shown to be of low acute toxicity when applied via the oral and dermal route. Therefore, the substance orange oil does not need to be classified for acute toxicity according to the criteria outlined in Annex I of 1272/2008/EC (CLP/EU-GHS)