Registration Dossier

Administrative data

Description of key information

Not adverse effects following oral and dermal exposure.

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:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study similar to OECD Guideline and subject to GLP audit
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
Limit test at 1 dose level
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Massachusetts
- Age at study initiation: Not reported
- Weight at study initiation: Male: 225-275 grams (before fasting)
- Fasting period before study: 18 hrs
- Housing: Individual stainless steel1/2 wire mesh cages.
- Sanitization: Waste material was removed daily. Cages and feeders were sanitized every two weeks
- Diet (e.g. ad libitum): Purina Certified Rodent Meal #5002, ad libitum, checked daily.
- Food analysis: No contaminants were detected.
- Water (e.g. ad libitum): Fresh tap water, fit for human consumption, ad libitum, using an automatic watering system supplied by Edstrom Industries Inc.
- Water analysis: Conducted by Pennsylvania Gas and Water Company
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hrs light, 12 hrs dark
Route of administration:
oral: gavage
Details on oral exposure:
VEHICLE
- Information not reported

MAXIMUM DOSE VOLUME APPLIED:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Potential route for human exposure
Doses:
Dose administration: 5000 mg/kg
Volume administration: 5 ml/kg
No. of animals per sex per dose:
5 females and 5 males
Details on study design:
- Frequency and duration administration: Once
- Length of the study: 15 days
- Frequency of observations and weighing: Weight and death body weights were recorded on Days -1, 1, 2, 3, 4, 7, 11.
- Necropsy of survivors performed: yes
- Other examinations performed: Twice daily rats were observed for clinical effects, CNS effects and mortality.
Statistics:
Not reported
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study
Clinical signs:
5 hrs after dosing: piloerection was observed in 7/10 rats
At Day 2: Diarrhea and piloerection, and decreased body were observed in 2 different rats.
At Day 3: Decreased body tone was observed in 1 rat.
Body weight:
No significant changes
Gross pathology:
No visible lesions
Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
The estimated acute oral LD50 in rats for Terpenes and terpenoids, turpentine oil, alpha-pinene fraction oligomers was determined to be greater than 5000 mg/kg.
Executive summary:

The study investigated the Acute oral toxicity of Terpenes and terpenoids, turpentine oil, alpha-pinene fraction oligomers on female and male Sprague-Dawley rat. A single dose of 5000 mg/kg was administered orally by gavage and animals were observed for 14 days. No mortality occurred during the study and no visible lesions were recorded at necroscopic analysis. Piloerection and diarrhea were observed in 7 rats after dosing. After 2 days diarrhea and piloerection, and decreased body were observed in 2 different rats, while after 3 days decreased body tone was observed in 1 rat.

In conclusion, the acute oral toxicity in rats was determined to be greater than 5000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study similar to OECD Guideline and subject to GLP audit
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Perfection Breeders, Inc.
- Weight at study initiation: 2-3 kg
- Fasting period before study:
- Housing: Separate isolation by test system
- Diet (e.g. ad libitum): Wayne Rabbit Ration, ad libitum, checked daily and added or replaced as needed.
- Food Analysis: Acute dose minimize the effect of contaminants. There were no contaminants.
- Water (e.g. ad libitum): Fresh tap water, fit for human consumption, ad libitum, using 16 ounce glass bottles with rubber stopper and stainless steel sipper tube or an automatic watering system supplied by Edstrom Industries Inc.
- Water Analyses: Conducted by Pennsylvania Gas and Water Company
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C+/-3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hrs light-12 hrs dark
Type of coverage:
occlusive
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk of animal, dorsal body surface area
- % coverage: 100%
- Type of wrap if used: Layer of gauze, rubber dam and an ace bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test site was wiped to remove any remaining material
- Time after start of exposure: After 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mg/kg
- Concentration (if solution):
- Constant volume or concentration used: yes

VEHICLE
- Information not reported
Duration of exposure:
24 hrs
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 females and 5 males
Control animals:
not required
Details on study design:
- Duration of observation period following administration: Observation were recorderd at 10-20 minutes, 1-2 and 4-6 hrs after the 24 hrs period of exposure, and twice daily thereafter for fourteen days.
- Frequency of observations and weighing: Body weights were recorderd on Days: -1, 1, 2, 3, 4, 7, 11, 15.
- Gross necropsy of survivors performed: yes
- Other examinations performed: treated and untreated skin was preserved in 10% buffered formalin and retained for possible histopathological examinations.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 other: mg/kg
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
Decreased body tone
Body weight:
No changes
Gross pathology:
No visible lesions

Erythema Score
Rabbit # Day 1 Day 2 Day 3 Day 4 Day 7 Day 14
1 2 1 1 1 0 0
2 2 2 2 2 1 0
3 1 0 0 0 2 0
4 1 1 1 1 1 0
5 2 1 1 1 1 0
6 1 1 1 1 0 0
7 2 1 0 0 1 0
8 1 2 2 2 0 0
9 1 1 2 1 1 0
10 2 2 1 1 1 0
Edema score
Rabbit # Day 1 Day 2 Day 3 Day 4 Day 7 Day 14
1 0 0 0 0 0 0
2 1 0 0 0 0 0
3 0 0 0 0 0 0
4 0 0 0 0 0 0
5 1 0 0 0 0 0
6 0 0 0 0 0 0
7 1 0 0 0 0 0
8 0 0 0 0 0 0
9 0 0 0 0 0 0
10 0 1 0 0 0 0
Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
Based on the observations made in the acute dermal toxicity Test in Rabbit, the estimated acute Dermal LD50 for Terpenes and terpenoids, turpentine oil, alpha-pinene fraction oligomers was determined to be greater than 2000 mg/kg.
Executive summary:

The study investigated the acute dermal toxicity of Terpenes and terpenoids, turpentine oil, alpha-pinene fraction oligomers in 10 male and female rabbits. The test material was applied to about 240 cm of the dorsal body surface skin, which was previously shaved. The application was done direclty onto the exposed skin of the animals and a layer of gauze was wrapped around the animals to cover the dosed area. In addition, the animals were wrapped with rubber dam and an ace bandage to retard evaporation. The skin was exposed for 24 hrs and the animals were observed for 14 days. The results of the test showed that the acute dermal LD50 was greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Pharmakon Research International, Inc. (1982) investigated the acute oral toxicity potential of Terpenes and terpenoids, turpentine oil, alpha-pinene fraction oligomers on female and male Sprague-Dawley rat. A single dose of 5 mg/kg was administered orally by gavage and animals were observed for 14 days. The results showed no mortality during the study and no visible lesions were recorded at necropsy. Piloerection and diarrhea were observed in 7 rats after dosing. After 2 days diarrhea and piloerection, and decreased body were observed in 2 different rats, while after 3 days decreased body tone was observed in 1 rat. In conclusion, the acute oral toxicity in rats was determined to be greater than 5000 mg/kg.

A second test on Terpenes and terpenoids, turpentine oil, alpha-pinene fraction oligomers was conducted to investigate the acute dermal toxicity potential (Pharmakon Research International Inc.,1982).The test material was tested on 10 male and female rabbits. Terpenes and terpenoids, turpentine oil, alpha-pinene fraction oligomers was applied to about 240 cm of the dorsal body surface skin, which was previously shaved. The application was done directly onto the exposed skin of the animals and a layer of gauze was wrapped around the animals to cover the dosed area. In addition, the animals were wrapped with a rubber dam to retard evaporation. The skin was exposed for 24 hrs and the animals were observed for 14 days. The results of the test showed that the acute dermal LD50 was greater than 2000 mg/kg.

Justification for classification or non-classification

Based on the available data, Terpenes and terpenoids, turpentine oil, alpha-pinene fraction oligomers does not meet the criteria for classification for acute toxicity under EU Regulation 1272/2008.