Reaction mass of Terpenes and terpenoids, turpentine-oil, alpha-pinene fraction, dimers and Terpenes and terpenoids, turpentine-oil, alpha-pinene fraction, trimers

Endpoint summary

Description of key 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 study used only as supporting study, was performed to determine the acute oral toxicity profile of test material Terpenes and Terpenoids, turpentine-oil, beta pinene fraction, polymd. The study performed at Chemical Hygiene Fellowship (CHF) in 1977 did not follow any guideline and the GLP conditions are not specified.

Ten male Hilltop-Wistar albino rats were exposed to 10 and 5 g/Kg of the test material in one unique dose. No signs of toxicity were recorded and no deaths occurred.

According to the results of this study, the LD50 acute oral of the test material Terpenes and Terpenoids, turpentine-oil, beta pinene fraction, polymd LD50 was >10 g/Kg.

Data on acute dermal toxicity are available on Terpenes and terpenoids, turpentine oil, alpha-pinene fraction oligomers (Pharmakon Research International Inc.,1982) and on

Terpenes and Terpenoids, turpentine-oil, beta pinene fraction, polymd (Chemical Hygiene Fellowship (CHF), 1977).

In the first key study, 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.

The second supporting study was performed to determine the acute dermal toxicity profile of test material Terpenes and Terpenoids, turpentine-oil, beta pinene fraction, polymd. The study, performed at Chemical Hygiene Fellowship (CHF) did not follow any guideline and the GLP conditions are not specified.

Five male Albino rabbit were exposed to 10 g/Kg of the test material. The material was applied to clipped, unbraded skin. It was dosed under polyethylene sheeting.

No signs of toxicity were recorded and no deaths occurred. The gross autopsy showed pale kidney, but no details are available.

According to the results of this study, the LD50 acute dermal of the test material Terpenes and Terpenoids, turpentine-oil, beta pinene fraction, polymd LD50 was >10 g/Kg.

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

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

Specific details on test material used for the study:

Test material: Zonares A25
Batch Number: AIA804
Date of receipt: 15 January 2018
Handling Instructions: Standard precautions

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system 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

Key result

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

Value:

5 000 mg/kg bw

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:

1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

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 or test system 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.

Key result

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

Value:

2 000 mg/kg bw

Justification for classification or non-classification

Not classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 orUN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).