Essential oil of Copaiba obtained from the exudate of Copaifera (Fabaceae) trees by distillation

Endpoint summary

Description of key information

Acute oral toxicity (method similar to OECD TG 401): LD50 >5000 mg/kg bw

Acute oral toxicity : LD50 >2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

clear colorless liquid SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: research Institute for Fragrance Materials
-RIFM number: 56452

Species:

rat

Strain:

Sprague-Dawley

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 150-300 g
- Fasting period before study: overnight

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% (v/v)
- Justification for choice of vehicle: according to guideline

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: toxic signs and mortality were observed forllowing dosing at one and four hours, and once daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Preliminary study:

Two aninals were given a single dose by gastric intubation. No deaths occured, so 8 additional animals were given the samen dose via the same route.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No

Clinical signs:

other: Signs of diahrrea, depression and piloerection were observed.

Gross pathology:

No gross findings

Interpretation of results:

other: not classied

Remarks:

based on CLP criteria (Annex I 1272/2008/EC)

Conclusions:

The oral LD50 value of Copaiba balsam oil in rats was established to be higher than 5000 mg/kg bw, under the conditions of this study. The substance therefore does not need to be classified for acute oral toxicity according to the criteria laid down in Annex I of 1272/2008/EC (CLP).

Executive summary:

The acute toxic potential of Copaiba Balsam oil was assessed in an acute oral toxicity limit test performed in 10 rats. The rats were exposed to 5000 mg/kg bw Copaibla balsam oil via the oral route, and observed for clinical signs and mortality over an examination period of 14 days. Observations were performed at one and four hours and daily thereafter. At the end of the study period no mortality was observed in any of the animals. Symptoms observed in the test animals were diarrhea, depression, piloerection. No gross findings were noted. The LD50 for acute oral toxicity was set at >5000 mg/kg bw.

Based on these results Copaiba Balsam oil does not have to be classified for acute oral toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

- Principle of test:medical properties of oleoresin were assessed, investigating the ant-inflammatory activity of the oleoresin, when administered by oral route on various animal models and have concomitantly tested its toxcicological effects. Models used were: Assessment of Carrageening-induced edeema, Cotton-pellet granuloma, Vasculair permeability, and determination of Toxicity

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Name: Copaiba oleoresin (oleoresin from Brazilian copaifera species)
- Source: The oleoresin was obtained from the Brazilian state of Pará by the Discipline of Pharmacognosy of the Faculty of Pharmaceutical Sciences of São Paulo University.

OTHER SPECIFICS:
-Viscous liquid, aromatoc odor dark brown
-Constituents were determined through GC and identified quantitatively by MS
-Refractive index (25°C) 1.5088
-Specific gravity (25°C) 0.9751

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Diet: Fasted, normal diet was Nuvilab CR-1 (Nutrivital)
- Water: ad libitum
- Weight at study initiation: 180 +- 10 grams

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

Not specified

Doses:

Carrageenin-induced edema: 0.7, 0.98, 1.37, 1.92, 2.96 ml/kg; (0.68, 0.96, 1.34, 1.87, 2.87 g/kg bw)
Cotton-pellet granuloma: 1.26 ml/kg bw; (1.23 g/kg bw)
Vasculair permeability: 1.26 ml/kg bw (1.23 g/kg bw)

No. of animals per sex per dose:

Not specified. (For granuloma tisue formation N=10, For vasculair permeability N=6, For determination of toxicity N=20.)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: Animals were observed for 72 hours for toxicity
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, histopathology, paw- volume, macroscopy of granulomatous tissue, subcutaneous tissue.

Statistics:

The LD50 was estimated by the method of Thompson and Weil (1951). Analysis of variance with one-way classification was used; sequesntial differences among means were calculated at a level of P < 0.05, using Yukey contrast analysis (Sokal and Rolhf, 1969).

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

3.79 mL/kg bw

Based on:

test mat.

95% CL:

> 3.21 - < 4.47

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

3 670 mg/kg bw

Based on:

test mat.

95% CL:

> 3 130 - < 4 360

Mortality:

Not specified

Clinical signs:

other: See below

Gross pathology:

Development of carrageenin induced pedal edema in dose-dependent manner. assessment of granulomaeous tissue revealed inhobitory effect. Effects in subcutaneous tissue were wignificant reduced permeability increase.

Other findings:

Effects of subacute toxicity on day 18, of experimental period the groups treated with 1.92 and 2.86 ml/kg showed a reduction in respect to body weight and in the consumption of food when compared to control group. The efffects were accompanied by diahrrea, sialorrhea, symptoms of depression and gastric irriation consisting of elongated red bands on stomach.

Interpretation of results:

other: not classified

Remarks:

based on CLP criteria (Annex I 1272/2008/EC)

Conclusions:

The oral LD50 value of Copaiba oleoresin in rats was calculated to be >2000 mg/kg bw (3.79 ml/kg bw) under the conditions of this study. Based on these results Copaiba oleoresin does not have to be classified for acute oral toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Executive summary:

The acute toxic potential of Copaiba oleoresin was assessed in various animal models. The rats were exposed to doses of 0.7, 0.98. 1.37, 1.92 and 2.96 ml/kg bw (0.68, 0.96, 1.34, 1.87, 2.87 g/kg bw, assessment of Carrageenin-induced edema), and to 1.26 ml/kg bw; (1.23 g/kg bw) to assess Cotton-pellet granuloma and Vasculair permeability via the oral route. Sub-acute symptoms observed in the test animals were for the higher doses reduction in respect to body weight and in the consumption of food. The effects were accompanied by diahrrea, sialorrhea, symptoms of depression and gastric irriation. The oral LD50 value of Copaiba oleoresin in rats was calculated to be >2000 mg/kg bw (3.79 ml/kg bw) under the conditions of this study. Based on these results Copaiba oleoresin does not have to be classified for acute oral toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute toxicity, oral (Hart 1971)

The acute toxic potential of Copaiba Balsam oil was assessed in an acute oral toxicity limit test performed in 10 rats. The rats were exposed to 5000 mg/kg bw Copaibla balsam oil via the oral route, and observed for clinical signs and mortality over an examination period of 14 days. Observations were performed at one and four hours and daily thereafter. At the end of the study period no mortality was observed in any of the animals. Symptoms observed in the test animals were diarrhea, depression, piloerection. No gross findings were noted. The LD50 for acute oral toxicity was set at >5000 mg/kg bw. Based on these results Copaiba Balsam oil does not have to be classified for acute oral toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Acute toxicity, oral (Basile 1988)

The acute toxic potential of Copaiba oleoresin was assessed in various animal models. The rats were exposed to doses of 0.7, 0.98. 1.37, 1.92 and 2.96 ml/kg bw (0.68, 0.96, 1.34, 1.87, 2.87 g/kg bw, assessment of Carrageenin-induced edema), and to 1.26 ml/kg bw; (1.23 g/kg bw) to assess Cotton-pellet granuloma and Vasculair permeability via the oral route. Sub-acute symptoms observed in the test animals were for the higher doses reduction in respect to body weight and in the consumption of food. The effects were accompanied by diahrrea, sialorrhea, symptoms of depression and gastric irriation. The oral LD50 value of Copaiba oleoresin in rats was calculated to be >2000 mg/kg bw (3.79 ml/kg bw) under the conditions of this study. Based on these results Copaiba oleoresin does not have to be classified for acute oral toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Justification for classification or non-classification

The oral LD50 of Copaiba Balsam oil was determined to be higher than 5000 mg/kg bw. Based on the available information, the test substance does not need to be classified for acute oral and dermal toxicity, according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).