Bergamot, ext.

Endpoint summary

Description of key information

Acute oral toxicity: LD50>10000 mg/kg bw (similar to OECD guideline 401)
Acute dermal toxicity: LD50>20000 mg/kg bw (similar to OECD guideline 402)

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:

1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test was conducted according to methods similar to OECD guideline 401 and was performed pre-GLP. A concise description of the protocol is available and only mortality data are reported. Although concise, report is valid for acute toxicity assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Study was performed prior to implementation of OECD guideline 401. Methodology is comparable, though limited information on study protocol and test outcomes are available.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 150-250grams
- Fasting period before study: 18 hrs prior to dosing

ENVIRONMENTAL CONDITIONS
No further information provided

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

- Concentration in vehicle: 2500, 5000 and 10000 mg/kg bw

Doses:

1 dose at t=0

No. of animals per sex per dose:

6 male rats per dose group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: no
- Other examinations performed: animals were examined for general toxic effects

Statistics:

No data provided.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

2 rats in the 10000 mg/kg bw dose group died within 1 day after administration.

Clinical signs:

other: No data provided.

Gross pathology:

No data provided.

Other findings:

Depression was observed. No further description provided.

	Cumulative Mortality
Dose (mg/kg bw)	Immediately	1 hrs.	4 hrs.	1 day	2 days	3 days	4 days	5 days	6 days	7 days
2500	0	0	0	0	0	0	0	0	0	0
5000	0	0	0	0	0	0	0	0	0	0
10000	0	0	0	2	2	2	2	2	2	2

Table 1. cumulative mortality of male albino rats after administration of bergamot oil by oral gavage.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of Bergamot oil in rats was established at exceeding 10000 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:

In an acute toxicity study, performed similar to OECD 401, male albino rats were exposed to bergamot oil (furocoumarin free quality). Rats were divided in 3 groups of 6 animals and were exposed via oral gavage to doses of resp. 2500, 5000 or 10000 mg/kg bw. Test animals were observed until 7 days after dosing. Within day 1 after dosing two rats in the 10000 mg/kg bw dose group died. No necropsies were performed. The oral LD50 value of Bergamot oil in rats was established at exceeding 10000 mg/kg body weight, under the conditions of this study. The substance therefore does not have to be classified according to the classification criteria as 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:

10 000 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:

1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test was conducted according to methods similar to OECD guideline 402 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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Study was performed prior to implementation of OECD guideline 401 but methodology used is regarded comparable.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

other: albino

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation:1400-1750 grams

ENVIRONMENTAL CONDITIONS
No data available

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Type of wrap if used: Saran wrap and bandages

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test material was removed (method unspecified)
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):20,000 mg/kg bw

VEHICLE
No vehicle was used

Duration of exposure:

24 hrs

Doses:

20000 mg/kg bw

No. of animals per sex per dose:

3 animals, sex unknown

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: animals were observed daily for signs of systemic toxicity; body weight gain and dermal erythema and/or edema was scored daily.
- Necropsy of survivors performed: gross autopsy at termination of the study (day 7)
- Other examinations performed: on day 5 blood samples were taken for hematology and clinical chemistry. Hematology included: erythrocyte, leucocyte and differential leucocyte counts; hematocrit and hemaglobin assessment. Clinical chemistry included serum glutamic oxaloacetic transaminase (SGOT); glucose; blood urea nitrogen (BUN); serum alkinase phosphatase (SAP); total serum protein; serum albumin; bilirubin; lactic acid dehydrogenase (LDH); cholesterol, serum calcium; serum phosphate and uric acid.

Statistics:

No data available

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 20 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died during the study.

Clinical signs:

other: All subject showed mild erythema following the 24-hour exposure period, but edema was not observed. Erythema persisted in all three animals during the experimental period.

Gross pathology:

No gross signs of toxicity were observed.

Other findings:

Hematology and clinical chemistry were within normal limits and comparable to control values.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 value of Bergamot oil in rabbits was established at exceeding 20000 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:

In an acute dermal toxicity test, performed according to a method comparable to OECD guideline 402, three albino rabbits were exposed to bergamot oil. Test animals were partially shaved. Bergamot oil was applied to the shaved skin under occlusion at an undiluted dosage of 20000 mg/kg bw. After 24 hours exposure, excess oil was removed and animals were observed for 7 days. Body weight, systemic toxicity and dermal irritation were recorded daily. On day 5 blood was drawn to determine hematology and clinical chemistry. At day 7, all animals were sacrificed and gross pathology was performed.

Bergamot oil did not produce mortality under the conditions of this study. All subjects developed mild erythema but edema was not observed. There were no gross signs of systemic toxicity and body weight gain, hematology and clinical chemistry were within normal limits and comparable to control values. Under the conditions of this study, the LD50 for dermal toxicity was established at > 20000 mg/kg bw. The substance therefore does not have to be classified according to the classification criteria as 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:

20 000 mg/kg bw

Additional information

Acute oral toxicity

The key study was an acute toxicity study, performed similar to OECD guideline 401, in which three groups of six male albino rats were exposed via oral gavage to doses of respectively 2500, 5000 or 10000 mg/kg bw of bergamot oil (furocoumarin free quality). Within day 1 after dosing two rats in the 10000 mg/kg bw dose group died. Based on these results, the oral LD50 value of Bergamot oil in rats was established at exceeding 10000 mg/kg bw, under the conditions of this study.

Acute dermal toxicity

The key study was an acute dermal toxicity test, performed according to a method comparable to OECD guideline 402, in which three albino rabbits were exposed to bergamot oil. Bergamot oil was applied under occlusion at an undiluted dosage of 20000 mg/kg bw. Bergamot oil did not produce mortality under the conditions of this study. Based on these results, the LD50 for dermal toxicity was established at > 20000 mg/kg bw under the conditions of this study.

Justification for selection of acute toxicity – oral endpoint
The selected study is the key study for this endpoint.

Justification for selection of acute toxicity – inhalation endpoint
Oral and dermal acute tox data available.

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 acute oral toxicity study, Bergamot oil does not have to be classified according to the classification criteria as outlined in Annex I of 1272/2008/EC (CLP/EU-GHS).

 

Based on the available acute dermal toxicity study, Bergamot oil does not have to be classified according to the classification criteria as outlined in Annex I of 1272/2008/EC (CLP/EU-GHS).