Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute toxicity oral:
- Standard acute method (Rat): LD50 = 2650 mg/kg (95% CI >= 2300 - <= 3000) (similar to OECD guideline 401)
Acute toxicity dermal:
- Standard actue method (Rabbit): LD50 > 5000 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:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study can be compared to the deleted OECD 401 guideline for testing acute oral toxicity. The study was not performed under GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200 to 250 grams
- Fasting period before study: Fasted for a minimum of 16 hours prior to administration of the test material
- Diet: ad libitum
- Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No data available
Doses:
1600, 2050, 2560, 3200, and 4000 mg/kg
No. of animals per sex per dose:
10 rats (male)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality were made at 1 and 6 hours after dosing, and daily thereafter for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
No data
Preliminary study:
Not relevant
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 2 650 mg/kg bw
95% CL:
>= 2 300 - <= 3 000
Mortality:
Observed mortality per dose was as follows: 1600 mg/kg: 1/10; 2050 mg/kg: 2/10; 2560 mg/kg: 4/10; 3200 mg/kg: 7/10; 4000 mg/kg: 10/10.
Clinical signs:
other: The rats experienced salvination, ataxia, hyperactiveness, loss of righting reflex, and depression.
Gross pathology:
No data
Other findings:
No data
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 calculated from the data is 2650 mg/kg with 95% confidence limits of 2300 and 3000 mg/kg. The substance does not have to be classified according to the EU classification criteria outlined in 67/548/EEC and 1272/2008.
Executive summary:

In this acute oral toxicity test, performed similar to the deleted OECD 401 guideline, the undiluted compound was fed orally to 50 Wistar strain albino male rats in increasing doses at 5 levels (1600, 2050, 2560, 3200, and 4000 mg/kg). Observations for mortality were made at 1 and 6 hours after dosing and daily thereafter for 14 days. Gross necropsies were performed on all survivors.

The rats experienced salvination, ataxia, hyperactiveness, loss of righting reflex, and depression. The oral LD50 calculated from the data is 2650 mg/kg (95% confidence limits of 2300 and 3000 mg/kg). The substance does not have to be classified according to the EU classification criteria outlined in 67/548/EEC and 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 650 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:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study can be compared to OECD guideline 402, 1987. The study was not performed under GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
yes
Remarks:
Observatiion period: 7 days
Principles of method if other than guideline:
Npt applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.0 to 2.2 kg
- Housing: no data

ENVIRONMENTAL CONDITIONS: no data
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped and abraded abdominal skin
- Type of wrap if used: The animals were wrapped with binders of rubber dam, gauze and adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
5000 mg/kg
No. of animals per sex per dose:
10 animals/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Daily for signs of dermal irritation; weights once at pre-treatment and at post-treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal irritation (erythema and edema signs)
Statistics:
Not relevant
Preliminary study:
Not relevant
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No animals died during the course of the study.
Clinical signs:
other: There was no evidence of toxicity from percutaneous absorption of the test material. All animals were essentially normal by the termination of the study. Slight to moderate erythema and edema was observed in all animals.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this acute dermal toxicity in rabbits no mortality occurred after administrating a single dose of 5000 mg/kg. The acute dermal LD50 for the test material as indicated by the data in this study is >5000 mg/kg when applied to the abraded skin of albino rabbits. Based on these results and according to EU criteria the test substance does not need to be classified as acute toxic (dermal) according to the classification criteria outlined in 67/548/EEC and 1272/2008.
Executive summary:

An acute dermal toxicity study was conducted similar to OECD guideline 402. A single 24-hour application of the test material (5000 mg/kg) was made to the clipped abraded abdominal skin of 10 rabbits (New Zealand White). Following exposure, daily observations were made for mortality, toxic effects, and dermal irritation (erythema and edema signs) for a period of 7 days. Individual body weights were recorded once at pre-treatment and at post-treatment. A gross necropsy was performed on all animals at the termination of the study.

No animals died during the course of the study. There was no evidence of toxicity from percutaneous absorption of the test material. All animals were essentially normal by the termination of the study. The individual animal weight changes were normal. Slight to moderate skin irritation was observed in all animals. No abnormalities were noted at necropsy.

The acute dermal LD50 for the test material as indicated by the data in this study is >5000 mg/kg when applied to the abraded skin of albino rabbits. Based on these results and according to EU criteria the test substance does not need to be classified as acute toxic (dermal) according to the classification criteria outlined in 67/548/EEC and 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

Three studies on the acute oral toxicity of Peppermint oil were available for the dossier. All studies used a standard acute method to determine the oral LD50 of Peppermint oil. The key study indicated a LD50 of 2650 +/- 350 mg/kg bw. Additional supporting studies show LD50s of 4441 +/- 653 mg/kg bw (24h), 2426 +/- 329 mg/kg bw (48h) and >4000 mg/kg bw, all in rats. Furthermore, a supporting study in mice is available, in which an LD50 of >4000 mg/kg bw was reported. As all studies indicate a LD50 >2000 mg/kg bw, peppermint oil does not meet the criteria for classification as acute toxicant.

For acute dermal toxicity of Peppermint oil the key study indicated a LD50 of>5000mg/kg bw. No supporting studies were available.

In addition, an acute intraperitoneal toxicity study with Peppermint oil was available. This supporting study indicated an LD50 of 819 +/- 126 mg/kg bw (24h).


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

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 information for oral, dermal and intraperitoneal acute toxicity, the substance Peppermint oil does not need to be classified as acute toxic based on the criteria outlined in Annex I of 1272/2008/EC and Annex VI of 67/548/EEC.

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