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Administrative data

Description of key information

Acute oral toxicity (OECDTG401): >5000 mg/kg bw

Acute dermal toxicity (OECDTG402): >5000 mg/kg bw

Acute inhalation toxicity using route to route extrapolation from the oral route: > 13000 mg/m3

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:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
limit test with 10 males
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
albino
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals (received on August 3, 1982)
- Weight at study initiation: 224-297 g
- Fasting period before study: 16-20 hours prior to dosing
- Housing: 5 animals per cage in suspended wire mesh cages.
- Diet (e.g. ad libitum): fresh Purina rat chow (Diet #5012) ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.81 mL
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals observed 3-4 hours post dosing and once daily after for 14 days for mortality, toxicity and pharmocological effects.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died.
Clinical signs:
All animals suffered from flaccid muscle tone and lethargy, other signs observed in the animals were ataxia (9 animals), chromorhinorrhea (4), chromodacryorrhea (1), ptosis (1), brown staining of the anogenital area (3).
Gross pathology:
No abnormalities were found.
Interpretation of results:
other: not classified
Remarks:
based on CLP criteria (1272/2008/EC and its updates)
Conclusions:
Under the conditions of this test, an acute oral LD50 of >5000 mg/kg bw was determined for Tetrahydromyrcenol.
Executive summary:

An acute oral toxicity study was performed according to a method similar to OECD TG 401. In this study, 10 rats were administered Tetrahydromyrcenol at dose levels 5000 mg/kg bw. The mortality rate of the rats was 0/10. Clinical signs observed were flaccid muscle tone and lethargy, ataxia, chromorhinorrhea, chromodacryorrhea, ptosis and brown staining of the anogenital area. Gross necropsy was performed at end of term, but no abnormalities were found. Under the conditions of this test, an acute oral LD50 of >5000 mg/kg bw was determined for Tetrahydromyrcenol.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
limit test with 9 females, 1 male
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Remarks:
Albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals (received on July 27 and August 24, 1982)
- Weight at study initiation: 1.9-2.5 kg
- Housing: 2 animals per cage in suspended wire mesh cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature controlled
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: abdomen
- % coverage: 10% of the body surface
- Type of wrap if used: gauze patch, wrapped wtih plastic, secured with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the site was wiped
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): between 11.6-14.0 ml
- Concentration (if solution): 0.82 g/ml
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
9 females, 1 male
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 24 hours post dose and on days 7 and 14 for mortality, toxicity and pharmacological effect.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died.
Clinical signs:
Dermal reactions (erythema and edema) were slight to moderate observed on day 1, severe on day 7, and minimal on dag 14.
Physical signs observed were: Alopecia, diarrhea, few feces, yellow nasal discharge, ptosis.
Body weight:
Body weight changes were normal for 7/10 rabbits. Three rabbits, which had exhibited diarrhea and/or few faces, lost weight.
Gross pathology:
No abnormalities were found on the internal organs on superficial examination for 7/10 rabbits. Of the remaining 3 animals, alopecia adjacent to the treated site and intestinal abnormalities were noted.
Interpretation of results:
other: not classified
Remarks:
according to EU CLP criteria (EC 1272/2008 and its updates)
Conclusions:
Under the conditions of this test, an acute dermal LD50 of >5000 mg/kg bw was determined for Tetrahydromyrcenol.
Executive summary:

An acute dermal toxicity study was performed according to a method similar to OECD TG 402. In this study, 10 healthy albino rabbits were dosed dermally with Tetrahydromyrcenol at 5000 mg/kg bw of body weight. The test article was kept in contact with the skin for 24 hours. All rabbits survived the 5000 mg/kg bw dermal dose. Physical signs noted in 3 or more rabbits included yellow nasal discharge, diarrhea, alopecia and few feces. Dermal responses, slight to moderate on Day 1, were severe on Day 7 and minimal on Day 14. Body weight changes were normal for 7/10 rabbits. Three rabbits, exhibited diarrhea and/or few feces, lost weight. The internal organs on superficial examination appeared normal for 7/10 rabbits. Of the remaining 3 animals, alopecia adjacent to the treated site and intestinal abnormalities were noted. Under the conditions of this test, an acute dermal LD50 of >5000 mg/kg bw was determined for Tetrahydromyrcenol.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
comparable to guideline study with acceptable restrictions

Additional information

Acute oral toxicity

An acute oral toxicity study was performed according to a method similar to OECD TG 401. In this study, 10 rats were administered Tetrahydromyrcenol at dose levels 5000 mg/kg bw. The mortality rate of the rats was 0/10. Clinical signs observed were flaccid muscle tone and lethargy, ataxia, chromorhinorrhea, chromodacryorrhea, ptosis and brown staining of the anogenital area. Gross necropsy was performed at end of term, but no abnormalities were found. Under the conditions of this test, an acute oral LD50 of >5000 mg/kg bw was determined for Tetrahydromyrcenol.

Acute dermal toxicity

An acute dermal toxicity study was performed according to a method similar to OECD TG 402. In this study, 10 healthy albino rabbits were dosed dermally with Tetrahydromyrcenol at 5000 mg/kg bw of body weight. The test article was kept in contact with the skin for 24 hours. All rabbits survived the 5000 mg/kg bw dermal dose. Physical signs noted in 3 or more rabbits included yellow nasal discharge, diarrhea, alopecia and few feces. Dermal responses, slight to moderate on Day 1, were severe on Day 7 and minimal on Day 14. Body weight changes were normal for 7/10 rabbits. Three rabbits, exhibited diarrhea and/or few feces, lost weight. The internal organs on superficial examination appeared normal for 7/10 rabbits. Of the remaining 3 animals, alopecia adjacent to the treated site and intestinal abnormalities were noted. Under the conditions of this test, an acute dermal LD50 of >5000 mg/kg bw was determined for Tetrahydromyrcenol.

Acute inhalation toxicity: Acute inhalation is predicted based on the acute oral toxicity in accordance with the ECHA CLP guidance document (2015, 3.1.3.3.4: 1 mg/kg bw = 0.0052 mg/l (5.2 mg/m3). The acute inhalation is predicted to be > 13000 mg/m3 (using 100% inhalation and 50% oral absorption and an LD50 oral of > 5000 mg/kg bw). The calculated saturated vapour pressure is 604 mg/m3 (MW in mg*VP in Pa/ 8.3 (gas constant*293oK). This means that the acute inhalation concentration cannot be reached and therefore no acute inhalation toxicity is anticipated.

Justification for classification or non-classification

Based on the available data, the substance does not need to be classified for acute oral, dermal and inhalation toxicity in accordance to EU CLP (1272/2008 and its amendments).