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EC number: 229-352-5 | CAS number: 6485-40-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
LD50 Oral (male/female): 5400mg/kg bw (OECD 401;GLP)
LD50 Dermal: >2000mg/kg bw (OECD 402; GLP)
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 29 May 1986 - 26 June 1986
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: Annex V 79/831/EEC Method B.1; OECD Guideline 401
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- other: CFY (Sprague Dawley origin)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Interfauna U.K. Ltd., Huntington, Cambridgshire, UK.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 90-142g
- Housing: Within treatment groups, by sex, in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): A standard rodent diet (Labsure LAD 1 diet) ad libitum.
- Fasting period before study: Access to food only was prevented overnight prior to and approx. 4 hours after dosing.
- Water (e.g. ad libitum): Drinking water ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean daily minimum and maximum were 21°C and 23°C
- Humidity (%): Mean daily relative humidity was 59%
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours aritifical light in each 24 hour period - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED:
3.30 mL/kg : 3.2 g/kg dose
5.15 mL/kg : 5.0 g/kg dose
8.25 mL/kg : 8.0 g/kg - Doses:
- Preliminary test: single dose of 5.0 g/kg bw of undiluted test substance
Main test: 3.2, 5.0, or 8.0 g/kg of undiluted test substance at a dose volume of 3.30, 5.15, or 8.25 mL/kg respectively. - No. of animals per sex per dose:
- Preliminary test: 2 male and 2 female animals
Main test: 5 male and 5 female animals - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observations: Soon after dosing, frequently on Day 1, on subsequent days once in the morning and the evening; 5 and 14 days observations for preliminary and main tests respectively.
Body weights were recorded on Days 1 (day of dosing), 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, terminal autopsy - Statistics:
- The acute median lethal oral dose was calculated by method of Weil.
(Weil, C.S. (1952) Biometrics, 8: 249.) - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 5 400 mg/kg bw
- 95% CL:
- 4 600 - 6 300
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 5 900 mg/kg bw
- 95% CL:
- 4 900 - 7 100
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 4 900 mg/kg bw
- 95% CL:
- 3 900 - 6 100
- Mortality:
- Preliminary test (males and females):
At 5 g/kg bodyweight: 0/4 deaths;
Main test (males):
At 3.2 g/kg: 0/5 deaths;
At 5 g/kg: 1/5 deaths (by day 4);
At 8 g/kg: 5/5 deaths (by day 3).
Main test (females):
At 3.2 g/kg: 0/5 deaths;
At 5 g/kg: 3/5 deaths (by day 4);
At 8 g/kg: 5/5 deaths (by day 5). - Clinical signs:
- other: All rats: piloerection, hunched posture, increased salivation; abnormal gait (waddling) in majority of rats; isolated cases of prostration and straub tail. At 3.2 g/kg: lethargy (one male), pallor of extremities, ataxia and body tremors; clinical signs
- Gross pathology:
- All rats surviving to the end of the observation period were killed on day 15 by cervical dislocation and examined macroscopically.
Terminal necropsy showed no macroscopic abnormalities except for unilateral hydronephrosis of 1 male in the lower dose
group. - Other findings:
- - Other observations: Autopsy revealed pallor of the kidneys, liver and/or spleen in all rats that died.
- Interpretation of results:
- not classified
- Conclusions:
- The acute median lethal oral doses (LD50) and their 95% confidence limits to rats of L-carvone were estimated to be:
LD50 (combined): 5400 mg/kg bw (4600 - 6300 mg/kg bw; 95% C.I)
LD50 (male): 5900 mg/kg bw (4900 - 7100 mg/kg bw; 95% C.I)
LD50 (female): 4900 mg/kg bw (3900 - 6100 mg/kg bw; 95% C.I) - Executive summary:
In an acute oral toxicity study (86771D/ULR 138/AC), groups of fasted, young CFY (Sprague Dawley origin) (5/sex) were given single oral doses of L-carvone undiluted at 3.2, 5.0, or 8.0 g/kg bw and observed for 14 days.
LD50 (combined): 5400 mg/kg bw (4600 - 6300 mg/kg bw; 95% C.I)
LD50 (male): 5900 mg/kg bw (4900 - 7100 mg/kg bw; 95% C.I)
LD50 (female): 4900 mg/kg bw (3900 - 6100 mg/kg bw; 95% C.I)
No mortalities were observed at 3.2 g/kg bw while no rat survived administration of L-carvone of 8 g/kg bw. Clinical signs were noted at all doses and resolved towards the end of the observation period in surviving animals. Body weights were lower during first week of observation but were as anticipated at end of second week of observation. Terminal necropsy showed no treatment-related macroscopic abnormalities.
This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study (OECD 401) in the rat.
Reference
Table 1: Time and number of deaths or rats dosed orally with L-carvone (Main study)
Day | ||||||||||||||
Sex | Dose (g/kg) | Number of deaths in a group of 5 | 1 | 2 | 3 | 4 | 5 | 6 to 15 | ||||||
a | b | a | b | a | b | a | b | a | b | a | b | |||
Male | 3.2 | 0 | ||||||||||||
5 | 1 | 1 | ||||||||||||
8 | 5 | 3 | 1 | 1 | ||||||||||
Female | 3.2 | 0 | ||||||||||||
5 | 3 | 2 | 1 | |||||||||||
8 | 5 | 2 | 1 | 2 |
(a): First observation
(b:) Second observation
.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 5 400 mg/kg bw
- Quality of whole database:
- The key study was the only study available and was assigned a Klimisch score of 1. The overall quality of the database is high.
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 01-09-99 to 22-09-99
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 402 (Acute Dermal Toxicity) and Method B.3 of Commission Directive 92/69/EEC
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: Sprague-Dawley CD (Crl : CD (SD) IGS BR)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: Approximately eight to twelve weeks old
- Weight at study initiation: Male - 226 to 241 g; Female - 216 to 233 g.
- Housing: The animals were housed in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Rat and Mouse SQC Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK ad libitum
- Water (e.g. ad libitum): Mains drinking water ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Within 19 to 25°C target range
- Humidity (%): Within 30 to 70% target range
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light - Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: Back and flanks of each animal were clipped free of hair. The substance was applied uniformly to an area of shorn skin.
- % coverage: Approximating to 10% of the total body surface area
- Type of wrap if used: Surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin and surrounding hair was wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: After 24h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.10 mL/kg (2000 mg/kg; specific gravity: 0.956) - Duration of exposure:
- 24 h
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 5 male and 5 female
- Control animals:
- not required
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observed for deaths or overt signs of toxicity: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Observations for evidence of primary irritation: Once daily every 14 days.
Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal reactions.
The dermal reactions were numerically graded daily for erythema and eschar formation [0 (no erythema) to 4 (severe erythema to slight eschar formation)] and edema [0 (no edema) to 4 (severe edema); see Draize scoring system below]. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Mortality:
- There were no deaths (Table 1).
- Clinical signs:
- other: No clinical signs of toxicity were noted during the study (Table 1).
- Gross pathology:
- No abnormal macroscopic findings at necropsy.
- Other findings:
- - Other observations: No signs of dermal irritation were noted during the study (Table 2; Draize scoring system) .
- Interpretation of results:
- not classified
- Conclusions:
- The acute dermal median lethal dose (LD50) of L-carvone in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bw.
- Executive summary:
In an acute dermal toxicity study (012_300), young adult Sprague-Dawley CD (Crl : CD (SD) IGS BR) rats (5/sex) were dermally exposed (semi-occlusive; approximately 10% of the total body surface area) to L-carvone for 24 hours in a limit test at a dose of 2000 mg/kg bw. Animals were then observed for 14 days.
The dermal LD50 Male/Female was greater than 2000 mg/kg bw (limit test). There were no treatment related clinical signs, necropsy findings, changes in body weight or signs of dermal irritation noted during the study.
This acute dermal study is classified as acceptable. It does satisfy the guideline requirement for an acute dermal study (OECD 402) in the rat.
Reference
Table 1: INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA
Dose Level mg/kg | Animal Number and Sex | Effects Noted After Dosing (Hours) | Effects Noted During Period After Dosing (Days) | ||||||||||||||||
2000 mg/kg | 0.5 | 1 | 4 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | ||
Male 1-0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Male 1-1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Male 1-2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Male 1-3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Male 1-4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Female 2-0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Fernale 2-1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Fernale 2-2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Female 2-3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Female 2-4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
0 = no signs of systemic toxicity
Study report attachments:
Table 2 Individual dermal reactions (012_300)
Table 3 Individual bodyweights and weekly bodyweight changes (012_300)
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- The key study was the only study available and was assigned a Klimisch score of 1. The overall quality of the database is high.
Additional information
Acute oral toxicity
There is one acute oral toxicity study in rats available.
In an acute oral toxicity study (OECD 401/GLP), groups of fasted, young CFY (Sprague Dawley origin) (5/sex) were given single oral doses of L-carvone undiluted at 3.2, 5.0, or 8.0 g/kg bw and observed for 14 days. No mortalities were observed at 3.2 g/kg bw while no rat survived administration of L-carvone of 8 g/kg bw. Clinical signs were noted at all doses and resolved towards the end of the observation period in surviving animals. Body weights were lower during first week of observation but were as anticipated at end of second week of observation. Terminal necropsy showed no treatment-related macroscopic abnormalities. The LD50 (combined) was 5400 mg/kg bw (4600 - 6300 mg/kg bw; 95% C.I). The LD50 (male) was 5900 mg/kg bw (4900 - 7100 mg/kg bw; 95% C.I). The LD50 (female) was 4900 mg/kg bw (3900 - 6100 mg/kg bw; 95% C.I).
Acute dermal toxicity
There is one acute dermal toxicity study in rats available.
In an acute dermal toxicity study (OECD 402/GLP), young adult Sprague-Dawley CD (Crl : CD (SD) IGS BR) rats (5/sex) were dermally exposed (semi-occlusive; approximately 10% of the total body surface area) to L-carvone for 24 hours in a limit test at a dose of 2000 mg/kg bw. Animals were then observed for 14 days. The dermal LD50 (male/female) was greater than 2000 mg/kg bw. There were no treatment related clinical signs, necropsy findings, changes in body weight or signs of dermal irritation noted during the study.
Both studies are suitable to use the in human health risk assessment.
Justification for classification or non-classification
Based on the available information in the dossier, the substance L-carvone (CAS No. 6485-40-1) does not need to be classified for acute toxicity or specific target organ toxicity - single exposure when the criteria outlined in Annex I of 1272/2008/EC are applied.
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