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EC number: 218-827-2 | CAS number: 2244-16-8
- 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
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- Solubility in organic solvents / fat solubility
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- Flash point
- Auto flammability
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- 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
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- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
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- Nanomaterial aspect ratio / shape
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- Nanomaterial catalytic activity
- Endpoint summary
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- 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
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Carcinogenicity
Administrative data
Description of key information
Carcinogenicity by oral route
Under the conditions of these 2-year gavage studies, d-carvone (2244-16-8) was considered to be not carcinogenic as there was no evidence of carcinogenic activity was observed, When male or female B6C3F1 mice administered d-carvone (2244-16-8)at 375 or 750 mg/ kg, 5 days per week for 2 years.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data from experimental study report
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Principles of method if other than guideline:
- The carcinogenicity study of d-carvone was performed in B6C3F1 mice.
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material: d-Carvone- IUPAC name: (5S)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one- Molecular formula: C10H14O- Molecular weight: 150.22 g/mole- Smiles :C1[C@H](CC=C(C1=O)C)C(C)=C- Inchl: 1S/C10H14O/c1-7(2)9-5-4-8(3)10(11)6-9/h4,9H,1,5-6H2,2-3H3/t9-/m0/s1- Substance type: Organic- Physical state: Colorless to pale-yellow liquid
- Species:
- mouse
- Strain:
- B6C3F1
- Details on species / strain selection:
- no data available
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: Frederick Cancer Research Facility(Frederick, MDl)- Age at study initiation: 8weeks ,6days - Weight at study initiation: no data available- Fasting period before study: no data available - Housing: Animals were housed five per cage,Polycarbonate (Hazleton Systems, Inc., Aberdeen, MD , Bedding: Beta Chips (Northeastern Products, Inc., Warrensburg, NY) Cage Filters Reemaye spun-bonded polyester filters (Snow Filtration, Cincinnati, om)- Diet NIH 07 Rat and Mouse Ration (ZeiglerBros., Inc., Gardners, PA); availablead libitum- Water (e.g. ad libitum): Automatic watering system (Edstrom Industries, Waterford, WI); available ad libitum - Acclimation period: 13 days ENVIRONMENTAL CONDITIONS- Temperature (°C): 15-28°C- Humidity (%):23% 90%- Air changes (per hr): 6-12room air Changes/h- Photoperiod (hrs dark / hrs light): 12h/dIN-LIFE DATES: From: To:
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:Test material soluble in corn oil DIET PREPARATION- Rate of preparation of diet (frequency): no data available- Mixing appropriate amounts with (Type of food): no data - Storage temperature of food: no data availableVEHICLE- Justification for use and choice of vehicle (if other than water): Because the feed blends of d-carvone were found to be unstable under the feed blending and simulated animal exposure conditions and because d carvoneis insoluble in water, - Concentration in vehicle: 0,375, or 750 mglkg- Amount of vehicle (if gavage):10ml/kg - Lot/batch no. (if required):no data - Purity:
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The corn oil solutions were extracted with methanol and analysed by high-performance liquid chromatography with a Brownlee RP-18 column and ultraviolet detection at 229 nm
- Duration of treatment / exposure:
- 103 wk (some mice received 1or 2 doses during wk 104)
- Frequency of treatment:
- 5 days /week
- Post exposure period:
- no data available
- Remarks:
- 0,375, or 750 mg/kg
- No. of animals per sex per dose:
- Total:3000mg/kg:50 male and 50 female 375mg/kg:50 male and 50 female750mg/kg:50 male and 50 female
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Because 1,500 mg/kg was lethal to both male and female mice in the 13-week studies, doses of d-carvone selected for mice for the 2-year studies were 375 and 750 mg/ kg, administered in corn oil by gavage, 5 days per week.
- Positive control:
- no data available
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes - Time schedule: twice day - Cage side observations checked in table [No.?] were included. DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: DERMAL IRRITATION (if dermal study): No data - Time schedule for examinations: BODY WEIGHT: Yes - Time schedule for examinations:weighed initially, 1 X wk for 13 wk, and then at least 1 X month FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data - Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data FOOD EFFICIENCY: - Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data - Time schedule for examinations: OPHTHALMOSCOPIC EXAMINATION: No data - Time schedule for examinations: - Dose groups that were examined: HAEMATOLOGY: No data - Time schedule for collection of blood: - Anaesthetic used for blood collection: Yes (identity) / No / No data - Animals fasted: Yes / No / No data - How many animals: - Parameters checked in table [No.?] were examined. CLINICAL CHEMISTRY: No data - Time schedule for collection of blood: - Animals fasted: Yes / No / No data - How many animals: - Parameters checked in table [No.?] were examined. URINALYSIS:No data - Time schedule for collection of urine: - Metabolism cages used for collection of urine: Yes / No / No data - Animals fasted: Yes / No / No data - Parameters checked in table [No.?] were examined. NEUROBEHAVIOURAL EXAMINATION: No data - Time schedule for examinations: - Dose groups that were examined: - Battery of functions tested: sensory activity / grip strength / motor activity / other: OTHER:
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes HISTOPATHOLOGY: Yes (all organs and tissues were examined for grossly visible lesions. Tissues were preserved in 10% neutral buffered formalin, embeddedin paraffin, sectioned, and stained with hematoxylin and eosin.)
- Other examinations:
- no data available
- Statistics:
- The logistic regression, alternativemethods of statistical analysis were used, andThese include the life table test (Cox, 1972; Tarone, 1975), appropriate for rapidly lethal tumors, and the Fisher exact test and the Cochran-Armitage trend test (Armitage,1971; Gart et aI., 1979), procedures based on the overall proportion of tumor-bearing animals.Tests of significance include pairwise comparisons of each dosed group with vehicle controls and a test for an overall dose-response trend. Continuity-corrected tests were used in the analysis of tumor incidence, and reported P values are one-sided. The procedures described above also were used to evaluate selected non neoplastic lesions
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No compound-related clinical signs were observed.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- The survival of both the 375mg/kg dose (after week 101) and 750 mg/kg dose (after week 92) groups of female mice were significantly greater than that of the vehicle controls. No significant differences were observed between any groups of male mice
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Mean body weights of dosed and vehicle control male mice were similar throughout most of the studies; mean body weights of dosed female mice were within 7% of those of vehicle controls throughout most of the studies.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- Atrophy of the olfactory epithelium and hyperplasia of the underlying Bowman's glands occurred together. These may have been related to reflux of d-carvone into the nose after the gavage needle was withdrawn, because inflammatory exudate and "foreign material" were often found in the nasal passage of dosed animals. Fibromas, sarcomas, fibrosarcomas, or neurofibrosarcomas (combined) were observed with a negative trend in male mice, and the reduced incidence was significant in 375mg/kg dose male mice (vehicle control, 9/50; 375mg/kg dose, 1/50; 750mg/kg dose, 3/50). Three haemangioma or haemangiosarcomas were observed in vehicle control male mice, but none was seen in dosed males; the difference was not significant. Abscesses of the ovary and the uterus occurred at a high incidence in vehicle control female mice and at much lower incidences in dosed female mice (ovary: vehicle control, 26/50; 375mg/kg dose, 9/48; 750mg/kg dose, 1/48; uterus: 10/50; 3/50; 0/50). The lesions were similar to those observed in other studies associated with Krebsiella sp. infections and are believed to be the cause of reduced survival in vehicle control female mice relative to that of dosed female mice.
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- No increases in tumor incidences were observed in mice administered d-carvone.
- Other effects:
- not specified
- Relevance of carcinogenic effects / potential:
- Under the conditions of these 2-year gavage studies, d-carvone (2244-16-8) was considered to be not carcinogenic as no increases in tumor incidences were observed in mice administered d-carvone. Despite the absence of clearly chemically related toxic effects in the 2-year studies, the doses used were considered adequate for assessment of potential carcinogenicity because higher doses caused deaths in the 13-week studies.
- Dose descriptor:
- NOAEL
- Effect level:
- 750 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- histopathology: neoplastic
- histopathology: non-neoplastic
- mortality
- Remarks on result:
- other: No increases in tumor incidences were observed in mice administered d-carvone.
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- Under the conditions of these 2-year gavage studies, d-carvone (2244-16-8) was considered to be not carcinogenic as there was no evidence of carcinogenic activity was observed, When male or female B6C3F1 mice administered d-carvone (2244-16-8)at 375 or 750 mg/ kg, 5 days per week for 2 years.
- Executive summary:
The carcinogenicity ofd-carvone (2244-16-8)was studied in male and femaleB6C3Flmicefor2years.50 males and 50 female per dose group were used. The test material in dose concentration0,375, or 750 mg/kg administered by oral gavage route in dose volume 10ml/kg for 5days /week in 103 wk (some mice received 1or 2 doses during wk 104). The feed blends of d-carvone were found to be unstable under the feed blending and simulated animal exposure conditions and becausedcarvone is insoluble in water, corn oil gavage was selected as the route of administration for these studies. The 21-day stability of d-carvone in corn oil at 0.5%(5mg/g) stored at room temperature or at 5° C was determined. The corn oil solutions were extracted with methanol and analysed by high-performance liquid chromatography with a Brownlee RP-18 column and ultraviolet detection at 229 nm. The d-carvone/corn oil solutions were found to be stable for at least 21 days when stored in the dark at room temperature or at 5° C. The corn oil solutions were also stable under simulated dosing conditions for at least 3 hours. Animals were housed five per cage. Feed and water were available ad libitum. All animals were observed two times per day. Body weights were recorded once per week for the first 13 weeks of the study and at least once per month thereafter. During necropsy, all organs and tissues were examined for grossly visible lesions. Tissues were preserved in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin.
No compound-related clinical signs were observed. The survival of both the 375mg/kg dose (after week 101) and 750 mg/kgdose(after week 92) groups of female mice were significantly greater than that of the vehicle controls. No significant differences were observed between any groups of male mice. Mean body weights of dosed and vehicle control male mice were similar throughout most of the studies; mean body weights of dosed female mice were within 7% of those of vehicle controls throughout most of the studies.
Atrophy of the olfactory epithelium and hyperplasia of the underlying Bowman's glands occurred together. These may have been related to reflux of d-carvone into the nose after the gavage needle was withdrawn, because inflammatory exudate and "foreign material" were often found in the nasal passage of dosed animals. Fibromas, sarcomas, fibrosarcomas, or neurofibrosarcomas (combined) were observed with a negative trend in male mice, and the reduced incidence was significant in 375mg/kg dose male mice (vehicle control, 9/50; 375mg/kg dose, 1/50; 750mg/kg dose, 3/50). Three haemangioma or haemangiosarcomas were observed in vehicle control male mice, but none was seen in dosed males; the difference was not significant. Abscesses of the ovary and the uterus occurred at a high incidence in vehicle control female mice and at much lower incidences in dosed female mice (ovary: vehicle control, 26/50; 375mg/kg dose, 9/48; 750mg/kg dose, 1/48; uterus: 10/50; 3/50; 0/50). The lesions were similar to those observed in other studies associated with Krebsiella sp. infections and are believed to be the cause of reduced survival in vehicle control female mice relative to that of dosed female mice.No increases in tumor incidences were observed in mice administered d-carvone. Despite the absence of clearly chemically relatedtoxic effects in the 2-year studies, the doses used were considered adequate for assessment of potential carcinogenicity because higher doses caused deaths in the 13-week studies. Hence Under the conditions of these 2-year gavage studies, d-carvone (2244-16-8) was considered to be not carcinogenic as there wasno evidence of carcinogenic activitywas observed, When male or female B6C3F1mice administered d-carvone (2244-16-8)at 375 or 750 mg/ kg, 5 days per week for 2 years.
Reference
Summary table of the carcinogenicity study
Dose Mg/kg bw /day | 0 | 375 | 750 | Dose related | ||||
| m | f | m | f | m | f |
| |
Mortality | 13/50 | 36/50 | 8/50 | 21/50 | 14/50 | 12/50 |
| |
Mean survival (days | 679 | 639 | 694 | 652 | 631 | 676 |
| |
Clinical signs | no toxicologically relevant effects |
| ||||||
Body weight gain | no toxicologically relevant effects |
| ||||||
Histopathology |
|
|
|
|
|
|
| |
-forestomach |
|
|
|
|
|
|
| |
acanthosis, focal | 2/48 | 5/47 | 3/48 | 2/47 | 5/47 | 7/49 |
| |
acanthosis, multifocal | 2/48 | 1/47 | 2/48 | 0/47 | 6/47 | 0/49 |
| |
-Nasal cavity |
|
|
|
|
|
|
| |
glands hyperplasia | 3/50 | 19/49 | 42/50* | 45/49* | 44/49* | 49/50* | dr | |
atrophy olfact. epithelium | 11/50 | 25/49 | 42/50* | 46/49* | 44/49* | 49/50* | dr | |
acute multifocal |
|
|
|
|
|
|
| |
inflammation turbinate | 0/50 | 5/49 | 3/50 | 22/49* | 27/49* | 39/50* | dr | |
-Kidney |
|
|
|
|
|
|
| |
chronic focal inflammation | 2/50 | 1/50 | 5/50 | 2/50 | 7/50 | 4/50 |
| |
-Rectum |
|
|
|
|
|
|
| |
acute focal inflammation | 19/48 | 5/47 | 15/45 | 15/45 | 18/44 | 22/45 | dr(f) | |
-Uterus |
|
|
|
|
|
|
| |
dilatation | - | 5/50 | - | 7/50 | - | 14/50 |
| |
endometrium hyperplasia | - | 5/50 | - | 26/50 | - | 27/50 |
| |
-Lymph node, mesenteric |
|
|
|
|
|
|
| |
multifocal lymph. hyperplas. | 11/50 | 2/46 | 7/50 | 3/47 | 10/48 | 14/48 | (f) | |
-Spleen |
|
|
|
|
|
|
| |
diffuse lymph. hyperplasia | 4/50 | 4/50 | 2/50 | 3/49 | 2/48 | 16/50 | (f) | |
multifocal lymph. hyperplas. | 12/50 | 1/50 | 11/50 | 2/49 | 10/48 | 3/50 |
| |
Tumor incidence (see also below) | no toxicologically relevant effects |
| ||||||
m/f = male/female, i/d = increased/decreased, is/ds = increased/decreased significantly, np = not performed, a/r =
absolute/relative, dr = dose-related. The probability of survival was estimated by the procedure of Kaplan and Meier. Life
Table tests, Logistic regression tests, Cochran-Armitage test and Fisher Exact test were applied to assess significance.
Summary of the incidence of neoplasms
Dose (mg/kg bw) | 0 | 375 | 750 | |||
Liver | m | f | m | f | m | f |
Hepatocellular carcinoma | 50 | 50 | 50 | 50 | 49 | 50 |
Hepatocellular adenoma | 5 | 0 | 3 | 2 | 3 | 1 |
Lymphoma malignant mixed | 2 | 1 | 4 | 0 | 4 | 0 |
Stomach, forestomach | 48 | 47 | 48 | 47 | 47 | 49 |
Papilloma squamous | 1 | 0 | 1 | 3 | 0 | 0 |
Uterus | - | 50 | - | 50 | - | 50 |
Polyp | - | 0 | - | 0 | - | 2 |
Lymph node, mesenteric | 50 | 46 | 50 | 47 | 49 | 48 |
Lymphoma malignant mixed | 1 | 0 | 1 | 3 | 1 | 2 |
Spleen | 50 | 50 | 50 | 49 | 48 | 50 |
Lymphoma malignant mixed | 2 | 1 | 1 | 4 | 1 | 4 |
Skin | 50 | 50 | 50 | 50 | 50 | 50 |
Back, subcutaneous tissue, fibroma | 2 | 0 | 0 | 0 | 1 | 0 |
Subcutaneous tissue, neurofibrosarcoma | 2 | 0 | 1 | 0 | 0 | 0 |
Subcutaneous tissue, sarcoma | 4 | 0 | 0 | 1 | 2 | 0 |
Lung | 50 | 50 | 50 | 50 | 50 | 50 |
Alveolar/bronchiolar adenoma | 7 | 1 | 4 | 6 | 5 | 3 |
Harderian gland | 50 | 50 | 50 | 50 | 50 | 50 |
adenoma | 1 | 2 | 2 | 0 | 1 | 0 |
Kidney | 50 | 50 | 50 | 50 | 50 | 50 |
Lymphoma malignant mixed | 1 | 0 | 0 | 1 | 0 | 2 |
Multiple organs | 50 | 50 | 50 | 50 | 50 | 50 |
Hemangioma | 2 | 0 | 0 | 0 | 0 | 0 |
Lymphoma malignant mixed | 4 | 1 | 1 | 4 | 1 | 4 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 750 mg/kg bw/day
- Study duration:
- chronic
- Species:
- mouse
- Quality of whole database:
- Data from NTP report
- System:
- other: not specified
- Organ:
- not specified
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Thus, comparing this value with the criteria of CLP regulation, d-carvone (2244-16-8) can be not classified for Carcinogenicity in mice by oral route exposed for 2 years.
Additional information
Carcinogenicity by oral routeI
In given study, d-carvone (2244-16-8) has been investigated for Carcinogenicity to a greater or lesser extent. Often the studies based on in vivo experiments in rodents, i.e. most commonly in mice for d-carvone (2244-16-8) summaries below.
In experimental study conducted by U. S. Department of Health and Human Services (National Toxicology Program, 1990, N'TP TR 381, NIH Publication No. 90-2836) The carcinogenicity of d-carvone (2244-16-8)was studied in male and femaleB6C3Flmicefor2years.50 males and 50 female per dose group were used. The test material in dose concentration0,375, or 750 mg/kg administered by oral gavage route in dose volume 10ml/kg for 5days /week in 103 wk (some mice received 1or 2 doses during wk 104). The feed blends of d-carvone were found to be unstable under the feed blending and simulated animal exposure conditions and because d carvone is insoluble in water, corn oil gavage was selected as the route of administration for these studies. The 21-day stability of d-carvone in corn oil at 0.5%(5mg/g) stored at room temperature or at 5° C was determined. The corn oil solutions were extracted with methanol and analysed by high-performance liquid chromatography with a Brownlee RP-18 column and ultraviolet detection at 229 nm. The d-carvone/corn oil solutions were found to be stable for at least 21 days when stored in the dark at room temperature or at 5° C. The corn oil solutions were also stable under simulated dosing conditions for at least 3 hours. Animals were housed five per cage. Feed and water were available ad libitum. All animals were observed two times per day. Body weights were recorded once per week for the first 13 weeks of the study and at least once per month thereafter. During necropsy, all organs and tissues were examined for grossly visible lesions. Tissues were preserved in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin.
No compound-related clinical signs were observed. The survival of both the 375mg/kg dose (after week 101) and 750 mg/kg dose(after week 92) groups of female mice were significantly greater than that of the vehicle controls. No significant differences were observed between any groups of male mice. Mean body weights of dosed and vehicle control male mice were similar throughout most of the studies; mean body weights of dosed female mice were within 7% of those of vehicle controls throughout most of the studies.
Atrophy of the olfactory epithelium and hyperplasia of the underlying Bowman's glands occurred together. These may have been related to reflux of d-carvone into the nose after the gavage needle was withdrawn, because inflammatory exudate and "foreign material" were often found in the nasal passage of dosed animals. Fibromas, sarcomas, fibrosarcomas, or neurofibrosarcomas (combined) were observed with a negative trend in male mice, and the reduced incidence was significant in 375mg/kg dose male mice (vehicle control, 9/50; 375mg/kg dose, 1/50; 750mg/kg dose, 3/50). Three haemangioma or haemangiosarcomas were observed in vehicle control male mice, but none was seen in dosed males; the difference was not significant. Abscesses of the ovary and the uterus occurred at a high incidence in vehicle control female mice and at much lower incidences in dosed female mice (ovary: vehicle control, 26/50; 375mg/kg dose, 9/48; 750mg/kg dose, 1/48; uterus: 10/50; 3/50; 0/50). The lesions were similar to those observed in other studies associated with Krebsiella sp. infections and are believed to be the cause of reduced survival in vehicle control female mice relative to that of dosed female mice. No increases in tumor incidences were observed in mice administered d-carvone. Despite the absence of clearly chemically related toxic effects in the 2-year studies, the doses used were considered adequate for assessment of potential carcinogenicity because higher doses caused deaths in the 13-week studies. Hence Under the conditions of these 2-year gavage studies, d-carvone (2244-16-8) was considered to be not carcinogenic as there was no evidence of carcinogenic activity was observed, When male or female B6C3F1mice administered d-carvone (2244-16-8)at 375 or 750 mg/ kg, 5 days per week for 2 years.
Thus, comparing this value with the criteria of CLP regulation, d-carvone (2244-16-8) can be not classified for Carcinogenicity in mice by oral route exposed for 2 years.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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