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EC number: 222-824-1 | CAS number: 3623-51-6
- 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
Carcinogenicity
Administrative data
Description of key information
No data is available for (±)-neomenthol. Reliable data are available from menthol (CAS 89 -78 -1).
Menthol and thus (±)-neomenthol do not show carcinogenic potential.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- Please refer to IUCLID section 13 for a detailed justification of the category approach.
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Details on results:
- A. Body Weights and Clinical Signs (Rats)
Mean body weights of the dosed male and female rats were slightly lower than those of the corresponding controls throughout the bioassay. No other clinical signs related to administration of the DL Menthol were noted. Clinical signs commonly observed among rats of this strain were noted at comparable rates in the control and dosed groups, particularly during the second year of the bioassay, and increased in incidence as the animals aged. These signs included eye changes (redness, paleness, cloudiness, lacrimination, a red discharge or bloody crust, and an enlarged or protruding eye), a hunched and/or thin appearance, urine stains on the abdominal fur, and occasionally, nasal discharge, sores on the body or the extremities, soft feces, and enlarged testes.
The incidence of palpable nodules and tissue masses in the dosed males was generally comparable to that in the control males, but was lower in the dosed females than in the control females.
B. Survival (Rats)
The Kaplan and Meier curves estimates the probabilities of survival for male and female rats administered menthol in the diet at the doses of this bioassay, together with those of the matched controls. The results of the Tarone test for dose-related trend in mortality and the results of the Cox test comparing the survival of the control group with each dosed group are not significant in either sex.
In male rats, 34/50 (68%) of the high-dose group, 33/50 (66%) of the low-dose group, and 31/50 (62%) of the controls were alive at week 105. In females, 38/50 (76%) of the high-dose group, 35/50 (70%) of the low-dose group, and 36/50 (72%) of the controls were alive at week 105. Sufficient numbers of rats of each sex were at risk for the development of late-appearing tumors.
C. Pathology (Rats)
Each of the tumor types observed has been encountered previously as spontaneous lesion, and occurred with no appreciable differences in frequency between control and dosed rats with a few exceptions. In female rats, chromophobe adenomas of the pituitary gland and fibroadenomas of the mammary gland were observed with greater frequency in female control rats. Chromophobe adenomas occurred in 28/48 controls, 25/47 low—dose, and 19/43 high—dose female rats. Mammary gland fibroadenomas were diagnosed in 20/50 female controls, 10/49 low—dose, and 7/49 high—dose rats. Mammary adenocarcinomas were seen in 1/50 controls, 3/49 low—dose, and 0/49 high—dose rats.
Chronic inflammation of the kidney was observed with greater frequency in the dosed males than in the control males (29/49 controls, 41/50 low—dose, 41/50 high—dose); however, this finding is of questionable importance, since such lesions are often found in aged male Fischer 344 rats.
All other inflammatory, degenerative, and hyperplastic lesions that occurred were similar in incidence and kind to those naturally occurring lesions found in aged Fischer 344 rats. - Relevance of carcinogenic effects / potential:
- Not found
- Dose descriptor:
- NOAEL
- Remarks:
- rat
- Effect level:
- > 375 mg/kg bw/day
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- gross pathology
- histopathology: neoplastic
- histopathology: non-neoplastic
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Remarks:
- 7500 ppm in diet applied to mice were converted to 375 mg/kg/day calculated for rat with a mean body weight of 400 g and 20 g/day of food consumption
- Dose descriptor:
- NOAEL
- Remarks:
- mouse
- Effect level:
- > 667 mg/kg bw/day
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- gross pathology
- histopathology: neoplastic
- histopathology: non-neoplastic
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Remarks:
- 4000 ppm in diet applied to mice were converted to 667 mg/kg/day calculated for Mice with a mean body weight of 30 g and 5 g/day of food consumption
- Conclusions:
- Based on the histopathologic examination, menthol was neither toxic nor carcinogenic to Fischer 344 rats and B6C3F1 mice under the conditions of this bioassay.
- Executive summary:
Carcinogenicity tests are available from structural analogue menthol (CAS 89-78-1) in rats and mice. It is concluded that (±)-neomenthol does not have a carcinogenic potential. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in carcinogenicity.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 375 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- The available information comprises adequate and reliable studies from read across based on grouping of substances (category approach) similar in structure and intrinsic properties. Read-across is justified based on structural similarities of menthols in PC/ECO/TOX properties (refer to category justification for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.
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
(±)-neomenthol does not meet the criteria for classification and labelling for carcinogenicity, as set out in Regulation (EC) NO. 1272/2008.
Additional information
There is no reliable carcinogenicity study on (±)-neomenthol available.
Justification for Read-across:
Based on the identical profiles of the different menthols and supported by the Read-Across Justification for menthols (IUCLID chapter 13) all studies on stereoisomers of (±)-neomenthol are used for read across. These isomers are L-menthol (CAS 2216-51-5), (+)-menthol (CAS 15356-60-2), D/L-menthol (CAS 1490 -04 -6) and menthol (CAS 89-78-1).Moreover, a comparative physico-chemical profile of these isomers reinforces this similarity. As structural isomers, the members of the menthol category share the same molecular weight. Of particular importance to environmental effects and human effects are the values for partition coefficient (log Pow between 3.12 and 3.45 at 25°C), vapour pressure (from 3.6 to 21 Pa at 25°C) and water solubility (moderately soluble from 231 to 456 mg/L at 25°C). The read across is consistent based on these physico-chemical parameters.
Key study:
In a carcinogenicity study (NCI, 1979), in both dose groups (0.375% or 0.75% menthol in diet of rats and 0.2 or 0.4% in the diet of mice), neither toxicity nor carcinogenicity in Fischer 344 rats or B6C3F1 mice was found after 103 weeks exposure.
In male rats, no tumors occurred at incidences which were considered to be associated with the administration of menthol.
In female rats, no tumors occurred at higher incidences in dosed groups than in control groups. Fibroadenomas of the mammary gland occurred at lower incidences in the low-dose (10/49) and high-dose (7/49) groups than in the control group (20/50), and alveaolar/bronchiolar adenomas or carcinomas of the lung occurred only in the controls (3/50).
In mice of either sex, no tumors occurred in dosed groups at incidences that were significantly different from those for corresponding control groups. The highest tested dose levels in rats correspond to approx. 375 mg/kg bw/da and in mice to approx. 667 mg/kg bw/day. Thus a carcinogenic potential for menthol was not observed in these studies.
In conclusion, menthol and thus (±)-neomenthol do not have carcinogenic potential.
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.
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