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EC number: 201-134-4 | CAS number: 78-70-6
- 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
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:
- weight of evidence
- Study period:
- No data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- The study was not conducted according to a guideline and not performed according to GLP. The publication is relatively short, however the design of the study seems proper and the results are described clearly.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Mammary tumors were induced by a single gastric intubation of 65 mg/kg 7,12-dimethylbenz[a]anthracene (DMBA) (in 0.5 mL sesame oil) 101 6-week-old female Sprague-Dawley rats, of which 50 were treated with 1% oxygenated (+/-)-linalool in diet for 20 weeks (start: 2 weeks before tumor induction). Number of tumors and latency were recorded in both groups to determine if linalool inhibited mammary carcinogenesis.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Route of administration:
- oral: feed
- Vehicle:
- other: powdered Way Lab Blox diet
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 20 weeks
- Frequency of treatment:
- Ad libitum
- Post exposure period:
- Not relevant
- Dose / conc.:
- 1 other: %
- Remarks:
- Basis: Nominal in diet
- No. of animals per sex per dose:
- Dose group: 50
Control group: 51 - Control animals:
- yes, plain diet
- Relevance of carcinogenic effects / potential:
- The chemopreventive potential of linalool was studied, but the substance was found not to possess this ability. Linalool did not increase the tumor frequency when compared to the untreated control group.
- Conclusions:
- Under the conditions of this study, it can be concluded that 20-week exposure to linalool in the diet did not inhibit DMBA induced mammary carcinogenesis.
- Executive summary:
This study was conducted to determine if the oxygenated monoterpene (+/-)-Linalool inhibits the mammary carcinogenesis in the rat. Therefore, mammary tumors were induced in 101 female rats, of which 50 were treated with 1% Linalool in the diet shortly before and after induction (total 20 weeks). Number of tumors and tumor latency were recorded in each group.
The results indicate that linalool did not significantly extend tumor latency or reduce the total number of tumors observed when compared to controls. Under the conditions of this study, it was concluded that 20-week exposure to linalool in the diet did not inhibit mammary carcinogenesis and as well did not increase tumor frequency.
- Endpoint:
- carcinogenicity
- Remarks:
- intraperitoneal
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- No data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Study was not conducted according to OECD guideline 451 and not under GLP conditions, as the study was initiated before introduction of the guideline and GLP. No individual data, but acceptable basic data.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- A mouse pulmonary tumor system developed by Andervont and Shimkin in 1940 was used for the testing of a series of food additives (Andervont, H. B., and Shimkin, M. B. Biologic Testing of Carcinogens. II. Pulmonary-Tumor-Induction-Technique. J. Nati. Cancer Inst., I: 225-239, 1940)
- GLP compliance:
- no
- Species:
- mouse
- Strain:
- other: Strain A/He
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Institute for Cancer Research, Philadelphia, National Cancer Institute, Maryland
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: 18 to 20 gr.
- Housing: In groups of 5 in plastic boxes. Commercial grade sawdust chips were used for bedding.
- Diet: Purina laboratory chow ad libitum
- Water: Ad libitum - Route of administration:
- intraperitoneal
- Vehicle:
- other: Tricaprylin
- Details on exposure:
- TEST MATERIAL
- Amount applied: 0.1 mL/dose
- Concentration: 0.6 and 3.0 g/kg mouse (total dose)
VEHICLE
- Justification for use and choice of vehicle: No data
- Amount applied: 0.1 mL i.p. injection - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 8 weeks
- Frequency of treatment:
- 3 times weekly for a total of 24 doses
- Post exposure period:
- 16 weeks; the experiments were terminated 24 weeks after the 1st injection.
- Dose / conc.:
- 3 000 mg/kg bw (total dose)
- Remarks:
- Basis: Actually injected
- Dose / conc.:
- 600 mg/kg bw (total dose)
- Remarks:
- Basis: Actually injected
- No. of animals per sex per dose:
- 15
- Control animals:
- yes, concurrent no treatment
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: In a preliminary toxicology test an MTD (maximally tolerated single dose) was determined. In the bioassay 2 dose levels were used, the MTD and a 1:5 dilution of the MTD.
- Positive control:
- Positive control groups consisting of animals treated with 2 dose levels of urethan (5 or 20 mg/mouse) were also maintained to ensure that the tumor response was comparable to that observed in previous studies with A mice.
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
- Time schedule for examinations: The animals were weighed every 2 weeks during the injection period and at monthly intervals thereafter. - Sacrifice and pathology:
- Termination after 24 weeks.
GROSS PATHOLOGY: Yes, macroscopic examination of lungs.
HISTOPATHOLOGY: Yes, the milky white nodules on the lung surface were counted and some were taken for histopathological examination. The lungs were also examined microscopically for the presence of other abnormalities, such as inflammatory reactions and adenomatosis. Liver, kidney, spleen, thymus, intestine, and salivary and endocrine glands were examined at autopsy for the presence of abnormalities. Suspicious tissues were examined as to type and cataloged with respect to incidence. - Other examinations:
- Not relevant
- Statistics:
- Mice are classified by the number of survivors with nodules. The data are also expressed as the mean number of nodules and their distribution in the groups. Tumor incidences in treated versus the vehicle control animals were compared by the standard x² test to determine whether the compound was positive.
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- GROSS PATHOLOGY: no effects
HISTOPATHOLOGY: NON-NEOPLASTIC: no effects
HISTOPATHOLOGY: NEOPLASTIC
Only the number of lung tumors in the treatment groups was signficantly different from the control group. All other tumors appeared to be evenly distributed among control and treated animals. They are considered to be "spontaneous" or the background neoplastic "noise" in this species and strain of animals.
HISTORICAL CONTROL DATA: The consistency of the A mouse pulmonary tumor system for carcinogenesis bioassays is reflected in this study. The occurrence of "spontaneous" lung tumors and the response to the reference carcinogen urethan is in accordance with observations reported over the last 33 years. - Relevance of carcinogenic effects / potential:
- This study did not reveal any carcinogenic potential of Linalool.
- Conclusions:
- Linalool was negative for pulmonary tumor response under the conditions used. It is concluded that Linalool is not capable to induce primary lung tumors in A/He mice.
- Executive summary:
Linalool was examined for its ability to induce primary lung tumors in A/He mice. A/He mice were given i.p. injections of Linalool, dissolved in 0.1 mL tricaprylin, 3 times a week for a maximum of 8 weeks. Two dose levels (600 and 3000 mg/kg total dose) and 15 males and 15 females per dose were used. Control groups received 0.1 ml tricaprylin alone or they were untreated. Positive control groups consisted of animals treated with 2 dose levels of urethan (5 or 20 mg/mouse). The animals were killed after of 24 weeks. After fixation of the lungs in Tellyesniczky's fluid, the surface tumors were counted. Response in the treated mice were compared by the x2 test to those in the vehicle controls. Linalool was negative for pulmonary tumor response under the conditions used. This study did not reveal any carcinogenic potential of Linalool.
- Endpoint:
- carcinogenicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- No data
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Remarks:
- Result is reported in a review publication, and only discussed very shortly. The publication is considered to be of doubtful relevance due to major reporting limitations.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The tumour-promoting effect of essential oils was investigated in mice. Three weeks after initiation of with 9,10-dimethyl-1,2-bezoanthracene by topical application, linalool was applied topically once a week for thirteen weeks.
- GLP compliance:
- no
- Species:
- mouse
- Strain:
- other: 101 (inbred) and stock albino (randombred)
- Sex:
- not specified
- Route of administration:
- dermal
- Vehicle:
- acetone
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 13 weeks (treatment with linalool was started three weeks after topically induction of skin tumour formation with 9,10-dimethyl-1,2-benzanthracene)
- Frequency of treatment:
- once a week
- Post exposure period:
- No data
- Dose / conc.:
- 20 other: %
- Remarks:
- Basis: Nominal concentration
- No. of animals per sex per dose:
- No data
- Relevance of carcinogenic effects / potential:
- Linalool as a 20% solution in acetone elicited a weak tumour-promoting response
- Key result
- Dose descriptor:
- other: See "Remarks on result"
- Remarks on result:
- other: Linalool as a 20% solution in acetone elicited a weak tumour-promoting response
- Remarks:
- Under the conditions of this study, linalool was identified as a weak tumour promotor
- Conclusions:
- Under the conditions of this study, linalool was identified as a weak tumour promotor
- Executive summary:
The tumour-promoting effect of linalool was studied in mice that were exposed to linalool for thirteen weeks, once a week, after initiation of skin tumour formation with 9,10-dimethyl-1,2-benzanthracene. Linalool was found to elicit a weak tumour-promoting response. However, due to major reporting limitations, the result cannot be evaluated properly.
Referenceopen allclose all
Linalool did not significantly extend tumor latency or reduce the total number of tumors observed when compared to controls. Control group animals had an average number of tumours per rat of 2.3, linalool-treated rats 1.9 tumors per rat.
Duration of experiment (wk) |
No. of i.p. injections |
Total dose (g/kg mouse) |
Sex |
Survivors/ initial |
No. of mice with lung tumors |
No. of lung tumors/ mouse |
No. of mice according to the no. of lung tumors/mouse |
|||
1 |
2 |
3-5 |
6-10 |
|||||||
24 |
24 |
3.00 |
M |
9/15 |
2 |
0.22 ± 0.07 |
2 |
0 |
0 |
0 |
|
|
3.00 |
F |
11/15 |
3 |
0.27 ± 0.08 |
3 |
0 |
0 |
0 |
|
|
0.60 |
M |
11/15 |
1 |
0.09 ± 0.03 |
1 |
0 |
0 |
0 |
|
|
0.60 |
F |
9/15 |
1 |
0.11± 0.04 |
1 |
0 |
0 |
0 |
A weak tumour-promoting response is reported, but no detailed data on results are available.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Justification for classification or non-classification
Based on the available information, linalool does not need to be classified as carcinogenic according to Regulation (EC) No 1272/2008, as amended for fifteenth time in Regulation (EU) No 2020/1182.
Additional information
Some supporting publications are available to the justification statement for the waiving of the carcinogenic bioassay.
- Stoner (1973) described no tumoriogenic potential of linalool in mice. This study was considered most reliable.
- Roe & Field (1965) described an experimental result indicating that linalool elicited a weak tumour-promoting response. However, the publication provides very limited information on the design and result of the experiment. Therefore, the result is regarded to be of doubtful relevance due to major reporting limitations.
- Russin (1989) described that oral administration of linalool for 20 weeks did not increase the number of tumors in rats.
These results and the results from (in vivo) genotoxicity tests (negative) and repeated dose toxicity studies (no pre-neoplastic effects found) indicate that linalool is not a potential carcinogenic substance.
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