Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 233-732-6 | CAS number: 10339-55-6
- 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

Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 28/06/1988 - 27/01/1990
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study was conducted according to an equivalent of OECD guideline 407 and under GLP conditions. Due to the read-across purpose it was given a Klimisch 2 rating, in accordance with the ECHA Practical guide #6 on the reporting of read-across in IUCLID. Ethyllinalool and linalool are structural homologues which differ only by a methyl-group. Their physical-chemical properties are comparable and available experimental data on same toxicological endpoints, showed identical toxicological properties. Therefore, it is assumed that all toxicological properties are as well comparable and thus read-across is justified.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 990
- Report date:
- 1990
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Principles of method if other than guideline:
- No remarks
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Linalool
- EC Number:
- 201-134-4
- EC Name:
- Linalool
- Cas Number:
- 78-70-6
- Molecular formula:
- C10H18O
- IUPAC Name:
- 3,7-dimethylocta-1,6-dien-3-ol
- Details on test material:
- - Name of test material (as cited in study report): B10 (Coriander oil containing 72.9% linalool)
- Physical state: Liquid
- Storage condition of test material: Protected from light in the refrigerator
- Stability under test conditions: Stable
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: approx. 43 days
- Weight at study initiation:
Males: 206.2-249.3 g
Females: 142.8-191.2 g
- Housing: Individually under standard laboratory conditions
- Diet (e.g. ad libitum): Ad libitum, rodent chow
- Water (e.g. ad libitum): Ad libitum, tap water
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72 +/- 6
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES:
From: 12 July 1988
To: 11 August 1988
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 1% methylcellulose
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
Calculated amount of test material was weighed into a beaker of appropriate size. The amount was then transferred into a pre-calibrated container using a rinsing process. Vehicle (1% methylcellulose) was added to achieve the appropriate volume and the container was placed on a magnetic stirrer and stirred for five minutes while being sonicated. Test mixtures were prepared fresh weekly.
VEHICLE
- Justification for use and choice of vehicle (if other than water): Not relevant
- Amount of vehicle (if gavage): 10 ml/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Based on peak area for selected constituents test material is stable in 1% methylcellulose (Memo Lorillard, 9 August 1988)
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- Daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
160, 400, 1000 mg coriander oil/kg/day, equivalent to 117, 292, 729 mg linalool/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- Not applicable
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
- Cage side observations: mortality and morbundity
DETAILED CLINICAL OBSERVATIONS: Yes, including physical examination
- Time schedule: Weekly
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes, weekly
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Prior to initiation of study and at termination
- Anaesthetic used for blood collection: Yes (ketamine)
- Animals fasted: Yes, overnight
- How many animals:
Initiation: 10 animals/sex
Termination: all animals
- Parameters checked:
Leukocyte count (WBC)
Erythrocyte count (RBC)
Hemoglobin (HGB)
Hematocrit (HCT)
Platelet count (PLATELET)
Leukocyte differential count
Cell morphology
Myeloid/erythroid ratio (M/E)-(Groups 1 and 4 only at Week 5)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Prior to initiation of study and at termination
- Animals fasted: Yes, overnight
- How many animals:
Initiation: 10 animals/sex
Termination: all animals
- Parameters checked:
Sodium (SODIUM)
Potassium (POTAS)
Chloride (CHLORIDE)
Total protein (T PROT)
Blood urea nitrogen (BUN)
Creatinine (CREAT)
Glucose (GLUCOSE)
Alanine aminotransferase (AL1)
Albumin (ALBUMIN)
Calcium (CALCIUM)
Total carbon dioxide (T C02)
Total bilirubin (T BILI)
Aspartate aminotransferase (AST)
Gamma glutamyltransferase (GGT)
Alkaline phosphatase (ALK P) - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, in all animals
External surfaces
All orifices
Cranial cavity
Carcass
Nasal cavity and paranasal sinuses
Cervical tissues and organs
External surface of the brain and spinal cord (at necropsy) ; the cut surfaces of the brain were examined at the time of tissue trimming
Thoracic, abdominal and pelvic cavities and their viscera
ORGAN WEIGHTS: Yes, in all animals. Fat was first removed.
Brain (including brainstem)
Spleen
Liver
Heart
Kidneys
Testes with epididymides
Thyroid with parathyroids
Adrenals
Ovaries
Pituitary
HISTOPATHOLOGY: Yes, tissues from all control and high-dose animals as presented below. Heart, liver, stomachs and lesions from all low- and mid-dose animals were also examined.
Femoral bone marrow
Lung (with mainstem bronchi)
Ovaries
Lesions
Kidneys
Adrenals
Testes with epididymides
Duodenum, Jeiunum, ileum
Brain with brainstem (medulla/pons cerebellar cortex, cerebral cortex)
Pancreas
Urinary bladder
Pituitary
Uterus
Thyroid (parathyroids)
Heart
Liver
Spleen
Colon, cecum, rectum
Stomach
Mesenteric lymph node
Following tissues from control and high-dose animals were preserved but not examined:
Thymus
Esophagus
Sciatic nerve w/skeletal muscle
Cervical, thoracic and lumbar spinal cord
Salivary gland (mandibular)
Trachea - Other examinations:
- A femoral bone marrow smear was prepared from all sacrificed animals and preserved in methanol and stained with Wright stain.
- Statistics:
- Mean body weight changes (Weeks 0-4), total food consumption (Weeks 1-4), clinical pathology data (except cell morphology), absolute organ weight and organ-to-body weight ratios of the control group were compared statistically to the data from the same sex of the treated groups.
Transformation of heterogeneous data was performed. If homogeneity of variances was not succesful analyses was performed on rank-transformed data. Group comparisons performed at 5% two-tailed probability level.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
One high-dose female was found dead on day 2 of the study and was replaced by another animal (as directed by the study director).
One high-dose male was found dead on day 9 of the study, cause of death was attributed to a handling incident.
Isolated incidences of alopecia and sores were noted in both males and females of several groups (also control group). One animal of the control group showed a small movable head mass at week 1.
CLINICAL CHEMISTRY
For males of the high and mid-dose group the glucose and albumin levels were significantly lower than that of control. Total protein was higher than that of control males in these groups. For males of the high-dose group also calcium levels were higher than that of control.
In females, only total protein and albumin were found higher in the high-dose group than that of controls.
ORGAN WEIGHTS
Absolute kidney weight was higher in males and females of the high-dose group, but relative kidney weight was higher in males of the mid- and high-dose group and females of the high-dose group. For males, this can be confined to the histopathological effects.
Absolute liver weight was higher in males of the mid- and high-dose group and in females of the low-, mid- and high-dose group. Relative liver weight was significantly different in the mid- and high-dose group of both males and females as compared to controls.
Absolute thyroid/parathyroid weight was lower in males of the low- and high-dose group, while relative thyroid/parathyroid weight was only significant different in low-dose males as compared to controls. In females, only absolute thyroid/parathyroid weight was significantly different from controls in the low-dose group. These findings were without clear-dose-response relationship.
GROSS PATHOLOGY
Prominent liver effects (mainly prominent reticular pattern in M+F, mottled liver in F) were found in males and females of the mid- and high-dose groups. No other prominent effects were observed when compared to controls.
Kidney effects were largely confined to males of the mid- and high-dose group (pale area). Females showed no prominent effects, while the control group did not show any effect.
Stomach effects (thickened mucosa, dark area) were observed in both males (high-dose) and females (mid- and high-dose). Control group showed no effect. It is unclear if this effect is caused by administration of the test article by gavage in the animals.
HISTOPATHOLOGY: NON-NEOPLASTIC
Increased periportal cytoplasmic vacuolization was observed in the liver of females of the low-, mid- and high-dose group. This was not observed in males or the control group. The cytoplasmic vacuolization was graded as slight in all affected animals, and is not expected to have an overall health of the animals or hepatic function. This is supported by ALT and AST levels being comparable to controls. Therefore this is not considered an adverse effect.
Regeneration and necrosis of tubules in the kidney were observed in males of the high-dose group. The effects seen were microscopically similar to those seen in the kidneys of male rats treated with a variety of hydrocarbons (due to interaction with the in abundance produced alpha-2-u globulin protein), which is a male rat-specific effect. In females, no prominent effects were observed as compared to controls.
Inflammation and acanthosis of the stomach was observed in females of the mid- and high-dose group. This was not seen in males and the control group. It is unclear if this effect is caused by administration of the test article by gavage in the animals.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 160 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: stomach and kidney effects (clinical chemistry and pathology)
- Dose descriptor:
- NOAEL
- Remarks:
- linalool
- Effect level:
- 117 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: stomach and kidney effects (clinical chemistry and pathology)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Read across:
Linalool, dehydrolinalool (CAS 29717-20-8) and ethyllinalool are structurally related substances having similar chemical structures. Difference between linalool and dehydrolinalool is the triple bond at position 1 in dehydrolinalool compared to a double bond at the same position in linalool. Both substances have similar physical-chemical properties. Ethyllinalool is a structural homologue of linalool which differs by a methyl-group only. The physical-chemical properties of ethyllinalool are comparable to the two other substances and available experimental data on the same toxicological endpoints, showed identical toxicological properties. Therefore, it is assumed that all toxicological properties are as well comparable and thus read-across is justified.
Two repeated toxicity studies, 2 reprotoxicity screening studies, and a developmental toxicity study using gavage application for linalool (either applied in coriander oil at 72.9% Linalool or as pure substance) and / or dehydrolinalool showed the following consistent results: Histopathologically, male animals had alpha-2u-globulin nephropathy after application of both substances. Liver (and kidney) weights were increased in both sexes with some indication of metabolic enzyme induction in the liver. Hypersalivation and sedation / ataxia were consistently noted in almost all studies. In one oral study, gavage application resulted in (fore)stomach lesions which might be the result of the irritant properties. In a repeated dermal toxicity study, the skin irritant properties of linalool were confirmed. The relevant oral NOAEL for linalool was determined to be 117 mg/kg bw/d with the LOEL being 292 mg/kg bw/d; dehydrolinalool has an oral NOAEL of 200 mg/kg bw/d with the LOEL being 750 mg/kg bw/d. The difference in the NOAELs is the result of the dose-setting regime. The dermal NOAEL for linalool was 250 mg/kg bw/d. Comparable results are predicted for ethyllinalool based on the read-across approach.
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this study, the No Observed Adverse Effect Level (NOAEL) was established to be 160 mg/kg bw/day. This corresponds with 117 mg/kg bw/day linalool. Based on the criteria outlined in Annex I of 1272/2008/EC, linalool does not need to be classified for oral repeated dose toxicity.
- Executive summary:
This report presents the findings of a 28-day oral toxicity. Study designed to evaluate the toxicity of coriander oil (B10, containing 72.9% linalool) in rats when administered daily by gavage to achieve dosage levels of 160, 400, and 1000 mg/kg of body weight per day . A concurrent control group received only the vehicle. Criteria evaluation for signs of compound effect included survival, clinical observations, body weights, food consumption, clinical pathology, gross pathology, organ weights, and histopathology.
No treatment-related effects on survival, clinical observations, body weights, or food consumption were observed. Treatment-related increases in total protein and serum albumin were observed in the mid- and high-dose males and the high-dose females. Serum calcium was also increased in these same treated groups, apparently as a secondary response to the increase in albumin, its major serum binding protein. The pathogenesis of these increases, however, is unknown. Treatment-related lesions were noted histopathologically in the kidney of the high-dose males, in the nonglandular region of the stomach in the mid- and high-dose females, and in the liver of the high-dose females. Similar lesions of the liver were also noted in the low- and mid-dose females, but at a lower incidence. The findings in liver of females were considered to be slight and unlikely to influence liver function. Liver enzymes like AST and ALT were not changed and the histopathological effect was therefore considered rather adaptive due to induction of metabolizing enzymes than an adverse effect. Kidney lesions were seen in males only and are related to alpha-2u-globulin nephropathy which is not of relevance for human. Stomach lesions are considered to be result of bulk administration of an irritant substance via gavage.
Therefore, the No Observed Adverse Effect Level (NOAEL) was established to be 160 mg/kg/day, which corresponds to a NOAEL of 117 mg/kg bw/day linalool. Based on the criteria outlined in Annex I of 1272/2008/EC, linalool does not need to be classified for oral repeated dose toxicity.
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.

EU Privacy Disclaimer
This website uses cookies to ensure you get the best experience on our websites.