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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
Immunotoxicity
Administrative data
Description of key information
Antibody Plaque Forming Cells (PFC) Assay and Host Resistance Assay (no guideline): NOAEL 375 mg/kg bw/day (intragastrically exposure)
Key value for chemical safety assessment
Effect on immunotoxicity: via oral route
Link to relevant study records
- Endpoint:
- immunotoxicity
- Remarks:
- acute
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1993
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- The study was not conducted according to an official OECD guideline, but is comparable to the US FDA program. The design of the study and the results are clearly described. No individual data is included, but basic data is acceptable.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Antibody Plaque Forming Cells (PFC) Assay and Host Resistance Assay (Listeria monocytogenes bacterial challenge according to:
1) Hinton D. M. (1992) Testing guidelines for evaluation of the immunotoxic potential or direct food additives. Critical Reviews in Food Science and Nutrition 32, 173-190.
2) Luster M. I..et al(1988) Development of a testing battery to assess chemical-induced immunotoxicity: National Toxicology Program's guidelines for immunotoxicity evaluation in mice. Fundamental and Applied Toxicology 10, 2-19.
3) Thomas P., et al (1985) Evaluation of host resistance and immune function in cadmium-exposed mice. Toxicology and Applied Pharmacology 80, 446-456. - GLP compliance:
- no
- Limit test:
- no
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories (Portage, MI, USA).
- Age at study initiation: approx. 6-8 weeks
- Housing: Group housed in polypropylene cages with hardwood chip bedding (Sani-Chips, Murphy Forest Products, Montville, N J, USA)
- Diet: Certified Purina Rodent Chow 5002 (Ralston Purina, St Louis, MO, USA) - ad libitum
- Water: tap water ad libitum
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26
- Humidity (%): 10-70
- Photoperiod (hrs dark / hrs light): 12 / 12 - Route of administration:
- other: intragastrically
- Vehicle:
- other: methyl cellulose
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle: Solubility
- Concentration in vehicle: 10 mL/kg
- Amount of vehicle: 1% - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 5 days
- Frequency of treatment:
- once daily for 5 consecutive days
- Dose / conc.:
- 94 mg/kg bw/day
- Dose / conc.:
- 188 mg/kg bw/day
- Dose / conc.:
- 375 mg/kg bw/day
- No. of animals per sex per dose:
- 30 mice/dose group (10 for PFC asssay and 20 for host resistance assay/dose group)
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose levels for the immunotoxicity assays were chosen based on the results of acute toxicity tests (5-day repeated oral dose range-finding studies) conducted with Linalool (NOAEL 375 mg/kg bw/day)
- Observations and clinical examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice each day (a.m. and p.m.)
BODY WEIGHT: Yes
- Time schedule for examinations: PFC assay: at the time of dosing initiation, exposure day 5, and at autopsy - Sacrifice and pathology:
- Not performed
- Cell viabilities:
- SPLEEN: Yes
- Method: Spleen cells were counted and viability was assessed by trypan blue exclusion
- Dose groups: Vehicle control, test article treated, naïve (untreated) and positive control groups
- No. of animals: 10 mice/dose group (PFC Assay)
THYMUS: No
BONE MARROW: No - Humoral immunity examinations:
- ANTIBODY PLAQUE FORMING CELLS (PFC) ASSAY: Yes
- Method: The anti-SRBC PFC response to sheep red blood cells (SRBCs) was performed according to the method of Cunningham and Szenberg (Cunningham A. J. and Szenberg A. (1968) Further improvements in the plaque technique for detecting single antibody-forming cells. Immunology 14, 599), as modified by Thomas et al. (Thomas P., et al (1985) Evaluation of host resistance and immune function in cadmium-exposed mice. Toxicology and Applied Pharmacology 80, 446-456).
- Dose groups: Vehicle control, three test article treated, naïve (untreated) and positive control groups
- No. of animals: 10 mice/dose group (5 mice/positive control group) - Specific cell-mediated immunity:
- OTHER ASSAYS
- Method: Host resistance assay (Listeria monocytogenes bacterial challenge) - Mortality
- Dose groups: Vehicle control, three test article treated, naïve (untreated) and positive control groups
- No. of animals: 20 mice/dose group - Positive control:
- For each PFC assay, five animals were injected ip with cyclophosphamide (80 mg/kg) 24 hr prior to assay.
- Statistics:
- Dunnett's test and chi-square analysis were used to evaluate mean survival time and mortality data in the Host resistance assay. For continuous response data, analysis of variance (two-tailed) and appropriate post-hoc comparisons using Dunnett's test were performed on natural logarithmic or logit transformed PFC data. For the positive control group, post-hoc comparisons were made to the naive control group using a Student's t-test. Individual groups of data were evaluated for outliers prior to statistical analysis (Dixon W. J. (1953) Processing data for outliers. Biometrics 9, 74-89). The level of significance in all tests was P<=0.05.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Gross pathological findings:
- not examined
- Cell viabilities:
- no effects observed
- Humoral immunity examinations:
- no effects observed
- Specific cell-mediated immunity:
- no effects observed
- Non-specific cell-mediated immunity:
- no effects observed
- Other functional activity assays:
- not examined
- Other findings:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 375 mg/kg bw/day
- Sex:
- female
- Basis for effect level:
- other: cell viability (spleen); humoral immunity (PFC assay); cell-mediated immunity (Host resistance assay (Listeria monocytogenes bacterial challenge)-mortality
- Conclusions:
- Linalool produced no significant alteration in the PFC response. No increase in mortality after bacterial challenge was observed. No changes in body weight, spleen and thymus weight as well as spleen cellularity were noted. These results indicated that Linalool did not modulate the cell-mediated or humoral immune response.
- Executive summary:
A rapid screening protocol incorporating key elements of the US National Toxicology Program's immunotoxicity tier testing strategy was used to evaluate the effect of Linalool on humoral and cell-mediated immune responses. The test compound was administered intragastrically on a daily basis for 5 days at 375, 188, and 94 mg/kg/day to female B6C3F1 mice, 6-8 wk old.
A host resistance assay (Listeria monocytogenes bacterial challenge) was conducted to assess cell-mediated immunity by observation of increase in mortality rate or reduction of survival time.
Humoral immunity was measured by the antibody plaque-forming cell (PFC) response to sheep red blood cells (SRBCs). Body weights, spleen and thymus weights and spleen cellularity were also measured. Cyclophosphamide (80 mg/kg) served as an immunosuppressive positive control agent.
Linalool produced no significant alteration in the PFC response and no increase in mortality after bacterial challenge was observed. No changes in bodyweight, thymus and spleen weight as well as spleen cellularity were noted. These results indicated that linalool did not modulate the cell-mediated or humoral immune response.
Reference
No effects were reported in both the Host resistance assay and the Antibody Plaque-forming cell assay.
Host resistance assay mortality observations: group mortality (%):
Control: 15 %
Dose level 94 mg/kg/d: 15 %
Dose level 188 mg/kg/d: 21 %
Dose level 375 mg/kg/d: 15 %
Anti-sheep red blood cell (SRBC) plaque-forming cell (PFC) assay observations: specific cellular activity (PFC/10*6 viable spleen cells):
Control: 1309 ± 234
Dose level 94 mg/kg/d: 1283 ± 192
Dose level 188 mg/kg/d: 2083 ± 195
Dose level 375 mg/kg/d: 1242 ± 175
Cyclophosphamide positive control: 77 ± 15
Anti-sheep red blood cell (SRBC) plaque-forming cell (PFC) assay observations: total spleen activity (PFC x 10*4 spleen):
Control: 7.0 ± 1.1
Dose level 94 mg/kg/d: 9.7 ± 1.7
Dose level 188 mg/kg/d: 12.1 ± 1.3
Dose level 375 mg/kg/d: 7.1 ± 1.2
Cyclophosphamide positive control: 0.4 ± 0.1
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 375 mg/kg bw/day
- Species:
- mouse
- Quality of whole database:
- Comparable to guideline study with acceptable restrictions
Effect on immunotoxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Effect on immunotoxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
In this rapid screening protocol, linalool produced no significant alteration in the PFC response, no increase in mortality after bacterial challenge was observed, and no other changes related to immunologic responses were observed. The results indicate that linalool did not modulate the cell-mediated or humoral immune response.
Justification for classification or non-classification
As no effects were observed, linalool does not need to be classified based on the criteria outlined in Annex I of Regulation (EC) No 1272/2008, as amended for fifteenth time in Regulation (EU) No 2020/1182.
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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