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EC number: 204-116-4 | CAS number: 115-95-7
- 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
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.75 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 75
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 236.2 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- Overall assessment factor (AF):
- 10
- Dose descriptor:
- other: NESIL
- Value:
- 23 620 mg/m³
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 236.2 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- Overall assessment factor (AF):
- 10
- Dose descriptor starting point:
- other: NESIL
- Value:
- 23 620 mg/m³
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
- Api AM, Basketter DA, Cadby PA, Cano M-F, Graham E, Gerberick F, Griem P, McNamee P, Ryan CA, Safford B (2006). Dermal Sensitization Quantitative Risk Assessment (QRA) for fragrance ingredients. Technical dossier. March 15, 2006 (revised May 2006).
- Api AM, Basketter, DA, Cadby PA, Cano M-F, Ellis G, Gerberick GF, Griem P, McNamee PM, Ryan CA, Safford R (2008). Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients. Reg Toxicol Pharmacol 52: 3-23.
For linalyl acetate, no suitable animal data adressing systemic toxicity after repeated exposure are available. Since linalyl acetate is expected to be hydrolysed to its metabolite linalool, repeated dose studies on linalool were included via read-across (see read across justification document). Furthermore, comparable toxicity profiles were noted for linalool and dehydrolinalool (CAS 29171 -20 -8) in acute toxicity studies and repeated dose studies, leading to alpha-2u-globulin nephropathy, metabolic enzyme induction in the liver, hypersalivation and sedation / ataxia after repeated application. Therefore the available repeated dose studies on dehydrolinalool were adopted to support the hazard assessment of linalyl acetate by read-across.
For the derivation of DNELs for systemic effects after long term exposure, the oral subacute 28 day repeated dose study in rats using linalool (HLA642-460), and the subchronic 90 day repeated dose dermal study in rats using linalool (T&O 79-201) were chosen.
The NOAEL of the 28 day gavage study was chosen as point of departure for derivation of the inhalative long term systemic DNEL by route to route extrapolation. On the basis of the present toxicokinetic data, linalool is rapidly and completely absorbed in rats after oral administration (Parke 1974), supporting the assumption, that 100% bioavailablilty after oral adoministration can be considered.
For the worker, the following DNELs were derived:
The NOAEL of the subacute oral study was set at 117 mg/kg bw/d linalool for males and females. For derivation of the inhalative DNEL, the oral NOAEL was converted into a corrected inhalative NOAEC of 206 mg/m3 according to the procedure, recommended in the current guidance document (R8, ECHA 2008).
Additionally an assessment factor (AF) of 75 (R8 ECHA 2008: allometric scaling = 1; remaining differences = 2.5; intraspezies = 5; exposure duration = 6 (subacute to chronic); dose-response = 1; quality of whole database = 1: AF = 1 x 2.5 x 5 x 6 x 1 x 1 = 75) was calculated. Consequently, the inhalative long-term systemic DNEL derived was 2.75 mg/m3 for the worker.
For derivation of the systemic dermal DNEL, the NOAEL of the subchronic 90 day dermal study (250 mg/kg bw/d) was chosen as the point of departure and an assessment factor (AF) of 100 was applied (R8 ECHA2008: allometric scaling = 4; remaining differences = 2.5; intraspezies = 5; exposure duration = 2 (subchronic to chronic); dose-response = 1; quality of whole database = 1: AF = 4 x 2.5 x 5 x 2 x 1 x 1 = 100) was calculated. Consequently, the dermal long-term systemic DNEL derived was 2.5 mg/kg bw/d for the worker.
To assess the DNEL for local effects after long term dermal exposure, data for skin sensitization were considered. Quantitiative information on the threshold for skin sensitization in animals can be derived from the present LLNAs (weighed EC3 value of 9.5%* or 2375 µg/cm2; Sköld 2005, RCC 2002, BASF 2017) and can be confirmed by a state-of-the-art human repeated insult patch test (HRL 2017). The HRIPT available represents a well performed study, in which 99 subjects (24 males, 75 females) received 9 applications of 0.3 ml aliquot of 2% (2362 μg/cm2) Linalylacetate in 3:1 DEP: EtOH for 24 hours in 3 successive weeks. Approximately 2 weeks after the last induction application, a 24 h challenge application with 2% (2362 μg/cm2) Linalylacetate in 3:1 DEP: EtOH was made to a naive site. When reactions to challenge were read 24 h, 48 h, 72 h and 96 h post patching, no skin sensitizing effects were observed.
Overall, the weighed mean induction threshold concentration based on the LLNAs (2375 µg/cm2) does not lead to skin sensitization in humans as confirmed in the HRIPT with a concentration of 2362 μg/cm2 tested. Therefore, a human specific lower potency of Linalylacetate induced skin sensitization compared to the murine test is not to evident, thus, the use of an additional interspecies assessment factor is not applicable. Furthermore, based on the ECHA guidance document (R8 p.23) no extrapolation and no assessment factor is necessary for interspecies differences in sensitivity, where human data are used as the starting point for risk characterization. It is recognized, that a general DNEL must take into account a variation of the threshold for skin sensitization between individuals. This may be due to differences in parameters such as genetic effects, sensitive subpopulations, inherent barrier function, age, gender, and ethnicity (Api et al., 2008). Whereas the latter three are recognized to have some effect on the sensitization threshold, it is generally recognized that genetic differences, the inherent barrier function and especially sensitive subpopulations play a major role (Api et al., 2008). The barrier function of the skin may be compromised which in turn may lead to a greater susceptibility of the individual. At the same time the barrier function is thought to be very similar from infancy to adulthood. The influence of the genetic setting is not well understood, however, may be plausible in the light of the immunological effect under consideration. The term sensitive subpopulations refers mostly to individuals who have previously been sensitized to other substances which may increase the susceptibility to further sensitizers (Api et al., 2006, Api et al., 2008). Overall, an assessment factor of 10 for intraspecies differences is applied to adequately address the combined influence of these effects. The underlying data are based on repeated dermal application of Linalylacetate and the read out covers both, skin irritation and skin sensitization properties at the given concentration. The relevant parameters, i. e. induction of skin irritation and skin sensitization, are considered to depend on threshold concentrations and not on exposure duration. Therefore no assessment factor concerning exposure duration is deemed necessary for the derivation of the long term local dermal DNEL. The concept of threshold concentrations for the induction of these effects is generally well accepted (see e.g. Api et al. 2006 or Api et al. 2008). Furthermore, the ECHA guidance document does not indicate at all, that an assessment factor for exposure duration needs to be taken into account for the derivation of a DNEL for skin sensitization.
Therefore, a DNEL for skin sensitization was set at 236.2 µg/cm2/day based on the confirmed no expected sensitization induction level (NESIL) in a HRIPT (2362 µg/cm2) and an assessment factor of 10 for intraspecies differences. The derived DNEL on the basis of skin sensitization is considered sufficiently conservative to ensure the absence of skin irritation after short or long term exposure. Using this DNEL allows for a quantitative risk characterization for both hazards, i.e. skin irritation and skin sensitization.
Furthermore, Linalyl acetate is to be classified as eye irritant (category 2) according to 1272/2008/EEC. Since no quantitative data addressing the hazard of eye irritation are available, a respective no effect concentration cannot be derived and included in the derivation of the short term/long term local dermal DNEL. However, a qualitative risk characterisation including the implementation of suitable risk management measures is performed in the CSR, when handled undiluted or at higher concentrations during manufacturing, compounding or formulation.
No DNELs were derived for local effects after short term or after long term inhalative exposure and no DNELs were also derived for systemic effects after short term dermal or inhalative exposure, as the substance exhibits no hazardous potential in terms of these endpoints.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.68 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 150
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.25 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 236.2 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- Overall assessment factor (AF):
- 10
- Dose descriptor:
- other: NESIL
- Value:
- 23 620 mg/m³
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 236.2 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- Overall assessment factor (AF):
- 10
- Dose descriptor starting point:
- other: NESIL
- Value:
- 23 620 mg/m³
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.2 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 600
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
- Api AM, Basketter DA, Cadby PA, Cano M-F, Graham E, Gerberick F, Griem P, McNamee P, Ryan CA, Safford B (2006). Dermal Sensitization Quantitative Risk Assessment (QRA) for fragrance ingredients. Technical dossier. March 15, 2006 (revised May 2006).
- Api AM, Basketter, DA, Cadby PA, Cano M-F, Ellis G, Gerberick GF, Griem P, McNamee PM, Ryan CA, Safford R (2008). Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients. Reg Toxicol Pharmacol 52: 3-23.
For linalyl acetate, no suitable animal data adressing systemic toxicity after repeated exposure are available. Since linalyl acetate is expected to be hydrolysed to its metabolite linalool, repeated dose studies on linalool were included via read-across (see read across justification document). Furthermore, comparable toxicity profiles were noted for linalool and dehydrolinalool (CAS 29171 -20 -8) in acute toxicity studies and repeated dose studies, leading to alpha-2u-globulin nephropathy, metabolic enzyme induction in the liver, hypersalivation and sedation / ataxia after repeated application. Therefore the available repeated dose studies on dehydrolinalool were adopted to support the hazard assessment of linalyl acetate by read-across.
For the derivation of DNELs for systemic effects after long term exposure, the oral subacute 28 day repeated dose study in rats using linalool (HLA642-460), and the subchronic 90 day repeated dose dermal study in rats using linalool (T&O 79-201) were chosen.
The NOAEL of the 28 day gavage study was chosen as point of departure for derivation of the inhalative long term systemic DNEL by route to route extrapolation. On the basis of the present toxicokinetic data, linalool is rapidly and completely absorbed in rats after oral administration (Parke 1974), supporting the assumption, that 100% bioavailablilty after oral adoministration can be considered.
For the consumer, the following DNELs were derived:
The NOAEL of the subacute oral study was set at 117 mg/kg bw/d linalool for males and females.
For an oral long term systemic DNEL, an assessment factor (AF) of 600 (R8, ECHA 2008: allometric scaling = 4; remaining differences = 2.5; intraspezies = 10; exposure duration = 6 (subacute to chronic); dose-response = 1; quality of whole database = 1: AF = 4 x 2.5 x 10 x 6 x 1 x 1 = 600) was calculated. Consequently, the oral long-term systemic DNEL derived was 0.195 mg/kg bw/d for the consumer.
For derivation of the inhalative DNEL, the oral NOAEL was converted into a corrected inhalative NOAEC of 101.7 mg/m3 according to the procedure, recommended in the current guidance document (R8, ECHA 2008).
Additionally an assessment factor (AF) of 150 (R8, ECHA 2008: allometric scaling = 1; remaining differences = 2.5; intraspezies = 10; exposure duration = 6 (subacute to chronic); dose-response = 1; quality of whole database = 1: AF = 1 x 2.5 x 10 x 6 x 1 x 1 = 150) was calculated. Consequently, the inhalative long-term systemic DNEL derived was 0.68 mg/m3 for the consumer.
For derivation of the systemic dermal DNEL, the NOAEL from the subchronic 90 day dermal study (250 mg/kg bw/d) was chosenas the point of departure and an assessment factors (AF) of 200 was applied (R8 ECHA 2008: allometric scaling = 4; remaining differences = 2.5; intraspezies = 10; exposure duration = 2 (subchronic to chronic); dose-response = 1; quality of whole database = 1: AF = 4 x 2.5 x 5 x 2 x 1 x 1 = 200) was calculated. Consequently, the dermal long-term systemic DNEL derived was 1.25 mg/kg bw/d for the consumer.
To assess the DNEL for local effects after long term dermal exposure, data for skin sensitization were considered. Quantitiative information on the threshold for skin sensitization in animals can be derived from the present LLNAs (weighed EC3 value of 9.5%* or 2375 µg/cm2; Sköld 2005, RCC 2002, BASF 2017) and can be confirmed by a state-of-the-art human repeated insult patch test (HRL 2017). The HRIPT available represents a well performed study, in which 99 subjects (24 males, 75 females) received 9 applications of 0.3 ml aliquot of 2% (2362 μg/cm2) Linalylacetate in 3:1 DEP: EtOH for 24 hours in 3 successive weeks. Approximately 2 weeks after the last induction application, a 24 h challenge application with 2% (2362 μg/cm2) Linalylacetate in 3:1 DEP: EtOH was made to a naive site. When reactions to challenge were read 24 h, 48 h, 72 h and 96 h post patching, no skin sensitizing effects were observed.
Overall, the weighed mean induction threshold concentration based on the LLNAs (2375 µg/cm2) does not lead to skin sensitization in humans as confirmed in the HRIPT with a concentration of 2362 μg/cm2 tested. Therefore, a human specific lower potency of Linalylacetate induced skin sensitization compared to the murine test is not to evident, thus, the use of an additional interspecies assessment factor is not applicable. Furthermore, based on the ECHA guidance document (R8 p.23) no extrapolation and no assessment factor is necessary for interspecies differences in sensitivity, where human data are used as the starting point for risk characterization. It is recognized, that a general DNEL must take into account a variation of the threshold for skin sensitization between individuals. This may be due to differences in parameters such as genetic effects, sensitive subpopulations, inherent barrier function, age, gender, and ethnicity (Api et al., 2008). Whereas the latter three are recognized to have some effect on the sensitization threshold, it is generally recognized that genetic differences, the inherent barrier function and especially sensitive subpopulations play a major role (Api et al., 2008). The barrier function of the skin may be compromised which in turn may lead to a greater susceptibility of the individual. At the same time the barrier function is thought to be very similar from infancy to adulthood. The influence of the genetic setting is not well understood, however, may be plausible in the light of the immunological effect under consideration. The term sensitive subpopulations refers mostly to individuals who have previously been sensitized to other substances which may increase the susceptibility to further sensitizers (Api et al., 2006, Api et al., 2008). Overall, an assessment factor of 10 for intraspecies differences is applied to adequately address the combined influence of these effects. The underlying data are based on repeated dermal application of Linalylacetate and the read out covers both, skin irritation and skin sensitization properties at the given concentration. The relevant parameters, i. e. induction of skin irritation and skin sensitization, are considered to depend on threshold concentrations and not on exposure duration. Therefore no assessment factor concerning exposure duration is deemed necessary for the derivation of the long term local dermal DNEL. The concept of threshold concentrations for the induction of these effects is generally well accepted (see e.g. Api et al. 2006 or Api et al. 2008). Furthermore, the ECHA guidance document does not indicate at all, that an assessment factor for exposure duration needs to be taken into account for the derivation of a DNEL for skin sensitization.
Therefore, a DNEL for skin sensitization was set at 236.2 µg/cm2/day based on the confirmed no expected sensitization induction level (NESIL) in a HRIPT (2362 µg/cm2) and an assessment factor of 10 for intraspecies differences. The derived DNEL on the basis of skin sensitization is considered sufficiently conservative to ensure the absence of skin irritation after short or long term exposure. Using this DNEL allows for a quantitative risk characterization for both hazards, i.e. skin irritation and skin sensitization.
No DNELs were derived for local effects after short term or after long term inhalative exposure and no DNELs were also derived for systemic effects after short term dermal or inhalative exposure, as the substance exhibits no hazardous potential in terms of these endpoints.
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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