Registration Dossier
Registration Dossier
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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
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:
- 24.58 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Dose descriptor starting point:
- NOAEL
- Value:
- 497.9 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 614.51 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Standard respiratory volume, human (sRVhuman) for 8 h per person (70 kg): 6.7 m3
Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m3/kg bw
Worker respiratory volume (wRV) for 8 hours with light physical activity per person: 10 m3
Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 1/2 (default)
Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker
Corrected NOAEC (inhalation) for workers:
NOECcorr = NOAELoral x 1/0.38 m³/kg bw/day x 6.7 m³/10m³ x 7d/5d x ABSoral/ABSinh
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation from subchronic to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).
- AF for other interspecies differences:
- 2.5
- Justification:
- The recommended AF for other interspecies differences is applied.
- AF for intraspecies differences:
- 5
- Justification:
- The default value for the relatively homogenous group "worker" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The OECD TG 408 toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Dose descriptor starting point:
- NOAEL
- Value:
- 250 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 350 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker
NOAELcorr = NOAELdermal x 7d/5d
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation from subchronic to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is applied.
- AF for other interspecies differences:
- 2.5
- Justification:
- The recommended AF for other interspecies differences is applied.
- AF for intraspecies differences:
- 5
- Justification:
- The default value for the relatively homogenous group "worker" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The study was conducted with only minor deviations from OECD TG 411 which did not affect the quality of the results. The study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.
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:
- 3 mg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 5
- Dose descriptor:
- other: non-sensitizing concentration (15 mg/cm2)
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 1
- Justification:
- Humans were repeatedly exposed, thus no additional AF was chosen for differences in duration of exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scaling is required as the study was conducted with humans.
- AF for other interspecies differences:
- 1
- Justification:
- Because the animal and human data for the endpoint skin sensitization are comparable, an assessment factor for inter-species variability of 1 was chosen.
- AF for intraspecies differences:
- 5
- Justification:
- To account for the variability within human species, the standard intra-species assessment factor of 5 was taken into account for workers.
- AF for the quality of the whole database:
- 1
- Justification:
- The HRIPT is considered to be a very robust study. Therefore, no further AF for remaining uncertainties is applied.
- AF for remaining uncertainties:
- 1
- Justification:
- The human RIPT was conducted under a accepted and common protocol for this type of study and was adequately reported. Therefore, no further AF for remaining uncertainties is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3 mg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 5
- Dose descriptor starting point:
- other: non-sensitizing concentration (15 mg/cm2)
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Humans were repeatedly exposed, thus no additional AF was chosen for differences in duration of exposure.
- AF for other interspecies differences:
- 1
- Justification:
- Because the animal and human data for the endpoint skin sensitization are comparable, an assessment factor for inter-species variability of 1 was chosen.
- AF for intraspecies differences:
- 5
- Justification:
- To account for the variability within human species, the standard intra-species assessment factor of 5 was taken into account for workers.
- AF for the quality of the whole database:
- 1
- Justification:
- The HRIPT is considered to be a very robust study. Therefore, no further AF for remaining uncertainties is applied.
- AF for remaining uncertainties:
- 1
- Justification:
- The human RIPT was conducted under a accepted and common protocol for this type of study and was adequately reported. Therefore, no further AF for remaining uncertainties is applied.
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
Systemic long-term DNEL for inhalation exposure
The respective NOAEC is based on a NOAEL of 497.9 mg/kg bw/day from a subchronic oral rat study and considering an oral bioavailability of 100%. It was modified using a human standard respiratory volume (sRVhuman) of 6.7 m3 for 8 hours per person (70 kg), a rat standard respiratory volume (sRVrat) of 0.38 m3/kg bw for 8 hours, a worker respiratory volume (wRV) of 10 m³ for 8 hours with light physical activity, the default quotient of ½ for oral absorption of the rat and inhalation absorption of humans (ABS oral-rat / ABS inh-human) and a correction for difference between human and experimental exposure conditions (7 days exposure of the rats/5 days exposure of worker per week) to 614.51mg/m3 using the equation provided in the Guidance Document on Information Requirement, Chapter R8:
NOECcorr = NOAELoral x 1/0.38 m³/kg bw/day x 6.7 m³/10m³ x 7d/5d x ABSoral/ABSinh
Using assessment factors of (i) 2 for duration of exposure, (ii) 2.5 for remaining species differences and (iii) 5 for intraspecies extrapolation, a DNEL of 24.58 mg/m3 for long-term, systemic inhalative exposure was calculated.
Systemic acute DNEL for inhalation exposure
Linalool shows an LC50 value greater than 3200 mg/m³ and is not classified for the inhalative route of exposure. Due to its low vapour pressure (27.3 Pa), high peak-inhalation exposure is not considered as relevant. The test item is unlikely to be available as a vapour to a large extent. The derivation of an acute inhalation DNEL is therefore not considered necessary. Furthermore, long-term DNELs are considered sufficient to ensure that acute effects do not occur.
Local long-term and acute DNELs for inhalation exposure
The test item is classified for skin and eye irritation (category 2) and for skin sensitization (category 1B) according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted. Appropriate qualitative risk managements measures should be implemented to avoid exposure. The substance is assigned to the low hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).
Systemic long-term DNEL for dermal exposure
The NOAEL of 250 mg/kg bw/day from a subchronic dermal toxicity study equivalent to OECD guideline 411 is used as POD. It was modified using a correction for difference between human and experimental exposure conditions (7 days exposure of the rats/5 days exposure of worker per week) to 350 mg/kg bw/day using the equation provided in the Guidance Document on Information Requirement, Chapter R8:
NOAELcorr = NOAELdermal x 7d/5d
Using assessment factors of (i) 2 for duration of exposure, (ii) 4 for interspecies differences (allometric scaling), (iii) 2.5 for remaining interspecies differences and (iiii) 5 for intraspecies extrapolation, a DNEL of 3.5 mg/kg bw/day for long-term, systemic dermal exposure was calculated.
Systemic acute DNEL for dermal exposure
Linalool shows an LD50 value greater than 2000 mg/kg bw/day and is not classified for the dermal route of exposure. The derivation of an acute dermal DNEL is therefore not considered necessary. Furthermore, long-term DNELs are considered sufficient to ensure that acute effects do not occur.
Local long-term and acute DNELs for dermal exposure
Linalool is irritating to the skin and eye and therefore appropriate personal protective equipment is recommended. For the endpoint skin sensitization, two studies are available: a Local Lymph Node Assay (LLNA) and a Human Repeated Insult Path Test (HRIPT). The EC3 from the LLNA is 8,875 µg/cm2 and the non-sensitizing concentration from the HRIPT is 15,000 µg/cm2. The HRIPT is a very robust study and was reported in 2005. It employed 135 subjects. Both the LLNA and the HRIPT studies lead to similar dose descriptors (i.e. the discrepancy between human data and animal data is lower than an order of magnitude). This shows a substance specific comparability of non-effect levels in the different systems. Based on a Weight-of-evidence approach, it was therefore conclude that the POD should be 15,000 µg/cm2. Because the animal and human data for the endpoint skin sensitization are comparable, an assessment factor for inter-species variability of 1 was chosen. To account for the variability within human species, the following standard intra-species an assessment factor of 5 was taken into account for worker. No other assessment factors should be used: 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 an assessment factor concerning exposure duration of 1 is justified 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; Dermal Sensitization Quantitative Risk Assessment (QRA) for fragrance ingredients - Technical dossier or Api et al. 2008; Reg Toxicol Pharmacol 52: 3-23). The derived DNEL of 3 mg/cm³ on the basis of skin sensitization results 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.
Conclusion:
DNEL local, long-term and acute, worker: 3 mg/cm2 (overall assessment factor of 5)
Hazard for the eyes
According to CLP Regulation (EC 1272/2008), linalool is classified as eye irritant (category 2). Thus, a qualitative risk assessment is conducted. Appropriate qualitative risk managements measures should be implemented to avoid exposure. The substance is assigned to the low hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.33 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 497.9 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 216.48 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Standard respiratory volume of the rat (sRVrat) for 24 hours: 1.15 m3/kg bw/day
Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 1/2 (default)
Corrected NOAEC (inhalation) for general population:
NOECcorr = NOAELoral x 1/1.15 m³/kg bw/day x ABSoral/ABSinh
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation from subchronic to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).
- AF for other interspecies differences:
- 2.5
- Justification:
- The recommended AF for other interspecies differences is applied.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively heterogenous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The OECD TG 408 toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
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
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Dose descriptor starting point:
- NOAEL
- Value:
- 250 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 250 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No modification is needed.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation from subchronic to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is applied.
- AF for other interspecies differences:
- 2.5
- Justification:
- The recommended AF for other interspecies differences is applied.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively heterogenous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The study was conducted with only minor deviations from OECD TG 411 which did not affect the quality of the results. The study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.
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:
- 1.5 mg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 10
- Dose descriptor:
- other: non-sensitizing concentration (15 mg/cm2)
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 1
- Justification:
- Humans were repeatedly exposed, thus no additional AF was chosen for differences in duration of exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scaling is required as the study was conducted with humans.
- AF for other interspecies differences:
- 1
- Justification:
- Because the animal and human data for the endpoint skin sensitization are comparable, an assessment factor for inter-species variability of 1 was chosen.
- AF for intraspecies differences:
- 10
- Justification:
- To account for the variability within human species, the standard intra-species assessment factor of 10 was taken into account for the general population.
- AF for the quality of the whole database:
- 1
- Justification:
- The HRIPT is considered to be a very robust study. Therefore, no further AF for remaining uncertainties is applied.
- AF for remaining uncertainties:
- 1
- Justification:
- The human RIPT was conducted under a accepted and common protocol for this type of study and was adequately reported. Therefore, no further AF for remaining uncertainties is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.5 mg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 10
- Dose descriptor starting point:
- other: non-sensitizing concentration (15 mg/cm2)
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scaling is required as the study was conducted with humans.
- AF for other interspecies differences:
- 1
- Justification:
- Because the animal and human data for the endpoint skin sensitization are comparable, an assessment factor for inter-species variability of 1 was chosen.
- AF for intraspecies differences:
- 10
- Justification:
- To account for the variability within human species, the standard intra-species assessment factor of 10 was taken into account for the general population.
- AF for the quality of the whole database:
- 1
- Justification:
- The HRIPT is considered to be a very robust study. Therefore, no further AF for remaining uncertainties is applied.
- AF for remaining uncertainties:
- 1
- Justification:
- The human RIPT was conducted under a accepted and common protocol for this type of study and was adequately reported. Therefore, no further AF for remaining uncertainties is applied.
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.49 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Dose descriptor starting point:
- NOAEL
- Value:
- 497.9 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 497.9 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No corrections are needed.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation from subchronic to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is applied.
- AF for other interspecies differences:
- 2.5
- Justification:
- The recommended AF for other interspecies differences is applied.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively heterogenous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The study was conducted according to OECD TG 408. The study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.
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
Systemic long-term DNEL for inhalation exposure
The respective NOAEC is based on a NOAEL of 497.9 mg/kg bw/day from a subchronic oral rat study and considering an oral bioavailability of 100%. It was modified using a rat standard respiratory volume (sRVrat) of 1.15 m3/kg bw/day for 24 hours and the default quotient of ½ for oral absorption of the rat and inhalation absorption of humans (ABS oral-rat / ABS inh-human) to 216,48 mg/m³ using the equation provided in the Guidance Document on Information Requirement, Chapter R8.
NOECcorr = NOAELoral x 1/1.15 m³/kg bw/day x ABSoral/ABSinh
Using assessment factors of (i) 2 for duration of exposure, (ii) 2.5 for remaining species differences and (iii) 10 for intraspecies extrapolation, a DNEL of 4.33 mg/m3 for long-term, systemic inhalative exposure was calculated.
Systemic acute DNEL for inhalation exposure
Linalool shows an LC50 value greater than 3200 mg/m³ and is not classified for the inhalative route of exposure. Due to its low vapour pressure (27.3 Pa), high peak-inhalation exposure is not considered as relevant. The test item is unlikely to be available as a vapour to a large extent. The derivation of an acute inhalation DNEL is therefore not considered necessary. Furthermore, long-term DNELs are considered sufficient to ensure that acute effects do not occur.
Local long-term and acute DNELs for inhalation exposure
The test item is classified for skin and eye irritation (category 2) and for skin sensitization (category 1B) according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted. Appropriate qualitative risk managements measures should be implemented to avoid exposure. The substance is assigned to the low hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).
Systemic long-term DNEL for dermal exposure
The NOAEL of 250 mg/kg bw/day from a subchronic dermal toxicity study equivalent to OECD guideline 411 is used as POD. It did not have to be modified according to Guidance Document on Information Requirement, Chapter R8.
Using assessment factors of (i) 2 for duration of exposure, (ii) 4 for interspecies differences (allometric scaling), (iii) 2.5 for remaining interspecies differences and (iiii) 10 for intraspecies extrapolation, a DNEL of 1.25 mg/kg bw/day for long-term, systemic dermal exposure was calculated.
Systemic acute DNEL for dermal exposure
Linalool shows an LD50 value greater than 2000 mg/kg bw/day and is not classified for the dermal route of exposure. The derivation of an acute dermal DNEL is therefore not considered necessary. Furthermore, long-term DNELs are considered sufficient to ensure that acute effects do not occur.
Local long-term and acute DNELs for dermal exposure
Linalool is irritating to the skin and eye and therefore appropriate personal protective equipment is recommended. For the endpoint skin sensitization, two studies are available: a Local Lymph Node Assay (LLNA) and a Human Repeated Insult Path Test (HRIPT). The EC3 from the LLNA is 8,875 µg/cm2 and the non-sensitizing concentration from the HRIPT is 15,000 µg/cm2. The HRIPT is a very robust study and was reported in 2005. It employed 135 subjects. Both the LLNA and the HRIPT studies lead to similar dose descriptors (i.e. the discrepancy between human data and animal data is lower than an order of magnitude). This shows a substance specific comparability of non-effect levels in the different systems. Based on a Weight-of-evidence approach, it was therefore conclude that the POD should be 15,000 µg/cm2. Because the animal and human data for the endpoint skin sensitization are comparable, an assessment factor for inter-species variability of 1 was chosen. To account for the variability within human species, the following standard intra-species an assessment factor of 10 was taken into account for the general population. No other assessment factors should be used: 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 an assessment factor concerning exposure duration of 1 is justified 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; Dermal Sensitization Quantitative Risk Assessment (QRA) for fragrance ingredients - Technical dossier or Api et al. 2008; Reg Toxicol Pharmacol 52: 3-23). The derived DNEL of 1.5 mg/cm³ on the basis of skin sensitization results 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.
Conclusion:
DNEL local, long-term and acute, general population: 1.5 mg/cm2 (overall assessment factor of 10)
Systemic long-term DNEL for oral exposure
The NOAEL of 497.9 mg/kg bw/day from a subchronic oral toxicity study according to OECD guideline 408 is used as POD considering a 100% oral absorption. It did not have to be modified according to Guidance Document on Information Requirement, Chapter R8
Using assessment factors of (i) 2 for duration of exposure, (ii) 4 for interspecies differences (allometric scaling), (iii) 2.5 for remaining interspecies differences and (iiii) 10 for intraspecies extrapolation, a DNEL of 2.49 mg/kg bw/day for long-term, systemic dermal exposure was calculated.
Systemic acute DNEL for oral exposure
Linalool shows an LD50 value greater than 2000 mg/kg bw/day and is not classified for the oral route of exposure. The derivation of an acute dermal DNEL is therefore not considered necessary. Furthermore, long-term DNELs are considered sufficient to ensure that acute effects do not occur.
Hazard for the eyes
According to CLP Regulation (EC 1272/2008), linalool is classified as eye irritant (category 2). Thus, a qualitative risk assessment is conducted. Appropriate qualitative risk managements measures should be implemented to avoid exposure. The substance is assigned to the low hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).
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