Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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).