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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
3 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
225 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL inhalation for long-term exposure was based on the absence of systemic effects at a concentration of 117 mg Linalool/kg bw/day which is equivalent to 128 mg ethylinalool /kg by / day in a subacute oral toxicity study.
AF for differences in duration of exposure:
6
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18 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):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
225 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL inhalation for short-term exposure was based on the absence of systemic effects at a dose level of 117 mg/kg bw/day of Linalool which is equivalent to 128 mg ethyllinalool /kg bw /day in a subacute oral toxicity study.
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5

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:
2.7 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
Modified dose descriptor starting point:
NOAEL
Value:
273 mg/kg bw/day
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.5 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):
50
Modified dose descriptor starting point:
NOAEL
Value:
273 mg/kg bw/day
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
other: NOAEL
Value:
15 mg/m³
AF for intraspecies differences:
10
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 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: NOAEL
Value:
15 mg/m³
AF for intraspecies differences:
10

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Local effects DNELs

Ethyllinalool is irritating for skin and eye and therefore appropriate personal protective equipment is recommended. To consider this local effect endpoint, the most relevant study is considered to be the human studies on skin sensitization. Harrison and Spey 2005, showed that a Linalool concentration of 12.7% (equivalent to 15 mg Linalool/cm2) was neither irritating nor sensitizing upon repeated dermal administration in a Human Repeated Insult Patch Test (HRIPT). This result is supported by the Human Maximization Test reported by RIFM 1975. In this study, a 30% concentration of Ethyllinalool was not sensitizing. In order to summarize all information available it should be noted that a Local Lymph Node Assay (LLNA, performed in 2016) resulted in an EC3 value of 48.2% (w/v).

However, the Human Repeated Insult Patch Test performed with Linalool is considered to be the adequate endpoint. Assessment factors considering interspecies differences are not needed for this scenario because the result was derived from human studies using 135 volunteers. However, an assessment factor of 10 is applied to adequately address intraspecies differences. The subjects were exposed intermittent for approximately 3 weeks and therefore no assessment factor for duration is required.

The local DNEL is 1.5 mg Linalool/cm2(equivalent to 1.27%) which is equivalent to 1.64 mg Ethyllinalool/cm2rounded 1.6 mg/cm2(equivalent to 1.39%).

Acute DNELs

Ethyllinalool has LD50 values greater than 2000 mg/kg bw and is not classified via the oral and dermal route of exposure. The derivation of acute DNELs is therefore not considered necessary. Reported DNELs are for short-term or long-term exposure.

Systemic DNELs for inhalation exposure

The most relevant NOAEL for inhalation DNELs is 117 mg/kg bw/d for Linalool. Thus, for inhalational DNEL derivation a NOAEL of 117 mg linalool/kg bw/d being equivalent to 128 mg ethyllinalool/kg bw/d is used. The oral absorption is 100% of the applied dose. The oral NOAEL of 128 mg ethyllinalool/kg bw/d is converted into inhalational NOAEC using the equation provided in the Guidance Document on Information Requirement, Chapter R8. It is calculated to 225 mg/m3.

Using assessment factors of (i) 5 for intraspecies extrapolation, (ii) 1 for duration exposure and (iii) 2.5 for the remaining species differences (AF = 12.5), this results in a DNEL of 18.0 mg/m3 for short-term exposure for workers.

Using assessment factors of (i) 5 for intraspecies extrapolation, (ii) 6 for duration exposure and (iii) 2.5 for the remaining species differences (AF = 75), this results in a DNEL of 3.0 mg/m3 for long-term exposure for workers.

Systemic dermal DNELs

The dermal NOAEL is 250 mg linalool/kg bw/d. For dermal DNEL a NOAEL of 250 mg linalool/kg bw/d being equivalent to 273 mg ethyllinalool/kg bw/d is used.

Using a NOAEL of 273 mg/kg bw/day from a subchronic dermal toxicity study in rats and taking into account assessment factors for (i) interspecies variation of 4, (ii) remaining species differences of 2.5, (iii) exposure duration of 1, and (iv) intraspecies variation of 5 (AF = 50), the systemic DNEL worker for short-term exposure via the dermal route is 5.5 mg/kg bw/day.

Using a NOAEL of 273 mg/kg bw/day from a subchronic dermal toxicity study in rats and taking into account assessment factors for (i) interspecies variation of 4, (ii) remaining species differences of 2.5, (iii) exposure duration of 2, and (iv) intraspecies variation of 5 (AF = 100), the systemic DNEL worker for long-term exposure via the dermal route is 2.7 mg/kg bw/day.

Systemic Oral DNELs

For worker a DNEL for oral exposure is not considered necessary as workers are not supposed to eat at their work environment.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.74 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
111 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL inhalation for long-term exposure was based on the absence of systemic effects at a concentration of 117 mg Linalool/kg bw/day which is equivalent to 128 mg ethylinalool /kg by / day in a subacute oral toxicity study.
AF for differences in duration of exposure:
6
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.4 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
Modified dose descriptor starting point:
NOAEC
Value:
111 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL inhalation for short-term exposure was based on the absence of systemic effects at a dose level of 117 mg/kg bw/day of Linalool which is equivalent to 128 mg ethyllinalool /kg bw /day in a subacute oral toxicity study.
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10

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:
1.4 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
Modified dose descriptor starting point:
NOAEL
Value:
273 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The dermal DNEL for long-term exposure was based on the absence of systemic effects at a dose level of 250 mg/kg bw/day of Linalool which is equivalent to 273 mg ethyllinalool /kg bw /day in a 90 -day repeated dose toxicity study.
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.7 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
Modified dose descriptor starting point:
NOAEL
Value:
273 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dermal DNEL  for long-term exposure was based on the absence of systemic effects at a dose level of 250 mg/kg bw/day of Linalool which is equivalent to 273 mg ethyllinalool /kg bw /day in a 90 -day repeated dose toxicity study.

AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
other: NOAEL
Value:
15 mg/m³
AF for intraspecies differences:
10
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 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: NOAEL
Value:
15 mg/m³
AF for intraspecies differences:
10

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
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
128 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The most relevant NOAEL for oral DNELs is 117 mg/kg bw/d for Linalool. Thus, for oral DNEL derivation a NOAEL of 117 mg Linalool/kg bw/d being equivalent to 128 mg Ethyllinalool/kg bw/d is used.


AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.3 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
128 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The most relevant NOAEL for oral DNELs is 117 mg/kg bw/d for Linalool. Thus, for oral DNEL derivation a NOAEL of 117 mg Linalool/kg bw/d being equivalent to 128 mg Ethyllinalool/kg bw/d is used.

AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Ethyllinalool is irritating for skin and eye and therefore appropriate personal protective equipment is recommended. To consider this local effect endpoint, the most relevant study is considered to be the human studies on skin sensitization. Harrison and Spey 2005, showed that a Linalool concentration of 12.7% (equivalent to 15 mg Linalool/cm2) was neither irritating nor sensitizing upon repeated dermal administration in a Human Repeated Insult Patch Test (HRIPT). This result is supported by the Human Maximization Test reported by RIFM 1975. In this study, a 30% concentration of Ethyllinalool was not sensitizing. In order to summarize all information available it should be noted that a Local Lymph Node Assay (LLNA, performed in 2016) resulted in an EC3 value of 48.2% (w/v).

However, the Human Repeated Insult Patch Test performed with Linalool is considered to be the adequate endpoint. Assessment factors considering interspecies differences are not needed for this scenario because the result was derived from human studies using 135 volunteers. However, an assessment factor of 10 is applied to adequately address intraspecies differences. The subjects were exposed intermittent for approximately 3 weeks and therefore no assessment factor for duration is required.

The local DNEL is 1.5 mg Linalool/cm2(equivalent to 1.27%) which is equivalent to 1.64 mg Ethyllinalool/cm2rounded 1.6 mg/cm2(equivalent to 1.39%).