Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
26.5 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):
10
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
264.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

The conversion of the oral NOAEL of 150 mg/kg bw/day to a corrected inhalatory human NOAEC was based on the different respiratory volume of the rat (0.38 m3/kg) and the different rate during light activity at work (10 m3) and standard conditions (6.7 m3). Per default, a higher absorption via inhalation was assumed as a worst case. Corrected NOAEL = 150 mg/kg * 1/0.38 m3/kg/day * 6.7 m3 (8h) / 10 m3 (8h) = 264.5 mg/m3. Since alcohols are well absorbed after oral exposure, no additional factor for increased absorption after inhalation is deemed necessary.

AF for dose response relationship:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEC, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
2
Justification:
Default factor for subchronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
already included in route to route extrapolation
AF for other interspecies differences:
1
Justification:
No specific target organ toxicity (aside from peroxisome proliferation, which is not relevant for humans) was observed. The NOAEL is based on general toxicity, mainly reduced body weight. There is no indication of a mechanism that shows humans would be more sensitive than predicted by allometric scaling factors alone.
AF for intraspecies differences:
5
Justification:
Default factor
AF for the quality of the whole database:
1
Justification:
GLP guideline study
AF for remaining uncertainties:
1
Justification:
Generally, toxicity of long chain alcohols decreases with increasing chain length and branching. As a conservative approach, the NOAEL of a branched C10 alcohol was used to derive the DNEL for C13-15, branched and linear alcohols. Since this already leads to the use of a lower NOAEL value, no additional safety factor is deemed necessary despite the use of read across data.
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:
7.5 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):
40
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal absorption is limited due to the high lipophilicity of the chemical. A maximum of 50% was assumed.

AF for dose response relationship:
1
Justification:
NOAEL used
AF for differences in duration of exposure:
2
Justification:
default factor for subchronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, allometric scaling extrapolates doses according to an overall assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power of 0.75. This results a default allometric scaling factor for the rat when compared with humans, namely 4.
AF for other interspecies differences:
1
Justification:
No specific target organ toxicity (aside from peroxisome proliferation, which is not relevant for humans) was observed. The NOAEL is based on general toxicity, mainly reduced body weight. There is no indication of a mechanism that shows humans would be more sensitive than predicted by allometric scaling factors alone.
AF for intraspecies differences:
5
Justification:
Default factor
AF for the quality of the whole database:
1
Justification:
GLP guideline study.
AF for remaining uncertainties:
1
Justification:
Generally, toxicity of long chain alcohols decreases with increasing chain length and branching. As a conservative approach, the NOAEL of a branched C10 alcohol was used to derive the DNEL for C13-15, branched and linear alcohols. Since this already leads to the use of a lower NOAEL value, no additional safety factor is deemed necessary despite the use of read across data.
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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.5 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):
20
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
130.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

The conversion of the rat oral NOAEL to a corrected inhalatory human NOAEC was based on the different respiratory volume of the rat (1.15 m3/kg/day). Per default, a higher absorption via inhalation was assumed as a worst case.

Corrected NOAEL = 150 mg/kg * 1/1.15 m3/kg/day = 130.4 mg/m3. Since alcohols are well absorbed after oral exposure, no additional factor for increased absorption after inhalation is deemed necessary.

AF for dose response relationship:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEC, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
2
Justification:
Default factor for subchronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
already included in route to route extrapolation
AF for other interspecies differences:
1
Justification:
No specific target organ toxicity (aside from peroxisome proliferation, which is not relevant for humans) was observed. The NOAEL is based on general toxicity, mainly reduced body weight. There is no indication of a mechanism that shows humans would be more sensitive than predicted by allometric scaling factors alone.
AF for intraspecies differences:
10
Justification:
Default factor
AF for the quality of the whole database:
1
Justification:
GLP guideline study
AF for remaining uncertainties:
1
Justification:
Generally, toxicity of long chain alcohols decreases with increasing chain length and branching. As a conservative approach, the NOAEL of a branched C10 alcohol was used to derive the DNEL for C13-15, branched and linear alcohols. Since this already leads to the use of a lower NOAEL value, no additional safety factor is deemed necessary despite the use of read across data.
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:
3.8 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):
80
Dose descriptor starting point:
NOAEL
Value:
150 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal absorption is limited due to the high lipophilicity of the chemical. A maximum of 50% was assumed.

AF for dose response relationship:
1
Justification:
NOAEL used
AF for differences in duration of exposure:
2
Justification:
default factor for subchronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, allometric scaling extrapolates doses according to an overall assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power of 0.75. This results a default allometric scaling factor for the rat when compared with humans, namely 4.
AF for other interspecies differences:
1
Justification:
No specific target organ toxicity (aside from peroxisome proliferation, which is not relevant for humans) was observed. The NOAEL is based on general toxicity, mainly reduced body weight. There is no indication of a mechanism that shows humans would be more sensitive than predicted by allometric scaling factors alone.
AF for intraspecies differences:
10
Justification:
Default factor
AF for the quality of the whole database:
1
Justification:
GLP guideline study.
AF for remaining uncertainties:
1
Justification:
Generally, toxicity of long chain alcohols decreases with increasing chain length and branching. As a conservative approach, the NOAEL of a branched C10 alcohol was used to derive the DNEL for C13-15, branched and linear alcohols. Since this already leads to the use of a lower NOAEL value, no additional safety factor is deemed necessary despite the use of read across data.
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)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.9 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):
80
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL used
AF for differences in duration of exposure:
2
Justification:
default factor for subchronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, allometric scaling extrapolates doses according to an overall assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power of 0.75. This results a default allometric scaling factor for the rat when compared with humans, namely 4.
AF for other interspecies differences:
1
Justification:
No specific target organ toxicity (aside from peroxisome proliferation, which is not relevant for humans) was observed. The NOAEL is based on general toxicity, mainly reduced body weight. There is no indication of a mechanism that shows humans would be more sensitive than predicted by allometric scaling factors alone.
AF for intraspecies differences:
10
Justification:
Default factor
AF for the quality of the whole database:
1
Justification:
GLP guideline study
AF for remaining uncertainties:
1
Justification:
Generally, toxicity of long chain alcohols decreases with increasing chain length and branching. As a conservative approach, the NOAEL of a branched C10 alcohol was used to derive the DNEL for C13-15, branched and linear alcohols. Since this already leads to the use of a lower NOAEL value, no additional safety factor is deemed necessary despite the use of read across data.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population