Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
313 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
Modified dose descriptor starting point:
NOAEC
Value:
3 128 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEL (oral): Correction respiratory volume rat (8 hour) 1/0.38 m³/kg bw/day, Correction for respiratory volume (worker): 6.7 m³/10 m³. Correction for oral to inhaled 1/2. Alcohols, C14-15 90 d oral NOAEL = 3548 mg/kg bw/day. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 3548*(1/0.38)*(6.7/10)*(1/2) = 3128 mg/m³

AF for dose response relationship:
1
Justification:
Default (starting point is NOAEL).
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic).
AF for interspecies differences (allometric scaling):
1
Justification:
Default (oral rat to inhalation human).
AF for other interspecies differences:
1
Justification:
The mammalian alcohol dehydrogenase system is a group of pathways which catalyse the conversion of alcohols and aldehydes, which includes different forms of the enzymes which vary in substrate specificity. The alcohol dehydrogenases (ADHs) are divided into six classes, denoted by ADH1-ADH6. Five of the six classes of alcohol dehydrogenase have been identified in humans. One of the classes, ADH3, is the ancestral form of all mammalian ADHs, and has been traced in all living species investigated. The alcohol dehydrogenase system is considered to be able to detoxify a wide range of alcohols and aldehydes without the generation of toxic radicals (Höög, J-O et al., 2001). Therefore the metabolism of all category members would be expected to follow the same pathway in rats and humans so an interspecies assessment factor to account for potential differences in metabolic pathway is not required and a value of 1 is appropriate. Reference: Höög, J-O, Hedberg, J. J., Strömberg, P., Svensson, S. (2001). Mammalian alcohol dehydrogenase - Functional and structural implications. Journal of Biomedical Science Volume 8, Issue 1, pp 71-76
AF for intraspecies differences:
5
Justification:
Default (worker).
AF for the quality of the whole database:
1
Justification:
Default (reliable study).
AF for remaining uncertainties:
1
Justification:
Default (no remaining uncertainties).
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:
155 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: The German national maximum exposure limit (AGW) for dodecan-1-ol is 155 mg/m³.
Overall assessment factor (AF):
1
Dose descriptor:
other: The German national maximum exposure limit (AGW) for dodecan-1-ol
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:
89 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
Modified dose descriptor starting point:
NOAEL
Value:
3 548 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Alcohols, C14-15 90 d oral NOAEL 3548 mg/kg bw/day  Oral rat to dermal human no correction to dose descriptor starting point required.

AF for dose response relationship:
1
Justification:
Default (starting point is NOAEL).
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (dermal rat to dermal human)
AF for other interspecies differences:
1
Justification:
The mammalian alcohol dehydrogenase system is a group of pathways which catalyse the conversion of alcohols and aldehydes, which includes different forms of the enzymes which vary in substrate specificity. The alcohol dehydrogenases (ADHs) are divided into six classes, denoted by ADH1-ADH6. Five of the six classes of alcohol dehydrogenase have been identified in humans. One of the classes, ADH3, is the ancestral form of all mammalian ADHs, and has been traced in all living species investigated. The alcohol dehydrogenase system is considered to be able to detoxify a wide range of alcohols and aldehydes without the generation of toxic radicals (Höög, J-O et al., 2001). Therefore the metabolism of all category members would be expected to follow the same pathway in rats and humans so an interspecies assessment factor to account for potential differences in metabolic pathway is not required and a value of 1 is appropriate. Reference: Höög, J-O, Hedberg, J. J., Strömberg, P., Svensson, S. (2001). Mammalian alcohol dehydrogenase - Functional and structural implications. Journal of Biomedical Science Volume 8, Issue 1, pp 71-76
AF for intraspecies differences:
5
Justification:
Default (worker)
AF for the quality of the whole database:
1
Justification:
Default (reliable study)
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

In summary of the toxicological properties of dodecan-1-ol:

Acute toxicity tests of dodecan-1-ol do not indicate any potential hazard for acute, dermal or inhalation toxicity, and would not be classified for acute toxicity endpoint under DSD or Regulation 1272/2008 (CLP).

Dodecan-1-ol is classified as an eye irritant (Cat 2) but is not irritating to skin, nor is it sensitising by skin contact.

Dodecan-1-ol is not classified for repeated dose toxicity effects (STOT-RE) or for reproductive toxicity.

In vitro and in vivo studies indicate that dodecan-1-ol is not genotoxic.

In summary, dodecan-1-ol is classified as an eye irritant under Regulation 1272/2008 (CLP).

On the basis of the toxicological study results supporting dodecan-1-ol, no adverse systemic effects were observed in any of the numerous systemic toxicity studies that have been conducted for the different endpoints. Nevertheless, systemic DNEL values have been derived for systemic effects based on the highest dose tested. There is some evidence that local dermal effects occur in test animals, although the substance does not require classification for dermal irritation in humans.

There is some evidence that local dermal effects occur in test animals exposed to certain members of the category, although dodecan-1 -ol does not require classification for dermal irritation in humans. Overall, it would however be prudent to recommend the precautionary use of gloves.

The German regulatory authority imposes a statutory national workplace limit concentration of several analogous alcohols in air in industrial workplaces (AGW); the value set for dodecan-1-ol is 155 mg/m³.

Overall it would however be prudent to recommend the precautionary use of gloves.

Studies indicate that dodecan-1-ol is irritating to eyes. However, a DNEL for this endpoint cannot be derived and therefore quantitative risk characterisation is not possible. Instead qualitative risk characterisation is required and risk management measures (such as the limitation of concentration in consumer formulations) to minimise any potential eye contact would be required.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
77 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
Modified dose descriptor starting point:
NOAEC
Value:
1 543 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEL (oral): Correction respiratory volume rat (24 hour) 1/1.15 m³/kg bw. Correction for oral to inhaled 1/2. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is:3548*(1/1.15)*(1.2) = 1543 mg/m³.

AF for dose response relationship:
1
Justification:
Default (NOAEL)
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (oral rat to inhalation human)
AF for other interspecies differences:
1
Justification:
The mammalian alcohol dehydrogenase system is a group of pathways which catalyse the conversion of alcohols and aldehydes, which includes different forms of the enzymes which vary in substrate specificity. The alcohol dehydrogenases (ADHs) are divided into six classes, denoted by ADH1-ADH6. Five of the six classes of alcohol dehydrogenase have been identified in humans. One of the classes, ADH3, is the ancestral form of all mammalian ADHs, and has been traced in all living species investigated. The alcohol dehydrogenase system is considered to be able to detoxify a wide range of alcohols and aldehydes without the generation of toxic radicals (Höög, J-O et al., 2001). Therefore the metabolism of all category members would be expected to follow the same pathway in rats and humans so an interspecies assessment factor to account for potential differences in metabolic pathway is not required and a value of 1 is appropriate. Reference: Höög, J-O, Hedberg, J. J., Strömberg, P., Svensson, S. (2001). Mammalian alcohol dehydrogenase - Functional and structural implications. Journal of Biomedical Science Volume 8, Issue 1, pp 71-76
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default (reliable study)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Modified dose descriptor starting point:
NOAEC

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:
44.5 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):
80
Modified dose descriptor starting point:
NOAEL
Value:
3 548 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Alcohols, C14-15 90 d oral NOAEL 3548 mg/kg bw/day Oral rat to dermal human no correction to dose descriptor starting point required.

AF for dose response relationship:
1
Justification:
Default (NOAEL)
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (dermal rat to dermal human)
AF for other interspecies differences:
1
Justification:
The mammalian alcohol dehydrogenase system is a group of pathways which catalyse the conversion of alcohols and aldehydes, which includes different forms of the enzymes which vary in substrate specificity. The alcohol dehydrogenases (ADHs) are divided into six classes, denoted by ADH1-ADH6. Five of the six classes of alcohol dehydrogenase have been identified in humans. One of the classes, ADH3, is the ancestral form of all mammalian ADHs, and has been traced in all living species investigated. The alcohol dehydrogenase system is considered to be able to detoxify a wide range of alcohols and aldehydes without the generation of toxic radicals (Höög, J-O et al., 2001). Therefore the metabolism of all category members would be expected to follow the same pathway in rats and humans so an interspecies assessment factor to account for potential differences in metabolic pathway is not required and a value of 1 is appropriate. Reference: Höög, J-O, Hedberg, J. J., Strömberg, P., Svensson, S. (2001). Mammalian alcohol dehydrogenase - Functional and structural implications. Journal of Biomedical Science Volume 8, Issue 1, pp 71-76
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default (reliable study)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
80
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
AF for other interspecies differences:
1
Justification:
The mammalian alcohol dehydrogenase system is a group of pathways which catalyse the conversion of alcohols and aldehydes, which includes different forms of the enzymes which vary in substrate specificity. The alcohol dehydrogenases (ADHs) are divided into six classes, denoted by ADH1-ADH6. Five of the six classes of alcohol dehydrogenase have been identified in humans. One of the classes, ADH3, is the ancestral form of all mammalian ADHs, and has been traced in all living species investigated. The alcohol dehydrogenase system is considered to be able to detoxify a wide range of alcohols and aldehydes without the generation of toxic radicals (Höög, J-O et al., 2001). Therefore the metabolism of all category members would be expected to follow the same pathway in rats and humans so an interspecies assessment factor to account for potential differences in metabolic pathway is not required and a value of 1 is appropriate. Reference: Höög, J-O, Hedberg, J. J., Strömberg, P., Svensson, S. (2001). Mammalian alcohol dehydrogenase - Functional and structural implications. Journal of Biomedical Science Volume 8, Issue 1, pp 71-76
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
44.5 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):
80
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:

Alcohols, C14-15 90 d oral NOAEL 3548 mg/kg bw/day Oral rat to oral human no correction to dose descriptor starting point required.

AF for dose response relationship:
1
Justification:
Default (NOAEL)
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (dermal rat to dermal human)
AF for other interspecies differences:
1
Justification:
The mammalian alcohol dehydrogenase system is a group of pathways which catalyse the conversion of alcohols and aldehydes, which includes different forms of the enzymes which vary in substrate specificity. The alcohol dehydrogenases (ADHs) are divided into six classes, denoted by ADH1-ADH6. Five of the six classes of alcohol dehydrogenase have been identified in humans. One of the classes, ADH3, is the ancestral form of all mammalian ADHs, and has been traced in all living species investigated. The alcohol dehydrogenase system is considered to be able to detoxify a wide range of alcohols and aldehydes without the generation of toxic radicals (Höög, J-O et al., 2001). Therefore the metabolism of all category members would be expected to follow the same pathway in rats and humans so an interspecies assessment factor to account for potential differences in metabolic pathway is not required and a value of 1 is appropriate. Reference: Höög, J-O, Hedberg, J. J., Strömberg, P., Svensson, S. (2001). Mammalian alcohol dehydrogenase - Functional and structural implications. Journal of Biomedical Science Volume 8, Issue 1, pp 71-76
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default (reliable study)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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

In summary of the toxicological properties of dodecan-1-ol:

Acute toxicity tests of dodecan-1-ol do not indicate any potential hazard for acute, dermal or inhalation toxicity, and would not be classified for acute toxicity endpoint under Regulation 1272/2008 (CLP).

Dodecan-1-ol is classified as an eye irritant (Cat 2) but is not irritating to skin. Nor is it sensitising by skin contact.

Dodecan-1-ol is not classified for repeated dose toxicity effects (STOT-RE) or for reproductive toxicity.

In vitro and in vivo studies indicate that dodecan-1-ol is not genotoxic.

In summary, dodecan-1-ol is classified as an eye irritant under Regulation 1272/2008 (CLP).

On the basis of the toxicological study results supporting dodecan-1 -ol no adverse systemic effects were observed in any of the numerous systemic toxicity studies that have been conducted for the different endpoints. Nevertheless, systemic DNEL values have been derived for systemic effects based on the highest dose tested. There is some evidence that local dermal effects occur in test animals exposed to certain members of the category, although substance does not require classification for dermal irritation in humans.

Studies indicate that dodecan-1-ol is irritating to eyes. However, a DNEL for this endpoint cannot be derived and therefore quantitative risk characterisation is not possible. Instead qualitative risk characterisation is required and risk management measures (such as the limitation of concentration in consumer formulations) to minimise any potential eye contact would be required.