Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
389 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:
3 892 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. Hexadecan-1-ol 90 day oral (rat) NOAEL >4257 mg/kg (bw) (male); >4567 mg/kg (bw) (female) mg/kg bw/day; average (used as initial starting point) 4415 mg/kg bw/day. Corrected NOAEL 4415*(1/0.38) *(6.7/10)*(1/2) = 3892 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 to inhalation).
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 (there are 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:
219.5 mg/m³
DNEL related information
DNEL derivation method:
other: The German national maximum exposure limit (AGW) for analogous aliphatic alcohols is 20 ppm. Under standard conditions 1 mole of a gas occupies 24.45 L, therefore 20 ppm of (Z)-octadec-9-enol is 219.5 mg/m³
Overall assessment factor (AF):
1
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:
110 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:
4 415 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Hexadecan-1-ol 90 day oral (rat) NOAEL >4257 mg/kg (bw) (male); >4567 mg/kg (bw) (female) mg/kg bw/day; average (used as initial starting point) 4415 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 (oral to dermal).
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 (there are 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
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

In summary of the toxicological properties of (Z)-octadec-9-enol and linear:

Acute toxicity tests of (Z)-octadec-9-enol 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).

(Z)-octadec-9-enol is not irritating to skin or eye, nor is it sensitising by skin contact.

(Z)-octadec-9-enol is not classified for repeated dose toxicity effects (STOT-RE) or for reproductive toxicity.

In vitro and in vivo studies indicate that (Z)-octadec-9-enol is not genotoxic.

In summary, (Z)-octadec-9-enol is not classified for human health hazard under Regulation 1272/2008 (CLP).

On the basis of the toxicological results available 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. The DNELs are therefore indicative only and is derived as a precautionary approach.

The German regulatory authority imposes a statutory national workplace limit concentration of several analogous

alcohols in air in industrial workplaces (AGW), though no value is set for (Z)-octadec-9-enol

itself. The value derived for (Z)-octadec-9-enol is equivalent to 219.5 mg/m³.

Overall it would however be prudent to highlight the necessity to ensure good general hygiene measures are adhered

to in the workplace, and to recommend the precautionary use of gloves.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
96 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:
1 920 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: 4415*(1/1.15) *(1/2) = 1920 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 to inhalation).
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:
Default (there are 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
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:
55 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:
Hexadecan-1-ol 90 day oral (rat) NOAEL >4257 mg/kg (bw) (male); >4567 mg/kg (bw) (female) mg/kg bw/day; average (used as initial starting point) 4415 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 (oral to dermal).
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:
Default (there are 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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
55 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:
4 415 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Hexadecan-1-ol 90 day oral (rat) NOAEL >4257 mg/kg (bw) (male); >4567 mg/kg (bw) (female) mg/kg bw/day; average (used as initial starting point) 4415 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 (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 (oral rat to oral 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:
Default (there are 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 (Z)-octadec-9-enol and linear:

Acute toxicity tests of (Z)-octadec-9-enol 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).

(Z)-octadec-9-enol is not irritating to skin or eye, nor is it sensitising by skin contact.

(Z)-octadec-9-enol is not classified for repeated dose toxicity effects (STOT-RE) or for reproductive toxicity.

In vitro and in vivo studies indicate that (Z)-octadec-9-enol is not genotoxic.

In summary, (Z)-octadec-9-enol is not classified for human health hazard under Regulation 1272/2008 (CLP).

On the basis of the toxicological results available 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. The DNELs are therefore indicative only and is derived as a precautionary approach.

The German regulatory authority imposes a statutory national workplace limit concentration of several analogous

alcohols in air in industrial workplaces (AGW), though no value is set for (Z)-octadec-9-enol

itself. The value derived for (Z)-octadec-9-enol is equivalent to 219.5 mg/m³.