Alcohols, C12-15-branched and linear

Toxicological Summary

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:

3 127 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) = 3127 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 the lowest molecular weight constituent, 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:

no hazard identified

Additional information - workers

In summary of the toxicological properties of Alcohols, C12-15-branched and linear:

Acute toxicity tests of Alcohols, C12-15-branched and linear 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).

Alcohols, C12-15-branched and linear is not irritating to skin or eye, nor is it sensitising by skin contact.

Alcohols, C12-15-branched and linear is not classified for repeated dose toxicity effects (STOT-RE) or for reproductive toxicity.

In vitro and in vivo studies indicate that Alcohols, C12-15-branched and linear is not genotoxic.

In summary, Alcohols, C12-15-branched and linear 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 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 Alcohols, C12-15-branched and linear itself. The value set for the lowest molecular weight constituent, dodecan-1-ol, is 155 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:

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 (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. 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 Alcohols, C12-15-branched and linear:

Acute toxicity tests of Alcohols, C12-15-branched and linear 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).

Alcohols, C12-15-branched and linear is not irritating to skin or eye, nor is it sensitising by skin contact.

Alcohols, C12-15-branched and linear is not classified for repeated dose toxicity effects (STOT-RE) or for reproductive toxicity.

In vitro and in vivo studies indicate that Alcohols, C12-15-branched and linear is not genotoxic.

In summary, Alcohols, C12-15-branched and linear 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 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 Alcohols, C12-15-branched and linear itself. The value set for the lowest molecular weight constituent, dodecan-1-ol, is 155 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.