Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
247 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

The UVCB substance to be registered is a mixture of the two Guerbet alcohols 2 -hexyldecan-1-ol & 2-octyldodecan-1 -ol and their corresponding esters with C12 and C14 fatty acids. The potential to induce toxic effects is mainly evaluated on the basis of experimental data for Guerbet alcohols and esters of branched alcohols with fatty acids. One experimental study (HPRT test) was conducted with the UVCB substance as such to support the evaluation of the mutagenic potential.

Of these two substance classes present in the UVCB substance, the Guerbet alcohols are considered to have the higher impact on the toxicological evaluation, for the following reasons:

-      The two Guerbet alcohols are the major components in the UVCB substance, accounting for appr. 30-50%

-      The ester components are expected to be metabolized to fatty acids and the two free Guerbet alcohols, thus contributing to the fraction of Guerbet alcohols

-      In comparison to the Guerbet alcohol esters, the free Guerbet alcohols have a lower molecular weight, which would favor their uptake

-      Having a free functional group, the Guerbet alcohols are more prone to undergo physiological reactions

 

DNEL - acute/short-term exposure - systemic effects:

DNELs for acute exposure for local or systemic effects do not need to be derived since all available data point to a low potential for acute toxicity.

 

DNEL - long-term exposure - systemic effects:

The key study for DNEL derivation is the subchronic oral toxicity study in rats 2-octyldodecan-1-ol, which is a major component of the UVCB to be registered, but also a major degradation product of the ester components in the UVCB. No substance-related effects were observed in this study, resulting in a NOAEL of 839.6 mg/kg bw/d.

The following assessment factors are proposed for thedermalDNEL: 4 for allometric scaling, 3 for intraspecies variation, and 2 for exposure extrapolation (subchronic to chronic) resulting in an overall assessment factor of 24. An additional factor for "remaining interspecies differences" as proposed by ECHA is scientifically not justified and arbitrary since the allometric scaling factor fully accounts for interspecies differences [ECETOC. Technical Report in preparation: Guidance on Assessment Factors to Derive DNELs (2010), and Publication No. 901 of the Committee for Hazardous Substances (AGS) of the German Federal Institute for Occupational Safety and Health (BAuA) April 2010 and Escher et al., Toxicology Letters 218 (2013) 159– 165]. Furthermore, ECETOC recommends in its Technical report No. 86 ("Derivation of Assessment Factors for Human Health Risk Assessment"; February 2003); and a default assessment factor for intraspecies differences of 3 for workers deviating from the ECHA proposed assessment factor of 5. Based on these assessment factors and assuming an equivalent resorption rate for oral and dermal exposure a dermal DNEL of 35 mg/kg bw/d for long-term exposure results. Forinhalationthe oral NOAEL of 839.6 mg/kg bw/d is converted into a corrected NOAEC assuming a standard 8h respiratory volume of 0.38 m³/kg for the rat, a standard 8h respiratory volume of 6.7 m³/Person for humans and a respiratory volume light activity of 10 m³/person for workers. This results in a corrected NOAEC of 1480 mg/m³. The following assessment factors are proposed for the inhalation DNEL: assessment factors of 1 for interspecies differences (inhalation), 3 for intraspecies variation and 2 for exposure extrapolation (subchronic to chronic). A worst case default factor of 2 for route-to-route extrapolation (oral-to-inhalation) proposed by ECHA is not assigned as a higher absorption via the inhalation route compared to the oral route is not expected because of the lipophilic properties of the substance. An evaluation of several substances for differences in their oral and inhalation absorption support this assumption [ECETOC. Technical Report in preparation: Guidance on Assessment Factors to Derive DNELs (2009)]. Based on these assessment factors the long-term exposure DNEL for inhalation is 247 mg/m³.

 

DNEL - acute/short-term and long-term exposure - local effects:DNELs for local effects do not need to be derived as available data indicate no significant local effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
73 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The UVCB substance to be registered is a mixture of the two Guerbet alcohols 2 -hexyldecan-1-ol & 2-octyldodecan-1 -ol and their corresponding esters with C12 and C14 fatty acids. The potential to induce toxic effects is mainly evaluated on the basis of experimental data for Guerbet alcohols and esters of branched alcohols with fatty acids. One experimental study (HPRT test) was conducted with the UVCB substance as such to support the evaluation of the mutagenic potential.

Of these two substance classes present in the UVCB substance, the Guerbet alcohols are considered to have the higher impact on the toxicological evaluation, for the following reasons:

-      The two Guerbet alcohols are the major components in the UVCB substance, accounting for appr. 30-50%

-      The ester components are expected to be metabolized to fatty acids and the two free Guerbet alcohols, thus contributing to the fraction of Guerbet alcohols

-      In comparison to the Guerbet alcohol esters, the free Guerbet alcohols have a lower molecular weight, which would favor their uptake

-      Having a free functional group, the Guerbet alcohols are more prone to undergo physiological reactions

 

DNEL - acute/short-term exposure - systemic effects effects:

DNELs for acute exposure for local or systemic effects do not need to be derived since based on the acute toxicity data the components of the UVCB substance have a low potential for acute toxicity.

 

DNEL - longterm exposure - systemic effects:

The key study for DNEL derivation is a subchronic oral toxicity study in rats of 2-octyldodecan-1-ol with a NOAEL of 839.6 mg/kg bw/d. No substance-related effects were observed in this study. The following assessment factors are proposed for thedermal DNEL: 4 for allometric scaling, 5 for intraspecies variation, and 2 for exposure extrapolation (subchronic to chronic) resulting in an overall assessment factor of 40. An additional factor for "remaining interspecies differences" as proposed by ECHA is scientifically not justified and arbitrary since the allometric scaling factor fully accounts for interspecies differences [ECETOC. Technical Report in preparation: Guidance on Assessment Factors to Derive DNELs (2009), and Publication No. 901 of the Committee for Hazardous Substances (AGS) of the German Federal Institute for Occupational Safety and Health (BAuA), April 2010 and Escher et al., Toxicology Letters 218 (2013) 159– 165]. Furthermore, ECETOC recommends in its Technical report No. 86 ("Derivation of Assessment Factors for Human Health Risk Assessment; February 2003) a default assessment factor for intraspecies differences for the general population of 5 deviating from the ECHA proposed assessment factor of 10. Based on these assessment factors and assuming an equivalent resorption rate for oral and dermal exposure a DNEL of 21 mg/kg bw/d for long-term oral and dermal exposure results. Forinhalation, the oral NOAEL of 839.6 mg/kg bw/d is converted into a corrected NOAEC assuming a standard 24h respiratory volume of 1.15 m³/kg/d for the rat. This results in a corrected NOAEC of 730 mg/m³ for humans. The following assessment factors are proposed for theinhalation DNEL: assessment factors of 1 for interspecies differences (inhalation), 5 for intraspecies variation and 2 for exposure extrapolation (subchronic to chronic). A worst case default factor of 2 for route-to-route extrapolation (oral-to-inhalation) proposed by ECHA is not assigned as a higher absorption via the inhalation route compared to the oral route is not expected because of the lipophilic properties of the substance. An evaluation of several substances for differences in their oral and inhalation absorption support this assumption [ECETOC. Technical Report in preparation: Guidance on Assessment Factors to Derive DNELs (2009)]. Based on these assessment factors the long-term exposure DNEL for inhalation is 73 mg/m³. For theoral DNELthe following assessment factors are proposed: 4 for allometric scaling, 5 for intraspecies variations, and 2 for exposure extrapolation resulting in an overall assessment factor of 40 and a DNEL of 21 mg/kg bw/d.

 

DNEL - acute/short-term and long-term exposure - local effects:

DNELs for local effects do not need to be derived as available data indicate no significant local effects.