Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 250 mg/kg bw
Quality of whole database:
With regard to acute oral toxicity, further results for Guerbet alcohols were evaluated by the respective REACH consortium. In a category approach, the consortium concluded that there is no evidence for acute oral toxicity with regard to this substance group.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
In accordance with column 2 of REACH Annex VIII, testing of the acute toxicity by inhalation is not appropriate as the substance is a liquid with a low vapour pressure (<= 2.3*10-7 atm ( <= 2.3*10-2 Pa;<= 2.3*1o-4 mbar) at 20 °C) and inhalation of the substance is unlikely. Therefore, testing of the dermal route is more appropriate.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
1 674 mg/kg bw
Quality of whole database:
The molecular weight range (242-509 Da) as well as the dermal penetration potential modeled with the QSAR program DERMWIN (v1.43) point to a poor systemic availability due to a limited dermal uptake. Especially for the ester components in the UVCB substance, the dermal penetration is expected to be negliglible (MW: 425-509 Da, dermal penetration as calculated by DERMWIN: <=4.16x10-3 cm/hr). Therefore, the oral (not the dermal) route represents the worst case with regard to bioavailability. The dermal LD50 was only tested up to a limit dose of 2 mL/kg bw. But due to the lower bioavailability, the dermal LD50 would be expected to be at least as high as the "worst case" oral LD50 (4250 mg/kg bw/d).

Additional information

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. Acute toxicity studies are not available for the UVCB substance as such. The acute toxic potential is evaluated on the basis of experimental data for Guerbet alcohols and their esters with fatty acids.

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

Acute oral toxicity:

With regard to acute oral toxicity, studies are available for two major components of the UVCB substance, namely the Guerbet alcohols 2 -hexyldecan-1-ol & 2-octyldodecan-1 –ol. No deaths, clinical symptoma or pathological findings were observed in any of the studies. Further results for the category of Guerbet alcohols were evaluated by the respective REACH consortium. In a category approach, the consortium concluded that there is no evidence for acute oral toxicity with regard to this substance group.

For the ester components present in the UVCB substance (reaction products of the Guerbet alcohols 2 -hexyldecan-1-ol & 2-octyldodecan-1 –ol withC12 and C14 fatty acids), no acute oral toxicity study is available. In addition to the metabolic consideration – ester cleavage into the corresponding Guerbet alcohols and dietary C12 / C14 fatty acids – an acute toxicity study for a close homologue is available. The close homologue (CAS 101227-09-2) is an ester of the Guerbet alcohol 2 -hexyldecan-1-ol with C16-18 fatty acids. It differs from the esters in the UVCB substance only with regard to the chain length of the fatty acids (close homologue: 2-6 carbon atoms more) and partly in the Guerbet alcohol chain length (close homologue: identical or 2 carbon atoms less). As demonstrated by the acute oral toxicity tests with 2 -hexyldecan-1-ol & 2 -octyldodecan-1 –ol, the variation in the chain length of the Guerbet alcohol has no impact on acute toxicity. From the difference in the carbon chain of the fatty acid structure in the ester, no different toxicological behavior is expected either. The structural variation does not introduce new functional groups, but only a minor extension of the molecule. Therefore, a read-across to CAS 101227-09-2 seems to be justified. The acute oral toxicity study with the close homologue CAS 101227-09-2 revealed only slightly reduced activity and piloerection, and only 1 hour after application, but no deaths. No pathological findings were seen at dissection of the animals.

As worst case assumption, the lowest LD50 of 4250 mg/kg bw (obtained in the study with CAS 101227-09-2) was used in the endpoint conclusion. All available data point to a very low acute oral toxicity of the UVCB substance.

Acute inhalation toxicity:

The UVCB substance to be registered has a low vapour pressure of <= 2.3*10-7 atm ( <= 2.3*10-2 Pa; <= 2.3*1o-4 mbar) at 20 °C) and a relatively high boiling point (>= 344 °C), indicating that inhalation as a vapour will be negligible. If the UVCB substance reaches the respiratory tract, passive diffusion is unlikely due to the high log Pow, the low water solubility the relatively high molecular weight. Theoretically, a systemic uptake could take place after micellular solubilisation.

In accordance with column 2 of REACH Annex VIII, testing of the acute toxicity by inhalation is not appropriate as the substance is a liquid with a low vapour pressure (<= 2.3*10-7 atm ( <= 2.3*10-2 Pa;<= 2.3*1o-4 mbar) at 20 °C) and inhalation of the substance is unlikely. Therefore, testing of the dermal route is more appropriate.

Acute dermal toxicity:

Acute dermal toxicity studies of the Guerbet alcohols 2 -hexyldecan-1-ol & 2-octyldodecan-1 –ol show a low dermal toxicity at doses of up to 2 ml/kg. No deaths occurred at any of the doses applied.

Due to the expected low dermal uptake and the resulting lower bioavailability, the oral route represents a worst case compared to the dermal route. Consequently, the actual dermal LD50 can be assumed to be in the range of the oral LD50 or even higher.


Justification for selection of acute toxicity – oral endpoint
Worst case assumption, lowest LD50.
Well conducted study similar to Guideline (Klimisch 2).

Justification for selection of acute toxicity – dermal endpoint
Well conducted study similar to Guideline (Klimisch 2).
2-Hexyldecan-1-ol is the major component in the UVCB.

Justification for classification or non-classification