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Key value for chemical safety assessment

Additional information

Alcohols, C20-30 (even numbered), is a UVCB substance that comprises several linear long chain alcohols, predominantly tetracosan-1-ol (C24), hexacosan-1-ol (C26), and octacosan-1-ol (C28). Together, these substances make up approximately 70% of the composition of Alcohols, C20-30 (even numbered). Other constituents include, to a much lesser extent, secondary long chain alcohols and complex mixtures of long chain carboxylate esters. On this basis, study data, where available, for each of the long chain alcohol constituents has been evaluated and considered together; this is consistent with the Category approach applied for Long Chain Alcohols (LCA) under REACH. 

Available data for D-002, a defined mixture of higher aliphatic alcohols (triacontanol, octacosanol, dotriacontrianol, hexacosanol, tetracosanol) isolated from beeswax, has also been considered in this evaluation.

In a conservative approach the most sensitive study result from the constituents of the LCA category have been identified and used to address the endpoint in question.

 

A key reliable (Klimisch 2) Ames study was conducted with docosan-1-ol in S. typhimurium strains TA 98, TA100, TA1535, TA1537 and TA 1538. This study was conducted following a protocol similar to OECD 471 but with some deviations (e.g. No TA102 or E. coli WP2 uvrA; 2-aminoanthracene only positive control with metabolic activation). This study reported that docosan1-ol was negative in this bacterial mutation assay. Study data from this study was used as read-across data to support the equivalent icosan-1-ol endpoint.

 

A second key study reported on a reliable (Klimisch 2) in vitro mammalian chromosome aberration test conducted with a protocol very similar to OECD guideline 473 with docosan-1-ol. Docosan-1-ol did not increase the incidence of chromosome aberrations in Chinese hamster V79 cells in the presence or absence of metabolising fraction at concentrations up to 20 µg/ml. There was no evidence of cytotoxicity at this dose level. Data from this study was used as read-across data to support the equivalent endpoint. Another reliable study (Klimisch 1) in vitro mammalian chromosome aberration test using D-002 in human peripheral blood lymphocytes showed no evidence of cytotoxic or genotoxic potential up to a concentration of 5 mg/mL.

 

In a reliable (Klimisch 2) micronucleus assay conducted according to a procotol similar to OECD 474 the in vivo mutagenicity of docosan-1-ol was assessed. In this study docosan-1-ol did not increase the incidence of micronuclei in mouse bone marrow cells after a single oral gavage dose of up to 500 mg/kg bw. Consequently docosan-1-ol was reported to be negative in this assay. Study data from this study was used as read-across data to support the equivalent endpoint for Nafol 24 -28. Another study (Klimish 1) performed a micronucleus assay similar to OECD 474 on rat bone marrow cells using D-002. The highest treatment group was 625 mg/kg/day for 90-days and showed no signs of genotoxic effects.

 

On the basis of the genetic toxicity information included as part of this submission and in line with the read-across justification included, Alcohols, C20-30 (even numbered), is not considered to be genotoxic.


Justification for selection of genetic toxicity endpoint
All studies were reliable (Klimish 2) and reported negative results, so no specific study were selected.

Short description of key information:
In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): Docosan-1-ol was negative with and without activation in S. typhimurium strains TA 98, TA100, TA1535, TA1537 and TA 1538 (OECD TG 471)
Cytogenicity in mammalian cells: Docosan-1-ol and D-002 was negative with and without activation in Chinese hamster ovary cells (similar to OECD TG 473)
Mutagenicity in mammalian cells: Docosan-1-ol was negative with and without activation in Chinese hamster lung V79 cells (similar to OECD TG 476)

In vivo:
Mouse micronucleus study: Docosan-1-ol was negative in bone marrow (similar to OECD 474)
Rat micronucleus study: D-002 was negative in bone marrow (similar to OECD 474)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

These findings do not warrant the classification of Alcohols, C20-30 (even numbered),as genotoxic under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP) and under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.