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Data are available for isostearyl alcohol CHECK NAME from an in vitro bacterial mutagenicity study. No further data are available for the registered substance, however, data are available for the related substances C12 and 13 alcohols; linear and monobranched, type 2 (CAS 67762-41-8) for cytogenicity to mammalian cells and from docosan-1-ol (C22) (CAS 661-19-8) from studies on cytogenicity and mutagenicity to mammalian cells. The bacterial study on the test substance did not include a strain capable of detecting cross-linking mutagens, however, information is available for the structural analogue C 12 -13 alcohol (80% branched) from a study that included an appropriate 5th strain. No evidence of genetic toxicity is shown in any of these studies.

The constituents of isostearyl alcohols CHECK NAME share a common chemistry, incorporating an alcohol functional group on an alkyl chain, with C-numbers in the range (C14-C20, predominantly C16-C18). The alkyl structures are predominantly monobranched (methyl or ethyl branching, at or beyond the 6-position) and may be considered ‘essentially linear’.

In this carbon number range, the in vivo behaviour tends to be dominated by the low solubility in water (ca 0.001 to 0.2 mg/L), low vapour pressure (ca. 1E-05 to 0.05 Pa) and high partition coefficient (log Kow 6 to 8), which are consistent or equivalent for constituents of isostearyl alcohols CHECK NAME and the structural analogues C12 and 13 alcohols; linear and monobranched, type 2 and docosan-1-ol (C22) (CAS 661-19-8). More broadly, the substances generally possess similar physico-chemical properties. Based on structure, the initial steps of the metabolic pathways (both bacterial and in vivo mechanisms) would be the same as for linear structures. No structural features that might indicate genetic toxicity are present. Therefore, a read-across approach is considered to be valid for genetic toxicity to mammalian cells, required for REACH registration at Annex IX, in the absence of reliable measured data.

Isooctadecan-1-ol has been tested for mutagenicity to bacteria, in a study which was conducted according to OECD 471, compliant with GLP (Van de Waart (1996)). No evidence of a test substance related increase in the number of revertants was observed with or without metabolic activation in the initial or the repeat experiments. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Information on the potential for mutagenicity to a cross-linking detecting strain of bacteria is provided by the structural analogue C12-13 alcohol (Dobanol 23, 80% linear), which has been tested according to a method that is similar to OECD 471 (Dean, B. J., and Brooks T. M. (1980)). The test substance did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium TA98, 100, 1535, 1537 and 1538 or tryptophan-dependent Escherichia coli strains WP2 and WP2 uvrA in the presence or absence of metabolic activation at dose levels up to 2000 µg/plate. Vehicle and positive controls produced expected results. There was no evidence of cytotoxicity at any dose level. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

The structural analogue alcohols, C10-16, (also known as C12 and 13 alcohols, linear and branched, type 2, and Compound 33A) has been tested in a valid study according to OECD TG 473 and under GLP in CHO K1 cells (van Delft and Vogel (1998)). The test substance did not increase the incidence of chromosome aberrations in Chinese hamster ovary cells at dose levels up to cytotoxic concentrations in the presence or absence of metabolic activation. The result of the repeat experiment confirmed that of the initial assay. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this test.

Further evidence for lack of cytogenicity comes from a study on the long chain linear alcohol docosan-1-ol, also known as behenyl alcohol (C22), which has been tested in a reliable study, conducted according to a protocol that is similar to OECD 473 (Iglesias et al., (2002)). No evidence of a test substance related increase in the incidence of chromosome aberrations in Chinese hamster V79 cells was observed 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. It is considered that the test substance is negative for cytogenicity under the conditions of this test.

Information is available from a reliable study for mutagenicity to mammalian cells using the structural analogue docosan-1-ol (C22) (Iglesias et al (2002)). The test substance did not increase the gene mutation rate in Chinese hamster V79 cells in the presence or absence of metabolic activation at concentrations up to 20 µg/ml. It is concluded that the test substance is negative for mutagenicity in mammalian cells under the conditions of this test.

The lack of mutagenic effects of branched alcohols in mammalian cells is supported by evidence from the branched C8 alcohol 2 -ethyl -hexan-1-ol (Kirby et al., (1983)). 2-ethyl hexan-1-ol was tested for mutagenicity to mammalian cells in a valid study using a method similar to OECD TG 476 up to toxic concentrations. No increase in the mutant frequency was observed. It was concluded that 2-ethyl hexan-1-ol is negative for mutagenicity to mammalian cells under the conditions of the test.

The lack of genotoxicity observed from in vitro studies is supported by in vivo data from three structural analogues.

The structural analogue docosan-1-ol (C22) has been tested in a reliable in vivo micronucleus study conducted according to a protocol that is similar to OECD 474 (Iglesias (2002)). No test substance related increase in the incidence of micronuclei in mouse bone marrow cells was observed after a single oral gavage dose of up to 500 mg/kg bw. It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test.

Another structural analogue octadecan-1-ol (stearyl alcohol; Kalcohl 80, 718) has been tested in a reliable in vivo micronucleus study conducted according to a protocol that is similar to OECD 474 (Hachiya (1982)). No test-substance related increase the incidence of micronucleated cells was observed in mouse bone marrow erythrocytes following a single oral dose level up to and including 1450 mg/kg bw (a total of 2920 mg/kg bw) administered as 4 doses in a 24 hour period. It is concluded that the test substance is negative for induction of micronuclei under the conditions of the test.

In vivo data are also available for dodecan-1-ol, which has been tested a reliable study, conducted according to OECD guideline 474 and in compliance with GLP (Banduhn (1992)). No increase in the incidence of micronuclei was observed in mice after a single oral dose of up to 5000 mg/kg bw. It is concluded that the test substance is negative for induction of micronuclei under the conditions of the test.


Short description of key information:
In vitro:

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 (OECD 471 (1983)) (Van de Waart E. J. (1996)).
Gene mutation (Bacterial reverse mutation assay / Ames test): read-across from structural analogue C12-13 alcohol (Dobanol 23, 80% linear): negative with and without metabolic activation in Salmonella typhimurium strains TA98, 100, 1535, 1537 and 1538 and Escherichia coli strains WP2 and WP2 uvrA (similar to OECD 471) (Dean, B. J., and Brooks T. M. (1980)).
Cytogenicity in mammalian cells: read-across from structural analogue alcohols, C10-16 (C12 and 13 alcohols; linear and monobranched, type 2) (CAS 67762-41-8): negative with and without metabolic activation in Chinese hamster ovary K-1 cells (OECD 473) (van Delft and Vogel (1998)).
Cytogenicity in mammalian cells: read-across from structural analogue docosan-1-ol (CAS 661-19-8) negative with and without metabolic activation in Chinese hamster V79 cells (similar to OECD 473) (Iglesias et al., (2002)).

In vivo:
Micronucleus assay in mouse (oral administration): read-across from structural analogue docosan-1-ol (C22): negative (similar to OECD 474) (Iglesisas (2002)).
Micronucleus assay in mouse (oral administration): read-across from structural analogue: octadecan-1-ol: negative (similar to OECD 474) (Hachiya (1982)).
Micronucleus assay in mouse (oral administration): read-across from structural analogue: dodecan-1-ol: negative (according to OECD 474) (Banduhn (1992)).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro and in vivo data, isostearyl alcohols CHECK NAME is not classified for mutagenicity according to Regulation 1272/2008/EC.