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Key value for chemical safety assessment

Additional information

No genetic toxicity data are available for Alcohols, C12 -15 -branched and linear. For all genetic toxicity endpoints, information is available from studies on closely related linear or branched alcohols of similar chain length. The choice of key study was based on reliability and similarity of chain length. The data available from standard in vitro and in vivo genetic toxicity assays for all related substances show no evidence of mutagenic potential.

Alcohols, C12-16, has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD TG 471, compliant with GLP. No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strainsTA 98, TA 100, TA 1535, TA 1537, and TA 102 in the initial or the repeat experiments up to limit concentration. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test (Ballantyne, 1996).

Docosan-1-ol has been tested in a valid study according to a protocol similar to OECD TG 473 up to limit concentration of 20 µg/ml. No increase in the number of cells with aberrations was observed either with or without metabolic activation in Chinese hamster lung fibroblasts (V79). Appropriate positive, solvent and negative controls were included and gave the expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this study (Iglesias, 2002b).

Alcohols, C10-16, has been tested in a valid study according to a protocol similar to OECD TG 473 up to cytotoxic concentrations. No increase in the number of cells with aberrations was observed either with or without metabolic activation in Chinese hamster Ovary (CHO). Appropriate positive and solvent controls were included and gave the expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this study (Sasol, 1998).

2 -Ethyl hexan-1-ol has been tested in a valid study according to a protocol similar to OECD TG 476 guideline. No statistically and biologically significant increase in the mutant frequency was observed when tested up to limit concentration in mouse lymphoma L5178Y cells with and without metabolic activation. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the test (Kirby, 1983).

Docosan-1-ol has been tested in a valid study according to a protocol similar to OECD TG 476 guideline. No statistically and biologically significant increase in the mutant frequency was observed when tested up to limit concentration in Chinese hamster fibroblasts (V79) with and without metabolic activation. Appropriate positive, solvent and negative controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the test (Iglesias, 2002b).

Octadecan-1-ol has been tested for the induction of micronuclei in mice according to a protocol similar to OECD TG 474 guideline. No evidence for a test substance induced increase in the incidence of micronucleated normochromatic erythrocytes in mice bone marrow. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that the test substance does not cause damage to chromosomes under the conditions of the test.

Dodecan-1-ol has been tested for the induction of micronuclei in mice according to OECD TG 474 and in compliance with GLP. No evidence for a test substance induced increase in the incidence of micronucleated normochromatic erythrocytes in mice bone marrow. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance does not cause damage to chromosomes under the conditions of the test (Banduhn, 1992).

Discussion of trends in the Category of C6-24 linear and essentially-linear aliphatic alcohols:

The in vitro and in vivo data available for members of the category and supporting substances indicate that

the C6-24 alcohols are not genotoxic. In addition, the category of LCAAs under consideration does not contain

any structural elements that are of concern for potential mutagenic activity (Ashby and Tenant, 1991).

Furthermore, primary LCAAs (linear and branched) in the range C1 to C5 do not have a mutagenic potential

(Bevan, 2001; OECD SIDS butan-1-ol, 2001). Moreover, in a review by WHO-JECFA a series of 22 saturated

aliphatic branched-chain primary LCAAs and the corresponding aldehydes and acids in the range C4 to C8 showed

no activity in a battery of in vitro and in vivo mutagenicity tests (WHO, 1999). On this basis it is concluded

that the category of LCAAs does not have a mutagenic potential and that read-across within the category can be

justified. Where data gaps exist, the gap is filled by read-across from reliable evidence within the C6-24

Alcohols Category, where possible using interpolation between at least two reliable studies using higher and

lower carbon number test substances.

Conclusion:

The category C6-24 LCAAs do not have a genotoxic potential.

Genetic toxicity data for the Category

 

CAS

CHEMICAL NAME

Bacterial mutagenicity

Result (Rel.)

Reference

C6

111-27-3

Hexan-1-ol

 Neg; (1)

 Henkel, 1990

C7, 8 and 9

 

Alcohols, C7-9

Neg. (1)

Shell, 1996

C8

111-87-5

Octan-1-ol

Neg; (2)

 Henkel, 1982a; HLS, 1996k

C8

104-76-7

2-ethylhexan-1-ol

Neg; (2)

Kirby, 1983

Supporting Substance

C8-10

none

Fatty alcohol blend (40.7% C8 and 55.3% C10)

Neg(2)

Dillon, D.M., McCartney, M.A. (1992)

Supporting Substance

C10

112-30-1

Decan-1-ol

Neg (4) 2 strains only

 (HLS, 1996l)

C12

112-53-8

Dodecan-1-ol

Neg. (1)l

 (Thomson, 1996a)Shimizu, 1985

C12 and 13

75782-87-5

Alcohols, C12-13

Neg (2, >80% lin)

 Dean, 1980

C12 and 13

740817-83-8

Alcohols, C12-13-branched and linear

Neg (1 50% lin),

Sasol, 1998f

C12

67762-25-8

C12-18 Alcohols, Type B

Neg (2)Ames

Henkel 1982c

Supporting

C 12-15

90604-40-3

Alcohols, C12-15-branched and linear

Neg (1)

Ballantyne, 1996

C14

112-72-1

Tetradecan-1-ol

Neg (1)

Thompson, 1996b

C16

36653-82-4

Hexadecan-1-ol

Neg (1)

Thompson, 1996c

Neg. (2)

Henkel, 1981d

C16

68002-94-8

C16-18 and C18 Unsaturated

Neg. Ames (2)

Banduhn, 1989)

Supporting

C18

112-92-5

Octadecan-1-ol

Neg (1)

Thomson, 1996d

Neg(2)

Henkel, 1981f

C18

97552-91-5

C18-22 Alcohol

Neg. Ames (2)

 Banduhn 1995

Supporting

C22

661-19-8

1-Docosanol

Neg (2),

Iglesias, 2002a, Thompson, 1997

C24-32

 

D-002***

 

 

* MN: Mouse bone marrow micronucleus test; Dom. Leth. Mouse Dominant Lethal test; UDS: Unscheduled DNA

Synthesis assay

** Tested in S. typhimurium TA 98 and TA100, only.

***Mixture of very long chain fatty alcohols from hydrolysed beeeswax

References:

Ashby, J., Tennant, R.W., 1991. Definitive relationships among chemical structure, carcinogenicity, and

mutagenicity for 301 chemicals tested by the US NTP. Mutation Research 257, 229–306.

WHO, 1999. Technical Report Series 884 Evaluation of certain food additives and contaminants. 49th Report of

the Joint FAO/WHO Expert Committee on Food Additives (JECFA), Geneva.


Justification for selection of genetic toxicity endpoint
Conclusion based on the following assays: Bacterial reverse mutation assay (Ames test); Mammalian cell gene mutation assay; In vivo chromosome aberration study (analogue substances). The studies were conducted according to appropriate OECD guidelines or to similar protocols.

Short description of key information:
In vitro information:
Gene mutation (Bacterial reverse mutation assay / Ames test): the related substance C7, 8 and 9 Alcohols; predominantly linear: negative with and without activation in S. typhimurium strains TA 98, TA100, TA1535, TA1537 and TA 1538 (similar to OECD TG 471)
Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in S. typhimurium strains TA 98, TA100, TA102 TA1535 and TA1537 ( OECD TG 471)
Cytogenicity in mammalian cells: the related substance C12 and 13 alcohols; linear and monobranched, type 2: negative in CHO cells (OECD TG 473)
Cytogenicity in mammalian cells: the related substance Docosan-1-ol was negative with and without activation in Chinese hamster ovary cells (similar to OECD TG 473)
Mutagenicity in mammalian cells: the related substance 2-ethylhexan-1-ol was negative with and without activation in L5178Y mouse lymphoma cells (similar to OECD TG 476)
Mutagenicity in mammalian cells: the related substance Docosan-1-ol was negative with and without activation in CHL V79 cells (similar to OECD TG 476)

In vivo
Mouse micronucleus study: the related substance dodecan-1-ol was negative in mice after oral administration (gavage) (OECD 474)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

C12, 13, 14 and 15 alcohols, linear and monobranched is a member of the category aliphatic alcohols. The category members contain no structural elements which may be of concern for potential mutagenic activity. In vitro tests over the carbon range (C6-22) of the long chain alcohols category members (primary aliphatic alcohols) and supporting substances (C5-C24-34), including branched alcohols, are negative, including a bacterial mutagenicity study on C12, 13, 14 and 15 alcohols. Evidence from in vivo studies on category members supports the conclusion that these alcohols are not genotoxic in vivo.