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Administrative data

Key value for chemical safety assessment

Additional information

There is no information on the genetic toxicity of (Z)-octadec-9 -en-ol so key studies were chosen from studies on closely related linear or branched alcohols of similar chain length, including a study on an unsaturated alcohol. 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, C16-18 and C18-unsaturated, 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 inSalmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, or TA 1538 in the initial or the repeat experiments up to precipitation 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 (Banduhn, 1989).

Docosan-1-ol has been tested in a valid study according to a protocol similar or equivalent 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).

Docosan-1-ol has been tested in a valid study according to a protocol similar to OECD TG 476. 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).

Docosan-1-ol has been tested for the induction of micronuclei in mice according to a protocol similar to OECD TG 474. 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 (Iglesias, 2002b).

Octadecan-1-ol has been tested for the induction of micronuclei in mice according to a protocol similar to OECD TG 474. 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 (Iglesias, 2002b).

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.

It is concluded that the category C6-24 LCAAs do not have a genotoxic potential. 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, 1998). 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 of LCAAs

 

CAS

CHEMICAL NAME

Bacterial mutagenicity

Mammalian cytogenicity

Mammalian mutagenicity

In vivo studies

Result (Rel.)

Reference

Result (Rel.)

Reference

Result (Rel.)

Reference

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

Supporting Substance

Neg; (2)

Kirby, 1983

 

 

Neg; (2)

Kirby, 1983

Neg; (2)

MN; rodent dominant. Lethal

C8-10

none

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

Supporting Substance

Neg(2)

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

(Putman, 1983; WHO, 1993)

 

Neg (1)

Cattanach, P., Riach, C. (1992)

Neg (1)

Micronucleus (Holstrom, M., Innes, D. (1992))

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

 

 

 

 

Neg. (2)

Micronucleus; (Banduhn, 1992)

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

Neg (1 (50% lin)

Sasol, 1998 g

 

 

 

 

C12

67762-25-8

C12-18 Alcohols, Type B

Supporting

Neg (2)Ames

Henkel 1982c

 

 

 

 

 

 

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

Supporting

Neg. Ames (2)

Banduhn, 1989)

 

 

 

 

 

 

C18

112-92-5

Octadecan-1-ol

Neg (1)

Thomson, 1996d

Not required

In vivo available

 

 

Neg (2) MN

Hachiya, 1982

Neg(2)

Henkel, 1981f

C18

97552-91-5

C18-22 Alcohol

Supporting

Neg. Ames (2)

 Banduhn 1995

 

 

 

 

 

 

C22

661-19-8

1-Docosanol

Neg (2),

Iglesias, 2002a, Thompson, 1997

Neg (2),

Iglesias, 2002a

Neg (2)

Iglesias, 2002a

Neg (2)

Micronucleus Iglesias, 2002aª

C24-32

 

D-002***

 

 

 

 

 

 

Neg (4)

MN; Dom. Leth.Rodeiro 1998

Supporting substance

* 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 mutagenicity; in vitro cytogenicity; mammalian mutagenicity; in vivo micronucleus assays in 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 C16-18 and C18 unsatd 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: 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 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: the related substances dodecanol and docosanol were negative in bone marrow (similar to OECD TG 474)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

(Z)-octadec-9-enol 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) are negative. Evidence from in vivo studies on other category members supports the conclusion that these alcohols are not genotoxic in vivo.