Alcohols, C16-18

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Alcohols, C16-18 is a member and is from Long Chain Alcohols (C6-22 primary aliphatic alcohols) category.
The Long Chain Alcohols (C6-22 primary aliphatic alcohols) category is considered suitable as a source of data for Alcohols, C16-18.
Considered valid for read-across for purposes of classification.
No further vertebrate testing can be justified.

Long Chain Alcohols (C6-22 primary aliphatic alcohols) category covers a family of 30 primary aliphatic alcohols within a carbon chain length range of C6-C22. Commercial products generally include several aliphatic alcohol components, with a range of carbon chain lengths present. The family consists of alcohols with varying compositions and structures. Composition depends on the route to manufacture and the related feedstocks. Most of the alcohols have linear carbon chains but certain manufacturing processes create branched structures. Data are also available for eleven other similar substances, which support the category. Non-sponsored alcohols may not be HPV or may not be produced by members of the consortium, but have structures similar to sponsored linear alcohols.

Key points are that the members share:
• The same structural features
• Similar metabolic pathways
• Common mode of ecotoxicological action
• Common levels and mode of human health related effects.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2022

Reference 2

Reference Type:

publication

Title:

Dossier on 1-Octadecanol.

Author:

Hachiya N, Takeya A, Takizawa Y

Year:

1982

Bibliographic source:

Japanese J. Public Health 29(5): 236-239. (In Japanese, translation available)

Reference 3

Reference Type:

publication

Title:

SIDS Dossier on 1-Octadecanol.

Author:

Environmental Protection Agency,

Year:

1993

Bibliographic source:

Environmental Protection Agency, Denmark. 6 June 1993.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

Method: other: mouse bone marrow micronucleus test to protocol to the Japanese Labour Ministry

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Octadecan-1-ol

EC Number:

204-017-6

EC Name:

Octadecan-1-ol

Cas Number:

112-92-5

Molecular formula:

C18H38O

IUPAC Name:

octadecan-1-ol

Details on test material:

Octadecanol (112-92-5) (Kalcohol 80, 718)

Test animals

Species:

mouse

Strain:

other: ddY

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: Mice
- Age: 6 weeks
- Weight at study initiation: not reported
- No. of animals per dose: Groups of 5 or 6

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

Vehicle used: olive oil

Details on exposure:

ADMINISTRATION: Gavage
- Vehicle: Olive oil, dosing volume 25 ml/kg
- Duration of test: 1 or 4 doses.
- Frequency of treatment: Once or 4 times in 24 hours.
- Sampling times and number of samples: 24 hours after a single does, 5 days after the first administraton of the repeated doses. 2000 red blood cells scored per smear for micronuclei, 1000 scored for reticulocytes.
- Control groups and treatment: Stearyl alcohol single oral doses of 0.36, 0.73 or 1.45 g/kg/day or 4 doses of 0.73 g/kg/day in a 24 hour period. Positive control mitomycin C 3 mg/kg intraperitoneally. Solvent control olive oil 25 ml/kg

Duration of treatment / exposure:

24 hours

Frequency of treatment:

single administration and 4 administrations

Post exposure period:

24 hours (single administration); 5 days from initial administration (repeat administration)

Doses / concentrations

Remarks:

Doses / Concentrations:
360, 730, 1450 mg/kg (single dose) or 730 mg/kg (adminstered 4 times in 24 hours)
Basis:
nominal conc.

No. of animals per sex per dose:

6 (single dose) 5 (repeat dose) sex not stated

Control animals:

yes, concurrent vehicle

Positive control(s):

- Positive control: mitomycin C
- Route of administration: ip injection
- Doses / concentrations: 3.0 mg/kg

Examinations

Tissues and cell types examined:

Bone marrrow; erythrocytes examined

Statistics:

STATISTICAL ANALYSIS: Kastenbaum & Bowman

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

MORTALITY: Not reported
CLINICAL SIGNS: Not reported
NECROPSY FINDINGS: Not reported
BODY WEIGHT CHANGES: Not reported
FOOD AND WATER CONSUMPTION CHANGES: Not reported
EFFECT ON MITOTIC INDEX OR PCE/NCE RATIO: There were no effects on the incidence of reticulocytes following a single dose of stearyl alcohol.
Repeated exposure showed a decrease [controls 61.3%; treated 52.9%]
GENOTOXIC EFFECTS: No significant increase increase in numbers (%) of micronucleated erythrocytes. 10000 - 12000 observed.
NOAEL (NOEL) (C) / LOAEL (LOEL) (C): A single dose of 1450 mg/kg/day or a total repeated dose of 2920 mg/kg did not increase the incidence of
micronuclei. There was no reported assessment of effects on the live animals.

Any other information on results incl. tables

Results of micronucleus assay

Treatment	Vehicle 25 ml/kg	Positive control 3.0 mg/kg	Low dose 0.36 g/kg	Mid dose 0.73 g/kg	High dose 1.45 g/kg	Mid dose 0.73 g/kg
No of injections	1	1	1	1	1	4
Micronucleated erythrocytes %	0.13 ±0.10	1.96 ± 0.64	0.03 ± 0.03	0.06 ± 0/04	0.09 ± 0.04	0.08 ± 0.08
Frequency of erythrocytes	81.3 ± 8.0	46.2 ± 9.4	61.5 ± 6.2	60.3 ± 9.2	67.4 ± 7.5	52.9 ± 7.6

 

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results : negative
Stearyl alcohol (Kalcohl 80, 718) did not increase the incidence of micronucleated cells in mouse bone marrow erythrocytes following a single oral dose level up to and including 1450 mg/kg or a total of 2920 mg/kg adminstered 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.