Octadecan-1-ol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

without detailed documentation

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

The toxicity of behenyl alcohol: I. Genotoxicity and subchronic toxicity in rats and dogs

Author:

Iglesias G, J J Hlywka, J E Berg, M H Khalil, L E Pope and D Tamarkin

Year:

2002

Bibliographic source:

Regulatory Tox. and Pharm. 36, 69-79, 2002

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

Principles of method if other than guideline:

Well-conducted study according to protocol very similar to OECD guideline 473

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Docosan-1-ol

EC Number:

211-546-6

EC Name:

Docosan-1-ol

Cas Number:

661-19-8

Molecular formula:

C22H46O

IUPAC Name:

docosan-1-ol

Test material form:

other: Waxy Solid

Method

Target gene:

not applicable

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

- Type and identity of media: minimum essential medium
- Properly maintained: no data
- Periodically checked for Mycoplasma contamination: no data
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: no data

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

liver microsomal fraction from male rats prepared according to Ames et al., 1977

Test concentrations with justification for top dose:

0.6, 10.0 and 20.0 µg/ml

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: solubility

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

ethylmethanesulphonate

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

with metabolic activation

Positive control substance:

cyclophosphamide

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: not applicable
- Exposure duration: 4 hours
- Expression time (cells in growth medium): not applicable
- Selection time (if incubation with a selection agent): not applicable
- Fixation time (start of exposure up to fixation or harvest of cells): 7 and 24 (or 28) hours at 20 µg/ml, 18 hours at 0.6, 10 and 20 µg/ml

SPINDLE INHIBITOR (cytogenetic assays): Colcemid, 0.2 µg/ml

STAIN (for cytogenetic assays): Giemsa

NUMBER OF REPLICATIONS: 2 cultures per concentration

NUMBER OF CELLS EVALUATED: 100 per slide, 200 per concentration

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

Evaluation criteria:

To be considered positive, either a statistically significant, concentration-related increase in the number of structural chromosome aberrations, or a statistically significant positive response at one of the concentrations

Statistics:

Chi-squared test performed for cells with aberration (excluding gaps)

Results and discussion

Test results

Key result

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: presumably >20 µg/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: insoluble
- Precipitation: no data
- Other confounding effects: no data

RANGE-FINDING/SCREENING STUDIES: yes, but no data presented

COMPARISON WITH HISTORICAL CONTROL DATA: no data

ADDITIONAL INFORMATION ON CYTOTOXICITY: at 20 µg/ml, mitotic index not reduced, plating efficiency not reduced

Remarks on result:

other: No mutagenic potential

Any other information on results incl. tables

Table 1 Cytogenicity: 7 hour fixation. Aberrations in 200 cells

Activation	Concentration µg/ml	Percent aberrant cells
		incl gaps	excl gaps	exchanges
Without	0*	4.0	1.5	0
	20	2.5	0.5	0
With	0*	4.0	1.5	0
	20	7.0	2.5	0

* Solvent control with ethanol

** Only 100 cells counted for positive controls

 

Table 2 Cytogenicity: 18 hour fixation. Aberrations in 200 cells

Activation	Concentration µg/ml	Percent aberrant cells
		incl gaps	excl gaps	exchanges
Without	Negative control	5.5	1.5	0
	0*	4.0	1.5	0.5
	0.6	4.5	2.0	0
	10	4.0	1.0	0.5
	20	3.0	0.5	0
	Positive control**	12.0	9.0	4.0
With	Negative control	2.5	1.5	0
	0*	2.5	1.5	0.5
	0.6	5.5	3.0	0.5
	10	4.0	2.5	0
	20	4.0	2.5	0.5
	Positive control**	16.0	13.0	5.5

* Solvent control with ethanol

** Only 100 cells counted for positive controls

Table 3 Cytogenicity: 18 hour fixation. Aberrations in 200 cells

Activation	Concentration µg/ml	Percent aberrant cells
		incl gaps	excl gaps	exchanges
Without	0*	6.0	2.5	0.5
	20	3.5	2.0	0
With	0*	1.0	0.5	0
	20	4.0	2.5	0.5

* Solvent control with ethanol

** Only 100 cells counted for positive controls

Applicant's summary and conclusion

Conclusions:

In a reliable study, according to a protocol that is similar to OECD 473, behenyl alcohol (C22) 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.

Executive summary:

In an in vitro chromosome aberration study, Chinese hamster lung fibroblasts (V79) were incubated with 0.6, 10.0 and 20.0 µg/ml of test material dissolved in ethanol for 4 hours, with and without metabolic activation.

The test substance did not increase the incidence of chromosome aberrations in Chinese hamster V79 cells in the presence or absence of metabolic activation when tested up to limit concentration. There was no evidence of cytotoxicity at this dose level. The study was comparable to guideline without detailed documentation (publication). It is considered that read across to the registered substance is valid and scientifically justifiable.