Alcohols, C7-9

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP. Read across to the registered substance is considered scientifically justified.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Alcohols, C10-16

EC Number:

267-019-6

EC Name:

Alcohols, C10-16

Cas Number:

67762-41-8

IUPAC Name:

tetradecan-1-ol

Details on test material:

- Name of test material (as cited in study report): Sasol(TM) 23 Alcohol C10-16 alcohols Type B (also known as Compound 33A)
- Substance type: UVCB substance
- Physical state: liquid
- Lot number: KPT/SAS/DA/2/98

Method

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

Test 1: 0.1 - 500 µg/ml; Test 2: with S9 1 -50 µg/ml, without S9 0.5 - 20 µg/ml

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: none given in report. Standard solvent

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

mitomycin C

Remarks:

without activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

with activation

Details on test system and experimental conditions:

ACTIVATION: 1 ml Aroclor induced rat liver S9 mix, NADP as cofactor
METHOD OF APPLICATION: in medium

DURATION

Exposure duration: Test 1: +S9 3 hours, -S9 18 hours, Test 2: +S9 3 hours; -S9  18 or 32 hours 
- Expression time (cells in growth medium): 18 hours
- Fixation time (start of exposure up to fixation or harvest of cells): Test 1 18 hours; Test 2 18 or 32 hours

SPINDLE INHIBITOR (cytogenetic assays): Colcemid (final concentration 0.1 mM)

TAIN (for cytogenetic assays): Giesma

NUMBER OF REPLICATIONS: Duplicate cultures, independent repeat assay

NUMBER OF CELLS EVALUATED: 100 per culture

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; other: observation of culture

OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: yes
- Other: interstitial deletions

Evaluation criteria:

CRITERIA FOR EVALUATING RESULTS: The test is considered positive if the aberration frequency of at least one concentration is significantly above concurrent control frequencies.

Statistics:

Fisher's exact probability test (two-sided)

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

+S9 40 µg/ml; -S9 15 µg/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

GENOTOXIC EFFECTS: - With and without metabolic activation:  
There were  no statistically significant increase in total numbers of chromosome aberrations at any dose level tested
There was no increase in the incidence of  polyploids or endoreduplicates.
PRECIPITATION CONCENTRATION: 125 µg/ml. 
MITOTIC INDEX: The mitotic index was measured on 1000 cells and was always >40% of control levels and usually >50% for the dose levels which   were scored for chromosome aberrations. 
STATISTICAL RESULTS: Fischers exact probability test (two-sided) did not indicate any significant difference between test and control groups.

Remarks on result:

other: strain/cell type: Chinese hamster ovary cells (CHO K-1 line)

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Chromosome aberration assay: Test 1

Treatment time 18 hrs
Treatment		Activation	Concentration µg/ml	Number of cells	Total - gaps	Total + gaps
Negative control DMSO		-MA	0	200	0	4
Test substance		-MA	2.5	200	0	6
		-MA	5	200	0	6
		-MA	10	200	2	8
Positive control Mitomycin C		-MA	0.025	200	48	48
Treatment time 3 hrs
Treatment			Concentration µg /ml	Number of cells	Total - gaps	Total + gaps
Negative control DMSO	+MA		0	200	0	2
Test substance	+MA		10	200	1	6
	+MA		20	200	1	5
	+MA		30	200	1	5
Positive control Cyclophosphamide	+MA		3.75	200	48	48

Chromosome aberration assay: Test 2

Treatment	-MA	Concentration  µg /ml	Number of cells	Total - gaps	Total + gaps
Treatment time 18 hrs
Negative control DMSO	-MA	0	200	1	5
Test substance	-MA	5	200	2	8
	-MA	7.5	200	0	5
	-MA	10	200	1	4
Positive control Mitomycin C	-MA	0.025	200	54	54
Treatment time 3 hrs, incubation 18 hours
Treatment		Concentration µg /ml	Number of cells	Total - gaps	Total + gaps
Negative control DMSO	+MA	0	200	0	8
Test substance	+MA	10	200	1	2
	+MA	20	200	1	7
	+MA	30	200	1	7
Positive control Cyclophosphamide	+MA	3.75	200	105	105
Treatment time 32 hrs
Treatment		Concentration µg /ml	Number of cells	Total - gaps	Total + gaps
Negative control DMSO	-MA	0	200	0	8
Test substance	-MA	10	200	0	7
Treatment time 3 hrs, incubation 32 hours
Treatment		Concentration  µg /ml	Number of cells	Total - gaps	Total + gaps
Negative control DMSO	+MA	0	200	2	3
Test substance	+MA	30	200	0	5

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without activation

C12 AND 13 ALCOHOLS; LINEAR AND MONOBRANCHED, TYPE 2 (also known as Compound 33A) has been tested in a valid study according to OECD TG 473 and under GLP in CHO K1 cells. 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.