Undecanal

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / micronucleus study

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD TG 487

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian cell micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Undecanal

EC Number:

203-972-6

EC Name:

Undecanal

Cas Number:

112-44-7

Molecular formula:

C11H22O

IUPAC Name:

undecanal

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): n-undecanal
- Physical state: liquid, colourless
- Purity: 92.8 %
- Batch no: 50000018013
- Storage condition of test material: at room temperature < 21°C, under nitrogen gas

Method

Species / strain

Species / strain / cell type:

other: human

Details on mammalian cell type (if applicable):

- Cell type. lymphocytes
- Type and identity of media: RPMI 1640 medium, containing fetal calf serum, gentamycin and heparin
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: no

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix, contained 10% v/v S9 fraction from Aroclor induced male Sprague Dawley rat liver fraction, and cofactors

Test concentrations with justification for top dose:

0, 1.25, 2.5, 5, 10, 20, 40, 80, 160, 300, and 600 µg/mL (precipitation at 600 µg/mL)

Vehicle / solvent:

- Vehicle used:DMSO
- Justification for choice of solvent/vehicle: low water solubility of the test substance

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: mitomycin and cyclophosphamide

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk

DURATION
- Preincubation period:
- Exposure duration: 4 hrs (withand without out S-9 mix) and 24 hrs inteh absnece of S-9 mix
- Expression time (cells in growth medium): 24 hrs
- Selection time (if incubation with a selection agent):
- Fixation time (start of exposure up to fixation or harvest of cells): up to 48 hrs

SELECTION AGENT (mutation assays):
SPINDLE INHIBITOR (cytogenetic assays): cytochalasin B
STAIN (for cytogenetic assays): acridine orange

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: 2000 binucleated cells/dose level

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index, CBPI (cytokinesis block proliferation index)

OTHER EXAMINATIONS:
- Determination of polyploidy: no

Evaluation criteria:

The vehicle/negative control results should lie within or close to the negative historical control range. The positive controls should produce a substantial increase in the incidence of MBC (at least twice) compared with the concurrent control; values should lay beyond the 99% upper limit of the historical negative/vehicle control range.

Results and discussion

Test results

Key result

Species / strain:

lymphocytes: human

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: at 600 µg/mL
- Other confounding effects:

COMPARISON WITH HISTORICAL CONTROL DATA: yes

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Summary of Results

Treatment		Conc. (mg/mL)		Average CBPI		Cytotoxicity (%)^a		Total No. of BC examined		Total Number of MBC		% MBC
4 hours treatment in the absence of S9 (0S9)
Vehicle		-		1.9		0		2000		12		0.6
n-Undecanal		80.0		1.8		10		2000		14		0.7
		160		1.9		6		2000		10		0.5
		300		1.8		14		2000		8		0.4
		600		1.5		45		1698^b		8		0.5
MMC		0.3		1.6		30		2000		134		6.7*
4 hours treatment in the presence of S9 (+S9)
Vehicle		-		1.9		0		2000		8		0.4
n-Undecanal		160		1.8		11		2000		16		0.8
		300		1.7		24		2000		9		0.5
		600		1.6		30		2000		12		0.6
CP		10		1.5		41		2000		91		4.6*
24 hours treatment in the absence of S9 (0S9)
Vehicle		-		2.0		0		2000		3		0.2
n-Undecanal		40.0		1.9		10		2000		4		0.2
		80.0		1.7		25		2000		10		0.5
		160		1.5		44		2000		15		0.8
		300		1.2		84		NR
MMC		0.2		1.6		42		2000		334		16.7*

CBPI                   Cytokinesis-Block Proliferation Index

BC, MBC            Binucleated cells, micronucleated binucleated cells (%MBC calculated based on rounded values)

NR                        Not reported as considered excessively toxic (Cytotoxicity > 60% relative to vehicle control)

*                            Substantial positive response (at least twice the concurrent vehicle control in terms of %MBC)

a                            Cytotoxicity calculation based on unrounded values

b                            Not enough cells available

 

Applicant's summary and conclusion

Conclusions:

N-undecanal was not clastogenic in an in-vitro micronucleus test using human lymphoctyes, with and without metabolic activation.

Executive summary:

N-undecanal (80, 160, 300, 600 µg/mL; dosed selection was based on preliminary studies. Precipitation at 600 µg/mL) was tested in an in-vitro micronucleus test using human lymphocytes, with and without metabolic activation, for its potential to induce micronuclei. The test was conducted under GLP conditions and according to the OECD guideline 487. Human blood cell cultures were treated for 48 hours with phytohemagglutinin to stimulate lymphocyte division. Cells were then treated with the test substance for 4 hours in the presence and absence of metabolic activation (and additionally for 24 hours in the absence of metabolic activation). At the end of a 24-hour expression period under cytochalasin B the cells were harvested, stained, and 2000 binucleated cells/dose level were then examined for the occurrence of micronuclei. The results were compared with those of the concurrent and historical vehicle (DMSO) and positive controls (mitomycin and cyclophosphamide).

 

N-undecanal was tested up into cytotoxic concentrations, but did not induce the formation of micronuclei, with or without metabolic activation. The negative and positive controls performed as expected. Thus, n-undecanal was not genotoxic (clastogenic) in this assay (Charles River, 2010).

This study is considered to be valid and useful for assessment.