Undecanal

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Undecanal was neither mutagenic in bacterial (Salmonella typhimurium) nor mammalian cells (HGPRT assay) in vitro. Undecanal was not clastogenic in-vitro in human leucocytes. All assays were conducted with and without metabolic activation.

Link to relevant study records

Reference

Reference 1

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.

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

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

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.

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'.

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

 

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.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 July - 10 September, 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

mammalian cell gene mutation assay

Target gene:

HPRT (hypoxanthine-guanine phosphoribosyl transferase)

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

- Type and identity of media: MEM (minimal essential medium) containing Hank’s salts, neomycin (5 µg/mL) and amphotericin B (1 %).
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital/ß-naphthoflavone induced rat liver S9 from male Wistar rats

Test concentrations with justification for top dose:

1st experiment: exposure 4 hours; 0.6-15 µg/mL without //7.2-230 with S-9 mix
2nd experiment:
exposure 24 hours; 0.6-25 µg/mL without S-9 mix;
exposure 4 hours; 7.8-500 µg/mL with S-9 mix

Vehicle / solvent:

- Vehicle used: DMSO
- Justification for choice of solvent/vehicle: low solubility of test article

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: EMS (ethylmethane sulfonate), DMBA (7,12-dimethylbenz(a)anthracene)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium;

DURATION
- Preincubation period: 24 hours
- Exposure duration: 4 hrs in the 1st experiment; 24 hrs without S-9 mix, 4 hrs with S-9 mix, in the 2nd experiment
- Expression time (cells in growth medium): 7 days
- Selection time (if incubation with a selection agent): 7 or 8 days
- Fixation time (start of exposure up to fixation or harvest of cells): 7 or 8 days

SELECTION AGENT (mutation assays): 6-thioguanine
SPINDLE INHIBITOR (cytogenetic assays): not required
STAIN (for cytogenetic assays): not required

NUMBER OF REPLICATIONS: 2

NUMBER OF EXPERIMENTS: 2

NUMBER OF CELLS EVALUATED: all surviving colonies counted

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency

Evaluation criteria:

A test item is classified as positive if it induces either a concentration-related increase of the mutant frequency or a reproducible and positive response (i.e. at least 3 times the spontaneous mutation frequency) at one of the test points.

Statistics:

A linear regression (least squares) was performed to assess a possible dose dependent increase of mutant frequencies. The number of mutant colonies obtained for the groups treated with the test item were compared to the solvent control groups. A trend is judged as significant whenever the p-value (probability value) is below 0.05.

Key result

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

7.5-20 µg/mL/without S-9 mix); 250 mµ/mL with S-9 mix

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: precipitation was seen at 115 µg/mL and above

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Tab 1: The cell cultures were evaluated at the following concentrations:

exposure period	S9 mix	concentrations in µg/mL
		Experiment I
4 hours	-	0.6	1.3	2.5	5.0	7.5	10.0*	15.0*
4 hours	+			28.8	57.5	115.0^P	172.5^P	230.0^P
		Experiment II
24 hours	-			2.5	5.0	10.0	15.0	20.0
4 hours	+			31.3	62.5	125.0^P	187.5^P	500.0^P

P = precipitation

*     mutagenicity evaluation was performed only in culture II

For further details see the Summary of results (attached document)

Conclusions:

Undecanal was not mutagenic in a mammalian cell HPRT assay.

Executive summary:

Undecanal was tested for its genotoxic potential in mammalian cells in-vitro (Chinese hamster, V79 cells) at concentrations from 0.6 to 500 µg/mL in the presence and absence of metabolic activation. The assay was conducted according to the OECD TG 476 and under GLP conditions. Precipitation of undecanal was seen at 115 µg/mL and above. In the first experiment, cytotoxicity was seen at 7.5 and 20 µg/mL and higher in the absence of metabolic activation after a 4-hour exposure period. In the second experiment, cytotoxicity was seen at 25 µg/ml without S-9 mix (exposure period 24 hours), and at 500 µg/mL (with S-9 mix, exposure period 4 hours).

Undecanal did not increase the mutation frequency such that the evaluation criteria for rating the test substance as positive were met. Vehicle and positive controls performed as expected and were comparable with historical control data of this laboratory. Therefore, undecanal was considered to be non-mutagenic in this HPRT assay (Harlan, 2010).

This study is considered to be valid and suitable for assesement.

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 23 APR 2010 to 13 JUL 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 471)

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

according to Chemikaliengesetz (Chemicals act) of the Federar Republio of Germany (ChemG) §19a and §19b and annexes 1 and 2 in the version of 02 July 2008 published in Bundesgesetzblatt No. 28/2008, pp. 1146 - 1184

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium, other: TA97a, TA98, TA100, TA102, TA1535

Metabolic activation:

with and without

Metabolic activation system:

microsomal fraction (S9) produced from the livers of male Sprague-Dawley rats treated i.p. with 500 mg Aroclor 1254/kg body weight

Test concentrations with justification for top dose:

1st experiment: 4982, 1495, 498, 150, and 50 µg/plate (plate incorporation)
2nd experiment: 5036,2518, 1259, 630, and 315 µg/plate (pre-incubation method)

Vehicle / solvent:

- Solvent: Ethanol
- Justification for choice of solvent/vehicle: high tolerance for the tester strains, complete dissolution of the test substance

Untreated negative controls:

yes

Remarks:

(water)

Negative solvent / vehicle controls:

yes

Remarks:

(ethanol and DMSO)

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: see below "Details on test system"

Details on test system and experimental conditions:

METHOD OF APPLICATION:
1st experiment: plate incorporation
2nd experiment: preincubation

DURATION
- Preincubation period: 20 min, 37 °C
- Exposure duration: 48 h, 37 °C

NUMBER OF REPLICATIONS: 4

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth ==> inhibition of growth of the background lawn

POSITIVE CONTROLS
sodium azide (1 µg/plate; TA 100 and TA 1535 without metabolic activation)
4-nitro-o-phenylenediamine (20 µg per plate; TA 97a, TA 98 and TA 102 without metabolic activation)
2-aminoanthracene (1 µg/plate; TA 97a, TA 100, TA 102 and TA 1535 with metabolic activation)
benzo(a)pyrene (20 µg/plate; TA 98 with metabolic activation)

Evaluation criteria:

A test item is considered to have mutagenic potential, if a significant, reproducible increase of in the number of revertant colonies per plate (increase factor (f(I)) >= 2) in at least one strain can be observed. A concentration-related increase can also be taken as a sign of mutagenic activity.

Statistics:

calculation of mean values with standard deviations

Key result

Species / strain:

S. typhimurium TA 97a

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

COMPARISON WITH HISTORICAL CONTROL DATA:
In general, the determined values for the spontaneous reversion rates as well as the positive controls were within the normal range of the laboratory.
In isolated cases of outliers, the differences to the respective maximum or minimum of the history were marginal only.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Mean revertant values of first experiment (plate incorporation assay)

Strain		TA97a		TA98		TA100		TA102		TA1535
Induction		-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
H20	Mean	121	115	10	20	119	101	178	155	10	9
	sd	9.0	1,7	1.9	3.7	7.7	23.5	15.5	13.6	3.4	1.5
DMSO	Mean	125	128	7	12	118	118	154	164	11	10
	sd	10.5	12.7	1.7	5.9	11.4	22.9	35.7	14.3	4.3	4.8
Ethanol	Mean	142	130	8	14	107	115	204	130	9	10
	sd	223	9.0	2.4	3.9	15.0	10.1	60.3	9.7	3.0	1.5
Pos.Contr.	Mean	652	878	1000	849	717	567	687	599	533	573
	sd	• 138	122	231	79	53	112	95	125	64	22
	f(l)	5,22	6.86	142.9	7075	6,03	4.81	4.46	3.65	53.30	57.30
4982 µg/pl.	Mean	116	121	11	9	108	108	169	154	11	9
	sd	6	4	2	1	17	14	10	31	4	1
	f(l)	0.82	0.93	1.38	0.64	1.01	0.94	0.83	1.18	112	0.90 12 2
1495 µg/pl.	Mean	121	122	7	10	120	122	154	169	12
	sd	15	8	3	1	22	17	22	12	2
	f(l)	0.85	0.94	0.88	0.71	1.12	1.06	0.75	1.30	1.33	1.20
498 µg/pl.	Mean	112	109	'11	10	111	102	124	129	9	12
	sd	9	12	1	4	5	16 0.89	9	17 0.99	3	2
	f(l)	0.79	0.84	1.38	0.71	1.04		0.61		1.00	1.20
150 µg/pl.	Mean	120	113	11	8	116	114	148	156	10	11
	sd	12	8	5	3	4	6 0.99	29	22	0	2
	f(l)	0.85 125	0.87	1,38	0.57	1.08		0.73	1.20	1.11	1.10
50 µg/pl.	Mean		113	9	13	116	117	152	147	12	13
	sd	15	6	3	2	11	4	25	39	5	4
	f(l)	0.88	0.87	1.13	0,93	1.08	1.02	0.75	1.13	1.33	1.30

f(I)= increase factor, see ecaluation criteria

Mean revertant values of second experiment (pre-incubation assay)

Strain		TA97a		TA98		TA100		TA102		TA1535
Induction		-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
H2O	Mean	109	121	9	7	135	93	204	212	10	16
	sd	6.3	11.0	1.4	0.5	3.9	19.1	27.0	42.6	1.9	1.3
DMS0	Mean	110	120	10	10	126	88	137	145	12	14
	sd	4.5	1.7	0.6	0.0	6.8	14.8	12.1	21.9	2.9	1.8
Ethanol	Mean	118	108	9	7	84	127	128	225	15	14
	sd	7.3	6.3	1.4	1.5	13.6	4.9	9.7	31.4	5.6	1.3
Pos.Contr.	Mean	504	824	218	185	465	727	401	717	291	584
	sd	81	178	16	49	41	231	33	82	94	148
	f(l)	4.58	6.87	21.80	18.50	3.44	8.26	2.93	4.94	29.10	41.71
5036µg/pl.	Mean	116	97	10	10	114	112	215	212	12	11
	sd f(l)	5	4 0.90	1	0	2	3	14	15	2	1
		0.98		1.11	1.43	1.36	0.88	1.68	0.94	0.80	0.79
2518µg/pl..	Mean	108	105	9	10	120	112	192	115	11	11
	sd	7	5	1	2	6	2	39	5	1	1
	f(l)	0.92	0.97	1.00	1.43 11	1.43 10	0.88	1.50	0.51	0.73	0.79
1259µg/pl.	Mean	114	113	11			11	138	137	13	16
	sd	11	13	2	3	1	3	14	17	2	1
	f(l)	0.97	1.05	1.22	1.57	0.12	0.09	1.08	0.61	0.87	1.14
630µg/pl.	Mean	110	108	8	8	117	127	135	151	10	13
	sd	11	7	2	2	10	5	19	17	1	3
	f(l)	0.93	1.00	0.89	1.14	1.39	1.00	1.05	0.67	0.67	0.93
315µg/pl.	Mean	117	109	10	10	130	104	130	145	13	12
	sd	15	4	1	0	16	3	27	14	2	1
	f(l)	0.99	1.01	1.11	1.43	1.55	0.82	1.02	0.64	0.87	0_86

 

Conclusions:

Interpretation of results (migrated information):
negative

N-undecanal was not mutagenic under the conditions of this study.

Executive summary:

N-undecanal (purity: 92.8%) was examined in the Ames-test according to OECD TG 471 under GLP conditions using the Salmonella typhimurium strains TA97a, TA98, TA100, TA102, and TA1535 both in the absence and presence of metabolic activation (S9 from male Aroclor 254 induced rat liver). The test substance concentrations in the first experiment were 4982, 1495, 498, 150, and 50 µg/plate (plate incorporation). To verify the results a second experiment was performed with the pre-incubation method using concentrations of 5036, 2518, 1259, 630, and 315 µg/plate.

Testing up to the limit dose required no cytotoxicity was observed with n-undecanal.

In both tests, the vehicle controls (DMSO, ethanol), the negative (water) and the positive controls performed as expected, while n-undecanal did not increase the number of revertants in any strain at any dose, with or without metabolic activation. Thus, n-undecanal was not mutagenic.

This study is classified as reliable without restrictions. It was performed in accordance with OECD test guideline 471 and GLP (LAUS, 2010).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

There are no studies available on in vivo genotoxicity of n-undecanal.

Endpoint conclusion

Endpoint conclusion:

no study available

Mode of Action Analysis / Human Relevance Framework

In the absence of a species specific mode of action the results of the available assays are regarded as relevant for humans.

Additional information

Bacterial cell mutagenicity

N-undecanal (purity: 92.8%) was examined in the Ames-test according to OECD TG 471 under GLP conditions (RL1) using the Salmonella typhimurium strains TA97a, TA98, TA100, TA102, and TA1535 both in the absence and presence of metabolic activation (S9 from male Aroclor 254 induced rat liver). The test substance concentrations in the first experiment were 4982, 1495, 498, 150, and 50 µg/plate (plate incorporation). To verify the results a second experiment was performed with the pre-incubation method using concentrations of 5036, 2518, 1259, 630, and 315 µg/plate.

Testing up to the limit dose required no cytotoxicity was observed with n-undecanal.

In both tests, the vehicle controls (DMSO, ethanol), the negative (water) and the positive controls performed as expected, while n-undecanal did not increase the number of revertants in any strain at any dose, with or without metabolic activation. Thus, n-undecanal was not mutagenic.

This study is classified as reliable without restrictions. It was performed in accordance with OECD test guideline 471 and GLP (LAUS, 2010).

In a study, which is lacking substantial data (not reliable, RL3), the test substance (Undecanal, purity at least 97%) was examined using the Ames-test (Spot test) with the Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 (with and without metabolic activation) at a concentration of 3 µmol/plate (~ 500 µg/plate). No cytotoxic and mutagenic effects were observed at this concentration tested (Florin et al., 1980).

Mammalian cell mutagenicity

Undecanal was tested for its genotoxic potential in mammalian cells in-vitro (Chinese hamster, V79 cells) at concentrations from 0.6 to 500 µg/mL in the presence and absence of metabolic activation. The assay was conducted according to the OECD TG 476 and under GLP conditions. Precipitation of undecanal was seen at 115 µg/mL and above. In the first experiment, cytotoxicity was seen at 7.5 and 20 µg/mL and higher in the absence of metabolic activation after a 4-hour exposure period. In the second experiment, cytotoxicity was seen at 25 µg/ml without S-9 mix (exposure period 24 hours), and at 500 µg/mL (with S-9 mix, exposure period 4 hours).

Undecanal did not increase the mutation frequency such that the evaluation criteria for rating the test substance as positive were met. Vehicle and positive controls performed as expected and were comparable with historical control data of this laboratory. Therefore, undecanal was considered to be non-mutagenic in this HPRT assay (Harlan, 2010).

Chromosome damage

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.

Justification for classification or non-classification

Based on the available information, no classification is required according to Regulation (EC) No 1272/2008.