Dodecan-1-ol, ethoxylated

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames assay

In an Ames test , test chemical  dissolved  in dimethyl sulfoxide from doses 0 - 1000 micrograms per plate was not mutagenic in Salmonella typhimurium strain TA 100, TA1535, TA1537 and TA98 with and without addition of S9 liver fractions from Aroclor induced hamsters and rats.

In vitro chromosomal abbreviation study

In an Chromosomal aberration test ,test chemical dissolved  in water from doses 0, 5,15 and 50 micrograms per plate was not mutagenic in Chinese Hampster Ovary (CHO) LB cells with and without addition of S9 liver fractions from Aroclor induced rats.

In vitro Mammalian cell gene mutation assay

Test chemical was evaluated for its mutagenic potential in mouse lymphoma by in vitro mammalian cell gene mutation. The test result was considered to be negative in Mouse lymphoma.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data from handbook or collection of data

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Preincubation Assay
The preincubation assay was performed . The test chemical, Salmonella culture, and S-9 mix or buffer were incubated at 37"C, without shaking, for 20 min. Chemicals known or suspected to be volatile were incubated in capped tubes. The top agar was added, and the contents of the tubes were mixed and poured onto the surface of petri dishes that contained Vogel-Bonner medium [Vogel and Bonner, 19561. The histidine-revertant (his') colonies arising on these plates were counted following 2 days incubation at 37°C. The plates were hand-counted when a precipitate was present; otherwise automatic colony counters were used.
All chemicals were tested initially in a toxicity assay to determine the appropriate dose range. The toxicity assay was performed by using TA100 or the system.
Toxic concentrations were those at which a decrease in the number of hisf colonies was seen or at which there was a clearing in the density of the background lawn.At least five doses of the chemical were tested in triplicate. Experiments were repeated at least 1 wk following the initial trial. Each chemical was tested initially at half-log doses up to a dose that elicited toxicity; subsequent trials occasionally used narrower dose increments. Chemicals that were not toxic were tested to a maximum dose of 10 mglplate. Chemicals that were poorly soluble were tested up to a dose defined by their solubility. A maximum of 0.05 ml solvent was added to each plate.Concurrent solvent and positive controls were run with each trial. The positive controls in the absence of metabolic activation were sodium azide (TA1535 and TA loo), 9-aminoacridine (TA97 and TA 1S37), and 4-nitro-o-phenylenediamine (TA98). The positive control for metabolic activation was 2-aminoanthracene for all strains. Although there were no specific response ranges established for the solvent and positive controls, each laboratory rejected experiments in which the positive control chemical did not produce a mutagenic response or in which the solvent controlvalues were higher (or lower in the case of TAlOO and TA97) than their expected values.During the initial stages of the testing program, chemicals were tested with 10% S-9. Other levels of S-9 were used when an equivocal result was obtained with 10%. The protocol evolved to one that used 30% S-9 when a negative response was obtained with 10% S-9.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

histidine-manufacturing gene.

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

other: All the bacterial strains used in the Ames test carry a defective (mutant) gene that prevents them from synthesizing the essential amino acid histidine from the ingredients in standard bacterial culture medium.

Metabolic activation:

with and without

Metabolic activation system:

10% HLI =induced male Syrian hamster liver S9 ; 10% RLI = induced male Sprague Dawley rat liver S9

Test concentrations with justification for top dose:

0,1,3,10,33,100,333 and 1000 µg/Plate

Vehicle / solvent:

Vehicle Control : Dimethyl Sulfoxide

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

water

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

Positive control for TA 100 and TA 1535 tested in the absence of S9 Migrated to IUCLID6: without S9

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

Water

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

Positive control for TA 98 tested in the absence of S9

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

Water

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

Positive control for TA 1537 tested in the absence of S9

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

Water

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene (or occasionally, sterigmatocystin)

Remarks:

For all strains(TA 100,TA 1535, TA1537, TA98) tested with S9

Details on test system and experimental conditions:

All chemicals were tested in Salmonella typhimurium strains TA98, TA100,TA1535, and TA1537 and/or TA97. The majority of chemicals were tested in TA1537,and a few were tested in TA97. The testing in both strains is the result of an evolution of the protocol described by Haworth et a1 [1983]. In this original protocol, TA1537 was used. In a later protocol, TA97 replaced TA1537, but the option to retest a chemical in TA1537 was retained for chemicals that produced a positive or questionable response in TA97 and negative responses in the other strains.All strains were obtained from Dr. Bruce Ames and were stored as recommended [Maron and Ames, 19831. Prior to their use for mutagenicity assays, all cultures were grown overnight with shaking at 37°C in Oxoid broth, and their phenotypes were analyzed.

Evaluation criteria:

The histidine-revertant (his') colonies were observed for mutagenicity.

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

with 10% HLI and 10% RLI

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

with 10% HLI and 10% RLI

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

with 10% HLI and 10% RLI

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

with 10% HLI and 10% RLI

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

TA 100

Dose	No Activation (Negative)		No Activation (Weakly Positive)		10% RLI (Negative)		10% RLI (Negative)		10% HLI (Negative)		10% HLI (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM
0	99	2	98	3.8	137	1.7	94	5.5	143	5.5	111	7
1			119	7
3	95	3.2	132	3.8			115	6.5			122	8.7
10	98	6	137	5	164	7.4	107	3.7	139	9.7	123	11.8
33	97	8.6	120	8.8	151	8.2	127	1.8	135	4.6	120	5.2
100	61	5.3	105	4.6	157	3	111	8.1	146	7.7	116	11
333	0	0			139	8	60	6.2	136	19.7	85	12.5
1000					23	4.4			11	2.2
Positive Control	322	6	405	7.1	885	103.7	419	26.3	1065	143.4	1204	108.6

TA 1535

Dose	No Activation (Negative)		No Activation (Negative)		10% RLI (Negative)		10% RLI (Negative)		10% HLI (Negative)		10% HLI (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM
0	25	3.8	20	.9	11	1.5	7	.9	6	1.3	7	2.3
1	29	1.5
3	29	1.5	26	4.2			7	.6			10	1.5
10	29	4	33	2.9	11	1.5	10	1.5	10	1.5	5	2
33	23	4.3	27	4.9	13	.7	9	2.3	9	3.5	11	1.7
100	32	3.2	19	4.8	9	2.7	7	1.2	13	.7	12	1.8
333			14	.9	7	.9	7	.7	12	1.7	7	2
1000					8	.9			6	2
Positive Control	452	12.8	352	41.8	162	11.8	183	11.5	437	22.8	502	41

TA 1537

Dose	No Activation (Negative)		No Activation (Negative)		10% RLI (Negative)		10% RLI (Negative)		10% HLI (Negative)		10% HLI (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM
0	3	1.3	5	1	9	2.2	4	.7	7	1.9	4	.9
1	7	2.5
3	7	.9	3	.6			8	2.1			10	2
10	7	1.3	5	2.3	6	.9	8	2.4	8	2.3	6	.3
33	6	1.9	3	.6	8	.6	9	1.5	7	2.8	8	.7
100	9	1.3	4	.7	10	1.2	6	.9	7	.3	8	1.2
333			2	.9	4	1.2	6	.6	9	2.1	6	.3
1000					4	.3			4	.6
Positive Control	149	27.8	110	9.7	116	23.4	122	17.1	409	14.9	246	27.1

TA 98

Dose	No Activation (Negative)		No Activation (Negative)		10% RLI (Negative)		10% RLI (Negative)		10% HLI (Negative)		10% HLI (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM
0	16	.7	16	2.1	24	3.9	31	3.6	31	0	30	3.2
1	14	2.6
3	16	1.2	13	.6			32	4.1			32	3.5
10	20	2.3	15	.7	25	5.7	29	1.5	36	2	35	4.3
33	22	3.9	11	2.3	27	3.8	26	2.3	32	1.3	35	1.8
100	17	4.7	13	2.5	29	2	31	3.5	29	.6	35	2.2
333			8	2.5	24	6.3	34	2.2	25	3	39	.3
1000					29	2.5			28	1.8
Positive Control	830	6	596	22.2	414	16.7	409	8.5	827	37.4	1072	104.4

RLI = induced male Sprague Dawley rat liver S9
HLI = induced male Syrian hamster liver S9

s = Slight Toxicity; p = Precipitate; x = Slight Toxicity and Precipitate; T = Toxic; c = Contamination

Conclusions:

In an Ames test , test chemical dissolved in dimethyl sulfoxide from doses 0 - 1000 micrograms per plate was not mutagenic in Salmonella typhimurium strain TA 100, TA1535, TA1537 and TA98 with and without addition of S9 liver fractions from Aroclor induced hamsters and rats.

Executive summary:

Genetic toxicity in vitro study was assessed for test chemical. For this purpose AMES test was performed .The test material was exposed to Salmonella typhimurium TA100, TA1535, TA98 and TA1537in the presence and absence of metabolic activation S9. The concentration of test material used in the presence and absence of metabolic activation were 0 ,1,3,10,33,100,333and 1000 µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore test chemical was considered to be non-mutagenic in Salmonella typhimurium TA100, TA1535, TA98 and TA1537by AMES test. Hence the substance cannot be classified as gene mutant in vitro.

Reference 2

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

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:

data from handbook or collection of data

Justification for type of information:

data from handbook or collection of data

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Approximately 24 hr before chemical treatment. cultures were initiated at a density of 1.75 X 10‘ cells/75 cm’ flask.In the AB trials without S9, the cultures were treated with the test chemical in medium for 8 hr, washed to remove the test chemical, and treated with colcemid M) for 2-2.5 hr before cell harvest. In the experiments with activation,cultures were exposed to the test chemical in serumfree medium with S9 and cofactors for 2 hr, washed to remove the test chemical and S9, and incubated at 37°C with fresh medium for 8 hr. Colcemid was then added, and the cells were harvested 2 hr later. Thus the total durations of the nonactivated and activated AB experiments were 10 hr and 12 hr, respectively, to give 10 hr growth in medium
with serum for each experiment. This differs from the protocol previously used when the total length of each AB trial was 10 hr (Galloway et al., 19871. Where cell cycle delay was noted in the corresponding SCE experiment, the cell growth period in the AB trial was extended approximately 6-8 hr. In the extended trials without S9, the chemical was present for the additional time. Colcemid was present only for the final 2--3 hr.

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

Target gene:

Not specified

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

RAT, LIVER, S-9, AROCLOR 1254

Test concentrations with justification for top dose:

Dose : 0, 5,15 and 50 µg/mL
At least five concentrations of the test chemical were selected; the concentrations were spaced using two merged half-log scales (e.g., 1,000, 500, 300, 150, 100, etc.), and the highest concentrations analyzed were those yielding a sufficient number of suitable metaphase cells. The concentrations analyzed generally covered a one-log range.

Vehicle / solvent:

water

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

water

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

mitomycin C

Remarks:

mitomycin C (Positive control for Without metabolic activation, Dose= 1 and 5 µg/ml)

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

water

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

cyclophosphamide (Positive control for With metabolic activation , Dose = 50 µg/ml

Details on test system and experimental conditions:

Controls:-
Medium and solvent controls were used with each assay.Solvent controls consisted of culture medium with or without S9 and contained the same concentration of solvent as the test cultures (0.5 or 1%).Mitomycin C (MMC; Sigma) was used in the experiments withoul metabolic activation, and cyclophosphaniide (CP; Sigma) was used in the experiments with activation as positive controls. Stock solutions of these chemicals were stored at 4°C and used for three months without loss of activity.Two MMC concentrations were used for the positive controls in the SCE assays, a low MMC concentration that was known to induce a 20-80% increase in SCEs and a high concentration that was used to give greater than a 100% increase in SCEs. The low-dose positive control was used to provide an indication of the ability of the individual experiment to detect a low-level, chemically induced response [Margolin and Resnick, 19851. A negative test chemical response was considered valid only if the low-dose positive control exceeded the solvent control by 20’70. Low and high positive control concentrations were as follows: experiments with S9 used CP at 0.4-0.5 and 2.5 pgiml, experiments
without S9 used MMC at 0.0015-0.002 and 0.010 pgiml .In the AB assays, a single CP dose of 50 pgiml was used in the test with S9, and an MMC dose of 5 pg/ml was used in the test without S9; these doses induced aberrations in approximately 50% of the cells. In some of the experiments,
a lower concentration of MMC, 0. I pgiml, was also used.

Evaluation criteria:

Staining and Scoring of Slides :
For ABs, slides were stained in 5% Giemsa for 5 min. In early studies, one hundred cells were scored for each of three concentrations: the highest test concentration in which sufficient metaphase cells could be scored and the next two lower concentrations, covering a one-log range. For later studies, 200 cells per dose were scored; however, fewer cells were scored if a test chemical produced a strong positive response or the chemical was toxic.
Cells were analyzed for the following categories of chromosomal aberrations: “simple,” defined as a chromatid gap, break, fragment, and deletion or chromosome gap,break, or double minutes; “complex,” defined as interstitial deletions, triradials, quadriradials, rings, and dicentric chromosomes; and “other,” defined as pulverized chromosomes or cells with greater than 10 aberrations. Chromatid and chromosome gaps were recorded but were not used in the analysis. The frequency of polyploid or endoreduplicated cells was noted only when it seemed excessive; however, these categories were not included in the totals or in the statistical analyses.

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: No mutagenic effects were observed

Chromosomal aberration (CA) data are presented as the percentage of cells with aberrations. To arrive at a statistical call for a trial, analyses were conducted to assess the presence of a dose-response (trend test) and the significance of the individual dose points compared to the vehicle control. The overall result for the CA assay was based on an evaluation of the responses in all trials within an activation condition.

Study Result:Negative
Activation				Trial							Trial Call
No Activation				1							Negative
Induced Rat Liver S9				1							Negative
Trial #:1   Activation:No Activation   Date:07/25/1985   Harvest Time:10.5 hrs   Trial Call:Negative
		Dose (µg/mL)	Total Cells Examined		Total Aberrations			Complex Aberrations				Simple Aberrations			Other Abs.
					No. of Abs.	Abs Per Cell	% Cells With Abs.	No. of Abs.	Abs Per Cell	% Cells With Abs.		No. of Abs.	Abs Per Cell	% Cells With Abs.	No. of Abs.	Abs Per Cell	% Cells With Abs.
Abs: Aberrations
Vehicle Control	Medium		100		4	0.040	2.0	0	0.000	0.0		4	0.040	2.0	0	0.000	0.0
Test Chemical	Ethoxylated dodecyl alcohol	5	100		0	0.000	0.0	0	0.000	0.0		0	0.000	0.0	0	0.000	0.0
		15	100		2	0.020	2.0	0	0.000	0.0		2	0.020	2.0	0	0.000	0.0
		50	100		2	0.020	2.0	0	0.000	0.0		2	0.020	2.0	0	0.000	0.0
Positive Control	Mitomycin-C	1	100		22	0.220	20.0	7	0.070	7.0		15	0.150	15.0	0	0.000	0.0
		5	50		23	0.460	36.0	5	0.100	10.0		18	0.360	28.0	0	0.000	0.0
	Trend				0.361			0.000				0.361
	Probability				0.359			0.000				0.359

Trial #:1   Activation:Induced Rat Liver S9   Date:07/25/1985   Harvest Time:12.0 hrs   Trial Call:Negative
		Dose (µg/mL)	Total Cells Examined	Total Aberrations			Complex Aberrations			Simple Aberrations			Other Abs.
				No. of Abs.	Abs Per Cell	% Cells With Abs.	No. of Abs.	Abs Per Cell	% Cells With Abs.	No. of Abs.	Abs Per Cell	% Cells With Abs.	No. of Abs.	Abs Per Cell	% Cells With Abs.
Abs: Aberrations
Vehicle Control	Medium		100	1	0.010	1.0	0	0.000	0.0	1	0.010	1.0	0	0.000	0.0
Test Chemical	Ethoxylated dodecyl alcohol	5	100	1	0.010	1.0	0	0.000	0.0	1	0.010	1.0	0	0.000	0.0
		15	100	0	0.000	0.0	0	0.000	0.0	0	0.000	0.0	0	0.000	0.0
		50	100	2	0.020	2.0	0	0.000	0.0	2	0.020	2.0	0	0.000	0.0
Positive Control	Cyclophosphamide	50	50	28	0.560	34.0	12	0.240	16.0	16	0.320	26.0	0	0.000	0.0
	Trend			0.472			0.000			0.472
	Probability			0.318			0.000			0.318

Conclusions:

In an Chromosomal aberration test ,test chemical dissolved in water from doses 0, 5,15 and 50 micrograms per plate was not mutagenic in Chinese Hampster Ovary (CHO) LB cells with and without addition of S9 liver fractions from Aroclor induced rats.

Executive summary:

Genetic toxicity in vitro study was assessed for test chemical. For this purpose in vitro mammalian chromosome aberration test was performed .The test material was exposed to Chinese hamster ovary cells in the presence and absence of metabolic activation S9. The concentration of test material used in the presence and absence of metabolic activation were 0, 5, 15 and 50 µg/mL. Chromosome aberration, Chromosome gaps and breaks were not observed in the presence or absence of metabolic activation. Therefore test chemical was considered to be non - mutagenic in Chinese hamster ovary cells by in vitro mammalian chromosome aberration test. Hence the substance cannot be classified as mutagenic in vitro.

Reference 3

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data from handbook or collection of data

Qualifier:

according to guideline

Guideline:

other: As mention bvelow

Principles of method if other than guideline:

To evaluate the mutagenic potential of test chemical in mouse lymphoma by in vitro mammalian cell gene mutation.

GLP compliance:

not specified

Type of assay:

other: In vitro mammalian cell gene mutation.

Target gene:

Not specified

Species / strain / cell type:

mouse lymphoma L5178Y cells

Details on mammalian cell type (if applicable):

not specified

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

not specified

Test concentrations with justification for top dose:

0,5,19,15,20,30,30,40,50 µg/mL

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Dimethyl Sulfoxide
- Justification for choice of solvent/vehicle: The test substance is soluble in water

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

Water

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

Water

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

3-methylcholanthrene

Details on test system and experimental conditions:

Details on test system and conditions
METHOD OF APPLICATION: In culture dish

DETERMINATION OF CYTOTOXICITY; relative total growth

Evaluation criteria:

The mammalian cells were observed for mutagenic frequency in cells.

Statistics:

Yes, SD ± Mean was observed.

Key result

Species / strain:

other: mouse lymphoma

Metabolic activation:

not specified

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: No mutaghenic effect were observed

Nonactivation Trial:2Experiment Call:Negative
		Conc. µg/mL	Cloning Efficiency	Relative Total Growth	Mutant Colonies	Mutant Frequency	AVG Mutant Frequency
Vehicle Control	Water	0	110	113	128	39	33
			108	83	114	35
			116	124	84	24
			108	80	115	36
Test Chemical	Ethoxylated dodecyl alcohol	5	106	107	113	35	30
			113	109	97	29
			115	119	93	27
		10	105	80	139	44	40
			107	97	171	53
			112	117	78	23
		15	105	107	136	43	41
			114	82	144	42
			115	71	125	36
		20	104	72	218	70	48
			105	74	101	32
			117	79	149	42
		30	107	29	114	35	51*
			110	34	208	63
			108	29	180	56
		40	LETHAL
			LETHAL
			LETHAL
Positive Control	Methyl Methane Sulfonate	5	105	60	1132	360	392*
			115	56	1120	326
			86	23	1257	489

Induced S9 Trial:2Experiment Call:Negative
		Conc. µg/mL	Cloning Efficiency	Relative Total Growth	Mutant Colonies	Mutant Frequency	AVG Mutant Frequency
Vehicle Control	Water	0	112	65	106	32	31
			113	94	107	32
			105	144	81	26
			116	98	129	37
Test Chemical	Ethoxylated dodecyl alcohol	5	97	96	112	39	33
			106	108	92	29
			106	95	102	32
		10	105	100	91	29	30
			100	78	90	30
			116	98	112	32
		15	97	56	118	41	39
			117	70	121	35
			113	61	144	42
		20	105	76	129	41	30
			121r	72	85	23
			112	51	67	20
		30	101	32	120	40	40
			105	43	139	44
			111	46	117	35
		40	104	13	84	27	39
			107	32	164	51
			LETHAL
		50	LETHAL
			LETHAL
			LETHAL
Positive Control	Methyl Methane Sulfonate	5	111	43	630	189	360*
			78	31	1010	432
			47	12	646	460

Conclusions:

Test chemical was evaluated for its mutagenic potential in mouse lymphoma by in vitro mammalian cell gene mutation. The test result was considered to be negative in Mouse lymphoma.

Executive summary:

Genetic toxicity in vitro study was assessed for test chemical. For this purpose in vitro mammalian cell gene mutation was performed .The test material was exposed to mouse lymphoma cells. The concentration of test material used in two experiment were 0,5,19,15,20,30,30,40,50 µg/mL. Mutagenic frequency were not observed in the mammalian cells. Therefore test chemical was considered to be non-mutagenic IN mouse lymphoma cells by in vitro mammalian cell gene mutation. Assay. Hence the substance cannot be classified as mutagenic in vitro.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Test substance was evaluated for its mutagenic potential in B6C3F1 male Mouse by In vivo Mammalian Somatic cell study. The test result was consider to be negative as there was no significant chromosome damage in micronucleated polychromatic erythrocytes.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data from handbook or collection of data

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

To evaluate the mutagenic potential of test chemical in B6C3F1 male Mouse by In vivo Mammalian Somatic cell study.

GLP compliance:

not specified

Type of assay:

not specified

Species:

mouse

Strain:

B6C3F1

Sex:

male

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: Phosphate Buffered Saline

Duration of treatment / exposure:

72 hour

Frequency of treatment:

3 times in 72 hours

Post exposure period:

No data

Remarks:

0,31.25,62.5 and 125 mg/Kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

yes, concurrent vehicle

Positive control(s):

Positive controls; Mitomycin-C
- Route of administration: Intraperitoneal Injection
- Doses / concentrations:0.2 mg/kg

Tissues and cell types examined:

Polychromatic and normochromatic erythrocytes were screened for the presence of micronuclei.

Details of tissue and slide preparation:

Details of tissue and slide preparation

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): 24 hour

Evaluation criteria:

The erythrocytes were observed for micronuclei. The MN results were tabulated as the mean frequency of micronucleated erythrocytes per 1000 cells per animal, plus or minus the standard error of the mean among animals within a treatment group.

Generally, a test was considered positive if (1) the trend test P value was 0.025 or less or (2) the P value for any single exposure group was 0.025/N or less where N is the number of test chemical treatment groups. Trend test P values between 0.025 and 0.05 were considered to be equivocal if accompanied by a monotonic increase in the frequency of micronuclei over the dose range investigated. All other responses were considered to be negative.

Statistics:

The frequency of micronucleated cells among NCE or PCE was analyzed by a statistical software package that tested for increasing trend over exposure groups using a one-tailed Cochran-Armitage trend test, followed by pairwise comparisons between each exposure group and the control group. In the presence of excess binomial variation, as detected by a binomial dispersion test, the binomial variance of the Cochran-Armitage test was adjusted upward in proportion to the excess variation. Pairwise comparisons between each treatment group and the concurrent solvent control group were performed using an
unadjusted one-tailed Pearson x2 test that incorporated the calculated variance inflation factor for the study.

Although statistical analyses were used as an important aid in evaluating the test results, statistical significance was not the only determining factor in arriving at an overall call for a chemical. A decision to classify a test as negative, equivocal, or positive for induction of micronuclei in this in vivo assay was based on a broader evaluation of a number of factors that determined the biological relevance of the results, including the appropriateness of the concurrent control data, the magnitude of the observed response and the presence of a dose-dependent increase in the frequency of micronucleated cells.

The percentage of polychromatic erythrocytes (%PCE) data were analyzed by a standard ANOVA to determine if significant PCE suppression or stimulation occurred.

Key result

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: No mutagenic potential

Additional information on results:

No data

Conclusions:

Test substance was evaluated for its mutagenic potential in B6C3F1 male Mouse by In vivo Mammalian Somatic cell study. The test result was consider to be negative as there was no significant chromosome damage in micronucleated polychromatic erythrocytes.

Executive summary:

In the study test substance was assessed for its possible mutagenic potential. For this purpose wasIn vivo Mammalian Somatic cell study in B6C3F1 male Mouse. The test substance was administrated by Intraperitoneal Injection by using corn oil as vehicle. The test substance was exposed at the concentration of 0, 0, 31.25, 62.5 and 125 mg/Kg for 72 hours. The dose was administrated thrice in 72 hours .The bone marrow cells were stained and observed for chromosome damage. No significant increase in the frequency of micronucleated polychromatic erythrocytes in treated animals was observed. Therefore test result was consider to be negative as there was no significant chromosome damage in micronucleated polychromatic erythrocytes. Hence the substance cannot be classified as mutant In Vivo.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Data for the various publication was reviewed to determine the mutagenic nature of Dodecan-1-ol, ethoxylated (CAS No; 9002-92-0 EC No; 500-002-6). The studies are as mentioned below:

In Vitro studies

Ames assay

Genetic toxicity in vitro study was assessed for test chemical. For this purpose AMES test was performed .The test material was exposed to Salmonella typhimurium TA100, TA1535, TA98 and TA1537in the presence and absence of metabolic activation S9. The concentration of test material used in the presence and absence of metabolic activation were 0-1000 µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore test chemical was considered to be non-mutagenic in Salmonella typhimurium TA100, TA1535, TA98 and TA1537by AMES test. Hence the substance cannot be classified as gene mutant in vitro.

In vitro chromosomal abbreviation study

Genetic toxicity in vitro study was assessed for test chemical. For this purpose in vitro mammalian chromosome aberration test was performed .The test material was exposed to Chinese hamster ovary cells in the presence and absence of metabolic activation S9. The concentration of test material used in the presence and absence of metabolic activation were 0, 5, 15 and 50 µg/mL. Chromosome aberration, Chromosome gaps and breaks were not observed in the presence or absence of metabolic activation. Therefore test chemical was considered to be non - mutagenic in Chinese hamster ovary cells by in vitro mammalian chromosome aberration test. Hence the substance cannot be classified as mutagenic in vitro.

In vitro Mammalian cell gene mutation assay

Genetic toxicity in vitro study was assessed for test chemical. For this purpose in vitro mammalian cell gene mutation was performed .The test material was exposed to mouse lymphoma cells. The concentration of test material used in two experiment were 0,5,19,15,20,30,30,40,50 µg/mL. Mutagenic frequency were not observed in the mammalian cells. Therefore test chemical was considered to be non-mutagenic IN mouse lymphoma cells by in vitro mammalian cell gene mutation. Assay. Hence the substance cannot be classified as mutagenic in vitro.

In vivo studies

In the study test substance was assessed for its possible mutagenic potential. For this purpose wasIn vivo Mammalian Somatic cell study in B6C3F1 male Mouse. The test substance was administrated by Intraperitoneal Injection by using corn oil as vehicle. The test substance was exposed at the concentration of 0, 0, 31.25, 62.5 and 125 mg/Kg for 72 hours. The dose was administrated thrice in 72 hours .The bone marrow cells were stained and observed for chromosome damage. No significant increase in the frequency of micronucleated polychromatic erythrocytes in treated animals was observed. Therefore test result was consider to be negative as there was no significant chromosome damage in micronucleated polychromatic erythrocytes. Hence the substance cannot be classified as mutant In Vivo.

 

Based on the data summarized, Dodecan-1-ol, ethoxylated (CAS No; 9002-92-0 EC No; 500-002-6) did not induce gene mutation .Hence it is not likely to be mutagenic in vitro and in vivo too.

Justification for classification or non-classification

Thus based on the above annotation and CLP criteria the test chemical Dodecan-1-ol, ethoxylated (CAS No; 9002-92-0 EC No; 500-002-6) not likely to induce gene mutation .Hence it is not likely to be mutagenic in vitro as well as in vivo.