Decan-1-ol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in S. typhimurium strains TA 98 and 100 (similar to OECD Test Guideline 471) (Huntingdon, 1996).

Gene mutation (Bacterial reverse mutation assay / Ames test): the related substance hexan-1-ol was negative with and without activation in S. typhimurium strains TA 98, 100, 1535, 1537, 1538 (similar to OECD Test Guideline 471) (Henkel, 1990).

Gene mutation (Bacterial reverse mutation assay / Ames test): the related substance octan-1-ol was negative with and without activation in S. typhimurium strains TA 98, TA100, TA1535, TA1537 and TA 1538 (similar to OECD Test Guideline 471) (Henkel, 1982).

Gene mutation (Bacterial reverse mutation assay / Ames test): the related substance Fatty alcohol blend (containing 40.77% C8 and 55.3% C10) was negative with and without activation in S. typhimurium strains TA 98, TA100, TA1535, TA1537 and TA 1538 (similar to OECD Test Guideline 471) (Inveresk, 1992).

Cytogenicity in mammalian cells: information not required because in vivo information for a closely related substance is available (Inveresk, 1992)

Mutagenicity in mammalian cells: the related substance Fatty alcohol blend (containing 40.77% C8 and 55.3% C10): negative with and without activation in L5178Y mouse lymphoma cells (similar to OECD Test Guideline 476) (Inveresk, 1992).

Mutagenicity in mammalian cells: the related substance 2-ethylhexan-1-ol: negative with and without activation in L5178Y mouse lymphoma cells (similar to OECD Test Guideline 476) (Kirby, 1983).

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04-Apr-1990 to 27-Apr-1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The restrictions were that the range of strains differs from the current guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

(no TA102 or E. coli WP2 uvrA; 2-AA only positive control with S9)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine

Species / strain / cell type:

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

Species / strain / cell type:

S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S9 Aroclor 1254 induced

Test concentrations with justification for top dose:

1st test: 8, 40, 200, 1000 and 5000 µg/plate
2nd test: 6.25, 25, 100, 400 and 1600 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: the test substance was suspended in sorbitan derivative (Tween 80)/water
- Justification for choice of solvent/vehicle: none stated

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA100, TA1535 without S9

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA1537 without S9

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylendiamine in TA98 and TA1538 without S9

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene in all strains with S9

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: none
- Exposure duration: 48 hours

NUMBER OF REPLICATES
- 3

Evaluation criteria:

Combination of: a) plate background of non-reverted bacteria not showing growth reduction relative to respective negative controls; b) spontaneous mutation rates within historical limits; c) at one or more doses tested the substance causes a 2-fold (TA 100) or 3-fold (other strains) increase in mutation rate above control levels.

Statistics:

None

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

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

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
None

COMPARISON WITH HISTORICAL CONTROL DATA:
The spontaneous mutation frequencies for untreated and solvent treated cultures were within the historical range for the laboratory for all strains in the absence and in the presence of S9.

No increase in the number of revertants relative to the solvent and negative controls was observed in any strain at any concentration in first and second experiments. The results of the first test are presented in tables 1 and 2 below. The results of the second test, conducted over a smaller range of concentrations, were very similar to the first. Table 1 Experiment 1 Plate incorporation: Number of revertants per plate (mean of 3 plates)

Strain	TA 98			TA 100			TA 1535
Concentration  µg/plate	+ MA	-MA	Toxicity	+ MA	-MA	Toxicity	+MA	-MA	Toxicity
Negative control	44.3	28.7	no	59.3	78.7	no	5.7	5.7	no
Solvent control	38.7	35.3	no	58.0	79.3	no	4.0	6.7	no
5000	7.7	0	yes	9.3	20.3	yes	i pp	i pp	yes
1000	20.3	5.0	yes	55.0	54.7	no	4.0	4.3	no
200	35.0	38.0	no	68.3	76.0	no	7.3	4.3	no
40	39.3	31.7	no	64.0	77.0	no	6.7	4.3	no
8	34.3	40.0	no	61.7	73.3	no	6.3	4.3	no
Positive control	791.7	519.0	no	765.0	223.3	no	74.0	213.3	no

i pp: inhibition of background lawn and pin-point colonies

Table 2 Experiment 1 Plate incorporation: Number of revertants per plate (mean of 3 plates)

Strain	TA 1537			TA 1538
Concentration  µg/plate	+ MA	-MA	Toxicity	+ MA	-MA	Toxicity
Negative control	4.0	3.7	no	15.0	10.0	no
Solvent control	3.7	3.7	no	12.3	8.0	no
5000	i pp	4.3	yes	11.3	i pp	no
1000	3.3	3.3	no	10.3	5.7	yes
200	4.7	2.3	no	13.0	7.0	no
40	5.0	5.3	no	13.3	8.0	no
8	4.0	4.3	no	11.3	8.7	no
Positive control	269.0	354.0	no	1134.3	884.0	no

Conclusions:

In a reliable study, the C6 alcohol Lorol C6 98% did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium at concentrations of up to 5000 µg/plate in the presence or absence of metabolic activation (cytotoxicity observed at 5000 µg/plate). The study was performed in compliance with GLP. Expected results were obtained with negative (buffer) solvent and positive controls. The repeat experiment gave the same results as the initial test.
It is concluded that the test substance is negative for mutagenicity in bacteria under the conditions of the study.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

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:

limited reporting

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

OECD Guidelines recommend using TA 102 or E. coli to detect cross-linking/oxidising agents.

Principles of method if other than guideline:

An in-house protocol similar to OECD No. 471

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537, and TA 1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver S9

Test concentrations with justification for top dose:

4, 20, 100, 500, and 2500 µg/plate

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

Water/Tween 80

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene (5 µg/plate), sodium azide (1 µg/plate), 4-nitro-o-phenylenediamine (40 µg/plate)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

NUMBER OF REPLICATIONS: Four per dose level.

Evaluation criteria:

No data

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 and 2500 μg/plate with and without metabolic activation

Vehicle controls validity:

not specified

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:

cytotoxicity

Remarks:

2500 μg/plate

Vehicle controls validity:

not specified

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:

cytotoxicity

Remarks:

at 2500 μg/plate

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 μg/plate with metabolic activation and 2500 μg/plate with and without metabolic activation

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 and 2500 μg/plate with and without metabolic activation

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: not reported

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- With metabolic activation: Total inhibition of bacterial growth at 2500 ug/plate for all strains tested; also at 500 ug/plate for strains TA1537, TA1538 and TA98.
- Without metabolic activation: Total inhibition of bacterial growth at 2500 ug/plate for all strains tested; also at 500 ug/plate for strains TA1538 and TA98.

Remarks on result:

other: No mutagenic potential

Conclusions:

In a reliable study, using a method similar to OECD test guideline 471, C8 alcohol Lorol C8 at concentrations up to 2500 µg/plate did not increase the reverse mutation rate in five histidine dependent bacterial strains of Salmonella typhimurium, in the presence or absence of a mammalian liver metabolic activation system (S9). Cytotoxicity was observed at the highest concentration tested.

Executive summary:

In a bacterial mutagenicity study, S. typhimurium cells TA 98, TA 100, TA 1535, TA 1537, and TA 1538 were exposed to 4, 20, 100, 500, and 2500 µg/plate of test material, without or with metabolic activation.

There was no increase in the reverse mutation rate in the five histidine dependent bacterial strains. Cytotoxicity was observed at the highest concentration. The study concludes that the test material is negative for mutagenicity to bacterial cells under the conditions of the study. The study was conducted according to a protocol similar to OECD TG 471, and in compliance with GLP.

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The restrictions were that the range of strains does not comply with current guidelines. Read-across to the registered substance is considered scientifically justified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

range of strains does not comply with current guidelines

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine operon

Species / strain / cell type:

S. typhimurium, other: TA 98; TA 100;TA 1535; TA 1537; TA 1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

Toxicity test: 33, 100, 333, 1000, 3333, 10000 µg/plate; Main experiment: 1.5, 5, 15, 50, 150, 500 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO was used in preliminary toxicity test, and high levels of toxicity demonstrated. At the concentrations used for the mutation assay, acetone was used as solvent as the levels of test substance could not be detected accurately in analysis when DMSO was the solvent.

- Justification for choice of solvent/vehicle: none given in report

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 1535 and TA 100 without metabolic activation: 2-aminoanthracene

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA 1537 without metabolic activation

Untreated negative controls:

other:

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 1538 and TA 98 without metabolic activation

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

all strains with metabolic activation

Details on test system and experimental conditions:

ACTIVATION; Aroclor induced rat liver S9; NADP and glucose-6-phosphate as co-factors; 0.5 ml 10% S9 in 2.7 ml agar and test material and test strains.
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION

- Preincubation period: none

- Exposure duration: 2 days

- Expression time (cells in growth medium): 2 days


SELECTION AGENT (mutation assays): histidine-poor agar

NUMBER OF REPLICATIONS: triplicate plates, two independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: other: condition of bacterial lawn

Evaluation criteria:

A positive response was recorded if there was a reproducible, dose dependent increase in the number of revertants to at least twice control values for TA 1535, TA 98, TA 1537 and TA 1538, and 1.5 times for strain TA 100.

Statistics:

Mean and standard deviation.

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1538

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

Table 1 Experiment 1: Reversions per plate (mean of 3 plates)

Concentration µg/plate	TA 1535		TA 1537		TA 1538		TA 98		TA 100
	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA
0*	18	23	10	14	23	19	26	39	124	132
Positive control	245	250	1334	150	286	569	186	522	747	598
1.5	18	15	14	16	18	14	24	31	121	145
5	17	17	18	17	19	21	32	35	147	136
15	15	21	16	14	18	20	25	36	130	115
50	14	15	8	16	18	13	22	33	121	110
150	14	19	8	16	13	20	23	27	119	118
500	10	13	2	6	3	7	7	20	58	89

* solvent control acetone

Table 2 Experiment 2: Reversions per plate (mean of 3 plates)

Concentration µg/plate	TA 1535		TA 1537		TA 1538		TA 98		TA 100
	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA
0*	14	16	11	11	20	26	30	31	129	123
Positive control	262	178	1331	166	235	252	224	247	557	523
1.5	13	15	8	10	19	24	28	28	125	112
5	20	12	14	14	19	21	28	34	136	121
15	19	17	14	14	20	25	26	35	137	111
50	21	17	14	7	18	17	21	25	129	105
150	18	16	11	8	13	18	24	27	112	109
500	-	12	-	5	-	6	-	23	-	59

* solvent control acetone

Conclusions:

Fatty alcohol blend was tested in a bacterial reverse mutation assay according to a protocol that is similar to OECD 471 and under GLP in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538. No increase in the number of revertants per plate was observed with or without activation in either the initial assay or the independent repeat assay. Solvent and positive controls gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Executive summary:

Fatty alcohol blend was tested in a bacterial reverse mutation assay according to a protocol that is similar to OECD 471 and under GLP in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538. No increase in the number of revertants per plate was observed with or without activation in either the initial assay or the independent repeat assay. Solvent and positive controls gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

The in vitro and in vivo data available for members of the category and supporting substances indicate that the C6-24 alcohols are not genotoxic. In addition, the category of LCAAs under consideration does not contain any structural elements that are of concern for potential mutagenic activity.

Reference 4

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Species / strain / cell type:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

Toxicity assay: 0.4, 4.3, 43.2, 432, 4320 µg/ml; Mutagenicity assay: 9.4, 18.8, 37.5, 75, 150, 300 µg/ml

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO was used in toxicity assay, acetone in mutagenicity assay
- Justification for choice of solvent/vehicle: due to impurity peaks in the chromatograms, solvent was changed to acetone.

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

without metabolic activation

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

3-methylcholanthrene

Remarks:

with metabolic activation

Details on test system and experimental conditions:

ACTIVATION: 1.0 ml S9 mix containing 10% S9 and cofactors NADP and glucose-6-phosphate added to give final volume of 10 ml

METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: none

- Exposure duration: 4 hours

- Expression time (cells in growth medium): 2 days

- Selection time (if incubation with a selection agent): 11-14 days


SELECTION AGENT (mutation assays): trifluorothymidine

NUMBER OF REPLICATIONS: duplicate cultures, independent repeat experiment

DETERMINATION OF CYTOTOXICITY
- Method: other: cloning efficiency

Evaluation criteria:

A substance was considered positive if there was an increase of at least 1.7 fold in at least one of the highest doses was significant and associated with an increase in mutant numbers and/or an upward trend in the remaining doses, in two experiments under the same activation conditions.

Statistics:

Statistical evaluation was performed if marginal responses were recorded.

Key result

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

43.2 µg/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Table 1 Experiment 1 Mutant frequency (average of 3 plates per culture)

Concentration µg/ml	Relative total growth %		Mean mutant count (MC)		Mutant fraction x 10¿¿		Increase over control
	-MA	+MA	-MA	+MA	-MA	+MA	-MA	+MA
Solvent control	81	92	19	24	27	36	-	-
	112	103	32	25	35	36
	102	101	25	31	30	35
	104	103	26	27	31	32
Positive control	75	34	182	151	264	299	8.6	7.6
	63	38	150	135	268	235
9.4	129	85	17	30	21	36	1.0	0.9
	100	88	29	18	39	26
18.8	111	92	27	21	31	25	1.2	0.7
	109	71	39	19	44	24
37.5	72	92	18	24	25	34	0.9	1.0
	79	71	27	27	33	35
75	-	-	NP	NP	-	-	-	-
	-	-	NP	NP	-	-
150	-	-	NP	NP	-	-	-	-
	-	-	NP	NP	-	-
300	-	-	NP	NP	-	-	-	-
	-	-	NP	NP	-

NP = Not plated, too toxic for assessment

Table 2 Experiment 2 Mutant frequency (average of 3 plates per culture)

Concentration µg/ml	Relative total growth %		Mean mutant count (MC)		Mutant fraction x 10¿¿		Increase over control
	-MA	+MA	-MA	+MA	-MA	+MA	-MA	+MA
Solvent control	94	99	25	35	28	43	-	-
	113	110	30	41	26	43
	92	99	29	31	28	37
	-	93	-	30	-	37
Positive control	84	20	152	107	182	315	7.5	7.7
	83	21	172	122	221	298
10	103	-	31	NP	33	-	1.3	-
	98	-	32	NP	39	-
20	128	-	30	NP	29	-	1.1	-
	86	-	28	NP	29	-
30	93	90	21	27	26	30	1.1	0.9
	91	79	29	40	32	39
40	57	90	34	38	48	42	1.3	0.9
	84	94	20	29	22	33
50	32	91	20	31	26	31	1.0	0.8
	29	93	21	32	30	36
60	-	71	NP	36	-	36	-	0.8
	-	56	NP	24	-	28
70	-	37	NP	22	-	25	-	0.6
	-	23	NP	25	-	26
80	-	-	NP	NP	-	-	-	-
	-	-	NP	NP	-	-

NP = Not plated: 3 highest dose levels, too toxic for assessment

Conclusions:

Fatty alcohol blend has been tested according to a protocol that is similar to OECD 476 and under GLP. No increase in the mutant frequency was observed with or without metabolic activation in either the initial or repeat experiment up to cytotoxic concentrations. Solvent and positive controls gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Executive summary:

Fatty alcohol blend has been tested according to a protocol that is similar to OECD 476 and under GLP. No increase in the mutant frequency was observed with or without metabolic activation in either the initial or repeat experiment up to cytotoxic concentrations. Solvent and positive controls gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

The in vitro and in vivo data available for members of the category and supporting substances indicate that the C6-24 alcohols are not genotoxic. In addition, the category of LCAAs under consideration does not contain any structural elements that are of concern for potential mutagenic activity.

Reference 5

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

not specified

Type of assay:

mammalian cell gene mutation assay

Species / strain / cell type:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

10 concentrations at log intervals between 0.013 and 1.0 µl/ml

Vehicle / solvent:

not indicated

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

not specified

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 4hours
- Expression time (cells in growth medium): 48 hours
- Selection time (if incubation with a selection agent): 10-12days

SELECTION AGENT (mutation assays): TFT

NUMBER OF REPLICATIONS: single treatement per dose, 10 doses

NUMBER OF CELLS EVALUATED: 3 E+06 calls

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Evaluation criteria:

A result was judged to be positive when a two-fold increase in the number of revertants relative to background was observed.

Key result

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

> 1.0 µl/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Conclusions:

2-Ethyl hexan-1-ol was tested for mutagenicity to mammalian cells in a valid study using a method similar to OECD TG 476 up to toxic concentrations. No increase in the number of revertants was observed. It was concluded that 2-Ethyl hexan-1-ol is negative for mutagenicity to mammalian cells under the conditions of the test.

Reference 6

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

20-Dec-1995 to 1- Jan-1996

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The study did not meet current guideline requirements for bacterial mutagenicity. It does, however, add weight of evidence for genetic toxicity.

Remarks:

Only 2 strains were tested and criteria for evaluation not reported.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

(only 2 strains)

Principles of method if other than guideline:

Similar to OECD guideline 471, but only 2 strains used

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

histidine

Species / strain / cell type:

S. typhimurium TA 98

Species / strain / cell type:

S. typhimurium TA 100

Metabolic activation:

with and without

Metabolic activation system:

S9 from Aroclor 1254-induced male rat liver

Test concentrations with justification for top dose:

0.5, 1.6, 5, 15.8 and 50 µg/plate

Vehicle / solvent:

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

Untreated negative controls:

yes

Remarks:

test substance (without activation) and S9 mix sterility controls

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

both strains with S9

Untreated negative controls:

yes

Remarks:

test substance (without activation) and S9 mix sterility controls

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA98 without S9

Untreated negative controls:

yes

Remarks:

test substance (without activation) and S9 mix sterility controls

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA100 without S9

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 2 days

DETERMINATION OF CYTOTOXICITY
- Method: other: condition of background lawn, reduction in number of revertants relative to control

OTHER: Dose selection was based on a preliminary toxicity screen with S. typhimurium strain TA98 in which dose levels up to 5000 µg/plate were tested

Evaluation criteria:

Not specified

Statistics:

None

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

50 µg/plate.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

50 µg/plate

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: no data
- Precipitation: none reported
- Other confounding effects: no data

RANGE-FINDING/SCREENING STUDIES:
- Preliminary study without metabolic activation: At dose levels of 250 µg/plate and above there was an absence of revertant colonies with background lawn thin or absent. At 50 µg/plate there was slight thinning of background lawn with good population of revertant colonies. At 25 µg/ml there was no thinning of background lawn.

COMPARISON WITH HISTORICAL CONTROL DATA: no data

ADDITIONAL INFORMATION ON CYTOTOXICITY: with and without metabolic activation: a slight thinning of the bacterial lawn was observed at 50 µg/plate.

Conclusions:

Decan-1-ol has been tested in a valid bacterial reverse mutation assay, conducted according to a protocol similar to OECD Test Guideline 471, without information about GLP compliance, using Salmonella typhimurium strains TA 98 and TA 100. No increase in the number of revertants was observed in any test strain, with or without metabolic activation when tested up to cytotoxic concentrations (50 µg/plate). Appropriate positive, negative and solvent controls were added and gave expected results. It is concluded that decan-1-ol is not mutagenic to bacteria under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Micronucleus study in mice: the related substance Fatty alcohol blend (containing 40.77% C8 and 55.3% C10) was negative after oral administration (OECD Test Guideline 474) (Inveresk, 1992).

Micronucleus study in mice: the related substance dodecan-1-ol was negative after oral administration (OECD Test Guideline 474) (Henkel, 1992).

Link to relevant study records

Reference

Reference 1

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 November 1991 to 11 February 1332

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

only 1000 PCE per animal were scored for micronuclei

GLP compliance:

yes

Type of assay:

micronucleus assay

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Limited, Manston Road, Kent

- Age at study initiation: 5-7 weeks

- Weight at study initiation: 27-30 g (males) 18-23 g (females)

- Assigned to test groups randomly: yes

- Fasting period before study: no information

- Housing: individually in polypropylene/stainless steel cages

- Diet: ad libitum

- Water: ad libitum

- Acclimation period: at least 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19

- Humidity (%): 38

- Air changes (per hr): no information

- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil

- Justification for choice of solvent/vehicle: none given; standard vehicle

- Concentration of test material in vehicle: sufficient to give required dose in appropriate volume of vehicle
- Amount of vehicle (if gavage or dermal): 10 mg/ml/day

Duration of treatment / exposure:

Animals were dosed on three consecutive days.

Frequency of treatment:

daily

Post exposure period:

96 hours

Dose / conc.:

500 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Dose / conc.:

2 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5 (positive control, low and mid dose) or 10 (vehicle control, high dose)

Control animals:

yes, concurrent vehicle

Positive control(s):

- Positive control substance: cyclophosphamide

- Justification for choice of positive control(s): none given - standard positive control

- Route of administration: no information

- Doses / concentrations: 40 mg/ kg bw

Tissues and cell types examined:

Bone marrow

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: no deaths occurred in preliminary toxicity assay

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Animals dosed at 0, 24 and 48 hours; samples taken at 72 and 96 hours

DETAILS OF SLIDE PREPARATION: Air dried slides were fixed in methanol then stained with 1% May-Grunwald for 5 minutes then counterstained in 15% Giesma for 15 minutes

METHOD OF ANALYSIS: 1000 PCE scored for micronuclei; PCE/NCE ratio was determined for 300 cells, using x 1000 oil immersion objective

Evaluation criteria:

An increase in micronucleus frequency of greater than 0.28%.

Statistics:

No statistical evaluation described.

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Table 1 Results of in vivo micronucleus study

Treatment mg/kg.bw /day	Time of dosing (h)	Time of sampling (h)	Sex	No. of surviving dosed mice	Erythrocytes
					Polychromatic cells (PCE)			Mean PCE/NCE
					PCE Analysed	No. of MN-PCE	% MN-PCE
Negative control	0+24+48	72	M/F	10	10000	14	0.14	0.93
		96	M/F	10	10000	10	0.10	1.02
Positive control	0+24+48	72	M/F	10	10000	150*	1.50	0.46
500	0+24+48	72	M/F	10	10000	9	0.09	1.00
1000	0+24+48	72	M/F	10	10000	9	0.09	0.94
2000	0+24+48	72	M/F	10	10000	8	0.08	0.86
		96	M/F	10	10000	24	0.24	0.90

PCE = Polychromatic erythrocytes                                                           

MN-PCE = Micronucleated PCE

MN-PCE = Micronucleated NCE

* = Positive response in PCE

Conclusions:

Fatty alcohol blend has been tested according to OECD 474 and under GLP. Male and female mice were dosed with 500, 1000 and 2000 mg/kg bw. No increase in the number of micronucleated PCE was observed (1000 PCE scored per animal). It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test. No toxicity to bone marrow or general toxicity was observed.

Executive summary:

Fatty alcohol blend has been tested according to OECD 474 and under GLP. Male and female mice were dosed with 500, 1000 and 2000 mg/kg bw. No increase in the number of micronucleated PCE was observed (1000 PCE scored per animal). It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test. No toxicity to bone marrow or general toxicity was observed.

Reference 2

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

11-Feb-1992 to 27-Apr-1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

1000 erythrocytes counted instead of 2000

GLP compliance:

yes

Type of assay:

micronucleus assay

Species:

mouse

Strain:

other: albino mice, CFW 1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann
- Age at study initiation: 7-8 weeks
- Weight at study initiation: males 21-27 g, females 21-26 g
- Assigned to test groups randomly: yes, under following basis: allocated to treatment groups according to randomization table generated by computer programme or manually
- Fasting period before study: yes, overnight until 3-4 hours after dosing
- Housing: males, 1/cage, macrolon cages type I; females, <=3/cage, macrolon cages type II; filled with clean softwood bedding
- Diet (e.g. ad libitum): standard animal diet, Altromin No. 1314, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: >=6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25 +- 3 (occasionally 20-25)
- Humidity (%): 40 - 50 (occasionally 45-70)
- Air changes (per hr): no data, except "air-conditioned room"
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES (main study): From: 25-Feb-1992 To: 28-Feb-1992

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: arachis oil
- Justification for choice of solvent/vehicle: test material easily soluble at required concentration
- Concentration of test material in vehicle: not stated, but provided a dose level of 5000 mg/kg bw, so 500 mg/ml
- Amount of vehicle (if gavage or dermal): 10 ml/kg bw (main study), 20 ml/kg bw (range finding study)
- Lot/batch no. (if required): no data
- Purity: no data

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: 500 mg/ml in arachis oil (main study)

Duration of treatment / exposure:

single administration

Frequency of treatment:

single administration

Post exposure period:

evaluated at 24, 48, 72 hours after administration

Dose / conc.:

5 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

6

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide
- Justification for choice of positive control(s): not stated
- Route of administration: oral
- Dose: 20 mg/kg bw

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: maximum tolerated dose, based on range-finding study (effects seen at 5000 mg/kg were piloerection only)

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): single administration, animals sacrificed 24, 48 and 72 hours after administration

DETAILS OF SLIDE PREPARATION: bone marrow collected from femurs, using foetal calf serum applied via a syringe, into a siliconised centrifuge tube; after centrifugation at 1000 rpm and removal of all but one drop of supernatant, cells of sediment carefully mixed; drop of cell suspension placed on clean, degreased microscope slide and immediately spread; 3 slides/animal; slides air dried at least overnight; stained with Giemsa; air dried and dipped in xylol for 3 minutes

METHOD OF ANALYSIS: 1 slide/animal chosen and given a random code; microscopic evaluation of slides from 5 males and 5 females per treatment group at 1000x magnification; number of micronucleated cells counted in 1000 polychromatic erythrocytes (PCEs)/animal; ratio of
polychromatic to normochromatic erythrocytes determined by counting and differentiating the first 1000 erythrocytes

OTHER: means and standard deviations calculated

Evaluation criteria:

Statistically significant (p<0.05) increase in PCE compared to controls at any sampling time in either sex
Acceptability of test: positive controls induced statistically significant increase in frequency of micronucleated PCEs; solvent control incidence of micronuclei should reasonably fall within historical control range for the testing facility.

Statistics:

Method used: Kastenbaum & Bowman

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

piloerection for 8 hours after administration; no mortality

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range: 5000 mg/kg bw
- Solubility: used at 250 mg/ml
- Clinical signs of toxicity in test animals: piloerection
- Evidence of cytotoxicity in tissue analyzed: not examined
- Rationale for exposure: based on limit test in rats in which acute oral LD50 was >5000 mg/kg bw
- Harvest times: animals observed for 3 days

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no statistically significant increase in micronucleus frequency in any treatment group
- Ratio of PCE/NCE (for Micronucleus assay): treated groups similar to controls
- Appropriateness of dose levels and route: maximum tolerated dose of 5000 mg/kg bw used; guideline recommends maximum dose of 2000 mg/kg bw; oral route selected "taking into account the possible route of human exposure during manufacture, handling and use"
- Statistical evaluation: no statistically significant increases in micronuclei in treated groups of either sex; positive control produced a statistically significant increase in micronuclei
- Control incidence of micronuclei: not reported but presumably therefore within historical control range

The test substance did not increase the frequency of micronucleated erythrocytes or the PCE:NCE ratio in mice at any time interval after treatment (24, 48 or 72 hours) at dose levels up to 5000 mg/kg bw when compared to vehicle controls.

Mean values per group in the micronucleus test with 1-Dodecanol

a) Number of micronucleated cells per 1000 polychromatic erythrocytes (PCE)

b) Ratio of polychromatic to normochromatic erythrocytes (PCE/NCE)

Treatment group; (sampling time)	Species and sex	Dose mg/kg	Micronucleated cells 1000 PCE		Ratio of PCE/NCE
			Mean	Range	Mean	Range
Negative control (24 hours) arachis oil	male mice	10 ml/kg	3.60	0 - 9	1.11	0.80 - 1.31
	female mice	10 ml/kg	2.00	0 - 4	1.34	1.02 - 1.07
Positve control (24 hours) cyclophosphamide	male mice	20	13.40	10 - 16	1.21	0.90 - 1.72
	female mice	20	10.80	7 - 14	0.95	0.67 - 1.28
1-Dodecanol (Lorol C12-99)
Limit dose (24 hours)	male mice	5000	2.60	0 - 5	1.08	0.94 - 1.26
	female mice	5000	2.40	2 - 3	1.01	0.90 - 1.18
Limit dose (48 hours)	male mice	5000	3.00	1 - 4	0.89	0.48 - 1.16
	female mice	5000	2.00	0 - 5	1.18	0.90 - 1.68
Limit dose (72 hours)	male mice	5000	2.60	2 - 4	1.65	0.91 - 2.14
	female mice	5000	1.60	0 - 4	1.33	1.08 - 1.55

 

Conclusions:

Dodecan-1-ol has been tested a reliable study, conducted according to OECD guideline 474, no genotoxicity was seen in mice after a single oral dose of 5000 mg/kg bw. The study was performed in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

The only information directly relating to decan-1-ol is a bacterial mutagenicity study, in which only two strains were tested. The key study for this endpoint is therefore a bacterial mutagenicity study on the related substance octan-1-ol. For endpoints where there is no information on decan-1-ol, key studies were chosen from studies on closely related linear or branched alcohols of similar chain length. The choice of key study was based on reliability and similarity of chain length. The data available from standard in vitro and in vivo genetic toxicity assays for all related substances show no evidence of mutagenic potential. Read-across substances were chosen based on carbon chain length and similarity of physicochemical properties. A full discussion of the Category and considerations of RAAF Assessment Entities can be found in the Human Health Alcohols C6-24 Category report (PFA, 2021).

Hexan-1-ol has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD Test Guideline 471, compliant with GLP. No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 1538 in the initial or repeat experiments up to limit concentrations. Appropriate positive, solvent and negative controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test (Henkel, 1990).

Octan-1-ol has been tested in a valid bacterial reverse mutation assay, according to a protocol similar to OECD Test Guideline 471, without information about GLP compliance, using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 3538 (Henkel, 1982). No increase in the number of revertants was observed in any test strain, with or without metabolic activation. Appropriate positive and solvent controls were added and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Decan-1-ol has been tested in a valid bacterial reverse mutation assay, conducted according to a protocol similar to OECD Test Guideline 471, without information about GLP compliance, using Salmonella typhimurium strains TA 98 and TA 100 (Huntingdon, 1996). No increase in the number of revertants was observed in any test strain, with or without metabolic activation when tested up to cytotoxic concentrations (50 µg/plate). Appropriate positive, negative  and solvent controls were added and gave expected results. It is concluded that decan-1-ol is not mutagenic to bacteria under the conditions of the test.

Fatty alcohol blend (containing 40.77% C8 and 55.3% C10) has been tested for mutagenicity to bacteria, in a study which was conducted according to OECD Test Guideline 471 and in compliance with GLP. No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimuriumstrains TA 1535, TA 1537, TA 98, TA 100 and TA 1538 in the initial or repeat experiments up to cytotoxic concentration. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacterial under the conditions of the test (Inveresk, 1992).

Alcohols, C12-13-branched and linear has been tested for clastogenicity in a valid study conducted according to OECD Test Guideline 473 and in compliance with GLP in CHO K1 cells (Sasol, 1998). 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. Appropriate positive and solvent controls were added and gave expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this test.

Fatty alcohol blend (containing 40.77% C8 and 55.3% C10) has been tested for mutagenicity in mouse lymphoma L5178Y cells according to OECD Test Guideline 476 and in compliance with GLP. No test-substance induced increase in the number of mutations was observed when tested up to cytotoxic concentrations. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the study (Inveresk, 1992).

2-Ethylhexan-1-ol has been tested for mutagenicity to mammalian cells in a valid study conducted according to a method similar to OECD Test Guideline 476, but without information on GLP compliance. No increase in the number of revertants was observed when tested in mouse lymphoma L5178Y cells with and without metabolic activation up to cytotoxic concentrations. Appropriate solvent and positive controls were included and gave expected results. It is concluded that 2-ethylhexan-1-ol is negative for mutagenicity to mammalian cells under the conditions of the test (Kirby, 1983).

Fatty alcohol blend has been tested according to OECD Test Guideline 474 and under GLP (Inveresk, 1992). No evidence for a test substance induced increase in the incidence of micronucleated PCE was observed (1000 PCE scored per animal). Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test. No toxicity to bone marrow or general toxicity was observed.

Dodecan-1-ol has been tested for the induction of micronuclei in mice according to OECD Test Guideline 474 and in compliance with GLP. No evidence for a test substance induced increase in the incidence of micronucleated normochromatic erythrocytes in mice bone marrow. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance does not cause damage to chromosomes under the conditions of the test (Henkel, 1992).

Discussion of trends in the Category of C6-24 linear and essentially-linear aliphatic alcohols:

The in vitro and in vivo data available for members of the category and supporting substances indicate that the C6-24 alcohols are not genotoxic. In addition, the category of LCAAs under consideration does not contain any structural elements that are of concern for potential mutagenic activity (Ashby and Tenant, 1991). Furthermore, primary LCAAs (linear and branched) in the range C1 to C5 do not have a mutagenic potential (Bevan, 2001; OECD SIDS butan-1-ol, 2001). Furthermore, in a review by WHO-JECFA a series of 22 saturated aliphatic branched-chain primary LCAAs and the corresponding aldehydes and acids in the range C4 to C8 showed no activity in a battery of in vitro and in vivo mutagenicity tests (WHO, 1998). On this basis it is concluded that the category of LCAAs does not have a mutagenic potential and that read-across within the category can be justified. Where data gaps exist, the gap is filled by read-across from reliable evidence within the C6-24 Alcohols Category, where possible using interpolation between at least two reliable studies using higher and lower carbon number test substances.

Conclusion:

The category C6-24 LCAAs do not have a genotoxic potential.

Genetic toxicity

	CAS	CHEMICAL NAME	Bacterial mutagenicity	Bacterial mutagenicity	Mammalian cytogenicity	Mammalian cytogenicity	Mamalian mutagenicity	Mamalian mutagenicity	In vivo studies	In vivo studies
			Result (Rel.)	Reference	Result (Rel.)	Reference	Result (Rel.)	Reference	Result (Rel.)	Study Type*(Ref)
C6	111-27-3	Hexan-1-ol	Neg; (1)	Henkel, 1990
C7, 8 and 9		Alcohols, C7-9	Neg. (1)	Shell, 1996
C8	111-87-5	Octan-1-ol	Neg; (2)	Henkel, 1982a; Huntingdon Life Sciences, 1996k
C8	104-76-7	2-ethylhexan-1-ol Supporting Substance	Neg; (2)	Kirby, 1983			Neg; (2)	Kirby, 1983	Neg; (2)	MN;Dom. Leth (Putman, 1983; WHO, 1993)
C8-10	none	Fatty alcohol blend (40.7% C8 and 55.3% C10) Supporting Substance	Neg(2)	Inveresk (1992)			Neg (1)	Inveresk (1992)	Neg (1)	Inveresk(1992)
C10	112-30-1	Decan-1-ol	Neg (4) 2 strains only	(Huntingdon Life Sciences, 1996l)
C12	112-53-8	Dodecan-1-ol	Neg. (1)l	(Safepharm Laboratories, 1996a)Shimizu, 1985					Neg. (2)	Micronucleus; (Henkel, 1992)
C12 and 13	75782-87-5	Alcohols, C12-13	Neg (2, >80% lin)	Sasol, 1980
C12 and 13	740817-83-8	Alcohols, C12-13-branched and linear	Neg (1 50% lin),	Sasol, 1998	Neg (1 (50% lin)	Sasol, 1998
C12	67762-25-8	C12-18 Alcohols, Type B Supporting	Neg (2)Ames	Henkel 1982
C 12-15	90604-40-3	Alcohols, C12-15-branched and linear	Neg (1)	Corning Hazleton, 1996
C14	112-72-1	Tetradecan-1-ol	Neg (1)	Safepharm Laboratories, 1996b
C16	36653-82-4	Hexadecan-1-ol	Neg (1)	Safepharm Laboratories, 1996c
C16	36653-82-4	Hexadecan-1-ol	Neg. (2)	Henkel, 1981
C16	68002-94-8	C16-18 and C18 Unsaturated Supporting	Neg. Ames (2)	Banduhn, 1989)
C18	112-92-5	Octadecan-1-ol	Neg (1)	Safepharm Laboratories, 1996d					Neg (2) MN	Hachiya, 1982
C18	112-92-5	Octadecan-1-ol	Neg(2)	Henkel, 1981
C18	97552-91-5	C18-22 Alcohol Supporting	Neg. Ames (2)	Banduhn 1995
C22	661-19-8	Docosan-1-ol	Neg (2),	Iglesias, 2002b, Thompson, 1997	Neg (2),	Iglesias, 2002b	Neg (2)	Iglesias, 2002b	Neg (2)	Micronucleus Iglesias, 2002bª
C24-32		D-002*** Supporting substance							Neg (4)	MN; Dom. Leth.Rodeiro 1998a

 

*MN: Mouse bone marrow micronucleus test; Dom. Leth. Mouse Dominant Lethal test; UDS: Unscheduled DNA Synthesis assay

** Tested in S. typhimurium TA 98 and TA100, only.

***Mixture of very long chain fatty alcohols from hydrolysed beeswax

References:

Ashby, J., Tennant, R.W., 1991. Definitive relationships among chemical structure, carcinogenicity, and mutagenicity for 301 chemicals tested by the US NTP. Mutation Research 257, 229–306.

WHO, 1999. Technical Report Series 884 Evaluation of certain food additives and contaminants. 49th Report of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), Geneva.

Justification for classification or non-classification

Based on the available data, decan-1-ol does not require classification for genetic toxicity according to Regulation (EC) No 1272/2008.