Hexan-1-ol

Genetic toxicity: in vitro

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Fatty Alcohol Blend

IUPAC Name:

Fatty Alcohol Blend

Method

Target gene:

Histidine operon

Species / strain

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

Controls

Controls 1

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

Controls 2

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

Controls 3

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

Controls 4

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.

Results and discussion

Test results

Key result

Species / strain:

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

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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.