Alcohols, C16-18

Genetic toxicity: in vitro

Administrative data

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Alcohols, C16-18 is a member and is from Long Chain Alcohols (C6-22 primary aliphatic alcohols) category.
The Long Chain Alcohols (C6-22 primary aliphatic alcohols) category is considered suitable as a source of data for Alcohols, C16-18.
Considered valid for read-across for purposes of classification.
No further vertebrate testing can be justified.

Long Chain Alcohols (C6-22 primary aliphatic alcohols) category covers a family of 30 primary aliphatic alcohols within a carbon chain length range of C6-C22. Commercial products generally include several aliphatic alcohol components, with a range of carbon chain lengths present. The family consists of alcohols with varying compositions and structures. Composition depends on the route to manufacture and the related feedstocks. Most of the alcohols have linear carbon chains but certain manufacturing processes create branched structures. Data are also available for eleven other similar substances, which support the category. Non-sponsored alcohols may not be HPV or may not be produced by members of the consortium, but have structures similar to sponsored linear alcohols.

Key points are that the members share:
• The same structural features
• Similar metabolic pathways
• Common mode of ecotoxicological action
• Common levels and mode of human health related effects.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2022

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Octadecan-1-ol

EC Number:

204-017-6

EC Name:

Octadecan-1-ol

Cas Number:

112-92-5

Molecular formula:

C18H38O

IUPAC Name:

octadecan-1-ol

Test material form:

solid: compact

Details on test material:

- Name of test material (as cited in study report): KALCOHL 8098 ; 1-octadecanol
- Substance type: white granular solid
- Physical state: solid
- Lot/batch No.: 3349
- Expiration date of the lot/batch: no data
- Storage condition of test material: room temperature in the dark
- Other: Date received: 22 January 1996

Method

Target gene:

histidine

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

S9 prepared from the livers of male Sprague-Dawley induced with Aroclor 1254

Test concentrations with justification for top dose:

50, 150, 500, 1500 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: not stated

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 1103 3 and 5 µg/plate respectively

Remarks:

TA100 and TA1535 without S9

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 25 0.2 µg/plate

Remarks:

TA98 without S9

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 28 80 µg/plate

Remarks:

TA1537 without S9

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 1342 4-nitro-o-phenylenediamine, 5 µg/plate

Remarks:

TA102 without S9

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 1342 2-aminoanthracene, 0.5, 1 or 2 µg/plate

Remarks:

All strains with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hrs

NUMBER OF REPLICATIONS: Duplicate tests each performed in triplicate

DETERMINATION OF CYTOTOXICITY
- Method: other: Thinning of background lawn

Evaluation criteria:

A dose related and statistically significant increase in reverse mutation rate in one or more bacterial strains at sub-toxic dose levels. For a negative result the numbers of induced revertants should be less than two fold compared to controls.

Statistics:

All data statistically analysed using the methods recommended by the UKEMS and normally Dunnett¿s method of linear regression used to evaluate the result.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

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: seen at >=500 µg/plate but this did not interfere with scoring of the plate, plates were counted manually at 5000 µg/plate
- Other confounding effects: no data

RANGE-FINDING/SCREENING STUDIES: The test material was non-toxic to strain TA100. Precipitation occurred at >=500 µg/plate.

COMPARISON WITH HISTORICAL CONTROL DATA: no data

ADDITIONAL INFORMATION ON CYTOTOXICITY: There was no evidence of cytotoxicity up to 5000 µg/plate with or without S9.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

 

Table 1 Experiment 1 Plate incorporation Revertants per plate (mean of three plates)

Concentration        µg/plate	TA 100		TA 1535		TA 102		TA 98		TA 1537
	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA
0*	122	124	29	35	20	26	23	34	7	12
50	115	121	28	35	16	27	24	31	7	12
150	126	114	33	36	24	28	25	35	8	10
500	130	116	30	36	17	27	21	39	8	11
1500	131	103	30	37	17	27	20	36	5	9
5000	123	107	32	32	14	21	17	34	5	9
Positive control	419	672	137	171	544	235	148	236	277	209

* Solvent control with ethanol

Table 2 Experiment 2 Plate incorporation Revertants per plate (mean of three plates)

Concentration        µg/plate	TA 100		TA 1535		TA 102		TA 98		TA 1537
	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA
0*	118	110	31	24	13	11	25	23	8	8
50	121	113	33	27	10	10	27	23	8	8
150	121	107	31	27	10	7	24	23	9	6
500	118	105	32	25	10	11	25	20	7	8
1500	103	101	30	29	8	14	24	25	7	6
5000	90	97	24	17	9	13	14	23	6	8
Positive control	530	600	171	195	589	196	152	305	496	206

* Solvent control with ethanol

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results :
negative with metabolic activation
negative without metabolic activation

In a reliable study conducted according to OECD guideline 471, the C18 alcohol Kalcohl 8098 did not increase the reverse mutation rate in any of the histidine dependent bacterial strains of Salmonella typhimurium tested in the presence or absence of metabolic activation at concentrations up to 5000 µg/plate. The top concentration was not cytotoxic. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.