Alcohols, C11-14-iso-, C13-rich

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report equivalent or similar to OECD guideline 471: GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Isotridecan-1-ol

EC Number:

248-469-2

EC Name:

Isotridecan-1-ol

Cas Number:

27458-92-0

Molecular formula:

C13H28O

IUPAC Name:

3,5,7 trimethyl decanol

Constituent 2

Reference substance name:

Isododecan-1-ol

Molecular formula:

C12H26O

IUPAC Name:

Isododecan-1-ol

Constituent 3

Reference substance name:

Isotetradecan-1-ol

Molecular formula:

C14H30O

IUPAC Name:

Isotetradecan-1-ol

Constituent 4

Reference substance name:

Isoundecan-1-ol

EC Number:

257-376-6

EC Name:

Isoundecan-1-ol

Cas Number:

51750-47-1

Molecular formula:

C11H24O

IUPAC Name:

3,5 dimethyl nonanol-1

Constituent 5

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H20

IUPAC Name:

water

Test material form:

liquid

Method

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Metabolic activation system:

S9 liver fractions from Aroclor exposed rats

Test concentrations with justification for top dose:

Test #1 (-S9): 0, 0.05, 0.0158, 0.005, 0.00158, 0.0005, 0.000158 uL/plate; (+S9): 0.5, 0.158, 0.05, 0.0158, 0.005, 0.00158 uL/plate
Test #2 (-S9): 0, 0.05, 0.0158, 0.005, 0.00158, 0.0005, 0.000158 uL/plate; (+S9): 0.5, 0.158, 0.05, 0.0158, 0.005, 0.00158 uL/plate
Test #3 (-S9): 0, 0.005, 0.00158, 0.0005, 0.000158, 0.00005, 0.0000158 uL/plate; (+S9): 0.158, 0.05, 0.0158, 0.005, 0.00158, 0.0005 uL/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

2-nitrofluorene

sodium azide

N-ethyl-N-nitro-N-nitrosoguanidine

other: 2-aminoanthracene and ICR191

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48 hours
SELECTION AGENT (mutation assays):
- his+ and trp+ revertants
DETERMINATION OF CYTOTOXICITY
- Method: concentrations eliciting less than 80% viability (as determined by a proportional reduction of ATP in a luminescence assay) and/or impacting the background lawn of bacterial growth

Evaluation criteria:

In order for a test substance to be considered positive in the bacterial gene mutation test, there must be a concentration-related increase over the range tested and/or a reproducible increase of 3-fold or higher over the background, at one or more concentrations in the number of revertant colonies per plate in at least one strain with or without metabolic activation system. If neither of the above is true, the test article was deemed to be negative.
If the test article was deemed negative in all five strains both in the presence and absence of metabolic activation system, a confirmatory run was performed. If the test article was deemed to be negative in the confirmatory run also (ie there is no reproducible increase of 3 fold or higher over the background, at any concentration, in the number of revertant colonies per plate in any strain with or without metabolic activation system) then the test article was deemed negative for mutagenicity.
Positive results from the bacterial reverse mutation test indicate that a substance induces point mutations by base substitution for frameshifts in the genome of either Salmonella typhimurium and/or Escherichia coli. Negative results indicate that under the test conditions, the test substance is not mutagenic.

Statistics:

For cytotoxicity, the mean % viability and standard deviation were calculated. For the main study and confirmatory run the mean revertant colonies, fold change, and standard deviation per treatment group were calculated.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at/above 18.5 nL/mL Exxal 13 (-S9), and at/above 585 nL/mL Exxal 13 (+S9)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

The bacterial reverse mutation test to assess the genotoxicity of Exxal 13 was negative.

Executive summary:

Exxal 13 was examined for mutagenic activity in the bacterial reverse mutation test using histidine-requiring Salmonella typhimurium strains TA 1535, 1537, 98 and 100 and the tryptophan requiring Escherichia coli strain WP2 uvrA, in the absence and presence of a liver S9 fraction for metabolic activation. Three tests were performed:Test #1 [(-S9): 0, 0.05, 0.0158, 0.005, 0.00158, 0.0005, 0.000158 uL/plate; (+S9): 0.5, 0.158, 0.05, 0.0158, 0.005, 0.00158 uL/plate], Test #2 [(-S9): 0, 0.05, 0.0158, 0.005, 0.00158, 0.0005, 0.000158 uL/plate; (+S9): 0.5, 0.158, 0.05, 0.0158, 0.005, 0.00158 uL/plate], Test #3 [(-S9): 0, 0.005, 0.00158, 0.0005, 0.000158, 0.00005, 0.0000158 uL/plate; (+S9): 0.158, 0.05, 0.0158, 0.005, 0.00158, 0.0005 uL/plate].

Test concentrations at/above 18.5 nL/mL Exxal 13 (-S9), and at/above 585 nL/mL Exxal 13 (+S9) were found to be cytotoxic. The results suggest that Exxal 13 is negative for mutagenicity under the experimental conditions of this study, as it does not induce a 3-fold increase in revertancy compared to negative controls in the presence or absence of S9 in the standard run or the confirmatory test.