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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

AMES assay

Experimental Study report of target substance Tridecanol (112-70-9) was observed by U. S. National Library of Medicine (CCRIS ,2018 ) to evaluate its mutagenic nature. Tridecanol was considered to be non mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA/ PKM101 by AMES test.

In vitro chromosomal abbreviation study

Test substance result  was considered to be negative in Mammalian cell line,both in the presence and absence of metabolic activation.Hence the substance cannot be classified as gene mutant in vitro.

Link to relevant study records

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Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Data is from CCRIS
Qualifier:
equivalent or similar to
Guideline:
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Principles of method if other than guideline:
To evaluate the mutagenic potential of Tridecanol in Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA /PKM101 by AMES test.

GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
- Name of test material (as cited in study report): 1-TRIDECANOL
- Common name : tridecan-1-ol
- Molecular formula : C13H28O
- Molecular weight : 200.37 g/mol
- Smiles notation : C(CCCCCCO)CCCCCC
- InChl : 1S/C13H28O/c1-2-3-4-5-6-7-8-9-10-11-12-13-14/h14H,2-13H2,1H3
- Substance type: Organic
- Physical state: Solid
Target gene:
Histidine for Salmonella typhimurium and tryptophan Escherichia coli
Species / strain / cell type:
bacteria, other: Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA/PKM101
Details on mammalian cell type (if applicable):
Not applicable.
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
not specified
Metabolic activation:
with and without
Metabolic activation system:
Rat liver, induced with PHenobarbital AND BETA-Naphthoflavone
Test concentrations with justification for top dose:
0, 0.61-10000 µg/plate
Vehicle / solvent:
Vehicle
- Vehicle(s)/solvent(s) used: DMSO
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
not specified
Details on test system and experimental conditions:
Details on test system and conditions
METHOD OF APPLICATION: Preincubation method
Rationale for test conditions:
Not specified
Evaluation criteria:
Evaluation was done considering a dose dependent increase in the number of revertants/plate.
Statistics:
Not specified
Species / strain:
bacteria, other: Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA/PKM101
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Remarks on result:
other: No mutagenic effect were observed.
Conclusions:
Test substance was evaluated for its mutagenic potential in Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA/PKM101 by AMES test. The test result was considered to be negative in all strain in the presence and absence of metabolic activation S9.
Executive summary:

Genetic toxicity in vitro study was assessed for test substance. For this purpose AMES test was performed similar to Guidelines for Screening Mutagenicity Testing of Chemicals (Japan).The test material was exposed to Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA /PKM101 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, 0.61-10000µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore test substance was considered to be non mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA/ PKM101 by AMES test. Hence the substance cannot be classified as gene mutant in vitro.

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from handbook or collection of data
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: As mention below
Principles of method if other than guideline:
Weight of evidence prepared from various studies
1,Chromosome Aberration Test was performed to determine the mutagenic nature of test substance.
2,The purpose of this study was to assess toxic and genotoxic effects of test chemical on Chinese Hamster Ovary (CHO) cells by using several different in vitro-based assays, including genotoxicity tests based on the OECD Guideline No. 476 “In Vitro Mammalian Cell Gene Mutation Test”.
GLP compliance:
not specified
Type of assay:
other: Mammalian Chromosome Aberration Test
Target gene:
Chinese hamster lung fibroblast cells (CHL cells)
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Details on mammalian cell type (if applicable):
not specified
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Cytokinesis block (if used):
not specified
Metabolic activation:
with and without
Metabolic activation system:
rat liver S9 mix
Test concentrations with justification for top dose:
1,+ S9 mix: Negative / Positive control, 0.5, 1.0 and 2.0 μg/mL
- S9 mix: Negative / Positive control, 0.5, 1.0 and 2.0 μg/mL
2,0, 1, 2.5, 5 or 10 mM
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: tetrahydrofuran (THF)
- Justification for choice of solvent/vehicle: The solubility test showed that the test substance was insoluble in water, dimethyl sulfoxide (DMSO), glycerol formal, but suspended in tetrahydrofuran. Tetrahydrofuran was selected as a vehicle.
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
1% of tetrahydrofuran
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
cyclophosphamide
mitomycin C
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
7,12-dimethylbenzanthracene
other: N-ethyl-N-nitrosourea (ENU) (Without S9)
Details on test system and experimental conditions:
1,- Short term exposure: CHL cells (5×10^4 cells per 5 mL in 60 mm petri-dish) were cultured for 72 hours and thereafter exposed in duplicate to the selected three doses of the test substance for 6 hours in the absence or in the presence of
S9 mix and recovered in fresh medium for 18 hours.
- Continuous exposure: CHL cells (5×10^4 cells per 5 mL in 60 mm petri-dish) were cultured for 72 hours and thereafter exposed in duplicate to the selected three doses of the test substance for 24 hours in the absence of S9 mix.
- Chromosome preparation: Cell cultures were treated with Colcemid for 2 hours prior to harvesting. Thereafter the cell cultures were centrifuged for 5 minutes at 1200 rpm and the supernatant was removed. Cells in the remaining pellet were swollen by a 30 min treatment with hypotonic solution (0.075 M KCl pre-warmed at 37􀬇). After hypotonic treatment, cells were fixed with 3 times of methanol: glacial acetic acid fixative (3 : 1 v/v).
- Slide preparation: Fixed cells were dropped onto pre-cleaned microscope slides which were then allowed to air-dry and thereafter stained in 5% (v/v) Giemsa solution.
- Slide analysis: All slides, including those of positive and negative controls, were independently coded before microscopic analysis. At least 200 well-spread metaphases were scored per concentration and control.

2,METHOD OF APPLICATION: In medium with pre-incubation

DURATION
- Preincubation period: One week involving 3 days of incubation with Hypoxanthine-aminopterin-thymidine (HAT) in medium as a mutant cleansing stage, followed by overnight incubation with hypoxanthine-thymidine (HT) in medium prior to a 3-4 days incubation in regular cell medium. After seeding and prior to treatment, the mutant-free cells were incubated for an additional of 24 hours.
- Exposure duration: 3 hours
- Expression time (cells in growth medium): 7 days
- Selection time (if incubation with a selection agent): 14 days
- Fixation time (start of exposure up to fixation or harvest of cells): 7 days (harvest of cells)

SELECTION AGENT (mutation assays): 6-thioguanine (TG)
SPINDLE INHIBITOR (cytogenetic assays): Not applicable
STAIN (for cytogenetic assays): Crystal violet

NUMBER OF REPLICATIONS: A minimum of 2 replicates per dose concentration including negative and positive control.

NUMBER OF CELLS EVALUATED: 5 x 10 E5 cells were plated 7 days after treatment and whatever cells left, after 14 days of incubation with the selection medium, were evaluated.

DETERMINATION OF CYTOTOXICITY
- Cytotoxicity test
After being exposed to the test chemical for 3 hours, in the absence or presence of S9, cells were trypsinized and 0.5 x 10 E5 cells per well was seeded in duplicates from two parallel duplicate cultures into 6-well plates in fresh medium. The relative total growth and cytotoxicity was evaluated 24 and 48 hours after seeding.

Evaluation criteria:
1) In each concentration, the number of aberrant cells in 200 metaphase cells was presented. Structural aberration was evaluated by classifying to chromosomal
2) Break and exchange, and chromatid break and exchange. A gap was defined as the deletion smaller than the width of chromatid and enumerated, nonetheless, it was not included in the total aberration frequency. As numerical aberration, only polyploidy higher than tetraploid.
3) endoreduplication were evaluated. A cell with more than one type of structural aberration was counted as
4) one positive cell, their percentage of aberration cell was estimated and considered to be the frequency of chromosome aberration. In addition, chromosome aberration types were recorded separately.
Statistics:
1) Statistical analysis of chromosomal aberration frequency excluding gaps was performed according to the OECD guideline.
2) In 200 metaphase cells of each group, the numbers of aberrant cells and normal cells were presented.
3) If the dose-dependent increase or the repeated increase was detected. It was evaluated to be positive. The significant difference in the frequence of chromosomal aberration
4) between the negative control and the test substance treatment group was analyzed using Fisher's exact test (Altman, 1993). The test substance was considered to be negative if P-value was lower than 0.05.
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
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: Non mutagenic
Conclusions:
Test substance result was considered to be negative in Mammalian cell line,both in the presence and absence of metabolic activation.Hence the substance cannot be classified as gene mutant in vitro.
Executive summary:

Data for the various test chemicals was reviewed to determine the mutagenic nature of Tridecanol (112-70-9). The studies are as mentioned below:

Structural chromosomal aberrations and polyploidy were not induced up to a maximum concentration of test chemical under conditions of continuous treatment, and short-term treatment with and without an exogenous metabolic activation system in Chinese hamster lung(CHL)cells. Hence the substance cannot be classified as genetox in vitro.

 

An in vitro mammalian cell gene mutation study was designed and conducted to determine the genotoxicity profile of test chemical when administered to Chinese Hamster Ovary (CHO) cells.

 

In the genotoxicity test, test substance was administered to CHO cells for 3 hrs at the dose levels of 0, 1.0, 2.5, 5.0 or 10.0 mM and in the absence or presence of exogenous metabolic activation. The results indicate that the test chemical does not give rise to gene mutations when used at concentrations of ≤ 5.0 mM, but when exposed to concentrations above 5.0 mM for 3 hrs, and in organisms with a fully functioning metabolic activation, the test chemical may induce gene mutations. When treated with test chemical and in the absence with S9 liver microsomal fraction, the results show no evidence of genotoxicity when CHO cells are exposed to concentrations of 1.0, 2.5, 5.0 or 10.0 mM, thus indicating that the test chemical does not give rise to gene mutations in organisms who have no or non-functional metabolic activation at the above mentioned concentrations. . Hence the substance cannot be classified as genetox in vitro.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Data for the various test chemicals was reviewed to determine the mutagenic nature of Tridecanol (112-70-9). The studies are as mentioned below:

 

Ames assay

Genetic toxicity in vitro study was assessed for test substance. For this purpose AMES test was performed similar to Guidelines for Screening Mutagenicity Testing of Chemicals (Japan).The test material was exposed to Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA /PKM101 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, 0.61-10000µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore test substance was considered to be non mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA/ PKM101 by AMES test. Hence the substance cannot be classified as gene mutant in vitro.

Salmonella/microsome test in the absence of exogenous metabolic activation and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters was performed to evaluate the mutagenic nature of test chemical using S. typhimurium tester strains TA1535, TA97, TA98 and TA100. The study was performed as per the preincubation assay. The test compound was used at a dosage level of 0, 1, 3, 10, 33, 100, 333, 166 µg/plate in the preincubation assay of 48 hrs. Test chemical failed to induce mutation in the S. typhimurium tester strains TA1535, TA97, TA98 and TA100 and hence is negative for mutation in vitro.

Gene mutation toxicity study was performed to determine the mutagenic nature of test chemical. Pre-incubation method was performed to determine its mutagenic nature. Test chemical did not induce gene mutations in the S. typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA in a bacterial reverse mutation assay. The assay was performed in the presence and absence of S9 metabolic activation system at dose levels of 0, 156, 313, 625, 1250, 2500, 5000 µg /plate. Test chemical did not induce gene mutations in the S. typhimurium strains TA100, TA1535, TA98, TA1537 and E. coli WP2 uvrA in a bacterial reverse mutation assay in the presence and absence of S9 metabolic activation system up to a concentration of 5000 µg/plate and hence is not likely to classify for gene mutation in vitro.

In vitro chromosomal abbreviation study

Structural chromosomal aberrations and polyploidy were not induced up to a maximum concentration of test chemical under conditions of continuous treatment, and short-term treatment with and without an exogenous metabolic activation system in Chinese hamster lung(CHL)cells. Hence the substance cannot be classified as genetox in vitro.

 

An in vitro mammalian cell gene mutation study was designed and conducted to determine the genotoxicity profile of test chemical when administered to Chinese Hamster Ovary (CHO) cells.In the genotoxicity test, test substance was administered to CHO cells for 3 hrs at the dose levels of 0, 1.0, 2.5, 5.0 or 10.0 mM and in the absence or presence of exogenous metabolic activation. The results indicate that the test chemical does not give rise to gene mutations when used at concentrations of ≤ 5.0 mM, but when exposed to concentrations above 5.0 mM for 3 hrs, and in organisms with a fully functioning metabolic activation, the test chemical may induce gene mutations. When treated with test chemical and in the absence with S9 liver microsomal fraction, the results show no evidence of genotoxicity when CHO cells are exposed to concentrations of 1.0, 2.5, 5.0 or 10.0 mM, thus indicating that the test chemical does not give rise to gene mutations in organisms who have no or non-functional metabolic activation at the above mentioned concentrations. . Hence the substance cannot be classified as genetox in vitro.

 

 

 

Based on the data summarized, Tridecanol (112-70-9) did not induce gene mutation .Hence it is not likely to be mutagenic in vitro.

 

Justification for classification or non-classification

Thus based on the above annotyation and CLP criteria available for the test chemical does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.