Tridecan-1-ol

Endpoint summary

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.

In Vitro Mammalian Cell Gene Mutation Test

In a reliable study, test chemical did not increase the gene mutation rate in Chinese hamster V79 cells in the presence or absence of metabolic activation at concentrations up to 20 ug/ml. It is concluded that the test substance is negative for mutagenicity in mammalian cells under the conditions of this test.

Link to relevant study records

Reference

Reference 1

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

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.

Reference 2

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

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:

Weight of evidence approach based on the available information from various test chemicals.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Principles of method if other than guideline:

Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)and OECD Guideline No. 473

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

Target gene:

No data

Species / strain / cell type:

mammalian cell line, other: Chinese hamster lung (CHL) cells

Additional strain / cell type characteristics:

not specified

Remarks:

5

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

- Type and identity of media: minimum essential medium
- Properly maintained: no data
- Periodically checked for Mycoplasma contamination: no data
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: no data

Additional strain / cell type characteristics:

other:

Remarks:

6

Metabolic activation:

with and without

Metabolic activation system:

5. S9 from rat liver, induced with phenobarbital and 5,6- benzoflavone
6. liver microsomal fraction from male rats prepared according to Ames et al., 1977

Test concentrations with justification for top dose:

5. -S9 mix(24hr continuous exposure): 0, 350, 700, 1400, 2800 µg/mL
-S9 mix(48hr continuous exposure): 0, 288, 575, 1150, 2300 µg/mL
-S9 mix(short-term exposure): 0, 875, 1750, 3500 µg/mL
+S9 mix(short-term exposure): 0, 875, 1750, 3500 µg/mL

6.0.6, 10.0 and 20.0 µg/ml

Vehicle / solvent:

5. 1% Carboxymethylcellulose sodium
6.
- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: solubility

Untreated negative controls:

no

Remarks:

5

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

mitomycin C

Remarks:

without S9

Untreated negative controls:

no

Remarks:

5

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

with S9

Untreated negative controls:

yes

Remarks:

6

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

Without metabollic activation

Untreated negative controls:

yes

Remarks:

6

Negative solvent / vehicle controls:

no

True negative controls:

yes

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

With metabollic activation

Details on test system and experimental conditions:

5. Study Design:
For continuous treatment, cells were treated for 24 or 48 hrs without S9. For short-term treatment, cells were treated for 6 hrs with and without S9 and cultivated with fresh media for 18 hrs.
Plates/test: 2

6.METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: not applicable
- Exposure duration: 4 hours
- Expression time (cells in growth medium): not applicable
- Selection time (if incubation with a selection agent): not applicable
- Fixation time (start of exposure up to fixation or harvest of cells): 7 and 24 (or 28) hours at 20 µg/ml, 18 hours at 0.6, 10 and 20 µg/ml

SPINDLE INHIBITOR (cytogenetic assays): Colcemid, 0.2 µg/ml

STAIN (for cytogenetic assays): Giemsa

NUMBER OF REPLICATIONS: 2 cultures per concentration

NUMBER OF CELLS EVALUATED: 100 per slide, 200 per concentration

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

Evaluation criteria:

5. No data
6. To be considered positive, either a statistically significant, concentration-related increase in the number of structural chromosome aberrations, or a statistically significant positive response at one of the concentrations

Statistics:

5. No data
6 Chi-squared test performed for cells with aberration (excluding gaps)

Species / strain:

mammalian cell line, other: Chinese hamster lung(CHL)cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks:

5

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: presumably >20 µg/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks:

6

Additional information on results:

5. This chemical did not induce structural chromosomal aberrations in the absence or presence of an exogenous metabolic activation system
6. TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: insoluble
- Precipitation: no data
- Other confounding effects: no data

RANGE-FINDING/SCREENING STUDIES: yes, but no data presented

COMPARISON WITH HISTORICAL CONTROL DATA: no data

ADDITIONAL INFORMATION ON CYTOTOXICITY: at 20 µg/ml, mitotic index not reduced, plating efficiency not reduced

Remarks on result:

other: No mutagenic potential observed

Conclusions:

Test chemical did not induce structural chromosomal aberrations in the absence or presence of an exogenous metabolic activation system in an in vitro mammalian chromosome aberration test in Chinese hamster lung(CHL)cells.

Executive summary:

5. 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

6. In an in vitro chromosome aberration study, Chinese hamster lung fibroblasts (V79) were incubated with 0.6, 10.0 and 20.0 µg/ml of test material dissolved in ethanol for 4 hours, with and without metabolic activation. The test substance did not increase the incidence of chromosome aberrations in Chinese hamster V79 cells in the presence or absence of metabolic activation when tested up to limit concentration. There was no evidence of cytotoxicity at this dose level. The study was comparable to guideline without detailed documentation (publication). It is considered that read across to the registered substance is valid and scientifically justifiable.

Reference 3

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:

Weight of evidence approach based on the available information from various test chemicals.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

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

Principles of method if other than guideline:

Well-conducted study according to a protocol very similar to OECD guideline 476

GLP compliance:

not specified

Type of assay:

other: mammalian cell gene mutation assay

Target gene:

8. HGPRT
9. No data

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Remarks:

8

Details on mammalian cell type (if applicable):

- Type and identity of media: no data
- Properly maintained: no data
- Periodically checked for Mycoplasma contamination: no data
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: no data

Species / strain / cell type:

mouse lymphoma L5178Y cells

Remarks:

9

Metabolic activation:

with and without

Metabolic activation system:

8. no data, but for Ames test, liver microsomal fractions from male rats prepared by "established methods"
9. Aroclor induced rat liver S9

Test concentrations with justification for top dose:

8. 2.0, 7.5, 15.0, and 20.0 ug/ml
9. 10 concentrations at log intervals between 0.013 and 1.0 µl/ml

Vehicle / solvent:

8. - Vehicle(s)/solvent(s) used: ethanol, final concentration in culture medium <=1% v/v
- Justification for choice of solvent/vehicle: solubility

9. not indicated

Untreated negative controls:

yes

Remarks:

8

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

1.0 ug/ml

Untreated negative controls:

yes

Remarks:

8

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

7,12-dimethylbenzanthracene

Remarks:

15.4 ug/ml

Untreated negative controls:

no

Remarks:

9

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

not specified

Details on test system and experimental conditions:

8. METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: not applicable
- Exposure duration: 4 hours
- Expression time (cells in growth medium): no data
- Selection time (if incubation with a selection agent): no data
- Fixation time (start of exposure up to fixation or harvest of cells): no data

SELECTION AGENT (mutation assays): thioguanine

NUMBER OF REPLICATIONS:
- 2 independent experiments, both with and without metabolic activation

NUMBER OF CELLS EVALUATED: no data

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

9.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

Rationale for test conditions:

no data

Evaluation criteria:

8. To be considered positive, statistically significant concentration-related increase in mutant frequency, or a reproducible and statistically significant positive response for at least one concentration

9.
A result was judged to be positive when a two-fold increase in the number of revertants relative to background was observed.

Statistics:

no data

Species / strain:

Chinese hamster lung fibroblasts (V79)

Remarks:

8

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: presumely >20µg/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

valid

Species / strain:

mouse lymphoma L5178Y cells

Remarks:

9

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

Additional information on results:

8. TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: insoluble
- Precipitation: no data
- Other confounding effects: no data

RANGE-FINDING/SCREENING STUDIES: yes, but no data presented

COMPARISON WITH HISTORICAL CONTROL DATA: no data

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- With metabolic activation: mean relative cell survival over the test concentrations ranged from 89.1% (20 ug/ml) to 93.8% (15 ug/ml).
- Without metabolic activation: mean relative cell survival ranged from 96% (15 ug/ml) to 120.2 % (20 ug/ml).

9.No data

Remarks on result:

other: No mutagenic potential observed

Conclusions:

In a reliable study, test chemical did not increase the gene mutation rate in Chinese hamster V79 cells in the presence or absence of metabolic activation at concentrations up to 20 ug/ml. It is concluded that the test substance is negative for mutagenicity in mammalian cells under the conditions of this test.

Executive summary:

8.In Vitro Mammalian Cell Gene Mutation Test was performed Chinese hamster lung fibroblasts (V79) to determine to genotoxicity of the test chemical. The test was performed on HGPRT target gene, with and without metabollic activation at concentartions of 2.0, 7.5, 15.0, and 20.0 ug/ml. 7,12-dimethylbenzanthracene and Ethylmethanosulphonate were used as positive control. Thus, the test chemical did not increase the gene mutation rate in Chinese hamster V79 cells in the presence or absence of metabolic activation at concentrations up to 20 ug/ml. It is concluded that the test substance is negative for mutagenicity in mammalian cells under the conditions of this test.

9.The test chemical was tested for mutagenicity to mammalian cells in a valid study using a method similar to OECD TG 476 up to toxic concentrations. The test was perfomed on mouse lymphoma L5178Y cells, with and without metabollic activation at 10 concentrations at log intervals between 0.013 and 1.0 µl/ml. No increase in the number of revertants was observed. It was concluded that the test chemical is negative for mutagenicity to mammalian cells under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

In a reliable study, test chemical did not increase the incidence of micronuclei in mouse bone marrow cells after a single oral gavage dose of up to 500 mg/kg bw.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

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:

comparable to guideline study with acceptable restrictions

Justification for type of information:

Weight of evidence approach based on the available information from various test chemicals.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Weight of evidance study on in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

GLP compliance:

not specified

Type of assay:

mammalian erythrocyte micronucleus test

Species:

mouse

Strain:

other: 2. NMRI 3.DDY

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Tierfarm Fullinsdorf, Switzerland
- Age at study initiation: >=10 weeks
- Weight at study initiation: no data
- Assigned to test groups randomly: no data
- Fasting period before study: 18 hours, but continued to receive water ad libitum
- Housing: Markrolon Type 1 cages with wire mesh tops and granulated soft wood bedding
- Diet (e.g. ad libitum): standard pellet diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): not regulated
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: no data

Route of administration:

oral: gavage

Vehicle:

2. - Vehicle(s)/solvent(s) used: polyethylene glycol
- Justification for choice of solvent/vehicle: no data
- Concentration of test material in vehicle: no data [calculated: 5, 15 and 50 mg/ml]
- Amount of vehicle (if gavage or dermal): 10 ml/kg bw
- Lot/batch no. (if required): no data
- Purity: no data

3. Olive oil

Details on exposure:

2. PREPARATION OF DOSING SOLUTIONS: few details; test material suspended in vehicle
3. No data

Duration of treatment / exposure:

2. single administration
3. 24 hours

Frequency of treatment:

2. single administration
3. single administration and 4 administrations

Post exposure period:

2. None
3. 24 hours (single administration); 5 days from initial administration (repeat administration)

Remarks:

5., 150 and 500 mg/kg bw/day (nominal) (2)

Remarks:

360, 730, 1450 mg/kg (single dose) or 730 mg/kg (adminstered 4 times in 24 hours) (3)

No. of animals per sex per dose:

2. 6
3. 6 (single dose) 5 (repeat dose) sex not stated

Control animals:

yes, concurrent vehicle

Positive control(s):

2. cyclophosphamide
- Justification for choice of positive control(s): no data
- Route of administration: presumably oral gavage
- Doses / concentrations: 40 mg/kg bw

3.
- Positive control: mitomycin C
- Route of administration: ip injection
- Doses / concentrations: 3.0 mg/kg

Tissues and cell types examined:

2. Bone marrow cells
3. Bone marrrow; erythrocytes examined

Details of tissue and slide preparation:

2. CRITERIA FOR DOSE SELECTION: based on previous study - 500 mg/kg bw estimated to be the "maximum attainable dose"
TREATMENT AND SAMPLING TIMES (in addition to information in specific fields): 24, 48 and 72 hours after dosing

DETAILS OF SLIDE PREPARATION: femurs removed, marrow flushed out with foetal calf serum, cell suspension centrifuged and supernatant discarded, small drop of cell pellet spread on slide, air dried, stained with May-Grunwald, mounted; 1 slide/sample

METHOD OF ANALYSIS: 1000 polychromatic erythrocytes (PCEs) scored for micronuclei; polychromatic:normochromatic (PCE:NCE) ratio scored

OTHER: only 5/sex per dose level evaluated

3. No data

Evaluation criteria:

2. To be considered positive, either a statistically significant dose-related increase in the number of micronucleated PCEs or a reproducible, statistically significant positive response for at least one dose level

3. No data

Statistics:

2. Mann-Whitney test
3. No data

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Remarks:

presumably toxic at >500 mg/kg bw

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

2.

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

3

Additional information on results:

2. RESULTS OF RANGE-FINDING STUDY
- Dose range: no data
- Solubility: no data
- Clinical signs of toxicity in test animals: no data
- Evidence of cytotoxicity in tissue analyzed: no data
- Rationale for exposure: no data
- Harvest times: no data
- High dose with and without activation: no data
- Other: presumably toxic above 500 mg/kg bw since this maximum dose was chosen for the main study on the basis of the results of the range-finding study

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): 0.03-0.09% for vehicle controls, 0.04-0.10% for test material treated, 0.71% for positive control
- Ratio of PCE/NCE (for Micronucleus assay): 1.05-1.27 for vehicle controls, 0.98-1.55 for test material treated, 0.93 for positive control
- Appropriateness of dose levels and route: appropriate (top dose was apparently the maximum tolerated dose, oral route relevant to humans)
- Statistical evaluation: no statistically significant increases in the frequency of micronuclei in mice treated with the test material; statistical significance not presented for positive control

3.MORTALITY: Not reported CLINICAL SIGNS: Not reported NECROPSY FINDINGS: Not reported BODY WEIGHT CHANGES: Not reported FOOD AND WATER CONSUMPTION CHANGES: Not reported EFFECT ON MITOTIC INDEX OR PCE/NCE RATIO: There were no effects on the incidence of reticulocytes following a single dose of stearyl alcohol.
Repeated exposure showed a decrease [controls 61.3%; treated 52.9%] GENOTOXIC EFFECTS: No significant increase increase in numbers (%) of micronucleated erythrocytes. 10000 - 12000 observed. NOAEL (NOEL) (C) / LOAEL (LOEL) (C): A single dose of 1450 mg/kg/day or a total repeated dose of 2920 mg/kg did not increase the incidence of micronuclei. There was no reported assessment of effects on the live animals

Conclusions:

In a reliable study, test chemical did not increase the incidence of micronuclei in mouse bone marrow cells after a single oral gavage dose of up to 500 mg/kg bw.

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:

2. A Mammalian Erythrocyte Micronucleus Test was performed on Male and Female NMRI Mouse to determine the genotoxic effect of test chemical. The chemical was administered orally via gavage at dose concentration of 50, 150 and 500 mg/kg bw/day. The examinations were done on Bone marrow cells at 24, 48 and 72 hrs. No increase in the incidence of micronuclei in mouse bone marrow cells after a single oral gavage dose of up to 500 mg/kg bw was observed. Hence, the test chemical was found not to be Genotoxic in nature.

3.

A Mammalian Erythrocyte Micronucleus Test was performed on Male and Female DDY Mouse to determine the genotoxic effect of test chemical. The chemical was dissolved in Olive oil and administered orally via gavage at dose concentration of 360, 730, 1450 mg/kg (single dose) or 730 mg/kg (adminstered 4 times in 24 hours). Positive control used was mitomycin C via ip injection at Doses / concentrations of 3.0 mg/kg. The examinations were done on Bone marrow cells. The test chemical did not increase the incidence of micronucleated cells in mouse bone marrow erythrocytes following a single oral dose level up to and including 1450 mg/kg or a total of 2920 mg/kg adminstered as 4 doses in a 24 hour period. It is concluded that the test substance is negative for induction of micronuclei under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Mode of Action Analysis / Human Relevance Framework

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

2. A Mammalian Erythrocyte Micronucleus Test was performed on Male and Female NMRI Mouse to determine the genotoxic effect of test chemical. The chemical was administered orally via gavage at dose concentration of 50, 150 and 500 mg/kg bw/day. The examinations were done on Bone marrow cells at 24, 48 and 72 hrs. No increase in the incidence of micronuclei in mouse bone marrow cells after a single oral gavage dose of up to 500 mg/kg bw was observed. Hence, the test chemical was found not to be Genotoxic in nature.

3.

A Mammalian Erythrocyte Micronucleus Test was performed on Male and Female DDY Mouse to determine the genotoxic effect of test chemical. The chemical was dissolved in Olive oil and administered orally via gavage at dose concentration of 360, 730, 1450 mg/kg (single dose) or 730 mg/kg (adminstered 4 times in 24 hours). Positive control used was mitomycin C via ip injection at Doses / concentrations of 3.0 mg/kg. The examinations were done on Bone marrow cells. The test chemical did not increase the incidence of micronucleated cells in mouse bone marrow erythrocytes following a single oral dose level up to and including 1450 mg/kg or a total of 2920 mg/kg adminstered as 4 doses in a 24 hour period. It is concluded that the test substance is negative for induction of micronuclei under the conditions of the test.

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

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

1.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.

2. 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.

3. 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

5. 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

6. In an in vitro chromosome aberration study, Chinese hamster lung fibroblasts (V79) were incubated with 0.6, 10.0 and 20.0 µg/ml of test material dissolved in ethanol for 4 hours, with and without metabolic activation. The test substance did not increase the incidence of chromosome aberrations in Chinese hamster V79 cells in the presence or absence of metabolic activation when tested up to limit concentration. There was no evidence of cytotoxicity at this dose level. The study was comparable to guideline without detailed documentation (publication). It is considered that read across to the registered substance is valid and scientifically justifiable.

In Vitro Mammalian Cell Gene Mutation Test

8.In Vitro Mammalian Cell Gene Mutation Test was performed Chinese hamster lung fibroblasts (V79) to determine to genotoxicity of the test chemical. The test was performed on HGPRT target gene, with and without metabollic activation at concentartions of 2.0, 7.5, 15.0, and 20.0 ug/ml. 7,12-dimethylbenzanthracene and Ethylmethanosulphonate were used as positive control. Thus, the test chemical did not increase the gene mutation rate in Chinese hamster V79 cells in the presence or absence of metabolic activation at concentrations up to 20 ug/ml. It is concluded that the test substance is negative for mutagenicity in mammalian cells under the conditions of this test.

9.The test chemical was tested for mutagenicity to mammalian cells in a valid study using a method similar to OECD TG 476 up to toxic concentrations. The test was perfomed on mouse lymphoma L5178Y cells, with and without metabollic activation at 10 concentrations at log intervals between 0.013 and 1.0 µl/ml. No increase in the number of revertants was observed. It was concluded that the test chemical is negative for mutagenicity to mammalian cells under the conditions of the test.

 

 

 

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 and In-Vivo. Hence the test chemical is not likely to classify as a gene mutant in vitro and In-Vivo.