Registration Dossier
Registration Dossier
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EC number: 279-420-3 | CAS number: 80206-82-2
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
There are conclusive but not suffcient data for the classification of substance Alcohols, C12-14 with regard to mutagenicity/genetic toxicity. It is concluded that the substance Alcohols, C12-14 does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- other: published data
- 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
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- (no TA102 or E. coli WP2 uvrA; 2-AA only positive control with S9)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 from Aroclor 1254-induced male rat livers
- Test concentrations with justification for top dose:
- 50, 150, 500, 1500 and 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: not stated - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- without S9, 3 µg/plate for TA100, 5 µg/plate for TA1535
- Positive control substance:
- other: 1103
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- without S9, 80 µg/plate for TA1537
- Positive control substance:
- other: 28
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- without S9, 5 µg/plate for TA1538
- Positive control substance:
- other: 1342 4-nitro-o-phenylenediamine
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- without S9, 0.2 µg/plate for TA98
- Positive control substance:
- other: 25
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- with S9, all strains, 0.5, 1 or 2 µg/plate
- Positive control substance:
- other: 1342 2-aminoanthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium; in agar (plate incorporation)
DURATION
- Preincubation period: not applicable
- Exposure duration: 48 hours
NUMBER OF REPLICATES: duplicate test, each performed with triplicate plates
DETERMINATION OF CYTOTOXICITY
- Method: growth of bacterial lawn - Evaluation criteria:
- For a substance to be considered positive, it should have induced a concentration-related and statistically significant increase in mutation rate in one or more starins of bacteria in the presence and/or absence of S9 in both experiments at sub-toxic concentrations. To be considered negative the number of induced revertants compared to spontaneous revertants should be less than two-fold at each concentration employed.
- Statistics:
- Methods recommended by the United Kingdom Environmental Mutagen Society and normally Dunnett's method of linear regression
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- but tested up to limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- but tested up to limit 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: at 5000 mg/plate, but this did not interfere with scoring of revertant colonies
- Other confounding effects: no data
RANGE-FINDING/SCREENING STUDIES: yes, non-toxic up to 5000 ug/plate in TA100
COMPARISON WITH HISTORICAL CONTROL DATA: vehicle control results said to be "within the normal range"
ADDITIONAL INFORMATION ON CYTOTOXICITY: no further data - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results :negative
In a reliable study, performed according to OECD guideline 471, the C16 alcohol Kahlcol 6098 did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at concentrations up to 5000 µg/plate. This concentration was not cytotoxic. - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- other: published data
- 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
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- no TA102 or E. coli WP2 uvrA; 2-aminoanthracene only positive control with metabolic activation)
- Principles of method if other than guideline:
- Well-conducted study according to a protocol very similar to OECD guideline 471
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- liver microsomal fractions from male rats prepared by "established methods"
- Test concentrations with justification for top dose:
- 10, 100, 333, 667, and 1000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: solubility - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA100, TA1535 without metabolic activation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-O-phenylenediamine
- Remarks:
- TA98, TA1537, TA1538 without metabolic activation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: aminoanthracene
- Remarks:
- all strains with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Preincubation period: none
- Exposure duration: no data
NUMBER OF REPLICATES:
- two independent experiments, both with and without metabolic activation
- each concentration (including controls) tested in triplicate
DETERMINATION OF CYTOTOXICITY
- Method: no data - Evaluation criteria:
- To be considered positive in TA100, >=2x increase in revertants over spontaneous rate; in TA98, TA1535, TA1537 and TA1538, >=3x increase; alternatively a concentration-dependent increase irrespective of 2- or 3-fold increase
- Statistics:
- none
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: not determined, but number of revertants reduced in TA 98 at 1000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: not determined, but number of revertants not reduced at 1000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- 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: insoluble
- Precipitation: no data
- Other confounding effects: no data
RANGE-FINDING/SCREENING STUDIES: yes, no data presented
COMPARISON WITH HISTORICAL CONTROL DATA: no
ADDITIONAL INFORMATION ON CYTOTOXICITY: none - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results :negative
In a valid and reliable study, behenyl alcohol (C22) did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at concentrations up to and including 1000 µg/plate. It is concluded that the test substance is negative for mutagenicity in bacteria under the conditions of the test.
Docosan-1-ol ( behenyl alcohol (C22) ) is closely related to the registered substance, Alcohols, C16-18, and it is considered that read-across is valid. - Executive summary:
In a valid and reliable study, behenyl alcohol (C22) did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at concentrations up to and including 1000 µg/plate. It is concluded that the test substance is negative for mutagenicity in bacteria under the conditions of the test. Docosan-1-ol ( behenyl alcohol (C22) ) is closely related to the registered substance, Alcohols, C16-18 and it is considered that read-across is valid.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- other: published data
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Principles of method if other than guideline:
- Well-conducted study according to protocol very similar to OECD guideline 473
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- not applicable
- 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:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- liver microsomal fraction from male rats prepared according to Ames et al., 1977
- Test concentrations with justification for top dose:
- 0.6, 10.0 and 20.0 ug/ml
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: solubility - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- without metabolic activation
- Positive control substance:
- ethylmethanesulphonate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- with metabolic activation
- Positive control substance:
- cyclohexylamine
- Details on test system and experimental conditions:
- 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 @ 20 ug/ml, 18 hours @ 0.6, 10 and 20 ug/ml
SPINDLE INHIBITOR (cytogenetic assays): colcemia, 0.2 ug/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
OTHER EXAMINATIONS:
- Determination of polyploidy: no data
- Determination of endoreplication: no data - Evaluation criteria:
- To be considered positive, either a statistically significant, concentration-related increase in the number of structural chromosome aberrations, or a statistically signficant positive response at one of the concentrations
- Statistics:
- Chi-squared test performed for cells with aberration (excluding gaps)
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: presumably >20 ug/ml
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- 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: 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 ug/ml, mitotic index not reduced, plating efficiency not reduced - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results :negative
In a reliable study, according to a protocol that is similar to OECD 473, behenyl alcohol (C22) did not increase the incidence of chromosome aberrations in Chinese hamster V79 cells in the presence or absence of metabolising fraction at concentrations up to 20 ug/ml. There was no evidence of cytotoxicity at this dose level.
Docosan-1-ol ( behenyl alcohol (C22) ) is closely related to the registered substance, Alcohols, C16-18 and it is considered that read-across is valid. - Executive summary:
In a reliable study, according to a protocol that is similar to OECD 473, behenyl alcohol (C22) did not increase the incidence of chromosome aberrations in Chinese hamster V79 cells in the presence or absence of metabolising fraction at concentrations up to 20 ug/ml. There was no evidence of cytotoxicity at this dose level. Docosan-1-ol ( behenyl alcohol (C22) ) is closely related to the registered substance, Alcohols, C16-18 and it is considered that read-across is valid.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- other: published data
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- (no TA102 or E. coli WP2 uvrA; 2-AA only positive control with S9)
- Principles of method if other than guideline:
- An in-house protocol based on OECD Guide-line 471
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 from the livers of Aroclor 1254-induced rats
- Test concentrations with justification for top dose:
- 4, 20, 100, 500, 2500 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water/Tween 80
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- without S9
- Positive control substance:
- other: 1342 sodium azide 1 µg/plate; 4-nitro-o-phenylene diamine 40 µg/plate.
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- with S9
- Positive control substance:
- other: 1342 2-amino anthracene 5 µg/plate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
NUMBER OF REPLICATES: no repeat assay, duplicate plates - Evaluation criteria:
- Not specifically reported assume as OECD 471.
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- with S9 only, at 500 and/or 2500 µg/plate.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- ADDITIONAL INFORMATION ON CYTOTOXICITY:
- With metabolic activation: Some evidence of a decrease in revertants at higher dose levels for TA 100 and TA 1535, effect on background lawn not
reported.
- Without metabolic activation: No clear cytotoxic effect. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results :negative
In a reliable study, the C16 alcohol Lanette 16 (Lorol 16) did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at concentrations up to 2500 µg/plate. There was some evidence of cytotoxicity in some strains at higher concentrations (500 and/or 2500 µg/plate) in the absence of metabolising fraction only. - Executive summary:
The C16 alcohol Lanette 16 (Lorol 16) did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at dose levels up to 2500 ug/plate. There was some evidence of cytotoxicity in some strains at higher dose levels (500 and/or 2500 ug/plate) in the absence of metabolising fraction.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- other: published data
- 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
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- (no TA102 or E. coli WP2 uvrA; 2-AA only as positive control with S9)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- yes
- Remarks:
- (no TA102 or E. coli WP2 uvrA; 2-AA only as positive control with S9)
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium TA 1538
- 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 - 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
- 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
- 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
- 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:
- TA1538 without S9
- 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.
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and 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
- Species / strain:
- S. typhimurium TA 1538
- 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'.
- 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. - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- other: published data
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- (no TA102 or E. coli WP2 uvrA; 2-AA only positive control with S9)
- Principles of method if other than guideline:
- An in-house protocol based on OECD Guide-line 471
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- Enzymes obtained from the livers of Aroclor 1254 pretreated rats (S9)
- Test concentrations with justification for top dose:
- 4, 20, 100, 500, 2500 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water/Tween 80
- Justification for choice of solvent/vehicle: not stated - Untreated negative controls:
- no
- Remarks:
- data controls either untreated or solvent-treated
- Negative solvent / vehicle controls:
- no
- Remarks:
- data controls either untreated or solvent-treated
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 1 µg/plate without S9
- Positive control substance:
- other: 2374
- Untreated negative controls:
- no
- Remarks:
- data controls either untreated or solvent-treated
- Negative solvent / vehicle controls:
- no
- Remarks:
- data controls either untreated or solvent-treated
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 40 µg/plate without S9
- Positive control substance:
- other: 1342 4-nitro-o-phenylene diamine
- Untreated negative controls:
- no
- Remarks:
- data controls either untreated or solvent-treated
- Negative solvent / vehicle controls:
- no
- Remarks:
- data controls either untreated or solvent-treated
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 5 µg/plate with S9
- Positive control substance:
- other: 1342 2-aminoanthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
NUMBER OF REPLICATIONS: Duplicates. One test only - Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 2500 µg/plate in TA98 and TA100
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- but cytotoxic in TA98 and TA100 at 2500 µg/plate
- 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: none reported
- Other confounding effects: no data
ADDITIONAL INFORMATION ON CYTOTOXICITY: With and without metabolic activation: Slight cytotoxicity observed at 2500 µg/plate as evidenced by reduction in numbers of revertants in strains TA98 and 100. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results :negative
In a reliable study conducted using a protocol similar to OECD guideline 471, the C18 alcohol Lanette 18 did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at concentrations up to 2500 µg/plate. Slight cytotoxicity was evident at 2500 µg/plate. - Executive summary:
The C18 alcohol Lanette 18 did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at dose levels up to 2500 ug/plate. Slight cytotoxicity was evident at 2500 ug/plate.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- other: published data
- 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
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- (no TA102 or E. coli WP2 uvrA, 2-AA only as positive control with S9)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium TA 1538
- Additional strain / cell type characteristics:
- other: histidine deficient
- Metabolic activation:
- with and without
- Metabolic activation system:
- Arochlor 1254-induced rat liver S9
- Test concentrations with justification for top dose:
- 0.5 (only TA1538 and 1537), 1.5, 5, 15, 50, 150 and 500 (only TA98, 100, 1535) µg/plate (based on a preliminary screening test)
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- N-ethyl-N-nitro-N-nitrosoguanidine
- Remarks:
- 3 ug/plate (TA100), 5 µg/plate (TA1535), without S9
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- 80 ug/plate (TA1537), without S9
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylene daimine
- Remarks:
- 5 ug/plate (TA1538), without S9
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- Remarks:
- 0.2 µg/plate (TA98), without S9
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- 1 ug/plate (TA100), 2 ug/plate (TA1535 and TA 1537), 0.5 µg/plate (TA1538 and TA98), with S9
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar
DURATION
- Exposure duration: 48 hours at 37 deg C
NUMBER OF REPLICATES: triplicates - Evaluation criteria:
- Considered positive if there is concentration-related and statistically significant increase in reverse mutation rate in one or more bacterial strains at sub toxic dose levels. To be considered negative, the number of induced revertants should be <2-fold the number of spontaneous revertants and concentrations should extend to the limits of solubility or toxicity up to a maximum of 5000 µg/plate.
- Statistics:
- Dunnetts linear regression method.
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- 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: An oily precipitate was observed at 1500 ug/plate and above in the preliminary toxicity assay, this did not interfere with the scoring of revertant colonies and was not reported when this concentration was tested in the repeat study.
- Other confounding effects: no data
COMPARISON WITH HISTORICAL CONTROL DATA: No
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- With and without metabolic activation: The test material exhibited a visible reduction in background lawn at and above 150 ug/plate in all the strains
tested. Strains TA1538, 1537 and 1535 also showed a reduction in background lawn at 50 ug/plate. This indicates that the material was tested to a
toxic level. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results :negative
In a reliable study, the C12 alcohol Kalcohl 2098 did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation. The material was tested to cytotoxic concentrations. The study was performed in compliance with GLP. It is concluded that dodecan-1-ol is negative for the induction of mutations in bacteria under the conditions of the test.
Dodecan-1-ol (C12) is supporting substance for Alcohols,C12-C14 and the main component. - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- other: published data
- 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
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- (no TA102 or E coli WP2 uvrA, 2-AA only positive control with S9)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- Arochlor 1254-induced rat liver S9
- Test concentrations with justification for top dose:
- Test 1: 15(-S9 only), 50, 150, 500, 1500, and 5000 µg/plate; Test 2: 50, 150, 500, 1500, and 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- N-ethyl-N-nitro-N-nitrosoguanidine
- Remarks:
- TA100 (3 ug/plate) and TA1535 (5 ug/plate) without S9
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA1537 (8 ug/plate) without S9
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylene daimine
- Remarks:
- TA1538 (5 ug/plate) without S9
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- Remarks:
- TA98 (0.2 ug/plate) without S9
- 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 (0.5, 1 or 2 ug/plate) with S9
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium; in agar (plate incorporation)
DURATION
- Exposure duration: approximately 48 hours
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Thinning or absence of background lawn of non-revertant cells
OTHER: The mutation experiment was repeated on a separate day using fresh cultures and fresh test material formulations. - Evaluation criteria:
- After incubation, numbers of revertant colonies were counted. For a substance to be considered positive in this test system, it should have induced a dose-related and statistically significant increase in mutation rate in one or more strains of bacteria in the presence and/or absence of S9 in both experiments at sub-toxic dose levels. For a negative result the numbers of induced revertants should be less than two fold compared to controls.
- Statistics:
- Dunnetts test was used and showed no statistically significant differences between test and control plates.
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit 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: precipitation of test substance was observed at dose levels of 1500 ug/plate and above. Plates were counted manually at 1500 ug/plate and above.
- Other confounding effects: no data
RANGE-FINDING/SCREENING STUDIES: Strain TA 100 was exposed to the test substance at concentrations of 0, 50, 150, 500, 1500 and 5000 ug/plate in a preliminary toxicity study.
COMPARISON WITH HISTORICAL CONTROL DATA: no data
CYTOTOXIC CONCENTRATION: Slight cytotoxicity was indicated in a preliminary toxicity screen with TA100 at dose levels >= 500 ug/plate without
metabolic activation. In the actual mutation study there was no evidence of cytotoxicity up to 5000 ug/plate with or without S9. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results :negative
In a reliable study, conducted in accordance with OECD guideline 471 and under GLP, the C14 alcohol Kalcol 4098 did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium 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 not mutagenic to bacteria under the conditions of the test.
Tetradecanol (C14) ) is supporting substance for Alcohols,C12-C14 and the one of the component in Alcohols,C12-C14 . - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- QSAR prediction: QSAR method for chemicals properties assessment. Relevant for in vitro (Ames test) mutagenicity endpoints.
- Qualifier:
- according to guideline
- Guideline:
- other: ToxTree: Benigni/Bossa rules for carcinogenicity and mutagenicity
- Principles of method if other than guideline:
- This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs). The SAs for mutagenicity are molecular functional groups or substructures known to be linked to the mutagenic activity of chemicals. As one or more SAs embedded in a molecular structure are recognised, the system flags the potential mutagenicity of the chemical. The present list of SAs is a subset of the original Toxtree list, obtained by eliminating the SAs for nongenotoxic carcinogenicity.
- GLP compliance:
- no
- Remarks:
- not applicable. QSAR model in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs) relevant for in vitro (Ames test) mutagenicity endpoints.
- Type of assay:
- other: QSAR model
- Target gene:
- This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs).
- Species / strain / cell type:
- S. typhimurium TA 100
- Test concentrations with justification for top dose:
- QSAR model in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs) relevant for in vitro (Ames test) mutagenicity endpoints.
- Untreated negative controls:
- other: QSAR model
- Negative solvent / vehicle controls:
- other: QSAR model
- True negative controls:
- other: QSAR model
- Positive controls:
- other: QSAR model
- Details on test system and experimental conditions:
- This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree.
- Evaluation criteria:
- This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs). The SAs for mutagenicity are molecular functional groups or substructures known to be linked to the mutagenic activity of chemicals. As one or more SAs embedded in a molecular structure are recognised, the system flags the potential mutagenicity of the chemical. The present list of SAs is a subset of the original Toxtree list, obtained by eliminating the SAs for nongenotoxic carcinogenicity.
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- other: QSAR model
- Untreated negative controls validity:
- other: QSAR model
- Positive controls validity:
- valid
- Additional information on results:
- Benigni/Bossa rules for carcinogenicity and mutagenicity:
- Structural Alert for genotoxic carcinogenicity NO
- Potential S. typhiunium TA100 mutagen based on QSAR NO
- Negative for genotoxic carcinogenicity YES - Conclusions:
- Interpretation of results :negative
No alert found.The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS.
The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS and therefore Alcohols, C12-14 does not cause in vitro mutagenicity (Ames test) - Executive summary:
The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS and therefore Alcohols, C12-14 does not cause in vitro mutagenicity (Ames test).
Referenceopen allclose all
STATISTICAL RESULTS: Dunnetts test was used and showed no statistically significant differences between test and control plates.
Table 1 Experiment 1 Revertants per plate (mean of 3 plates)
Concentration µg/plate |
TA 100 |
TA 100 |
TA 1535 |
TA 1535 |
TA 1538 |
TA 1538 |
TA 98 |
TA 98 |
TA 1537 |
TA 1537 |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
|
0 |
107 |
99 |
33 |
19 |
15 |
21 |
19 |
34 |
8 |
12 |
50 |
91 |
85 |
34 |
12 |
14 |
25 |
24 |
34 |
11 |
10 |
150 |
92 |
89 |
27 |
15 |
17 |
28 |
25 |
35 |
11 |
11 |
500 |
88 |
86 |
23 |
15 |
20 |
29 |
25 |
43 |
10 |
13 |
1500 |
95 |
98 |
30 |
16 |
16 |
19 |
25 |
40 |
9 |
13 |
5000 |
95 |
95 |
29 |
18 |
16 |
26 |
23 |
39 |
6 |
12 |
Positive control |
419 |
672 |
137 |
171 |
544 |
235 |
148 |
236 |
277 |
209 |
Table 2 Experiment 2 Revertants per plate (mean of 3 plates)
Concentration µg/plate |
TA 100 |
TA 100 |
TA 1535 |
TA 1535 |
TA 1538 |
TA 1538 |
TA 98 |
TA 98 |
TA 1537 |
TA 1537 |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
|
0 |
90 |
113 |
20 |
11 |
14 |
11 |
17 |
27 |
7 |
12 |
50 |
82 |
111 |
21 |
12 |
19 |
14 |
18 |
26 |
8 |
9 |
150 |
87 |
102 |
25 |
12 |
10 |
13 |
17 |
32 |
9 |
8 |
500 |
81 |
107 |
14 |
15 |
13 |
13 |
17 |
27 |
8 |
7 |
1500 |
89 |
104 |
19 |
14 |
8 |
9 |
17 |
24 |
9 |
10 |
5000 |
74 |
90 |
15 |
11 |
8 |
11 |
17 |
28 |
9 |
10 |
Positive control |
530 |
600 |
171 |
195 |
589 |
196 |
152 |
305 |
496 |
206 |
Table 1 Revertants per plate (mean of 3 plates)
Concentration µg/plate |
TA 98 |
TA100 |
TA1535 |
TA1537 |
TA1538 |
|||||
- S9 |
+ S9 |
- S9 |
+ S9 |
- S9 |
+ S9 |
- S9 |
+ S9 |
- S9 |
+ S9 |
|
Negative control |
15.3 |
17.0 |
82.3 |
833.7 |
5.7 |
8.0 |
5.0 |
4.0 |
14.3 |
16.7 |
0* |
15.3 |
15.7 |
83.3 |
77.3 |
8.3 |
8.3 |
7.0 |
5.0 |
14.7 |
15.0 |
10.0 |
14.0 |
19.0 |
70.7 |
80.3 |
10.7 |
9.7 |
3.0 |
5.0 |
14.3 |
14.0 |
100.0 |
9.3 |
15.3 |
85.0 |
82.0 |
7.7 |
9.0 |
4.0 |
4.3 |
14.7 |
15.7 |
333.3 |
11.7 |
15.7 |
80.0 |
79.7 |
8.0 |
12.3 |
4.7 |
5.0 |
15.0 |
15.3 |
666.6 |
12.0 |
12.7 |
74.0 |
82.3 |
8.3 |
6.3 |
4.3 |
5.3 |
14.0 |
15.3 |
1000 |
6.7 |
8.0 |
76.0 |
86.3 |
4.7 |
3.3 |
3.7 |
5.0 |
13.7 |
14.7 |
Positive control |
1573 |
2337.7 |
1158 |
2414 |
601.7 |
345 |
109.7 |
85.3 |
1980 |
495.7 |
* Solvent control with
Table 1 Cytogenicity: 7 hour fixation. Aberrations in 200 cells
Activation |
Concentration µg/ml |
Percent aberrant cells |
||
incl gaps |
excl gaps |
exchanges |
||
Without |
0* |
4.0 |
1.5 |
0 |
20 |
2.5 |
0.5 |
0 |
|
With |
0* |
4.0 |
1.5 |
0 |
20 |
7.0 |
2.5 |
0 |
|
* Solvent control with ethanol
** Only 100 cells counted for positive controls
Table 2 Cytogenicity: 18 hour fixation. Aberrations in 200 cells
Activation |
Concentration µg/ml |
Percent aberrant cells |
||
incl gaps |
excl gaps |
exchanges |
||
Without |
Negative control |
5.5 |
1.5 |
0 |
0* |
4.0 |
1.5 |
0.5 |
|
0.6 |
4.5 |
2.0 |
0 |
|
10 |
4.0 |
1.0 |
0.5 |
|
20 |
3.0 |
0.5 |
0 |
|
Positive control** |
12.0 |
9.0 |
4.0 |
|
With |
Negative control |
2.5 |
1.5 |
0 |
0* |
2.5 |
1.5 |
0.5 |
|
0.6 |
5.5 |
3.0 |
0.5 |
|
10 |
4.0 |
2.5 |
0 |
|
20 |
4.0 |
2.5 |
0.5 |
|
Positive control** |
16.0 |
13.0 |
5.5 |
|
* Solvent control with ethanol
** Only 100 cells counted for positive controls
Table 3 Cytogenicity: 18 hour fixation. Aberrations in 200 cells
Activation |
Concentration µg/ml |
Percent aberrant cells |
||
incl gaps |
excl gaps |
exchanges |
||
Without |
0* |
6.0 |
2.5 |
0.5 |
20 |
3.5 |
2.0 |
0 |
|
With |
0* |
1.0 |
0.5 |
0 |
20 |
4.0 |
2.5 |
0.5 |
|
* Solvent control with ethanol
** Only 100 cells counted for positive controls
Table 1 Experiment 1 Plate incorporation Revertants per plate (mean of three plates)
Concentration µg/plate |
TA 100 |
TA 1535 |
TA 1538 |
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 1538 |
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
GENOTOXIC EFFECTS:
- With and without metabolic activation: There was no increase in reverse mutation rate in any of the test strains at any dose level, positive and
negative controls gave appropriate responses.
STATISTICAL RESULTS: No statistically significant increase in reverse mutation rate at any dose level tested with or without metabolic activation.
Table 1 Experiment 1 Revertants per plate (mean of 3 plates)
Concentrationµg/plate |
TA 100 |
TA 1535 |
TA 1538 |
TA 98 |
TA 1537 |
|||||
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
|
0 |
113 |
111 |
23 |
18 |
13 |
26 |
27 |
31 |
7 |
9 |
0.5 |
N/T |
N/T |
N/T |
N/T |
14 |
N/T |
N/T |
N/T |
7 |
N/T |
1.5 |
113 |
111 |
25 |
15 |
15 |
25 |
25 |
30 |
7 |
10 |
5 |
115 |
105 |
21 |
12 |
15 |
24 |
23 |
30 |
7 |
9 |
15 |
111 |
107 |
23 |
12 |
16 |
27 |
27 |
29 |
8 |
10 |
50 |
88 |
92 |
26 |
15 |
9 |
28 |
25 |
25 |
6 |
9 |
150 |
48 |
72 |
24 |
11 |
0 |
11 |
14 |
24 |
0 |
5 |
500 |
0 |
27 |
0 |
7 |
N/T |
0 |
7 |
18 |
N/T |
0 |
Positive control |
529 |
1001 |
136 |
232 |
685 |
513 |
185 |
842 |
879 |
309 |
N/T Not tested
Table 2 Experiment 2 Revertants per plate (mean of 3 plates)
Concentration µg/plate |
TA 100 |
TA 1535 |
TA 15381 |
TA 98 |
TA 1537 |
|||||
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
-MA |
+MA |
|
0 |
86 |
99 |
15 |
13 |
14 |
22 |
21 |
36 |
9 |
11 |
0.5 |
96 |
102 |
13 |
N/T |
11 |
2.5 |
20 |
N/T |
6 |
N/T |
1.5 |
92 |
100 |
13 |
16 |
12 |
22 |
19 |
36 |
8 |
10 |
5 |
93 |
100 |
13 |
15 |
12 |
20 |
20 |
35 |
9 |
9 |
15 |
93 |
101 |
14 |
11 |
15 |
25 |
22 |
30 |
6 |
12 |
50 |
68 |
99 |
12 |
11 |
11 |
21 |
18 |
37 |
7 |
12 |
150 |
25* |
70 |
6* |
12 |
0* |
19 |
9* |
28 |
0* |
10 |
500 |
N/T |
N/T |
N/T |
8 |
N/T |
N/T |
N/T |
13 |
N/T |
1 |
1500 |
N/T |
N/T |
N/T |
2* |
N/T |
N/T |
N/T |
0* |
N/T |
0* |
Positive control |
449 |
1008 |
293 |
210 |
708 |
442 |
134 |
602 |
1011 |
337 |
* Very thin or absent background lawn
N/T Not tested
Table 1:Number of revertants per plate (mean of 3 plates) for Test 1
Conc.
|
[TA 100] |
[TA 1535] |
[TA 1538] |
[TA 98] |
[TA 1537] |
||||||||||
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
|
0* |
72 |
116 |
no |
14 |
15 |
no |
14 |
25 |
no |
20 |
29 |
no |
6 |
9 |
no |
15 |
71 |
- |
no |
12 |
- |
no |
11 |
- |
no |
18 |
- |
no |
7 |
- |
no |
50 |
65 |
112 |
no |
12 |
15 |
no |
11 |
27 |
no |
17 |
24 |
no |
6 |
12 |
no |
150 |
64 |
98 |
no |
12 |
12 |
no |
12 |
22 |
no |
18 |
35 |
no |
7 |
12 |
no |
500 |
57 |
89 |
no |
12 |
14 |
no |
11 |
28 |
no |
21 |
27 |
no |
8 |
10 |
no |
1500 |
55 |
72 |
no |
12 |
17 |
no |
11 |
22 |
no |
19 |
27 |
no |
7 |
9 |
no |
5000 |
52 |
74 |
no |
12 |
11 |
no |
12 |
22 |
no |
23 |
30 |
no |
10 |
7 |
no |
Positive control |
597 |
831 |
no |
348 |
195 |
no |
636 |
488 |
no |
217 |
485 |
no |
550 |
282 |
no |
*solvent control with DMSO
Table 2: Number of revertants per plate (mean of 3 plates) for Test 2
Conc.
|
[TA 100] |
[TA 1535] |
[TA 1538] |
[TA 98] |
[TA 1537] |
||||||||||
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
- MA |
+ MA |
Cytotoxic |
|
0* |
86 |
85 |
no |
19 |
12 |
no |
11 |
16 |
no |
15 |
24 |
no |
7 |
9 |
no |
50 |
67 |
83 |
no |
15 |
13 |
no |
10 |
14 |
no |
19 |
28 |
no |
7 |
8 |
no |
150 |
70 |
66 |
no |
11 |
9 |
no |
9 |
13 |
no |
20 |
29 |
no |
5 |
7 |
no |
500 |
66 |
71 |
no |
17 |
10 |
no |
9 |
14 |
no |
15 |
26 |
no |
6 |
11 |
no |
1500 |
66 |
72 |
no |
9 |
11 |
no |
7 |
12 |
no |
13 |
20 |
no |
5 |
8 |
no |
5000 |
66 |
58 |
no |
9 |
10 |
no |
6 |
13 |
no |
12 |
23 |
no |
7 |
9 |
no |
Positive control |
459 |
1005 |
no |
211 |
208 |
no |
524 |
344 |
no |
175 |
345 |
no |
762 |
266 |
no |
*solvent control with DMSO
1.6. Profiling results:
DNA binding by OECD
No alert found
Est rogen Receptor Binding
Non binder, non cyclic structure
OECD HPV Chemical Categories
Long chain alcohols
Protein binding by OECD
No alert found
Protein binding potency
Not possible to classify according to these rules (GSH)
Superfragments
No superfragment
Toxic hazard classification by Cramer (original)
Low (Class I)
US-EPA New Chemical Categories
Neutral Organics
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- other: published data
- 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
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- other: albino mice, CFW 1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Winkelmann
- Age at study initiation: 7-8 weeks
- Weight at study initiation: males 21-27 g, females 21-26 g
- Assigned to test groups randomly: yes, under following basis: allocated to treatment groups according to randomization table generated by computer programme or manually
- Fasting period before study: yes, overnight until 3-4 hours after dosing
- Housing: males, 1/cage, macrolon cages type I; females, <=3/cage, macrolon cages type II; filled with clean softwood bedding
- Diet (e.g. ad libitum): standard animal diet, Altromin No. 1314, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: >=6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25 +- 3 (occasionally 20-25)
- Humidity (%): 40 - 50 (occasionally 45-70)
- Air changes (per hr): no data, except "air-conditioned room"
- Photoperiod (hrs dark / hrs light): 12 / 12
IN-LIFE DATES (main study): From: 25-Feb-1992 To: 28-Feb-1992 - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: arachis oil
- Justification for choice of solvent/vehicle: test material easily soluble at required concentration
- Concentration of test material in vehicle: not stated, but provided a dose level of 5000 mg/kg bw, so 500 mg/ml
- Amount of vehicle (if gavage or dermal): 10 ml/kg bw (main study), 20 ml/kg bw (range finding study)
- Lot/batch no. (if required): no data
- Purity: no data - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: 500 mg/ml in arachis oil (main study)
- Duration of treatment / exposure:
- single administration
- Frequency of treatment:
- single administration
- Post exposure period:
- evaluated at 24, 48, 72 hours after administration
- Remarks:
- Doses / Concentrations:
5000 mg/kg bw
Basis:
nominal conc. - No. of animals per sex per dose:
- 6
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Justification for choice of positive control(s): not stated
- Route of administration: oral
- Dose: 20 mg/kg bw - Tissues and cell types examined:
- bone marrow
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: maximum tolerated dose, based on range-finding study (effects seen at 5000 mg/kg were piloerection only)
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): single administration, animals sacrificed 24, 48 and 72 hours after administration
DETAILS OF SLIDE PREPARATION: bone marrow collected from femurs, using foetal calf serum applied via a syringe, into a siliconised centrifuge tube; after centrifugation at 1000 rpm and removal of all but one drop of supernatant, cells of sediment carefully mixed; drop of cell suspension placed on clean, degreased microscope slide and immediately spread; 3 slides/animal; slides air dried at least overnight; stained with Giemsa; air dried and dipped in xylol for 3 minutes
METHOD OF ANALYSIS: 1 slide/animal chosen and given a random code; microscopic evaluation of slides from 5 males and 5 females per treatment group at 1000x magnification; number of micronucleated cells counted in 1000 polychromatic erythrocytes (PCEs)/animal; ratio of
polychromatic to normochromatic erythrocytes determined by counting and differentiating the first 1000 erythrocytes
OTHER: means and standard deviations calculated - Evaluation criteria:
- Statistically significant (p<0.05) increase in PCE compared to controls at any sampling time in either sex
Acceptability of test: positive controls induced statistically significant increase in frequency of micronucleated PCEs; solvent control incidence of micronuclei should reasonably fall within historical control range for the testing facility. - Statistics:
- Method used: Kastenbaum & Bowman
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- piloerection for 8 hours after administration; no mortality
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 5000 mg/kg bw
- Solubility: used at 250 mg/ml
- Clinical signs of toxicity in test animals: piloerection
- Evidence of cytotoxicity in tissue analyzed: not examined
- Rationale for exposure: based on limit test in rats in which acute oral LD50 was >5000 mg/kg bw
- Harvest times: animals observed for 3 days
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no statistically significant increase in micronucleus frequency in any treatment group
- Ratio of PCE/NCE (for Micronucleus assay): treated groups similar to controls
- Appropriateness of dose levels and route: maximum tolerated dose of 5000 mg/kg bw used; guideline recommends maximum dose of 2000 mg/kg bw; oral route selected "taking into account the possible route of human exposure during manufacture, handling and use"
- Statistical evaluation: no statistically significant increases in micronuclei in treated groups of either sex; positive control produced a statistically significant increase in micronuclei
- Control incidence of micronuclei: not reported but presumably therefore within historical control range - Conclusions:
- Interpretation of results: negative
Dodecan-1-ol has been tested a reliable study, conducted according to OECD guideline 474, no genotoxicity was seen in mice after a single oral dose of 5000 mg/kg bw. . The test substance, dodecan-1-ol is closely related to the registration substance, Alcohols, C12-14 and it is considered that read-across is valid.Dodecan-1-ol (C12) is supporting substance for Alcohols,C12-C14 and the main component. - Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- other: published data
- Adequacy of study:
- key study
- Study period:
- not stated
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- (only 1000 PCEs per animal scored for micronuclei)
- Principles of method if other than guideline:
- Well-conducted study according to protocol very similar to OECD guideline 474
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- NMRI
- 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:
- - 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 - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: few details; test material suspended in vehicle
- Duration of treatment / exposure:
- single administration
- Frequency of treatment:
- single administration
- Post exposure period:
- none
- Remarks:
- Doses / Concentrations:
50, 150, 500 mg/kg bw
Basis:
nominal conc. - No. of animals per sex per dose:
- 6
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Justification for choice of positive control(s): no data
- Route of administration: presumably oral gavage
- Doses / concentrations: 40 mg/kg bw - Tissues and cell types examined:
- bone marrow cells
- Details of tissue and slide preparation:
- 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 - Evaluation criteria:
- 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
- Statistics:
- Mann-Whitney test
- 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
- Additional information on results:
- 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 - Conclusions:
- Interpretation of results: negative
In a reliable study, behenyl alcohol (C22) 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. - Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- other: published data
- 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
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Principles of method if other than guideline:
- Method: other: mouse bone marrow micronucleus test to protocol to the Japanese Labour Ministry
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- other: ddY
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ORGANISMS: Mice
- Age: 6 weeks
- Weight at study initiation: not reported
- No. of animals per dose: Groups of 5 or 6 - Route of administration:
- oral: gavage
- Vehicle:
- Vehicle used: olive oil
- Details on exposure:
- ADMINISTRATION: Gavage
- Vehicle: Olive oil, dosing volume 25 ml/kg
- Duration of test: 1 or 4 doses.
- Frequency of treatment: Once or 4 times in 24 hours.
- Sampling times and number of samples: 24 hours after a single does, 5 days after the first administraton of the repeated doses. 2000 red blood cells scored per smear for micronuclei, 1000 scored for reticulocytes.
- Control groups and treatment: Stearyl alcohol single oral doses of 0.36, 0.73 or 1.45 g/kg/day or 4 doses of 0.73 g/kg/day in a 24 hour period. Positive control mitomycin C 3 mg/kg intraperitoneally. Solvent control olive oil 25 ml/kg - Duration of treatment / exposure:
- 24 hours
- Frequency of treatment:
- single administration and 4 administrations
- Post exposure period:
- 24 hours (single administration); 5 days from initial administration (repeat administration)
- Remarks:
- Doses / Concentrations:
360, 730, 1450 mg/kg (single dose) or 730 mg/kg (adminstered 4 times in 24 hours)
Basis:
nominal conc. - No. of animals per sex per dose:
- 6 (single dose) 5 (repeat dose) sex not stated
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - Positive control: mitomycin C
- Route of administration: ip injection
- Doses / concentrations: 3.0 mg/kg - Tissues and cell types examined:
- Bone marrrow; erythrocytes examined
- Statistics:
- STATISTICAL ANALYSIS: Kastenbaum & Bowman
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- 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:
- Interpretation of results : negative
Stearyl alcohol (Kalcohl 80, 718) 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:
- genetic toxicity in vivo, other
- Remarks:
- Alcohols, C12-14 is Not expected to be genotoxic in vivo.
- Data waiving:
- other justification
- Justification for data waiving:
- other:
Referenceopen allclose all
Lorol 12 did not increase the frequency of micronucleated erythrocytes or the PCE:NCE ratio in mice at any time interval after treatment (24, 48 or 72 hours) at dose levels up to 5000 mg/kg bw when compared to vehicle controls.
Mean values per group in the micronucleus test with 1-Dodecanol (Lorol C12-99)
a) Number of micronucleated cells per 1000 polychromatic erythrocytes (PCE)
b) Ratio of polychromatic to normochromatic erythrocytes (PCE/NCE)
Treatment group; (sampling time) |
Species and sex |
Dose mg/kg |
Micronucleated cells 1000 PCE |
Ratio of PCE/NCE |
||
Mean |
Range |
Mean |
Range |
|||
Negative control (24 hours) arachis oil |
male mice |
10 ml/kg |
3.60 |
0 - 9 |
1.11 |
0.80 - 1.31 |
female mice |
10 ml/kg |
2.00 |
0 - 4 |
1.34 |
1.02 - 1.07 |
|
Positive control (24 hours) cyclophosphamide |
male mice |
20 |
13.40 |
10 - 16 |
1.21 |
0.90 - 1.72 |
female mice |
20 |
10.80 |
7 - 14 |
0.95 |
0.67 - 1.28 |
|
1-Dodecanol (Lorol C12-99)
|
|
|
|
|
|
|
Limit dose (24 hours) |
male mice |
5000 |
2.60 |
0 - 5 |
1.08 |
0.94 - 1.26 |
female mice |
5000 |
2.40 |
2 - 3 |
1.01 |
0.90 - 1.18 |
|
Limit dose (48 hours) |
male mice |
5000 |
3.00 |
1 - 4 |
0.89 |
0.48 - 1.16 |
female mice |
5000 |
2.00 |
0 - 5 |
1.18 |
0.90 - 1.68 |
|
Limit dose (72 hours) |
male mice |
5000 |
2.60 |
2 - 4 |
1.65 |
0.91 - 2.14 |
female mice |
5000 |
1.60 |
0 - 4 |
1.33 |
1.08 - 1.55 |
|
Toxicity unclear, but possibly one male and one female mouse [per group?] died either spontaneously or due to gavage error.
Table 1 Results of micronucleus assay 24 hour sampling time
Treatment |
Suspending agent |
Low dose |
Mid dose |
High dose |
Concentration mg/kg bw |
0 |
40 |
50 |
150 |
Harvest time |
24 |
24 |
24 |
24 |
Micronucleated PCE (%) |
0.03 |
0.71 |
0.07 |
0.08 |
Ratio PCE/NCE |
1.27 |
0.93 |
0.98 |
1.07 |
Table 2 Results of micronucleus assay 48 hour sampling time
Treatment |
Suspending agent |
Test substance |
Test substance |
Test substance |
Concentration mg/kg bw |
0 |
50 |
150 |
500 |
Harvest time |
48 |
48 |
48 |
48 |
Micronucleated PCE (%) |
0.09 |
0.1 |
0.04 |
0.05 |
Ratio PCE/NCE |
1.05 |
1.06 |
1.01 |
1.23 |
Table 3 Results of micronucleus assay 72 hour sampling time
Treatment |
Suspending agent |
Low dose |
Mid dose |
High dose |
Concentration mg/kg bw |
0 |
50 |
150 |
500 |
Harvest time |
72 |
72 |
72 |
72 |
Micronucleated PCE (%) |
0.09 |
0.09 |
0.05 |
0.07 |
Ratio PCE/NCE |
1.41 |
1.33 |
1.55 |
1.46 |
Results of micronucleus assay
Treatment |
Vehicle 25 ml/kg |
Positive control 3.0 mg/kg |
Low dose |
Mid dose |
High dose |
Mid dose |
No of injections |
1 |
1 |
1 |
1 |
1 |
4 |
Micronucleated erythrocytes % |
0.13 ±0.10 |
1.96 ± 0.64 |
0.03 ± 0.03 |
0.06 ± 0/04 |
0.09 ± 0.04 |
0.08 ± 0.08 |
Frequency of erythrocytes |
81.3 ± 8.0 |
46.2 ± 9.4 |
61.5 ± 6.2 |
60.3 ± 9.2 |
67.4 ± 7.5 |
52.9 ± 7.6 |
Additional information
Additional information from genetic toxicity in vitro:
Mutagenicity
Alcohols, C12-14 is from the category of Long Chain aliphatic Alcohols within a carbon chain length range of C6-C22.
The results of the available in vitro and in vivo mutagenicity data for Long Chain aliphatic Alcohols within a carbon chain length range of C12-C22 are summarised in Table 1
Table 1 .Summary of the mutagenicity data for Long Chain aliphatic Alcohols within a carbon chain length range of C12-C22
chain length range alcohol |
C12 |
C16 |
C18 |
C22 |
CAS No. |
112-53-8 |
36653-82-4 |
112-92-5 |
661-19-8 |
In VitroAssay |
|
|
|
|
Gene mutation |
|
Negative |
Negative |
Negative |
Chromosomal Aberration |
|
|
|
Negative |
In vivoAssay |
|
|
|
|
Mouse Micronucleus |
Negative |
|
Negative |
Negative |
In vitro Studies
Bacterial tests
In a reliable study (Thompson, P.W. , 1996), performed according to OECD guideline 471, the C16 alcohol Kahlcol 6098 did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at concentrations up to 5000 µg/plate. This concentration was not cytotoxic. Hexadecan-1-ol (C16) is closely related to the registered substance, Alcohols, C16-18 and it is considered that read-across is valid.
In a valid and reliable study (Iglesias G, J J Hlywka, J E Berg, M H Khalil, L E Pope and D Tamarkin,2002), behenyl alcohol (C22) did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at concentrations up to and including 1000 µg/plate. It is concluded that the test substance is negative for mutagenicity in bacteria under the conditions of the test. Docosan-1-ol ( behenyl alcohol (C22) ) is closely related to the registered substance, Alcohols, C16-18 and it is considered that read-across is valid.
In a reliable study (Henkel KGaA.,1981), the C16 alcohol Lanette 16 (Lorol 16) did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at concentrations up to 2500 µg/plate. There was some evidence of cytotoxicity in some strains at higher concentrations (500 and/or 2500 µg/plate) in the absence of metabolising fraction only. Hexadecan-1-ol (C16) is closely related to the registered substance, Alcohols, C16-18 and it is considered that read-across is valid.
In a reliable study (Thompson, P.W. ,1996) 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. Octadecan-1-ol (C18) is closely related to the registered substance, Alcohols, C16-18 and it is considered that read-across is valid.
In a reliable study (Henkel KGaA., 1981), conducted using a protocol similar to OECD guideline 471, the C18 alcohol Lanette 18 did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at concentrations up to 2500 µg/plate. Slight cytotoxicity was evident at 2500 µg/plate. Octadecan-1-ol (C18) is closely related to the registered substance, Alcohols, C16-18 and it is considered that read-across is valid.
Non-bacterial test
In a reliable study (Iglesias G, J J Hlywka, J E Berg, M H Khalil, L E Pope and D Tamarkin,2002), according to a protocol that is similar to OECD 473, behenyl alcohol (C22) did not increase the incidence of chromosome aberrations in Chinese hamster V79 cells in the presence or absence of metabolising fraction at concentrations up to 20 ug/ml. There was no evidence of cytotoxicity at this dose level. Docosan-1-ol ( behenyl alcohol (C22) ) is closely related to the registered substance, Alcohols, C16-18 and it is considered that read-across is valid.
In vivo Studies
Dodecan-1-ol (C12) has been tested a reliable study (Henkel KGaA., 1992), conducted according to OECD guideline 474, no genotoxicity was seen in mice after a single oral dose of 5000 mg/kg bw. . The test substance, dodecan-1-ol is closely related to the registration substance, Alcohols, C16-18 and it is considered that read-across is valid.
In a reliable study (Iglesias G, J J Hlywka, J E Berg, M H Khalil, L E Pope and D Tamarkin,2002), behenyl alcohol (C22) 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. Docosan-1-ol ( behenyl alcohol (C22) ) is closely related to the registered substance, Alcohols, C16-18 and it is considered that read-across is valid.
Stearyl alcohol (Hachiya N, Takeya A, Takizawa Y,1982), 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. Octadecan-1-ol (C18) is closely related to the registered substance, Alcohols, C16-18 and it is considered that read-across is valid.
Conclusion:Alcohols, C12-14 is from the category of Long Chain aliphatic Alcohols within a carbon chain length range of C6-C22 and do not have a genotoxic potential.
Justification for classification or non-classification
Based on the hazard assessment of Alcohols, C12-14 in section 2.1 and 2.2. in IUCLID 6, available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health”, according to the EU’s list of dangerous substances (OJEC No L200/130.7.99)and according to the criteria described in Directive 67/548 and in the CLP Regulation:
|
Mutagenicity-Genetic Toxicity Muta. Cat. 1; R46 May cause heritable genetic damage. Muta. Cat. 2; R46 May cause heritable genetic damage. Muta. Cat. 3; R68 Possible risk of irreversible effects. |
CLP |
Germ cell mutagenicity Muta. 1A Muta. 1B Muta. 2 H340: May cause genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H341: Suspected of causing genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. |
It is concluded that the substance Alcohols, C12-14 does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity
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