Registration Dossier
Registration Dossier
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EC number: 205-471-8 | CAS number: 141-23-1
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
No evidence of mutagenicity or genotoxicity
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- The analogue approach is used for the hazard assessment of toxicological, eco-toxicological and environmental fate endpoints for the registration of 12-hydroxstearate methyl ester (CAS 141-23- 1). The hypothesis is that data can be read-across between this ester and its structural analogues, based on structural similarity and which cause the same type of effect(s) in physical and biological systems (Scenario 2 of the Read-Across Assessment Framework (RAAF, ECHA, 2015). The primary fatty acids in this read-across are lauric acid (C12) and myristic acid (C14), as these are well studied with high-quality experimental data. Supplemental analogues are used which contribute understanding of the effects of other structural features not contained in the two primary analogues.
There are no GHS classifications for 12-hydroxstearate methyl ester for endpoints which are reliant on read-across. There is a high degree of confidence that hazards for these endpoints are not underestimated, based on a strong weight of evidence from multiple data sources.
Read-across data, all evaluated as reliable according to Klimisch scores of 1 or 2, to estimate the toxicity of the registered substance is used for fulfilling the data requirements of the REACH registration and classifying potential hazards. This read-across approach is adequate for the purposes of risk assessment and classification and labeling. - Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- GLP compliance:
- yes
- Type of assay:
- other: chromosomal aberrations
- Specific details on test material used for the study:
- Dodecanoic acid methyl ester (abbreviation: MD, CAS No.:111-82-0, lot number: GB01, manufactured by Tokyo Chemical Industry Co., Ltd.) is a colorless transparent liquid and has a melting point of 5 ° C, a boiling point of 141 ° C. (15 mmHg) , Molecular formula C13 H26 O2, molecular weight 214.35, purity 98% (impurity unknown).
- Target gene:
- chromosomes
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- CHL/IU cells derived from Chinese hamster, obtained from Research · Resource Bank (JCRB) (February 1988, at passage: 4th passage, now 12th) were used in the test within 10 years of thawing succession age.
- Cytokinesis block (if used):
- colcemid
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 fraction from livers of rats induced with phenobarbital and 5,6-benzoflavone
- Test concentrations with justification for top dose:
- A preliminary toxicity test was conducted based on cell proliferation rates. The proliferation inhibitory action of the test substance on CHL/IU cells was determined by measuring the proliferation of each group using a monolayer culture cell densitometer (Monocellater ™ , Olympus Optical Co., Ltd.), and the solvent control group as baseline.
- Vehicle / solvent:
- acetone
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- Details on test system and experimental conditions:
- DURATION
-Exposure duration:
a) Continuous treatment: 24 hrs, 48 hrs
b) Short-term treatment: 6hrs; 18 hrs for recovery
-Fixation time (start of exposure up to fixation or harvest of cells):
a) Continuous treatment: 24 hrs, 48 hrs
b) Short-term treatment: 24 hrs
SPINDLE INHIBITOR: Colcemid
STAIN: Giemsa stain
NUMBER OF CELLS EVALUATED:
Stractural aberrations: 200 cells/group
Polyploidy: 800 cells/group
DETERMINATION OF CYTOTOXICITY:
-Method: relative total growth - Rationale for test conditions:
- guideline
- Evaluation criteria:
- Criteria for a positive call: a statistically significant increase in the frequency of cells with chromosomal aberrations in the treated group compared with that of the solvent control group, and a statistically significant difference in the dose trend test. An inconclusive result will be designated when there is a significant increase in the frequency of cells with aberrations without a postive dose response trend test.
The test will be considered negative when there is no significant difference in frequency of cells with chromosomal aberrations.
The test is inconclusive when the number of cells observed has fewer than 100 structural aberrations, and less than 400 polyploidy due to cytotoxicity. - Statistics:
- Fisher's direct probability method is used to distinguish between the solvent background chromosomal aberration levels and those of the test substance- treated group, with a significance level of p <0.05. In addition, when significant differences were found by Fisher's exact stochastic method, the Cochran-Armitage's trend test is applied (p <0.05) to test for significance of the dose dependency.
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- In the preliminary toxicity screening test, concentrations up to 2.0 mg/ml resulted in significant decrease in cell growth in the 24 and 48 hour continuous cultures with and without S9, and in the 6 hour culture with S9. Cells in the 6-hour culture without S9 tolerated the test material with growth rates above 50%. Therefore, the maximum concentration of the test substance used in the continuous exposure assay was 0.06 mg / ml, and was 0.1 mg / ml in the short-term assay in the presence of S9 mix. In the short term assay without S9 mix, 2.1 mg / ml (10 mM) was the maximum concentration tested. Toxicity was observed (> 50 mitotic index) in the main study of continuous exposure at the high dose of 0.06 mg/ml, but not in the other modules of the study.
- Conclusions:
- A guideline OECD 473-compliant chromosomal aberration test was undertaken with the test material in acetone, with and without rat liver S9 fraction, with valid positive controls. Cytotoxicity was seen at the higher doses in a preliminary dose-range finding study. There were no increase in the number of chromosome aberrations (excluding gaps) or polyploidy observed. The test substance does not induce chromosomal aberrations in CHL/IU cells under the conditions of this study.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- The analogue approach is used for the hazard assessment of toxicological, eco-toxicological and environmental fate endpoints for the registration of 12-hydroxstearate methyl ester (CAS 141-23- 1). The hypothesis is that data can be read-across between this ester and its structural analogues, based on structural similarity and which cause the same type of effect(s) in physical and biological systems (Scenario 2 of the Read-Across Assessment Framework (RAAF, ECHA, 2015). The primary fatty acids in this read-across are lauric acid (C12) and myristic acid (C14), as these are well studied with high-quality experimental data. Supplemental analogues are used which contribute understanding of the effects of other structural features not contained in the two primary analogues.
There are no GHS classifications for 12-hydroxstearate methyl ester for endpoints which are reliant on read-across. There is a high degree of confidence that hazards for these endpoints are not underestimated, based on a strong weight of evidence from multiple data sources.
Read-across data, all evaluated as reliable according to Klimisch scores of 1 or 2, to estimate the toxicity of the registered substance is used for fulfilling the data requirements of the REACH registration and classifying potential hazards. This read-across approach is adequate for the purposes of risk assessment and classification and labeling. - Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- Dodecanoic acid methyl ester (abbreviation: MD, CAS No.:111-82-0, lot number: GB01, manufactured by Tokyo Chemical Industry Co., Ltd.) is a colorless transparent liquid and has a melting point of 5 ° C, a boiling point of 141 ° C. (15 mmHg) , Molecular formula C13 H26 O2, molecular weight 214.35, purity 98% (impurity unknown).
- Target gene:
- histidine, tryptophan
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A pKM 101
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver induced with phenobarbital and 5,6-benzoflavone
- Test concentrations with justification for top dose:
- Significant toxicity was observed with the test material in dose-range finding studies for the Salmonella strains TA 98 and TA 1535, without S9 activation. The doses in the main assay were:
-S9, for TA 98 and TA 1537: 0, 6.26, 12.5, 25 and 50, 100 and 200 μg / plate
-S9, for TA 100 and TA 1535: 0, 1.56, 3.13, 6.25,12.5, 25, 50 μg / plate
-S9, for WP2 uvrA: 0, 313, 625, 1250, 2500, 5000 μg / plate
+S9, for all Salmonella strains: 0, 12.5, 25, 50, 100, 200, 400, 800, 1600 μg / plate
+S9, for WP2 uvrA: 0, 313, 625, 1250, 2500, 5000 μg / plate
The high dose of 5000 µg/plate is according to OECD TG471 guideline.
In summary, for WP 2 uvrA, the dose of methyl dodecanoate was adjusted to 313 to 5000 μg / plate without addition of S 9 mix and for both TA 100 and TA 1537 at 1.56 to 50 μg / Plate, TA 1535 and TA 98 in 6.25-200 μg / plate. With S9 mix addition, doses were, for TA1537 in 12.5-400 μg / plate, TA 100 and TA 1535 in 25 - 800 μg / plate, TA 98 in 50-1600 μg / plate. - Vehicle / solvent:
- Acetone is solvent for test material; controls are soluble in DMSO or water (sodium azide).
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- acetone, DMSO, water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- sodium azide
- other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamine; 2-aminoanthracene
- Details on test system and experimental conditions:
- The plate incorporation method was used according to OECD TG471. Standard strains, dosing, metabolic activation, incubation conditions, criteria for acceptance and criteria for evaluation of positive results were adopted from the guideline. Cultures were plated in triplicate, and a replicate assay was conducted. All testing was performed under the auspices of Good Laboratory Practices.
- Rationale for test conditions:
- The main test was performed with several doses up to the growth inhibition doses or the maxiumum recommended dose of 5000 µg/plate. Growth inhibition of the bacterial lawn was an indication of toxicity of the test substance.
- Evaluation criteria:
- A positive finding was an increase in the number of revertant colonies more than twice that of the negative control (solvent control) in any tester strain with or without metabolic activation, dose-related and reproducible.
- Statistics:
- none
- Key result
- Species / strain:
- S. typhimurium TA 1535
- 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 applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- 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 applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- 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 applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium 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 applicable
- Positive controls validity:
- not examined
- Key result
- Species / strain:
- E. coli WP2 uvr A pKM 101
- 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 applicable
- Positive controls validity:
- valid
- Additional information on results:
- A dose determination pretest was performed to assess toxicity. The test substance did not increase (more than twofold) the number of revertant colonies. Growth inhibition of the bacterial lawn with the chemical was observed in at 100 µg/plate (without S-9) and at 1600 µg/plate (with S-9). The main test was performed with at least 4 doses or the maxumum recommended dose of 5000 µg/plate. The test substance did not increase the number of revertant colonies with or without metabolic activation. The positive control substances increased the number of revertant colonies more than twice that of the solvent control. The number of revertant colonies for the negative and positive control were within the range of standard values derived from historical control data in this laboratory.
- Conclusions:
- The test substance was assayed in the reverse mutation test (OECD TG471, Ames Assay) in bacteria under standard conditions and found to be non-mutagenic. The criteria for classification of mutagenicity according to Regulation EC No. 1272/2008 are not met.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- Acceptable to OECD SIAR. In spite of no detailed source information, there are enough descriptions about methods and results of the study
- Justification for type of information:
- The analogue approach is used for the hazard assessment of toxicological, eco-toxicological and environmental fate endpoints for the registration of 12-hydroxstearate methyl ester (CAS 141-23- 1). The hypothesis is that data can be read-across between this ester and its structural analogues, based on structural similarity and which cause the same type of effect(s) in physical and biological systems (Scenario 2 of the Read-Across Assessment Framework (RAAF, ECHA, 2015). The primary fatty acids in this read-across are lauric acid (C12) and myristic acid (C14), as these are well studied with high-quality experimental data. Supplemental analogues are used which contribute understanding of the effects of other structural features not contained in the two primary analogues.
There are no GHS classifications for 12-hydroxstearate methyl ester for endpoints which are reliant on read-across. There is a high degree of confidence that hazards for these endpoints are not underestimated, based on a strong weight of evidence from multiple data sources.
Read-across data, all evaluated as reliable according to Klimisch scores of 1 or 2, to estimate the toxicity of the registered substance is used for fulfilling the data requirements of the REACH registration and classifying potential hazards. This read-across approach is adequate for the purposes of risk assessment and classification and labeling. - Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- Version 2, 1997. This test predates adoption of Version 3, 2016.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- Predates revisions 2016
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian cell gene mutation tests using the thymidine kinase gene
- Specific details on test material used for the study:
- Name of test material (as cited in study report): methyl laurate (Notox test substance 202170/A)
- CAS No of test material (as cited in study report): 111-82-0
- Physical state: clear colourless liquid
- Analytical purity: 99.33%
- Lot/batch No.: SME02/1301/K
- Stability under storage conditions: stable
- Expiry date: February 2011 - Target gene:
- TK
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells:
- Suitability of cells:
- Cell cycle length, doubling time or proliferation index:
- Sex, age and number of blood donors if applicable:
- Whether whole blood or separated lymphocytes were used if applicable:
- Number of passages if applicable:
- Methods for maintenance in cell culture if applicable:
- Modal number of chromosomes:
- Normal (negative control) cell cycle time:
MEDIA USED
- Type and identity of media including CO2 concentration if applicable: RPMI 1640 Hepes buffered containing pen/strep
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically 'cleansed' against high spontaneous background: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- Induced rat liver S9 fraction
- Test concentrations with justification for top dose:
- first mutagenicity test:
3 h without S9mix: 0.3 μg/mL, 1 μg/mL, 3 μg/mL, 10 μg/mL, 30 μg/mL, 50 μg/mL, 65 μg/mL, 80 μg/mL, 100 μg/mL, 120 μg/mL, 150 μg/mL, 175 μg/mL, 200 μg/mL, and 225 μg/mL
3 h with 8% (v/v) S9mix: 0.3 μg/mL, 1 μg/mL, 3 μg/mL, 10 μg/mL, 30 μg/mL, 100 μg/mL, 125 μg/mL, 150 μg/mL, 175 μg/mL, 200 μg/mL, 225 μg/mL, 250 μg/mL, 275 μg/mL, and 300 μg/mL
The dose levels selected to measure mutation frequencies at the TK-locus were:
Without S9mix: 0.3 μg/mL, 1 μg/mL, 3 μg/mL, 10 μg/mL, 30 μg/mL, 70 μg/mL, 80 μg/mL, and 95 μg/mL exposure medium
With S9mix: 0.3 μg/mL, 1 μg/mL, 3 μg/mL, 10 μg/mL, 30 μg/mL, 150 μg/mL, 175 μg/mL, and 200 μg/mL exposure medium
second mutagenicity test:
24 hours without S9mix: 0.3 μg/mL, 1 μg/mL, 3 μg/mL, 10 μg/mL, 30 μg/mL, 40 μg/mL, 50 μg/mL, 60 μg/mL, 70 μg/mL, 80 μg/mL, 90 μg/mL, and 100 μg/mL
3 hours with 12% (v/v) S9mix: 0.3 μg/mL, 1 μg/mL, 3 μg/mL, 10 μg/mL, 30 μg/mL, 100 μg/mL, 120 μg/mL, 140 μg/mL, 160 μg/mL, 180 μg/mL, 200 μg/mL, and 220 μg/mL
The dose levels selected to measure mutation frequencies at the TK-locus were:
Without S9mix: 1 μg/mL, 3 μg/mL, 10 μg/mL, 30 μg/mL, 40 μg/mL, 50 μg/mL, 60 μg/mL, and 70 μg/mL exposure medium
With S9mix: 0.3 μg/mL, 1 μg/mL, 3 μg/mL, 10 μg/mL, 30 μg/mL, 140 μg/mL, 180 μg/mL, and 220 μg/mL exposure medium
Top dose chosen based on solubility and survival/toxicity - Vehicle / solvent:
- ethanol
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- methylmethanesulfonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
1st experiment: 3 hours with and without S9-mix.
2nd experiment: 3 hours with S9-mix and 24 h without S9-mix.
- Exposure duration: 3 and 24 hours
- Expression time (cells in growth medium): Two days after the end of the treatment, cells were plated for determination of the cloning efficiency and the mutation frequency in microtiter plates containing TFT selective medium. The microtiter plates were incubated for 11 or 12 days.
- Selection time (if incubation with a selection agent): 11-12 days
- Fixation time (start of exposure up to fixation or harvest of cells): 14-15 days
SELECTION AGENT (mutation assays): 5 μg/mL trifluorothymidine (TFT)
NUMBER OF REPLICATIONS: two independent experiments in microtiter plates
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency and relative total growth
OTHER:
Small and large colonies were differentiated, as small colonies are capable to indicate chromosomal mutations.
Methyl laurate concentrations were used within 0.5 h after preparation. - Rationale for test conditions:
- According to guideline
- Evaluation criteria:
- Increase of mutation frequency in a dose-dependent manner in comparison with historical control range.
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- yes (minimal and cell survival at 333 μg/mL)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- other: not mutagenic
- Remarks:
- Negative
- Conclusions:
- In a report issued by the OECD SIAR CoCam 4, 2013, a guideline OECD 476 Mouse Lymphoma Assay was undertaken on the test substance, with a finding of no mutagenicity. The substance is evaluated as non-mutagenic, and is not classified according to Regulation EC No. 1272/2008.
Referenceopen allclose all
Table 1: Continuous
Group |
Concentration (mg/ml) |
Time of Exposure (h) |
No of Cells analysed |
No. of structural aberrations |
Others3) |
No. of cells with aberrations |
Polyploid4)(%) |
Trend test5) |
||||||||
|
|
|
gap |
ctb |
cte |
csb |
cse |
mul2) |
total |
TAG (%) |
TA (%) |
|
SA |
NA |
||
Control |
|
|
200 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 (0.0) |
0 (0.0) |
0.13 |
NT |
NT |
Solvent1) |
0 |
24 |
200 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 (0.0) |
0(0.0) |
0.38 |
||
MD |
0.015 |
24 |
200 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 (0.0) |
0 (0.0) |
0.13 |
||
MD |
0.03 |
24 |
200 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 (0.5) |
0 (0.0) |
0.25 |
||
MD |
0.06 |
24 |
173 |
0 |
1 |
0 |
1 |
0 |
0 |
2 |
1 |
2 (1.2) |
2 (1.2) |
0.556) |
||
MC |
0.00005 |
24 |
200 |
11 |
40 |
133 |
2 |
3 |
0 |
189 |
2 |
110 (55.0) |
105 (52.5) |
0.00 |
||
|
||||||||||||||||
Solvent1) |
0 |
48 |
200 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 (0.0) |
0 (0.0) |
0.00 |
NT |
NT |
MD |
0.015 |
48 |
200 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 (0.0) |
0 (0.0) |
0.25 |
||
MD |
0.03 |
48 |
200 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 (0.0) |
0 (0.0) |
0.13 |
||
MD |
0.06 |
48 |
200 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 (0.0) |
0 (0.0) |
0.63 |
||
MC |
0.00005 |
48 |
200 |
6 |
35 |
137 |
4 |
6 |
20 |
208 |
6 |
94 (47.0) |
94 (47.0) |
0.25 |
||
Table 2: Short-term
Group |
Concentration (mg/ml) |
S9 mix |
Time of Exposure (h) |
No of cells analyzed |
No. of structural aberrations |
Others3) |
No. of cells with aberrations |
Polyploid4)(%) |
Trend test5) |
||||||||
|
|
|
|
gap |
ctb |
cte |
csb |
cse |
mul2) |
total |
TAG (%) |
TA (%) |
|
SA |
NA |
||
Control |
|
|
|
200 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 (0.0) |
0 (0.0) |
0.63 |
NT |
NT |
Solvent1) |
0 |
- |
6-(18) |
200 |
0 |
0 |
1 |
0 |
1 |
0 |
2 |
0 |
2 (1.0) |
2 (1.0) |
0.63 |
||
MD |
0.53 |
- |
6-(18) |
200 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 (0.0) |
0 (0.0) |
0.25 |
||
MD |
1.1 |
- |
6-(18) |
200 |
1 |
1 |
0 |
0 |
0 |
0 |
2 |
0 |
2 (1.0) |
1 (0.5) |
0.25 |
||
MD |
2.1 |
- |
6-(18) |
200 |
0 |
0 |
1 |
0 |
0 |
0 |
1 |
0 |
1 (0.5) |
1 (0.5) |
0.25 |
||
CPA |
0.005 |
- |
6-(18) |
200 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
0 |
1 (0.5) |
1 (0.5) |
0.13 |
||
|
|||||||||||||||||
Solvent1) |
0 |
+ |
6-(18) |
200 |
1 |
0 |
1 |
0 |
0 |
0 |
2 |
1 |
2 (1.0) |
1 (0.5) |
0.25 |
NT |
NT |
MD |
0.025 |
+ |
6-(18) |
200 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 (0.0) |
0 (0.0) |
0.5 |
||
MD |
0.05 |
+ |
6-(18) |
200 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 (0.5) |
0 (0.0) |
0.75 |
||
MD |
0.1 |
+ |
6-(18) |
200 |
0 |
0 |
2 |
0 |
0 |
0 |
2 |
0 |
1 (0.5) |
1 (0.5) |
1.38 |
||
CPA |
0.005 |
+ |
6-(18) |
200 |
7 |
40 |
126 |
1 |
2 |
0 |
176 |
0 |
95 (47.5) |
93 (46.5) |
0.25 |
||
Table 1: S. typhimurium
With (+) or without (-) S9 mix |
Test substance dose (μg/plate) |
Number of revertants (Number of colonies/plate, Mean ±SD) |
||||
Base-pair substitution type |
Frameshift type |
|||||
TA100 |
TA1535 |
|
TA98 |
TA1537 |
||
S9 mix (-) |
0 |
124, 106, 135 |
10, 11, 15 |
|
24, 28, 20 |
9, 3, 12 |
(122 ± 14.6) |
( 12 ± 2.6) |
( 24 ± 4.0) |
( 8 ± 4.6) |
|||
1.56 |
141, 150, 134 |
ND |
|
ND |
14, 10, 6 |
|
( 142 ± 8.0) |
( 10 ± 4.0) |
|||||
3.13 |
143, 156, 110 |
ND |
|
ND |
8, 12, 14 |
|
( 136 ± 23.7) |
( 11 ± 3.1) |
|||||
6.25 |
112, 117, 107 |
17, 15, 18 |
|
22, 19, 17 |
6, 14, 9 |
|
( 112 ± 5.0) |
( 17 ± 1.5) |
( 19 ± 2.5) |
( 10 ± 4.0) |
|||
12.5 |
128, 114, 103 |
16, 20, 12 |
|
17, 24, 18 |
4, 9, 7 |
|
( 115 ± 12.5) |
( 16 ± 4.0) |
( 20 ± 3.8) |
( 7 ± 2.5) |
|||
25 |
137*, 116*, 133* |
9, 15, 9 |
|
24, 16, 22 |
9*, 5*, 11* |
|
( 129 ± 11.2) |
( 11 ± 3.5) |
( 21 ± 4.2) |
( 8 ± 3.1) |
|||
50 |
98*, 102*, 125* |
9, 13, 11 |
|
20, 16, 15 |
4*, 7*, 11* |
|
( 108 ± 14.6) |
( 11 ± 2.0) |
( 17 ± 2.6) |
( 7 ± 3.5) |
|||
100 |
|
12*, 13*, 10* |
|
19, 16, 20 |
|
|
( 12 ± 1.5) |
( 18 ± 2.1) |
|||||
200 |
|
12*, 12*, 18* |
|
17*, 24*, 20* |
|
|
( 14 ± 3.5) |
( 20 ± 3.5) |
|||||
S9 mix (+) |
0 |
138, 130, 126 |
9, 13, 12 |
|
26, 25, 41 |
23, 16, 15 |
(131 ± 6.1) |
( 11 ± 2.1) |
( 31 ± 9.0) |
( 18 ± 4.4) |
|||
12.5 |
ND |
ND |
|
ND |
23, 18, 19 |
|
( 20 ± 2.6) |
||||||
25 |
158, 157, 138 |
15, 16, 14 |
|
ND |
9, 15, 21 |
|
( 151 ± 11.3) |
( 15 ± 1.0) |
( 15 ± 6.0) |
||||
50 |
130, 154, 156 |
18, 13, 17 |
|
39, 28, 33 |
28, 15, 25 |
|
( 147 ± 14.5) |
( 16 ± 2.6) |
( 33 ± 5.5) |
( 23 ± 6.8) |
|||
100 |
142, 140, 148 |
18, 15, 10 |
|
33, 30, 27 |
18, 17, 17 |
|
( 143 ± 4.2) |
( 14 ± 4.0) |
( 30 ± 3.0) |
( 17 ± 0.6) |
|||
200 |
143, 106, 138 |
16, 8, 13 |
|
38, 25, 29 |
17, 14, 14 |
|
( 129 ± 20.1) |
( 12 ± 4.0) |
( 31 ± 6.7) |
( 15 ± 1.7) |
|||
400 |
108*, 103*, 96* |
13, 14, 8 |
|
28, 27, 30 |
9*, 9*, 8* |
|
( 102 ± 6.0) |
( 12 ± 3.2) |
( 28 ± 1.5) |
( 9 ± 0.6) |
|||
800 |
86*, 94*, 88* |
16*, 10*, 12* |
|
25*, 18*, 23* |
|
|
( 89 ± 4.2) |
( 13 ± 3.1) |
( 22 ± 3.6) |
||||
1600 |
|
|
|
12*, 11*, 13* |
|
|
( 12 ± 1.0) |
||||||
Positive control S9 mix (-) |
Chemical |
AF2 |
SA |
|
AF2 |
9AA |
Dose (μg/plate) |
0.01 |
0.5 |
|
0.1 |
80 |
|
Number of colonies/plate |
682, 650, 670 |
232, 245, 242 |
|
954, 935, 930 |
1103, 1071, 999 |
|
(667 ± 16.2) |
(240 ± 6.8) |
(940 ± 12.7) |
(1058 ± 53.3) |
|||
Positive control S9 mix (+) |
Chemical |
2AA |
2AA |
|
2AA |
2AA |
Dose (μg/plate) |
1 |
2 |
|
0.5 |
2 |
|
Number of |
1262, 1111, 1309 |
299, 270, 290 |
|
455, 457, 566 |
300, 295, 294 |
|
colonies/plate |
(1227±103.5) |
( 286 ± 14.8) |
(493 ± 63.5) |
(296 ± 3.2) |
||
AF2: 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide, SA: Sodium azide, 9AA: 9-Aminoacridine, 2AA: 2-Aminoanthracene |
||||||
Table 2: WP2uvrA
With (+) or without (-) S9 mix |
Test substance dose (μg/plate) |
Number of revertants (Number of colonies/plate, Mean ±SD) |
||||
Base-pair substitution type |
Frameshift type |
|||||
|
|
WP2uvrA |
|
|
||
S9 mix (-) |
0 |
|
|
29, 28, 25 |
|
|
( 27 ± 2.1) |
||||||
313 |
|
|
24, 16, 25 |
|
|
|
( 22 ± 4.9) |
||||||
625 |
|
|
31, 28, 32 |
|
|
|
( 30 ± 2.1) |
||||||
1250 |
|
|
21, 19, 26 |
|
|
|
( 22 ± 3.6) |
||||||
2500 |
|
|
29, 20, 29 |
|
|
|
( 26 ± 5.2) |
||||||
5000 |
|
|
20, 28, 23 |
|
|
|
( 24 ± 4.0) |
||||||
S9 mix (+) |
0 |
|
|
23, 26, 16 |
|
|
( 22 ± 5.1) |
||||||
313 |
|
|
24, 25, 27 |
|
|
|
( 25 ± 1.5) |
||||||
625 |
|
|
27, 19, 20 |
|
|
|
( 22 ± 4.4) |
||||||
1250 |
|
|
24, 34, 25 |
|
|
|
( 28 ± 5.5) |
||||||
2500 |
|
|
11, 20, 19 |
|
|
|
( 17 ± 4.9) |
||||||
5000 |
|
|
26, 20, 23 |
|
|
|
( 23 ± 3.0) |
||||||
Positive control S9 mix (-) |
Chemical |
|
|
AF2 |
|
|
Dose (μg/plate) |
|
|
0.01 |
|
|
|
Number of colonies/plate |
|
|
108, 151, 190 |
|
|
|
(150 ± 41.0) |
||||||
Positive control S9 mix (+) |
Chemical |
|
|
2AA |
|
|
Dose (μg/plate) |
|
|
10 |
|
|
|
Number of colonies/plate |
|
|
1510, 1537, 1546 |
|
|
|
(1531 ± 18.7) |
||||||
TEST-SPECIFIC
CONFOUNDING FACTORS
- Water solubility: poorly solubility in aqueous solutions: therefore
the highest tested concentration was 333 μg/mL medium.
- Precipitation: Methyl laurate precipitated in the exposure medium at
concentrations of 100 μg/mL and above.
RANGE-FINDING/SCREENING STUDIES:
The suspension growth expressed as the reduction in cell growth after
approx. 24 h and 48 h or only 24 h cell growth, compared to the cell
growth of the solvent control, was used to determine an appropriate dose
range for the main test. In the absence of S9 mix, the relative
suspension growth was 29% at 100 μg/mL. Hardly any cell survival was
observed at 333 μg/mL. In the presence of S9 mix, no toxicity was
observed at 100 μg/mL, but hardly any cell survival was observed at 333
μg/mL.
COMPARISON WITH HISTORICAL CONTROL DATA: The spontaneous mutation frequencies in the solvent-treated control cultures were between the minimum and maximum value of the historical control data range and within the acceptability criteria of this assay.
Table. Cytotoxic and mutagenic responses
|
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Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Mode of Action Analysis / Human Relevance Framework
Not applicable
Additional information
Justification for classification or non-classification
In vitro testing of mutagenicity of read-across analogues resulted in negative findings, documenting a lack of genotoxicity.
The read-across is based on known biochemical lipid cycles and empiric evidence for target and source substances, and is valid for fulfilling the information requirements of this endpoint. Test results do not meet the criteria for classification of the registered substance for mutagenicity according to Regulation EC No. 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
