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EC number: 203-996-7 | CAS number: 112-67-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
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- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Palmitoyl chloride is not mutagenic in the Salmonella typhimurium and Escherichia coli reverse mutation assay.
Available date for the source substances docosanoic acid CAS 112-85-6 and decanoic acid CAS 334-48-5.
Gene mutation (OECD 471/472): negative, CAS 112-85-6 (Nakajima, 2002)
Chromosome aberration (OECD 473): negative, CAS 112 -85 -6 (Nakajima, 2002)
Chromosome aberrration (similar to OECD 473 ): negative, CAS 334-48-5 (MHW Japan, 2018)
Gene mutation in mammalian cells (TK locus; OECD 476): negative; CAS 334-48-5 (Trenz, 2010)
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- not applicable
- Species / strain / cell type:
- mammalian cell line, other: Chinese hamster lung (CHL) cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: Eagle-MEM liquid medium
- Properly maintained: yes - Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 from rat liver, induced with phenobarbital and 5,6-benzoflavone
- Test concentrations with justification for top dose:
- -S9 mix (short-term exposure): 0, 875, 1750, 3500 µg/mL
+S9 mix (short-term exposure): 0, 875, 1750, 3500 µg/mL
-S9 mix (24 h continuous exposure): 0, 350, 700, 1400, 2800 µg/mL
-S9 mix (48-hour continuous exposure): 0, 288, 575, 1150, 2300 µg/mL - Vehicle / solvent:
- 1.0 % carboxymethylcellulose sodium
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: continuous exposure: mitomycin C (0.05 µg/mL for 24 hours and 0.025 µg/mL for 48 hours); short-term exposure: cyclophosphamide (12.5 µg/mL)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Preincubation period: 3 days
- Exposure duration: 6 (short-term exposure), 24, 48 h
STAIN (for cytogenetic assays): Giemsa
NUMBER OF CELLS EVALUATED: 200
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth - Evaluation criteria:
- The frequency of polyploid cells or cells with abnormal structure of each test group were determined according to the criteria of Ishidate.
- Species / strain:
- mammalian cell line, other: Chinese hamster lung (CHL) cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: insoluble in water, soluble in alcohol, ether, chloroform and acetone
- Precipitation: observed on the slide of continuous exposure high dose group
RANGE-FINDING/SCREENING STUDIES: see 'Any other information on material and method incl. tables'
COMPARISON WITH HISTORICAL CONTROL DATA: this test was valid, since the frequency of chromosomal aberration in positive control was within background data. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- The test substance did not induce structural chromosomal aberrations in the absence or presence of an exogenous metabolic activation system.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 28 Jun - 23 Aug 2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- 1997
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 490 (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)
- Version / remarks:
- 2016
- Deviations:
- yes
- Remarks:
- Several deviations based on the changes from OECD TG 476 (1997) to OECD TG 490 (2016).
- Principles of method if other than guideline:
- Deviations from OECD test guideline 490 (2016):
The cell line used for the MLA was described as L5178Y without further differentiation if the required TK+/- -3.7.2C subline of L5178Y cells was used. The expression period for the short-term exposure experiments was 3 days (instead of 2 days). The mutation frequency was calculated based on number of mutant colonies adjusted by cloning efficiency instead of determination of cloning efficiency for the selection and cloning efficiency plates. Differences in acceptability criteria, i.e. suspension growth was not assessed as acceptability criterium. The Global Evaluation factor (GEF) was not evaluated. - GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- TK locus
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: RPMI 1640 complete medium
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes - Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Type and composition of metabolic activation system:
- source of S9
: prepared at BSL BIOSERVICE GmbH
Male rats were induced with phenobarbital (80 mg/kg bw) and beta-naphtoflavone (100 mg/kg bw). A stock of the supernatant containing the microsomes was frozen and stored at <= 75°C. The protein concentration in the S9 preparation (Lot: 110310) was 31 mg/mL.
- method of preparation of S9 mix: according to Ames et al., 1977
An appropriate quantity of the S9 supernatant was thawed and mixed with S9 cofactor solution to result in a final protein concentration of 0.75 mg/mL in the culture. Cofactors were added to the S9 mix to reach the concentration below:
8 mM MgCl2
33 mM KCl
5 mM glucose-6-phosphate
5 mM NADP in
in 100 mM sodium-phosphate-buffer pH 7.4.
- quality controls of S9: The following quality control determinations were performed:
a) Biological activity in the Salmonella typhimurium assay using 2-aminoanthracene and biological activity in the chromosome aberration assay using benzo[a]pyrene and cyclophosphamide.
b) Sterility test - Test concentrations with justification for top dose:
- Pre-Test:
Experiment 1:
- with and without metabolic activation: 0.5, 2, 4, 6, 8, 10 mM
Experiment 2:
- without metabolic activation. 0.005, 0.05, 0.2, 0.7, 1.3, 2.0 mM
Main Test:
Experiment 1:
- with metabolic activation: 0.70, 0.82, 0.94, 1.06, 1.18, 1.30, 1.42, 1.54 mM
- without metabolic activation. 0.22, 0.46, 0.58, 0.70, 0.82, 0.94, 1.06, 1.18 mM
Experiment 2:
- with metabolic activation: 1.0, 1.12, 1.24, 1.36, 1.48, 1.60, 1.72, 1.84 mM
- without metabolic activation. 0.0005, 0.001, 0.002, 0.005, 0.01, 0.06, 0.18, 0.3 mM - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: RPMI cell culture medium
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- since medium was used as solvent, no further solvent control was necessary
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: -S9: methylmethanesulfonate (10 µg/mL, dissolved in 0.9% NaCl); ethylemethanesulphanate (200 and 500 µg/mL, dissolved in medium); +S9: benzo(a)pyrene (3.5 µg/mL, dissolved in DMSO (1% final concentration in medium))
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration:
Experiment 1: 4 h (short-term exposure) with and without metabolic activation
Experiment 2: 4 h (short-term exposure) with metabolic activation and 24 h (long-term exposure) without metabolic activation
- Expression time (cells in growth medium): 3 days (short-term exposure) or 2 days (long-term exposure)
- Selection time (if incubation with a selection agent): 11 - 14 days
- Fixation time (start of exposure up to fixation or harvest of cells): 13 - 18 days
SELECTION AGENT (mutation assays): 5 µg/mL trifluorothymidine (TFT)
NUMBER OF REPLICATIONS: single cultures per concentration each in two independent experiments; cells from each experimental group were seeded in 4 96-well-plates for determination of mutation frequencies
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth; cloning efficiency
OTHER:
Small and large colonies were differentiated, as small colonies are capable to indicate chromosomal mutations
- Criteria for small (slow growing) and large (fast growing) colonies: Small colonies approx. <= 1/4 of well diameter; large colonies approx. > 1/4 of well diameter
- Method used: microwell plates for the mouse lymphoma assay - Evaluation criteria:
- There are several criteria for a positive result:
- clear and dose-related increase in the mutant frequency
- biologically relevant response (at least a 2-fold increase of mutant frequencies related to the respective negative control values and higher than the historical range of negative controls) for at least one of the dose groups
- combined with a positive effect in the mutant frequency, an increased occurrence of small colonies (slow growth colonies) indicated by a low large/Small colonies ratio (1.5 times the ratio of clastogenic control MMS and/or B[a]P) is an indication for potential clastogenic effects and/or chromosomal aberrations.
The test substance is considered to be negative if there is no biologically relevant increase in the induction of mutant cells above concurrent control levels, at any dose level. - Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 1.54 mM with metabolic activation and at 1.18 mM without metabolic activation in experiment 1, respectively; at 1.84 mM with metabolic activation and at 0.30 mM without metabolic activataion in experiment 2, respectively.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: within the physiological range
- Effects of osmolality: within the physiological range
- Precipitation: in the pre-test with metabolic activation from concentrations of 4 mM and higher
RANGE-FINDING/SCREENING STUDIES:
All mutant values were found to be within the range of the historical control data of the test facility BSL Bioservice (about 51 to 170 mutants per 10^6 cells)
COMPARISON WITH HISTORICAL CONTROL DATA:
All mutant values were found to be within the range of the historical negative control data of the test facility (about 51 to 170 mutants per 10^6 cells). For more information on the historical control data (HCD), please refer to Table 5 under "Any other information on results incl. tables".
Gene mutation tests in mammalian cells:
- Results from cytotoxicity measurements:
Growth inhibition was observed in both experiments with and without metabolic acitivation:
In experiment I with S9 the relative total growth (RTG) was 9.84% for the highest concentration (1.54 mM) evaluated. The highest concentration evaluated without S9 was 1.18 mM with a RTG of 11.04%.
In experiment II with S9 the RTG was 19.98% for the highest concentration (1.84 mM) evaluated. The highest concentration evaluated without S9 was 0.30 mM with a RTG of 19.77%.
- Genotoxicity results:
In experiment I with S9 mix all mutant values found were within the HCD of the test facility. A slight dose-response relationship could be observed. The mutation frequencies found in the groups treated with the test item did not show a biologically relevant increase compared to the negative controls. Mutation frequencies of the negative controls were found to be 93.87 and 79.67 mutants/10^6 cells and in the range of 76.43 and 139.92 mutants/10^6 cells with the test item, respectively. The highest mutation factor was 1.61 compared to the negative controls found at a concentration of 1.54 mM with a RTG of 9.84%. Without metabolic activation no dose-response relationship or any biologically rel
evant increase compared to the negative controls were observed. In experiment II with and wihout S9 mix all mutant values were within the HCD of the test facility. No dose-response relationship nor any biologically relevant increase were observed. For more information, please refer to the tables under "Any other information on results incl. tables". - Conclusions:
- In conclusion, in the described mutagenicity test under the experimental conditions reported, the test item decanoic acid is considered to be non-mutagenic in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y. The study was conducted according to OECD TG 476 (1997) and in accodance with GLP. Even though there are some deviations from the current OECD TG 490 (2016), the study is considered valid and suitable for the assessment of the potential of the test item to cause gene mutations in mammalian cells in vitro.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Salmonella typhimurium: (his-)
Escherichia coli: (trp-) - Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- S-9 mix from Aroclor 1254 induced rat liver
- Test concentrations with justification for top dose:
- 20 - 5000 µg/ plate (Standard plate test, SPT)
4 - 2500 µg/ plate (Preincubation test, PIT) - Vehicle / solvent:
- acetone
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: see free text
- Details on test system and experimental conditions:
- Standard plate test
Test tubes containing 2 ml soft agar kept in a water bath at 45°C, and remaining components added in the following order:
0.1 ml test solution or vehicle
0.1 ml bacterial suspension
0.5 ml S-9 mix (in tests with metabolic activation) or 0 .5 ml phosphate buffer (in tests without metabolic activation).
After mixing, the samples are poured onto Vogel-Bonner agar plates.
Preincubation test
0.1 ml test solution, 0.1 ml bacterial suspension and 0.5 ml S-9 mix are incubated at 37°C for the duration of 20 minutes. Subsequently, 2 ml of soft agar is added and, after mixing, the samples are poured onto the Vogel-Bonner agar plates within approx. 30 seconds.
In each experiment 3 test plates per dose or per control used; after fter incubation at 37°C for 48 - 72 hours in the dark, the bacterial colonies (his or trp revertants) are counted.
Positive control
with metabolic activation: 2.5 and 60 μg/plate 2-aminoanthracene for each S. typhimurium strain and the E.coli strain, respectively;
without metabolic activation: 5 μg/plate N-methyl-N'-nitro-N-nitrosoguanidine for TA 100 and TA 1535, 10 μg/plate 4-nitro-o-phenylendiamine
for TA 98, 100 μg 9-aminoacridine chloride monohydrate for TA 1537 and 10 µg N-ethyl-N'-nitro-N-nitrosoguanidin for E. coli. All substances were dissolved in DMSO.
The titer was determined and in regularly measurements the strain characteristics were checked. Sterility control performed. - Evaluation criteria:
- Positive results
- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the results - Statistics:
- Mean and standard deviation calculated in result tables. No further data.
- Species / strain:
- other: S. typhimurium TA 98, TA 100, TA 1535, TA 1537; E. coli WP2 uvrA
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- A bacteriotoxic effect was observed from about 500 - 2500 µg/plate onward
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- A test substance precipitation was found from about 500 µg/plate onward.
- Conclusions:
- According to the results of the present study, the test substance Palmitoyl chloride is not mutagenic in the Salmonella typhimurium and Escherichia coli reverse mutation assay under the experimental conditions chosen here.
- Executive summary:
The study was conducted according to the OECD Guidelines 471 and 472, respectively and is reliable without restrictions. Palmitoyl chloride was tested in the standard plate test and in the preincubation test with and without metabolic activation in S. typhimurium TA98, TA100, TA1535, TA1537 and E. coli WP2 uvrA at dose levels of 20 - 5000 and 4 - 2500 µg/plate, respectively. No increase in the number of revertants was detected in any strain with and without MA. Vehicle controls and positive controls were valid. Cytotoxicity was found depending on the strain and metabolic activation. Precipitation was reported.
Referenceopen allclose all
Colony sizing was performed for the highest concentrations of the test item and for the negative and positive controls. A mutation frequency above 2 in combination with an increased occurrence of small colonies (defined by slow growth and/or morphological alteration of the cell clone), indicated by a low large/small colony ratio (ratio of the clastogenic controls MMS and/or B[a]P with a coefficient of 1.5), is an indication for potential clastogenic effects and/or chromosomal aberrations.
Although in experiment 1 with metabolic activation an increased number of small colonies was noted at doses of 1.30 mM and 1.42 mM (26 and 31 small colonies, respectively, compared to 11 and 9 at control) all dose groups were considered as not clastogenic since no mutagenicity was found at these doses.
All other dose groups in the other experiments were also found not to be clastogenic, respectively.
Table 1: Experiment I - 4 h exposure - With Metabolic Activation
Concentration | Cloning efficiency [%] | Relative Total Growth [%] | Mutants per 1E+06 surviving cells | Mutation factor | Colony Sizing Quotient Large/Small |
0 | 100 | 100 | 86.77 | 1 | 3.66 |
0.7 | 96.63 | 95.51 | 95.86 | 1.10 | -- |
0.82 | 104.12 | 92.71 | 88.56 | 1.02 | -- |
0.94 | 109.36 | 95.60 | 76.43 | 0.88 | -- |
1.06 | 110.11 | 78.73 | 78.58 | 0.91 | -- |
1.18 | 109.36 | 60.06 | 86.55 | 1.00 | -- |
1.30 | 116.10 | 40.14 | 100.88 | 1.16 | 1.77 |
1.42 | 112.36 | 31.61 | 121.24 | 1.40 | 1.55 |
1.54 | 96.63 | 9.84 | 139.92 | 1.61 | 2.78 |
B[a]P, 3.5 µg/mL | 99.63 | 69.03 | 623.89 | 7.19 | 1.24 |
B[a]P: Benzo[a]pyrene
Table 2: Experiment I - 4 h exposure - Without Metabolic Activation
Concentration | Cloning efficiency [%] | Relative Total Growth [%] | Mutants per 1E+06 surviving cells | Mutation factor | Colony Sizing Quotient Large/Small |
0 | 100 | 100 | 79.39 | 1 | 2.75 |
0.22 | 100.33 | 90.09 | 78.53 | 0.99 | -- |
0.46 | 86.38 | 79.76 | 124.63 | 1.57 | -- |
0.58 | 91.03 | 79.70 | 77.88 | 0.98 | -- |
0.70 | 98.34 | 89.53 | 70.89 | 0.89 | -- |
0.82 | 98.34 | 71.30 | 69.28 | 0.87 | -- |
0.94 | 95.02 | 64.50 | 62.74 | 0.79 | 1.60 |
1.06 | 99.00 | 47.66 | 74.59 | 0.94 | 3.17 |
1.18 | 91.69 | 11.04 | 97.49 | 1.23 | 1.12 |
EMS, 500 µg/mL | 86.38 | 62.27 | 1337.77 | 16.85 | -- |
MMS, 10 µg/mL | 85.71 | 66.62 | 841.03 | 10.59 | 0.69 |
EMS: Ethyl methane sulphonate
MMS: Methyl methane sulphonate
Table 3: Experiment II - 4 h Exposure - With Metabolic Activation
Concentration | Cloning efficiency [%] | Relative Total Growth [%] | Mutants per 1E+06 surviving cells | Mutation factor | Colony Sizing Quotient Large/Small |
0 | 100 | 100 | 82.64 | 1.00 | 2.07 |
1 | 96.97 | 85.91 | 82.23 | 1.00 | -- |
1.12 | 101.68 | 89.08 | 61.54 | 0.74 | -- |
1.24 | 98.99 | 86.20 | 86.92 | 1.05 | -- |
1.36 | 99.66 | 83.65 | 75.75 | 0.92 | -- |
1.48 | 90.91 | 64.04 | 118.05 | 1.43 | -- |
1.60 | 96.07 | 35.51 | 70.23 | 0.85 | 2.38 |
1.72 | 91.58 | 38.25 | 84.77 | 1.03 | 2.13 |
1.84 | 98.99 | 19.98 | 98.81 | 1.20 | 4.73 |
B[a]P, 3.5 µg/mL | 86.20 | 60.39 | 829.02 | 10.03 | 0.89 |
B[a]P: Benzo[a]pyrene
Table 4: Experiment II - 24 h exposure - Without Metabolic Activation
Concentration | Cloning efficiency [%] | Relative Total Growth [%] | Mutants per 1E+06 surviving cells | Mutation factor | Colony Sizing Quotient Large/Small |
0 | 100 | 100 | 104.66 | 1 | 2.61 |
0.0005 | 95.24 | 94.64 | 76.34 | 0.73 | -- |
0.001 | 101.36 | 103.58 | 68.22 | 0.65 | -- |
0.002 | 94.56 | 95.29 | 66.56 | 0.64 | -- |
0.005 | 101.36 | 105.73 | 52.63 | 0.50 | -- |
0.01 | 102.04 | 98.98 | 64.06 | 0.61 | -- |
0.06 | 102.72 | 96.75 | 61.54 | 0.59 | 3.30 |
0.18 | 96.60 | 55.56 | 91.91 | 0.88 | 2.24 |
0.30 | 91.16 | 19.77 | 99.26 | 0.95 | 1.94 |
EMS, 200 µg/mL | 70.75 | 34.84 | 2516.55 | 24.05 | -- |
MMS, 10 µg/mL | 59.18 | 27.33 | 2625.00 | 25.08 | 0.81 |
EMS: Ethyl methane sulphonate
MMS: Methyl methane sulphonate
Table 5: Historical laboratory control data (Jan - Aug 2010)
| Negative Control | Positive Control | ||||
| -S9 | +S9 | EMS (500 µg/mL) | EMS (200 µg/mL) | MMS (10 µg/mL) | B[a]P (3.5 µg/mL) |
Mean of mutants per 1E+06 cells | 90.81 | 89.22 | 1464.40 | 2245.20 | 1281.16 | 691.08 |
Minimum of mutants per 1E+06 cells | 51.46 | 50.83 | 244.01 | 593.04 | 202.45 | 332.60 |
Maximum of mutants per 1E+06 cells | 173.95 | 170.04 | 2531.86 | 4745.21 | 2654.69 | 1148.82 |
Standard deviation | 28.66 | 28.13 | 642.39 | 973.54 | 2654.69 | 216.65 |
Relative standard deviation [%] | 31.56 | 31.53 | 43.87 | 43.36 | 2859.71 | 31.35 |
Number of control values | 50 | 50 | 14 | 13 | not reported | 25 |
Standard plate test (20 - 5000 µg/plate) |
|||||
Strain |
Metabolic activation system |
Replicates |
maximum revertant factor |
dose dependency |
Assessment |
TA 98 |
no |
3 |
0.9 |
no |
negative |
|
yes |
3 |
1.0 |
no |
negative |
TA 100 |
no |
3 |
1.0 |
no |
negative |
|
yes |
3 |
0.8 |
no |
negative |
TA 1535 |
no |
3 |
1.1 |
no |
negative |
|
yes |
3 |
1.1 |
no |
negative |
TA 1537 |
no |
3 |
0.8 |
no |
negative |
|
yes |
3 |
0.9 |
no |
negative |
WP2 uvr A |
no |
3 |
1.0 |
no |
negative |
|
yes |
3 |
1.0 |
no |
negative |
Preincubation test (4 - 2500 µg/plate) |
|||||
Strain |
Metabolic activation system |
Replicates |
maximum revertant factor |
dose dependency |
Assessment |
TA 98 |
no |
3 |
1.0 |
no |
negative |
|
yes |
3 |
1.0 |
no |
negative |
TA 100 |
no |
3 |
1.0 |
no |
negative |
|
yes |
3 |
1.0 |
no |
negative |
TA 1535 |
no |
3 |
0.9 |
no |
negative |
|
yes |
3 |
0.9 |
no |
negative |
TA 1537 |
no |
3 |
0.9 |
no |
negative |
|
yes |
3 |
0.8 |
no |
negative |
WP2 uvr A |
no |
3 |
0.9 |
no |
negative |
|
yes |
3 |
0.8 |
no |
negative |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Mode of Action Analysis / Human Relevance Framework
No further details.
Additional information
For the target substance palmitoyl chloride only a study for gene mutation in bacteria are available. To cover the other endpoints studies from the source substances docosanoic acid (CAS 112-85-6) and decanoic acid (CAS 334-48-5) are taken.
Gene mutation in bacteria
Palmitoyl chloride was tested in the standard plate test and in the preincubation test with and without metabolic activation in S. typhimurium TA98, TA100, TA1535, TA1537 and E. coli WP2 uvrA at dose levels of 20 - 5000 and 4 - 2500 µg/plate, respectively. The study was conducted according to the OECD Guidelines 471 and 472, respectively and is reliable without restrictions. No increase in the number of revertants was detected in any strain with and without MA. Vehicle controls and positive controls were valid. Cytotoxicity was found depending on the strain and metabolic activation. Precipitation was reported. According to the results of the pesent study, the test substance palmitoyl chloride ist not nutagenic in the Salmonella typhimurium and Escherichia coli reverse mutation assay under the experimantaa conditions chosen here. (BASF, 1998).
Available studies for the source substance decanoic acid (CAS 334-48-5) and docosanoic acid (CAS 112-85-6).
Genetic toxicity in bacteria was evaluated in a study performed according to GLP and OECD guideline 471and 472, and Japanese Guidelines for Screening Mutagenicity Testing of Chemicals. S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 andE. coli WP2 uvr Awere treated with docosanoic acid (CAS 112-85-6) dissolved in DMSO at concentrations of 156, 313, 625, 1250, 2500 and 5000 µg/plate with and without metabolic activation by S9 mix from livers of male Sprague-Dawley rats induced with phenobarbital and 5,6-benzoflavone. No increase in revertants compared to the vehicle control was observed in any of the strains at all test concentrations. No toxicity was noted up to a concentration of 5000 µg/plate. Thus, docosanoic acid can be regarded as non-mutagenic in bacteria (Nakajima, 2002).
Decanoic acid (CAS 334-48-5) was tested for genetic toxicity in the S. typhimurium strains TA 97, TA 98, TA 100, TA1535 and TA1537 similar to OECD guideline 471. For metabolic activation, cofactor supplemented post-mitochondrial fraction (S9 mix) were used, containing rat or hamster liver enzymes (S9) in a concentration of 10% or 30%. Using the preincubation method 10, 33, 100, 333 and 666 µg decanoic acid/plate with metabolic activation did not reveal any genotoxicity. Also concentrations of 3, 10, 33, 100, 333 and 666 µg/plate without metabolic activation did not reveal an increase in the mean number of revertants compared to the negative control. Slight cytotoxicity was observed at 666 µg/plate (NTP, 1985).
Cytogenicity in mammalian cells
In an vitro mammalian chromosome aberration test was conducted with docosanoic acid (CAS 112-85-6) in accordance with GLP and OECD guideline 473 and Japanese Guidelines for Screening Mutagenicity Testing of Chemicals. Properly maintained Chinese hamster lung (CHL) cells were treated with docosanoic acid dissolved in 1% carboxymethylcellulose sodium at concentrations of 875, 1750 and 3500 µg/mL for 6 hours with and without metabolic activation by S9 mix prepared from phenobarbital- and 5,6-benzoflavone-induced rat livers. The highest test concentration of 3500 µg/mL reflect 0.01 M of the test substance as required in the in OECD guideline 473. In addition, the cells were incubated with 350, 700, 1400, 2800 µg/mL without metabolic activation for 24 hours and with 288, 575, 1150 and 2300 µg/mL without metabolic activation for 48 hours, respectively. The highest concentration of the test item used was set to the maximum one showing no apparent cytotoxic effects during continuous treatment. No increase in chromosomal aberrations nor polyploidy were observed up to the maximum concentration under short-term and continuous treatment with and without metabolic activation.The positive controls included during short-term and continuous exposure showed the expected results and thus verified the sensitivity of the assay (Nakajima, 2002).
The chromosomal aberration-inducing capability (equal or similar to OECD 473) of decanoic acid (CAS 334-48-5) was investigated using female Chinese hamster lung-derived CHL/IU cells, by the short-term treatment method with and without metabolic activation, and by the 24-hour continuous treatment method. Chromosomal observation was performed at 4 doses up to 216 µg/mL (27.0, 54.1, 108 and 216 µg/mL) in the short-term treatment method, and at 4 doses up to 90.0 µg/mL (11.3, 22.5, 45.0 and 90.0 µg/mL) in the 24-hour continuous treatment method. On the short-term treatment at a dose of 54.1 µg/mL without metabolic activation, the incidence of cells having structural aberration was statistically significantly higher than in the negative control. Nevertheless, the incidence of cells having structural aberration was 1.7%, which is within the fluctuation range of the negative control calculated from the background data, the incidence of cells having structural aberration in the negative control was low, at 0%, and the increase was not dosedependent, and so this increase was judged to be accidental rather than a biologically meaningful increase. Moreover, no statistically significant increases were observed at other doses on short-term treatment without metabolic activation, short-term treatment with metabolic activation, or 24-hour continuous treatment. It was therefore judged that exposure to the test substance afforded no biologically significant increase in the incidence of cells having structural chromosomal aberration, or of polyploidy. From the above results, it was judged that this test substance has no chromosomal aberration inducing capability under the conditions of this study (MHW Japan, 2018).
Gene mutation in mammalian cells
An in vitro mammalian cell gene mutation assay was performed with decanoic acid (CAS 334-48-5) under GLP according to OECD guideline 476. In two independent experiments, mouse lymphoma L5178Y cells were treated with decanoic acid at concentrations up to 1.18 mM without metabolic and up to 1.54 mM with metabolic activation by phenobarbital and beta-naphthoflavone-induced rat liver S9-mix, respectively. The exposure duration was 4 hours and 24 hours in experiments without S9 mix and 4 hours in the experiments with S9 mix. The treatment of cells in all experiments was followed by an expression period of 2 days and a selection period of 11-14 days in the presence of trifluorothymidine. Although cytotoxicity was observed at the highest concentrations tested, all mutant values were found to be within the range of the historical control data of the test facility, so that decanoic acid was regarded not to be mutagenic. In addition, colony sizing was performed for the highest concentrations used to detect potential clastogenic effects and/or chromosomal aberrations. As result, decanoic acid was found not to be clastogenic at all dose groups tested. The positive controls caused a pronounced increase in the mutation frequency demonstrating the sensitivity of the test system (Trenz, 2010).
Justification for classification or non-classification
No classification suggested for mutagenicity as criteria of regulation 1272/2008/EC are not met.
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