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EC number: 204-622-5 | CAS number: 123-35-3
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Negative results were obtained with myrcene in in vitro tests (mutation in bacterial strains, cytogenicity and gene mutation tests in mammalian cells).
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1999
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- GLP study conducted equivalent or similar to OECD Guideline 471 with deviations: one stain missing and no individual plate counts available.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- one stain missing and no individual plate counts
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Not applicable
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- not applicable
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- 10 or 30% S9 fraction of Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver
- Test concentrations with justification for top dose:
- 0, 33, 100, 333, 1000, 3333 or 10000 µg/plate
- Vehicle / solvent:
- No data
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene (with all strains)
- Remarks:
- with metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: sodium azide (TA100 and TA1535), 9-aminoacridine (TA97), 4-nitro-o-phenylenediamine (TA98)
- Remarks:
- without metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: In agar (plate incorporation)
DURATION
- Exposure duration: 20 minutes at 37 °C and 2 days at 37 °C
NUMBER OF REPLICATIONS: Triplicate - Evaluation criteria:
- - A positive response is defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination.
- An equivocal response is defined as an increase in revertants that is not dose related, is not reproducible, or is not of sufficient magnitude to support a determination of mutagenicity.
- A negative response is obtained when no increase in revertant colonies is observed following chemical treatment.
- There is no minimum percentage or fold increase required for a chemical to be judged positive or weakly positive.
- Statistics:
- No data
- Key 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:
- cytotoxicity
- Remarks:
- at or above 3333 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- None
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- β-Myrcene was not mutagenic in S. typhimurium TA1535, TA 1537, TA 98 and TA 100 with and without metabolic activation.
- Executive summary:
An Ames test was performed to determine the mutagenicity potential of β‑myrcene according to a method equivalent or similar to Guideline OECD 471 in compliance with Good Laboratory Practice Regulations.
Salmonella typhimurium strains TA1535, 1537, 98 and 100 were treated with β‑myrcene using the plate incorporation method at concentration range of 33 - 10000 µg/plate both with and without metabolic activation (10 or 30% S9 fraction of Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver). Concurrent strain-specific positive and solvent controls, both with and without metabolic activation, were included in each assay.
Positive controls induced appropriate responses in the corresponding strains. β-Myrcene showed no substantial increase in revertant colony members over control at any concentrations in presence and absence of metabolic activation.
Therefore, β-myrcene is not considered as mutagenic according to Directive 67/548/EEC and CLP regulation (EC) N° 1272/2008.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2007
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Study performed similary to OECD Guideline 471 with deviations: only 3 strains tested and no individual plate counts available.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- only 3 strains tested, no individual plate counts
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Not applicable
- Species / strain / cell type:
- S. typhimurium TA 98
- Details on mammalian cell type (if applicable):
- not applicable
- Additional strain / cell type characteristics:
- not specified
- Species / strain / cell type:
- S. typhimurium TA 100
- Details on mammalian cell type (if applicable):
- not applicable
- Additional strain / cell type characteristics:
- not specified
- Species / strain / cell type:
- E. coli WP2 uvr A pKM 101
- Details on mammalian cell type (if applicable):
- not applicable
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- 10% rat liver S9
- Test concentrations with justification for top dose:
- - TA98 and TA100: 0, 10, 25, 50, 75, 100, 250, 500 or 750 µg/plate
- Escherichia coli WP2 uvrA/pKM101: 0, 50, 100, 500, 1000, 2000, 5000 or 10000 µg/plate - Vehicle / solvent:
- No data
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene (with all strains)
- Remarks:
- with metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: sodium azide (TA100), 4-nitro-o-phenylenediamine (TA98) and methyl methanesulfonate (pKM101)
- Remarks:
- without metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: In agar (plate incorporation);
DURATION
- Exposure duration: 20 minutes at 37 °C and 2 days at 37 °C
NUMBER OF REPLICATIONS: Triplicate - Evaluation criteria:
- - A positive response is defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination.
- An equivocal response is defined as an increase in revertants that is not dose related, is not reproducible, or is not of sufficient magnitude to support a determination of mutagenicity.
- A negative response is obtained when no increase in revertant colonies is observed following chemical treatment.
- There is no minimum percentage or fold increase required for a chemical to be judged positive or weakly positive.
- Statistics:
- No data
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- 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
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- 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
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- None
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- β-Myrcene was not mutagenic in S. typhimurium TA 98 and TA 100 or Escherichia coli WP2uvrA/pKM101 with and without metabolic activation.
- Executive summary:
An Ames test was performed to determine the mutagenicity potential of β‑myrcene according to method equivalent or similar to OECD Guideline 471 in compliance with Good Laboratory Practice Regulations.
Salmonella typhimurium strains (TA98 and 100) or Escherichia coli WP2uvrA/pKM101 were treated with β‑myrcene at concentration range of 0 -750 µg/plate or 0 -10000 µg/plate, respectively both with and without metabolic activation (10% S9 fraction of rat liver) using the plate incorporation method. Concurrent strain-specific positive and solvent controls, both with and without metabolic activation, were included in each assay.
Positive controls induced appropriate responses in the corresponding strains. β-Myrcene showed no substantial increase in revertant colony members over control at any concentrations in presence and absence of metabolic activation.
Therefore, β-myrcene is not considered as mutagenic according to Directive 67/548/EEC and CLP regulation (EC) N° 1272/2008.
- 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
- Study period:
- 1991
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Study conducted similarly to guideline 473 with minor deviations: no details on test material, one concentration higher than limit of solubility is missing, no diploidy and endoreplication recorded, only one experiment performed, duration of exposures with test item
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- no details on test material, one concentration higher than limit of solubility is missing, no diploidy and endoreplication recorded, only one experiment performed, duration of exposures with test item
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- no
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- Not applicable
- Species / strain / cell type:
- lymphocytes: Human
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix prepared from liver homogenate from Aroclor-1254-induced rats with an addition of cofactors
- Test concentrations with justification for top dose:
- 100, 500 and 1000 µg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: ethyl methanesulfonate without S9, cyclophosphamide with S9
- Details on test system and experimental conditions:
- The test was performed according to published recommendations [Preston et al., 1987].
Peripheral blood samples were obtained from two healthy probands (one male, one female, both non-smokers). 0.3 mL whole blood was cultivated in chromosome medium B (Biochrom, final volume: 2.5 mL) for 72 h at 37°C. The test substance was added after 48 h either for a period of 24 h without S9-mix or for 2 h with S9-mix. Colcemid (5 x 10-7 M) was added for the last two hours. After the treatment, the medium was changed. The cultures were centrifuged for 10 min at 900 rpm and rinsed once with Hank's solution.
Chromosomes were prepared according to standard procedures. Hypotonic treatment was performed with 0.4% KCI (37°C) for 15 min. The cells were fixed with methanol: acetic acid 3:1 and the fixative was changed twice. Air dried slides were stained with Giemsa (5% in Sorensen buffer). Chromosome aberrations were scored in 100 metaphases acording to the following criteria:
- Gap: acromatic region in one chromatid (chromatid-type) or both chromatids (chromosome-type) smaller than the width of a chromatid.
- Break: acromatic region in one chromatid (chromatid-type) or both chromatids (chromosome-type) greater than the width of a chromatid or a discontinuity with displacement.
- Exchange: aberrations arising from an exchange between chromosomes or within a chromosome. Chromosome-type exchanges occur as dicentric or ring chromosomes in metaphase cells while chromatid-type exchanges are recognized as different types of "exchange figures".
The mitotic index (MI) was determined for 1000 cells and given as number of mitoses per 1000 cells. - Evaluation criteria:
- No data
- Statistics:
- None
- Key result
- Species / strain:
- lymphocytes: Human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- No data
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- beta-Myrcene was not clastogenic in human lymphocytes exposed in vitro and does not need to be classified according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.
- Executive summary:
In a study conducted similarly to OECD Guideline 473, human lymphocytes were exposed to beta-myrcene dissolved in ethanol, at 100, 500 and 1000 μg/mL with and without S9 metabolic activation. Whole blood was cultivated in chromosome medium B for 72 h at 37°C. The test substance was added after 48 h either for a period of 24 h without S9-mix or for 2 h with S9-mix. Colcemid was added for the last two hours.
Positive controls (ethyl methanesulfonate without S9, cyclophosphamide with S9) induced the appropriate response. Negative controls (medium only and solvent) were also valid. No cytotoxicity was observed but beta-myrcene was tested up to precipitating concentrations. Chromosome aberrations were not induced over background at any tested concentrations in the absence and the presence of activation system.
Therefore, beta-myrcene was not clastogenic in human lymphocytes exposed in vitro and does not need to be classified according to Directive 67/548/EEC and CLP Regulation (EC) No 1272 /2008.
- 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:
- 1991
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Study conducted similarly to guideline 476 with minor deviations: no details on test material, only one replicate of treated cultures/dose (also for solvent) and only 3 doses tested instead of 4
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- yes
- Remarks:
- no details on test material, only one replicate of treated cultures/dose (also for solvent) and only 3 doses tested instead of 4
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- no
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- V79 gene
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- The V79-gene mutation test was performed according to the guidelines published for CHO-cells by Li et al., 1987
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix prepared from liver homogenate from Aroclor-1254-induced rats with an addition of cofactors
- Test concentrations with justification for top dose:
- 100, 500 and 1000 µg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: ethyl methanesulfonate without S-9, benzo[a]pyrene with S-9
- Details on test system and experimental conditions:
- The V79-gene mutation test was performed according to the guidelines published for CHO-cells by Li et al., 1987.
About 5 x 10^6 cells were tested in each experiment. The cells were exposed to myrcene or the control substances for 3 h either in the presence or in the absence of S-9-mix. The relative plating efficiency (PE1) was determined by plating 200 cells into 5 replica Petri dishes at the end of the treatment. Cells were transferred as needed during the expression period. After 7 days, 2 x 10^5 cells were plated into 5 replica Petri dishes with selective medium (10 µg/mL 6-thioguanine). At the time of replating into selective medium, the plating efficiency (PE2) was determined in non-selective medium (five 60 mm replica Petri dishes with 200 cells each). After 1 week, the colonies were fixed with methanol, stained, and counted. - Evaluation criteria:
- No data
- Statistics:
- None
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- The results are expressed as mutants per million surviving cells.
No (or marginal) signs of citotoxicity were observed. No increase of thioguanine-resistant colonies was found compared with the control. - Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- beta-Myrcene was not mutagenic in CHO cells and does not need to be classified according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.
- Executive summary:
In a study conducted similarly to OECD Guideline 476, CHO cells were exposed to beta-myrcene dissolved in ethanol, at 100, 500 and 1000 µg/mL with and without S9 metabolic activation for 3 h. V79 gene was the target gene. About 5 x 106 cells were tested in each experiment. The relative plating efficiency (PE1) was determined by plating 200 cells into 5 replica Petri dishes at the end of the treatment. Cells were transferred as needed during the expression period. After 7 days, 2 x 105 cells were plated into 5 replica Petri dishes with selective medium (10 µg/mL 6-thioguanine). At the time of replating into selective medium, the plating efficiency (PE2) was determined in non-selective medium (five replica Petri dishes with 200 cells each). After 1 week, the colonies were fixed with methanol, stained, and counted.
Positive controls (ethyl methanesulfonate without S9, benzo[a]pyrene with S9) induced the appropriate response. Negative controls (medium only and solvent) were also valid. No cytotoxicity was observed. No increase of thioguanine-resistant colonies was found compared with the control at any tested concentrations in the absence and the presence of activation system.
Therefore, beta-myrcene was not mutagenic in CHO cells and does not need to be classified according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.
- Endpoint:
- in vitro DNA damage and/or repair study
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1991
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Study conducted similarly to guideline 479 with minor deviations: no details on test substance.
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 479 (Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells)
- Deviations:
- yes
- Remarks:
- no details on test substance
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- no
- Type of assay:
- sister chromatid exchange assay in mammalian cells
- Target gene:
- Not applicable
- Species / strain / cell type:
- lymphocytes: Human
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix prepared from liver homogenate from Aroclor-1254-induced rats with an addition of cofactors
- Test concentrations with justification for top dose:
- 100, 500 and 1000 µg/mL
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: ethyl methanesulfonate without S9, cyclophosphamide with S9
- Key result
- Species / strain:
- lymphocytes: Human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- beta-Myrcene was not clastogenic in human lymphocytes exposed in vitro and does not need to be classified according toDirective 67/548/EEC and CLP Regulation (EC) No 1272/2008.
- Executive summary:
In a study conducted similarly to OECD Guideline 479, human lymphocytes were exposed to beta-myrcene dissolved in ethanol, at 100, 500 and 1000 μg/mL with and without S9 metabolic activation. Whole blood was cultivated in chromosome medium B for 72 h at 37°C. Bromodeoxyuridine (BrdU) was added at the start of the culture in a concentration of 10 µg/mL. The test substance was added after 48 h either for a period of 24 h without S9-mix or for 2 h with S9-mix. Colcemid was added for the last two hours. After the treatment, the medium was changed. The cultures were centrifuged and rinsed. Slides were stained according to a modified fluorescent plus Giemsa technique. Twenty five second division metaphases were evaluated for each SCE data point.
Positive controls (ethyl methanesulfonate without S9, cyclophosphamide with S9) induced the appropriate response. Negative controls (medium only and solvent) were also valid. No cytotoxicity was observed but beta-myrcene was tested up to precipitating concentrations. SCE were not induced over background at any tested concentrations in the absence and the presence of activation system.
Therefore, beta-myrcene was not clastogenic in human lymphocytes exposed in vitro and does not need to be classified according to Directive 67/548/EEC and CLP Regulation (EC) No 1272 /2008.
Referenceopen allclose all
Table 1: Mutagenicity of β-Myrcene in Salmonella typhimuriuma
Strain |
Dose (µg/plate) |
Revertants/Plateb |
|||||
–S9 |
+hamster S9 |
+rat S9 |
|||||
Trial 1 |
Trial 2 |
10% |
30% |
10% |
30% |
||
Study performed at SRI International |
|||||||
TA100 |
0 |
103 ± 2.0 |
114 ± 6.0 |
104 ± 8.0 |
108 ± 6.0 |
107 ± 8.0 |
110 ± 5.0 |
|
33 |
113 ± 6.0 |
96 ± 11.0 |
98 ± 6.0 |
|
126 ± 22.0 |
|
|
100 |
100 ± 6.0 |
116 ± 0.0 |
103 ± 7.0 |
94 ±6.0 |
116 ± 10.0 |
119 ± 4.0 |
|
333 |
96 ± 8.0 |
107 ± 10.0 |
101 ± 10.0 |
101 ± 4.0 |
115 ± 21.0 |
113 ± 4.0 |
|
1000 |
100 ± 6.0 |
117 ± 3.0 |
81 ± 4.0 |
111 ± 4.0 |
90 ± 14.0 |
111 ± 10.0 |
|
3333 |
66 ± 6.0c |
70 ± 9.0c |
59 ± 4.0c |
107 ± 10.0 |
55 ± 8.0c |
103 ± 4.0 |
|
10000 |
|
|
|
75 ± 6.0c |
|
77 ± 2.0c |
Trial summary |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
|
Positive controld |
781 ± 17.0 |
765 ± 39.0 |
597 ± 8.0 |
663 ± 31.0 |
488 ± 23.0 |
553 ± 52.0 |
|
TA1535 |
0 |
9 ± 2.0 |
13 ± 2.0 |
10 ± 2.0 |
9 ± 0.0 |
9 ± 1.0 |
12 ± 1.0 |
|
33 |
9 ± 2.0 |
8 ± 2.0 |
12 ± 3.0 |
|
10 ± 1.0 |
|
|
100 |
6 ± 1.0 |
10 ± 2.0 |
9 ± 1.0 |
11 ± 1.0 |
12 ± 1.0 |
11 ± 1.0 |
|
333 |
10 ± 1.0 |
9 ± 1.0 |
8 ± 3.0 |
9 ± 1.0 |
11 ± 1.0 |
10 ± 1.0 |
|
1000 |
9 ± 1.0 |
9 ± 1.0 |
9 ± 2.0 |
10 ± 2.0 |
10 ± 1.0 |
9 ± 0.0 |
|
3333 |
6 ± 0.0c |
7 ± 1.0c |
4 ± 1.0c |
5 ± 1.0 |
5 ± 0.0c |
10 ± 1.0 |
|
10000 |
|
|
|
5 ± 2.0c |
|
8 ± 0.0c |
Trial summary |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
|
Positive controld |
700 ± 13.0 |
819 ± 48.0 |
92 ± 11.0 |
363 ± 5.0 |
89 ± 12.0 |
196 ± 8.0 |
|
TA97 |
0 |
106 ± 0.0 |
126 ± 16.0 |
162 ± 9.0 |
144 ± 4.0 |
172 ± 7.0 |
145 ± 7.0 |
|
33 |
104 ± 7.0 |
111 ± 9.0 |
167 ± 5.0 |
|
157 ± 6.0 |
|
|
100 |
100 ± 8.0 |
127 ± 10.0 |
159 ± 3.0 |
149 ± 4.0 |
154 ± 10.0 |
128 ± 11.0 |
|
333 |
96 ± 4.0 |
142 ± 13.0 |
151 ± 16.0 |
112 ± 2.0 |
161 ± 7.0 |
106 ± 5.0 |
|
1000 |
106 ± 6.0 |
144 ± 14.0 |
142 ± 18.0 |
117 ± 11.0 |
153 ± 8.0 |
121 ± 10.0 |
|
3333 |
63 ± 29.0c |
77 ± 6.0c |
106 ± 3.0c |
125 ± 7.0 |
89 ± 21.0c |
132 ± 2.0 |
|
10000 |
|
|
|
117 ± 9.0c |
|
124 ± 2.0c |
Trial summary |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
|
Positive controld |
293 ± 22.0 |
575 ± 53.0 |
689 ± 1.0 |
609 ± 28.0 |
648 ± 15.0 |
431 ± 35.0 |
|
TA98 |
0 |
22 ± 4.0 |
16 ± 2.0 |
19 ± 4.0 |
16 ± 1.0 |
19 ± 3.0 |
17 ± 2.0 |
|
33 |
12 ± 2.0 |
9 ± 1.0 |
23 ± 2.0 |
|
26 ± 1.0 |
|
|
100 |
16 ± 2.0 |
11 ± 1.0 |
19 ± 1.0 |
18 ± 2.0 |
20 ± 3.0 |
13 ± 2.0 |
|
333 |
19 ± 5.0 |
11 ± 2.0 |
22 ± 4.0 |
18 ± 4.0 |
19 ± 1.0 |
16 ± 1.0 |
|
1000 |
24 ± 5.0 |
11 ± 1.0 |
20 ± 1.0 |
23 ± 4.0 |
18 ± 0.0 |
13 ± 2.0 |
|
3333 |
8 ± 2.0c |
7 ± 1.0c |
8 ± 1.0c |
22 ± 2.0 |
12 ± 3.0c |
18 ± 3.0 |
|
10000 |
|
|
|
9 ± 1.0c |
|
11 ± 3.0c |
Trial summary |
Negative |
Negative |
Negative |
Negative |
Negative |
Negative |
|
Positive controld |
294 ± 8.0 |
269 ± 5.0 |
278 ± 21.0 |
237 ± 16.0 |
206 ± 26.0 |
251 ± 21.0 |
|
a The detailed protocol for the SRI International study is presented by Zeiger et al. (1992); the study performed at SITEK Research
Laboratories used a modification of that protocol, 0 µg/plate was the solvent control
b Revertants are presented as mean ± standard error from three plates.
c Slight toxicity
d The positive controls in the absence of metabolic activation were sodium azide (TA100 and TA1535), 9-aminoacridine (TA97) and 4-nitro-o-phenylenediamine (TA98. The positive control for metabolic activation with all strains was 2-aminoanthracene.
Table 1: Mutagenicity of β-Myrcene in Salmonella typhimurium
| Strain | Dose (µg/plate) | Revertants/Plate | ||||
| –S9 | +10% rat S9 | |||||
| Trial 1 | Trial 2 | Trial 3 | Trial 1 | Trial 2 | ||
| Study performed at SITEK Research Laboratories | ||||||
| TA100 | 0 | 57 ± 7.0 | 36 ± 3.0 | 45 ± 3.0 | 83 ± 12.0 | 56 ± 2.0 |
| 10 | 66 ± 6.0 | 47 ± 5.0 | 54 ± 1.0 | 78 ± 11.0 | ||
| 25 | 35 ± 6.0 | 48 ± 5.0 | 28 ± 1.0 | |||
| 50 | 7 ± 1.0 | 42 ± 3.0 | 24 ± 2.0 | 65 ± 6.0 | 61 ± 3.0 | |
| 75 | 8 ± 1.0 | 42 ± 5.0 | 27 ± 2.0 | |||
| 100 | Toxic | Toxic | 28 ± 4.0 | 69 ± 8.0 | 56 ± 6.0 | |
| 250 | 62 ± 3.0 | 42 ± 4.0 | ||||
| 500 | 48 ± 4.0 | 20 ± 2.0 | ||||
| 750 | 12 ± 1.0 | |||||
| Trial summary | Negative | Negative | Negative | Negative | Negative | |
| Positive control | 387 ± 19.0 | 403 ± 12.0 | 653 ± 32.0 | 738 ± 31.0 | 665 ± 29.0 | |
| TA98 | 0 | 21 ± 2.0 | 35 ± 3.0 | 30 ± 4.0 | 22 ± 2.0 | |
| 10 | 16 ± 1.0 | 15 ± 4.0 | 27 ± 3.0 | |||
| 25 | 6 ± 0.0 | |||||
| 50 | 6 ± 0.0 | 14 ± 3.0 | 26 ± 2.0 | 27 ± 3.0 | ||
| 75 | 4 ± 1.0 | |||||
| 100 | 5 ± 1.0 | 10 ± 0.0 | 25 ± 2.0 | 28 ± 5.0 | ||
| 250 | 7 ± 3.0 | 23 ± 1.0 | 25 ± 4.0 | |||
| 500 | 5 ± 1.0 | 16 ± 1.0 | 23 ± 2.0 | |||
| 750 | 11 ± 2.0 | |||||
| Trial summary | Negative | Negative | Negative | Negative | ||
| Positive control | 295 ± 14.0 | 417 ± 31.0 | 418 ± 22.0 | 372 ± 38.0 | ||
| Escherichia coli WP2 uvrA/pKM101 | ||||||
| 0 | 181 ± 46.0 | 144 ± 6.0 | 158 ± 4.0 | 168 ± 2.0 | 200 ± 7.0 | |
| 50 | 111 ± 5.0 | |||||
| 100 | 86 ± 4.0 | |||||
| 500 | 57 ± 6.0 | 84 ± 5.0 | 149 ± 4.0 | 174 ± 1.0 | 204 ± 6.0 | |
| 1000 | 74 ± 6.0 | 74 ± 4.0 | 149 ± 2.0 | 156 ± 5.0 | 218 ± 15.0 | |
| 2000 | 70 ± 5.0 | 147 ± 6.0 | 164 ± 4.0 | 190 ± 12.0 | ||
| 5000 | 99 ± 7.0 | 76 ± 1.0 | 134 ± 6.0 | 166 ± 11.0 | 190 ± 3.0 | |
| 10000 | 82 ± 3.0 | 84 ± 5.0 | 149 ± 7.0 | 177 ± 14.0 | 186 ± 18.0 | |
| Trial summary | Negative | Negative | Negative | Negative | Negative | |
| Positive control | 1183 ± 140.0 | 807 ± 71.0 | 806 ± 76.0 | 814 ± 45.0 | 823 ± 3.0 | |
Table 1: effect of myrcene on chromosome aberrations in human lymphocytes without S9
Treatment |
Donor |
MI |
Cells scored |
% cells with aberrations |
Chromatid-type |
Chromosome-type |
|||||
With gaps |
Without gaps
|
Gap |
Break |
Exchange |
Gap |
Break |
Exchange |
||||
Control |
f |
47 |
100 |
7 |
1 |
5 |
1 |
- |
1 |
- |
- |
m |
48 |
100 |
6 |
3 |
3 |
3 |
- |
- |
- |
- |
|
Solvent |
f |
19 |
100 |
6 |
3 |
2 |
3 |
- |
1 |
- |
- |
m |
47 |
100 |
12 |
3 |
10 |
4 |
- |
1 |
- |
- |
|
Myrcene (µg/mL) |
|
|
|
|
|
|
|
|
|
|
|
100 |
f |
50 |
100 |
4 |
1 |
3 |
1 |
- |
- |
- |
- |
m |
32 |
100 |
7 |
1 |
7 |
1 |
- |
- |
- |
- |
|
500 |
f |
48 |
100 |
2 |
0 |
2 |
- |
- |
- |
- |
- |
m |
30 |
100 |
8 |
3 |
5 |
2 |
- |
1 |
1 |
- |
|
1000 |
f |
31 |
100 |
10 |
3 |
8 |
3 |
- |
1 |
- |
- |
m |
32 |
100 |
10 |
3 |
8 |
3 |
- |
- |
- |
- |
|
EMS (5 x 10-3 M) |
f |
14 |
50 |
66 |
48 |
8 |
18 |
12 |
2 |
2 |
- |
m |
21 |
50 |
46 |
20 |
11 |
12 |
- |
3 |
- |
- |
|
Table 2: effect of myrcene on chromosome aberrations in human lymphocytes with S9
Treatment |
Donor |
MI |
Cells scored |
% cells with aberrations |
Chromatid-type |
Chromosome-type |
|||||
With gaps |
Without gaps
|
Gap |
Break |
Exchange |
Gap |
Break |
Exchange |
||||
Control |
f |
41 |
100 |
2 |
0 |
2 |
- |
- |
- |
- |
- |
m |
60 |
100 |
3 |
0 |
2 |
- |
- |
1 |
- |
- |
|
Solvent |
f |
nd |
100 |
- |
- |
- |
- |
- |
- |
- |
- |
m |
55 |
100 |
4 |
3 |
1 |
3 |
- |
- |
- |
- |
|
Myrcene (µg/mL) |
|
|
|
|
|
|
|
|
|
|
|
100 |
f |
36 |
100 |
4 |
1 |
2 |
1 |
- |
- |
- |
- |
m |
51 |
100 |
6 |
0 |
3 |
- |
- |
- |
- |
- |
|
500 |
f |
50 |
100 |
4 |
0 |
5 |
- |
- |
- |
- |
- |
m |
56 |
100 |
6 |
1 |
5 |
- |
- |
- |
- |
1 |
|
1000 |
f |
65 |
100 |
4 |
0 |
4 |
- |
- |
- |
- |
- |
m |
55 |
100 |
5 |
0 |
5 |
- |
- |
- |
- |
- |
|
CP (2 x 10-4 M) |
f |
54 |
50 |
22 |
12 |
5 |
5 |
1 |
3 |
- |
- |
m |
59 |
50 |
30 |
16 |
5 |
6 |
1 |
1 |
- |
1 |
|
Nd: no data due to contamination of the culture
Table 1: effect of myrcene on gene mutations in the in vitro V79 HPRT assay without S9-mix
|
Plating efficiency |
Mutation frequency/ 106survivors |
|
Treatment |
PE1 (%) |
PE2 (%) |
|
Control |
100 |
100 |
10 |
Solvent |
100 |
97 |
0 |
Myrcene (µg/mL) |
|
|
|
100 |
92 |
103 |
10 |
500 |
94 |
95 |
13 |
1000 |
90 |
99 |
5 |
EMS (5 x 10-3 M) |
90 |
92 |
218 |
Table 2: effect of myrcene on gene mutations in the in vitro V79 HPRT assay with S9-mix
|
Plating efficiency |
Mutation frequency/ 106survivors |
|
Treatment |
PE1 (%) |
PE2 (%) |
|
Control |
100 |
100 |
6 |
S9-mix (4%) |
84 |
50 |
0 |
Myrcene (µg/mL) |
|
|
|
100 |
90 |
117 |
0 |
500 |
101 |
94 |
0 |
1000 |
108 |
98 |
4 |
BP (5 x 10-5 M) |
78 |
100 |
262 |
Table 1: effect of myrcene on SCE in human lymphocytes without S9
Treatment |
Mitotic index |
Proliferation index |
SCE ± SEM |
Female blood
|
|
||
Control |
24 |
2.0 |
8.9 ± 0.7 |
Solvent |
20 |
1.9 |
8.0 ± 0.6 |
Myrcene (µg/mL)
|
|
|
|
100 |
22 |
1.9 |
8.8 ± 0.7 |
500 |
27 |
2.0 |
8.3 ± 0.6 |
1000 |
21 |
1.8 |
7.9 ± 0.7 |
EMS (10-3 M) |
18 |
1.8 |
26.3 ± 1.7 |
Male blood |
|
||
Control |
45 |
2.0 |
7.9 ± 0.6 |
Solvent |
23 |
2.0 |
8.5 ± 0.5 |
Myrcene (µg/mL) |
|
||
100 |
24 |
1.8 |
8.7 ± 0.9 |
500 |
23 |
2.0 |
7.8 ± 0.6 |
1000 |
23 |
1.9 |
8.2 ± 0.6 |
EMS (10-3M) |
25 |
2.2 |
20.8 ± 0.9 |
Table 2: effect of myrcene on SCE in human lymphocytes with S9
Treatment |
Mitotic index |
Proliferation index |
SCE ± SEM |
Female blood
|
|
||
Control |
43 |
2.0 |
6.0 ± 0.5 |
Solvent |
45 |
2.1 |
7.0 ± 0.5 |
Myrcene (µg/mL)
|
|
|
|
100 |
45 |
2.0 |
6.4 ± 0.4 |
500 |
41 |
2.1 |
8.1 ± 0.6 |
1000 |
47 |
2.2 |
7.0 ± 0.6 |
CP (5x10-5 M) |
28 |
1.8 |
37.6 ± 2.0 |
Male blood |
|
||
Control |
52 |
2.3 |
9.0 ± 0.7 |
Solvent |
19 |
2.0 |
8.5 ± 0.7 |
Myrcene (µg/mL) |
|
||
100 |
26 |
1.9 |
9.0 ± 0.6 |
500 |
41 |
2.0 |
7.2 ± 0.5 |
1000 |
37 |
1.9 |
9.6 ± 0.7 |
CP (5x10-5 M) |
23 |
1.8 |
48.9 ± 2.6 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Negative results were obtained with myrcene in in vivo tests (chromosome aberration test on rat bone marrow cells and micronucleus test in mouse erythrocytes).
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2001
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- GLP study conducted similarly to OECD Guideline 474 with deviations: positive control not used, individual animal data not reported, delay between end of treatment and harvest of cells not mentioned
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- positive control not used, individual animal data not reported, delay between end of treatment and harvest of cells not mentioned
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Taconic Farms, Inc. (Germantown, USA)
- Age at study initiation: 5-6 weeks
- Housing: 1 (males) or 5 (females) animals/cage; polycarbonate cages; changed at least twice weekly
- Diet (e.g. ad libitum): Irradiated NTP-2000 wafer feed (Zeigler Brothers, Inc., Gardners, PA), available ad libitum; changed at least weekly
- Water (e.g. ad libitum): Tap water (City of Columbus municipal supply) via automatic watering system, available ad libitum
- Acclimation period: 13 (females) or 14 (males) days
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72 ± 3 °F
- Humidity (%): 50 ± 15 %
- Air changes (per h): 10/h
- Photoperiod (h dark / h light): 12 h dark / 12 h fluorescent light - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: Corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Dosing solutions were prepared with corn oil
- Duration of treatment / exposure:
- 14 weeks
- Frequency of treatment:
- 5 days/week
- Post exposure period:
- Not applicable
- Remarks:
- Doses / Concentrations:
0, 250, 500, 1000 and 2000 mg/kg bw
Basis:
actual ingested - No. of animals per sex per dose:
- 0-1000 mg/kg bw groups: 5 animals/sex/dose
2000 mg/kg bw: 1 male and 2 females - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- None
- Tissues and cell types examined:
- Peripheral blood samples
- Details of tissue and slide preparation:
- TREATMENT AND SAMPLING TIMES: Peripheral blood samples were obtained from male and female mice at the end of 3 month study
DETAILS OF SLIDE PREPARATION: Smears were immediately prepared and fixed in absolute methanol. The methanol fixed slides were stained with acridine orange and coded.
METHOD OF ANALYSIS: Slides were scanned to determine the frequency of micronuclei in 2000 normochromatic erythrocytes (NCEs) per animal. In addition, the percentage of polychromatic erythrocytes (PCEs) in a population of 1000 erythrocytes was determined as a measure of bone marrow toxicity - Evaluation criteria:
- No data
- Statistics:
- - Results were analyzed by a statistical software package
- Significance of micronucleated NCEs/1000 NCEs tested by the one-tailed Cochran-Armitage trend test (significant at P ≤ 0.025), followed by Pairwise comparison with the vehicle controls (significant at P ≤ 0.008)
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- not applicable
- Additional information on results:
- RESULTS OF DEFINITIVE STUDY
- Frequency of micronuclei in peripheral blood erythrocytes: See table 1 - Conclusions:
- β-Myrcene was not mutagenic in the mouse peripheral blood micronucleus test.
- Executive summary:
A mouse peripheral blood micronucleus test was conducted to determine the mutagenicity potential of β-myrcene according to method equivalent or similar to OECD Guideline 474 in compliance with GLP.
Peripheral blood samples were obtained from male and female mice at the end of a 3 -month study. β-Myrcene (0, 250, 500, 1000 and 2000 mg/kg bw) was administered orally (gavage) to male and female B6C3F1 mice (5/sex/dose) for 14 weeks. Smears slides were immediately prepared and scanned to determine the frequency of micronuclei in 2000 normochromatic erythrocytes (NCEs) per animal. In addition, the percentage of polychromatic erythrocytes (PCEs) in a population of 1000 erythrocytes was determined as a measure of bone marrow toxicity.
No increase in the frequency of micronucleated NCEs was observed in peripheral blood samples in male or female B6C3F1 mice that administered β‑myrcene. The percentage of reticulocytes among total erythrocytes (% PCEs) increased slightly with dose, but remained within the normal range, suggesting an absence of β‑myrcene-induced bone marrow toxicity over this dose range.
Therefore, β‑myrcene was not mutagenic in the mouse peripheral blood micronucleus test.
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1993
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- GLP study conducted similarly to OECD Guideline 474 with deviations: only 4 animals/dose but 8 at the highest dose, only 50 cells analysed/animal, treatment with colchicine only 1 h before harvest
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- only 4 animals/dose but 8 at the highest dose, only 50 cells analysed/animal, treatment with colchicine only 1 h before harvest
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- no
- Type of assay:
- chromosome aberration assay
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: FIOCRUZ breeding stock
- Weight at study initiation: males: 250 g (223 to 270 g); females: 178 g (168 to 186 g) - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: Corn oil
- Duration of treatment / exposure:
- Test substance administered once
- Frequency of treatment:
- Test substance administered once
- Post exposure period:
- 24 or 48 h
- Remarks:
- Doses / Concentrations:
0.1, 0.5 and 1.0 g/kg bw
Basis:
actual ingested - No. of animals per sex per dose:
- 2 or 4
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide, 30 mg/kg bw
- Tissues and cell types examined:
- Bone marrow from femur.
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- β-myrcene was not clastogenic in the in vivo bone marrow chromosome aberration test.
- Executive summary:
A chromosome aberration test on rat bone marrow was conducted similarly to OECD Guideline 475. 2 to 4 rats/sex/dose were administered beta-myrcene in corn oil at 100, 500 and 1000 mg/kg bw. A positive control group received cyclophosphamide, 30 mg/kg bw, by the intraperitoneal route.
A mitotic inhibitor (colchicine, 5 mg/kg ip) was injected 1 h before sacrifice.
A single sampling time of 24 h after drug or vehicle administration was fixed for all but one of the groups. An additional group with a sampling time of 48 h was included for the highest myrcene dose. Fifty metaphase cells were examined per animal and chromosome aberrations (chromatid-type and chromosome-type breaks and exchanges) were scored.
Myrcene administration to the rats caused a dose-related increase in mitotic index but not increase in chromosome aberrations, contrary to the positive control group.
Therefore, β‑myrcene was not clastogenic in the in vivo bone marrow chromosome aberration test.
Referenceopen allclose all
Table 1: Frequency of micronuclei in peripheral blood erythrocytes of mice following administration of β-myrcene by gavage for 3 monthsa
Compound |
Exposure concentration (mg/kg bw) |
Number of Mice with Erythrocytes Scored |
Micronucleated NCEs/ 1000 NCEsb |
P Valuec |
PCEsb (%) |
Male |
|||||
Corn oild |
0 |
5 |
1.00 ± 0.22 |
|
1.720 ± 0.27 |
β-myrcene |
250 |
5 |
0.40 ± 0.19 |
0.9457 |
2.420 ± 0.35 |
500 |
5 |
1.00 ± 0.27 |
0.5 |
2.820 ± 0.38 |
|
1000 |
5 |
1.40 ± 0.24 |
0.207 |
2.480 ± 0.21 |
|
2000e |
1 |
|
|
|
|
|
|
P=0.069f |
|
|
|
Female |
|||||
Corn oil |
0 |
5 |
1.30 ± 0.34 |
|
2.060 ± 0.27 |
β-myrcene |
250 |
5 |
0.40 ± 0.19 |
0.9855 |
2.500 ± 0.23 |
500 |
5 |
1.50 ± 0.35 |
0.3526 |
2.640 ± 0.37 |
|
1000 |
5 |
1.20 ± 0.34 |
0.5793 |
2.180 ± 0.27 |
|
2000e |
2 |
|
|
|
|
|
|
P = 0.299 |
|
|
|
a Study was performed at SITEK Research Laboratories; PCE=polychromatic erythrocyte; NCE=normochromatic erythrocyte.
b Mean ± standard error
c Pairwise comparison with the vehicle control group; significant at P ≤ 0.008
d Vehicle control
e Insufficient number of animals available for statistical analysis
f Significance of micronucleated NCEs/1000 NCEs tested by the one-tailed trend test, significant at P ≤ 0.025
Myrcene administration to the rats caused a dose-related increase in mitotic index.
Table 1: frequency of chromosome aberrations in bone marrow cells of rats treated with beta-myrcene
Treatment |
No. |
Sex |
Sampling time (h) |
Metaphase cells |
Mitotic index (mean ± SD) |
|||||
Examined No. |
With aberrations |
With gaps |
||||||||
No. |
% |
|||||||||
No. |
% |
|||||||||
Corn oil |
2 |
M |
24 |
100 |
0 |
0 |
1.0 |
1.0 |
11.5 |
|
2 |
F |
24 |
100 |
0 |
0 |
1.0 |
1.0 |
12.5 |
||
4 |
M+F |
24 |
200 |
0 |
0 |
2.0 |
1.0 |
12.0 ± 2.9 |
||
B-Myrcene 0.1 g/kg |
2 |
M |
24 |
100 |
1.0 |
1.0 |
0.0 |
0.0 |
14.0 |
|
2 |
F |
24 |
100 |
0 |
0 |
0.0 |
0.0 |
17.0 |
||
4 |
M+F |
24 |
200 |
1.0 |
0.5 |
0.0 |
0.0 |
15.5 ± 8.5 |
||
0.5 g/kg |
2 |
M |
24 |
100 |
1.0 |
1.0 |
2.0 |
2.0 |
19.5 |
|
2 |
F |
24 |
100 |
0 |
0 |
1.0 |
1.0 |
19.0 |
||
4 |
M+F |
24 |
200 |
1.0 |
0.5 |
3.0 |
1.5 |
19.2 ± 1.7 * |
||
1.0g/kg |
4 |
M |
24 |
200 |
1.0 |
0.5 |
3.0 |
1.5 |
21.0 |
|
4 |
F |
24 |
200 |
0 |
0 |
5.0 |
2.5 |
23.0 |
||
8 |
M+F |
24 |
400 |
1.0 |
0.25 |
8.0 |
2.0 |
22.0 ± 6.1 * |
||
1.0g/kg |
2 |
M |
48 |
100 |
0 |
0 |
1.0 |
1.0 |
16.5 |
|
2 |
F |
48 |
100 |
0 |
0 |
0.0 |
0.0 |
12.0 |
||
4 |
M+F |
48 |
200 |
0 |
0 |
1.0 |
0.5 |
14.2 ± 3.6 |
||
Cyclophosphamide |
2 |
M |
24 |
100 |
18.0 |
18.0 |
4.0 |
4.0 |
10.5 |
|
2 |
F |
24 |
100 |
20.0 |
20.0 |
2.0 |
2.0 |
8.5 |
||
30 mg/kg bw, ip |
4 |
M+F |
24 |
200 |
38.0 |
19.0 |
6.0 |
3.0 |
9.5 ± 3.7 |
|
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Myrcene was found negative in all the following in vitro tests, in absence and in presence of metabolic activation: reverse mutation in bacterial strains (TA98, TA100, TA1535, TA1537 and in E. coli WP2uvrA/pKM101), chromosome aberration test in human lymphocytes, gene mutation in CHO cells and sister chromatid exchange in human lymphocytes.
Myrcene was also found negative in in vivo tests: chromosome aberration test on rat bone marrow cells and micronucleus test in mouse erythrocytes.
Justification for classification or non-classification
Negative results were obtained with myrcene in all in vitro tests (mutation in bacterial strains, cytogenicity and gene mutation tests in mammalian cells) and in vivo tests (chromosome aberration test on rat bone marrow cells andmicronucleustest inmouse erythrocytes). Therefore, myrcene does not need to be classified for mutagenicity according to CLP Regulation (EC) No 1272/2008 and Directive 67/548/EEC.
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