Registration Dossier
Registration Dossier
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EC number: 925-698-2 | CAS number: -
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: According to OECD guideline 473
- Justification for type of information:
- A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: According to OECD guideline 473
- Justification for type of information:
- A discussion and report on the read across strategy is given as an attachment in Section 13.
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- lymphocytes: human
- Details on mammalian cell type (if applicable):
- - Type and identity of media: Dulbeccos's modified Eagle's medium/Ham's F12 medium
- Properly maintained: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver S9
- Test concentrations with justification for top dose:
- With metabolic activation:
Experiment IA: 4.1, 7.2, 12.7, 22.2, 38.8, 67.9, 118.8, 207.9, 363.8, 636.7, 1114.3, 1950.0 µg/mL
Experiment II: 25.0, 50.0, 100.0, 200.0, 300.0, 400.0, 500.0, 600.0, 700.0, 800.0 µg/mL
Without metabolic activation:
Experiment IA: 12.7, 22.2, 38.8, 67.9, 118.8, 207.9, 363.8, 636.7, 1114.3, 1950.0 µg/mL
Experiment IB: 40.4, 80.7, 121.1, 161.5, 201.8, 242.2, 282.5, 322.9, 363.3, 403.6, 444.0 µg/mL
Experiment II: 0.8, 1.4, 2.4, 4.1, 7.2, 12.7, 22.2, 38.8, 67.9, 118.8, 207.9, 363.8, 636.7, 1114.3, 1950.0 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Ethanol
- Justification for choice of solvent/vehicle: solubility and relatively low cytotoxicity in accordance to the OECD Guideline 473 - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Details on test system and experimental conditions:
- Three independent experiments were performed. In Experiment IA and IB, the exposure period was 4 hours with and without S9 mix. In Experiment II, the exposure period was 4 hours with S9 mix and 22 hours without S9 mix. The chromosomes were prepared 22 hours after start of treatment with the test item.
METHOD OF APPLICATION: in culture medium
DURATION
- Exposure duration: 4 hours (+/- S9 mix) and 22 hours (- S9 mix)
- Fixation time (start of exposure up to fixation or harvest of cells): 22 hours
SPINDLE INHIBITOR (cytogenetic assays): Colcemid
STAIN (for cytogenetic assays): Giemsa
NUMBER OF REPLICATIONS: about 1.5
NUMBER OF CELLS EVALUATED: 100 per culture, except for the positive control in Experiment II in the absence of S9 mix, where only 50 metaphases were scored
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index - Evaluation criteria:
- Evaluation of the cultures was performed (according to standard protocol of the "Arbeitsgruppe der Industrie, Cytogenetik") using NIKON microscopes with 100x oil immersion objectives. Breaks, fragments, deletions, exchanges, and chromosome disintegrations were recorded as structural chromosome aberrations. Gaps were recorded as well but not included in the calculation of the aberration rates. 100 well spread metaphases per culture were scored for cytogenetic damage on coded slides, except for the positive control in Experiment II without metabolic activation, where only 50 metaphases were scored.
Only metaphases with characteristic chromosome numbers of 46 ± 1 were included in the analysis. To describe a cytotoxic effect the mitotic index (% cells in mitosis) was determined. - Statistics:
- Statistical significance was confirmed by means of the Fisher´s exact test (p < 0.05).
- Species / strain:
- lymphocytes:
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Highest concentration for Experiment IB and II
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- The test item CAS 94581-15-4 (Resin acids and rosin acids, fumarated, esters with pentaerythritol), dissolved in ethanol, was assessed for its potential to induce chromosomal aberrations in human lymphocytes in vitro in the absence and presence of metabolic activation by S9 mix.
Three independent experiments were performed. In Experiment IA and IB, the exposure period was 4 hours with and without S9 mix. In Experiment II, the exposure period was 4 hours with S9 mix and 22 hours without S9 mix. The chromosomes were prepared 22 hours after start of treatment with the test item.
In each experimental group two parallel cultures were analysed. 100 metaphases per culture were scored for structural chromosomal aberrations, except for the positive control in Experiment II in the absence of S9 mix, where only 50 metaphases were scored. 1000 cells were counted per culture for determination of the mitotic index.
The highest treatment concentration in this study, 1950.0 µg/mL was chosen with respect to the OECD Guideline for in vitro mammalian cytogenetic tests considering the solubility properties of the test item in an appropriate solvent (ethanol).
In Experiment IA visible precipitation of the test item in the culture medium was observed at 67.9 µg/mL and above in the absence and presence of S9 mix. In Experiment IB precipitation occurred in the absence of S9 mix at 201.8 µg/mL and above. In Experiment II precipitation occurred at 118.8 µg/mL and above in the absence of S9 mix and at 200.0 µg/mL in the presence of S9 mix. No relevant influence in the osmolarity or pH value was observed (Exp. IA: solvent control: 392 mOsm, pH 7.4 versus 372 mOsm and pH 7.4 at 1950.0 µg/mL; Exp. IB: solvent control: 395 mOsm, pH 7.4 versus 407 mOsm and pH 7.4 at 444.0 µg/mL; Exp. II: solvent control: 411 mOsm, pH 7.5 versus 352 mOsm and pH 7.4 at 1950.0 µg/mL).
In Experiment IA in the absence and presence of S9 mix, concentrations showing clear cytotoxicity were not scorable for cytogenetic damage. In Experiment IB with narrow concentration spacing in the absence of S9 mix and in Experiment II in the absence of S9 mix, clear cytotoxicity was observed at the highest evaluated concentration (44.1 and 44.0 % of control, respectively). In Experiment II in the presence of S9 mix it was not possible to obtain evaluable concentrations in a cytotoxic range.
In all experiments, in the absence and presence of S9 mix, no biologically relevant increase in the number of cells carrying structural chromosome aberrations was observed. The aberration rates of the cells after treatment with the test item (0.0 – 1.5 % aberrant cells, excluding gaps) were close to the range of the solvent control values (0.5 – 2.0 % aberrant cells, excluding gaps) and within the range of the laboratory´s historical solvent control data.
No evidence of an increase in polyploid metaphases was noticed after treatment with the test item as compared to the control cultures.
In both experiments, either EMS (770.0 or 825.0 µg/mL) or CPA (7.5 or 15.0 µg/mL) were used as positive controls and showed distinct increases in cells with structural chromosome aberrations. - Remarks on result:
- other: strain/cell type: human lymphocytes
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results:
negative with metabolic activation
negative without metabolic activation
CAS 94581-15-4 (Resin acids and rosin acids, fumarated, esters with pentaerythritol) is considered to be non-clastogenic in this chromosome aberration test, when tested up to cytotoxic and/or precipitating concentrations. Therefore, the test material is not classifiable for Germ Cell Mutagenicity according to Directive 67/548/EEC, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. - Executive summary:
The test item CAS 94581-15-4 (Resin acids and rosin acids, fumarated, esters with pentaerythritol), dissolved in ethanol, was assessed for its potential to induce structural chromosomal aberrations in human lymphocytesin vitro in three independent experiments. The following study design was performed:
Without S9 mix
With S9 mix
Exp.& IB
Exp. II
Exp.& II
Exposure period
4 hrs
22 hrs
4 hrs
Recovery
18 hrs
-
18 hrs
Preparation interval
22 hrs
22 hrs
22 hrs
In each experimental group two parallel cultures were analysed. Per culture 100 metaphases were scored for structural chromosomal aberrations, except for the positive control in Experiment II, in the absence of S9 mix, where only 50 metaphases were scored. The highest applied concentration in the pre-test on toxicity (1950.0 µg/mL of the test item) was chosen with regard to the solubility properties of the test item and with respect to the current OECD Guideline 473. Dose selection of the cytogenetic experiment was performed considering the toxicity data and the occurrence of test item precipitation in accordance with OECD Guideline 473.
In the absence and presence of S9 mix, concentrations showing clear cytotoxicity were not scorable for cytogenetic damage. In Experiment IB with narrow concentration spacing in the absence of S9 mix and in Experiment II in the absence of S9 mix, clear cytotoxicity was observed at the highest evaluated concentration. In Experiment II in the presence of S9 mix it was not possible to obtain evaluable concentrations in a cytotoxic range.
In all independent experiments, neither a statistically significant nor a biologically relevant increase in the number of cells carrying structural chromosomal aberrations was observed after treatment with the test item.
No evidence of an increase in polyploid metaphases was noticed after treatment with the test item as compared to the control cultures. Appropriate mutagens were used as positive controls. They induced statistically significant increases (p < 0.05) in cells with structural chromosome aberrations.
Summary of results of the chromosomal
aberration study with CAS 94581-15-4
(Resin acids and rosin acids, fumarated, esters with pentaerythritol)
Exp. |
Preparation |
Test item |
Mitotic indices |
Aberrant cells |
|
|||||
|
interval |
concentration |
in % |
in % |
|
|||||
|
|
in µg/mL |
of control |
incl. gaps* |
excl. gaps* |
carrying exchanges |
|
|||
|
Exposure period 4 hrs without S9 mix |
|
||||||||
IA |
22 hrs |
Solvent control1 |
100.0 |
0.5 |
0.5 |
0.0 |
|
|||
|
|
Positive control2 |
96.8 |
8.5 |
7.5S |
1.0 |
|
|||
|
|
38.8 |
94.9 |
0.5 |
0.5 |
0.0 |
|
|||
|
|
67.9P |
81.0 |
0.0 |
0.0 |
0.0 |
|
|||
|
|
118.8P |
71.7 |
2.5 |
1.5 |
0.0 |
|
|||
IB |
22 hrs |
Solvent control1 |
100.0 |
2.0 |
2.0 |
0.0 |
|
|||
|
|
Positive control3 |
61.2 |
10.5 |
10.5S |
0.5 |
|
|||
|
|
121.1 |
88.0 |
2.0 |
1.5 |
0.0 |
|
|||
|
|
161.5 |
84.8 |
0.5 |
0.5 |
0.0 |
|
|||
|
|
201.8P |
44.1 |
0.5 |
0.5 |
0.0 |
|
|||
|
Exposure period 22 hrs without S9 mix |
|||||||||
II |
22 hrs |
Solvent control1 |
100.0 |
1.5 |
1.0 |
0.0 |
|
|||
|
|
Positive control#2 |
35.1 |
39.0 |
38.0S |
11.0 |
|
|||
|
|
38.8 |
95.5 |
0.5 |
0.5 |
0.0 |
|
|||
|
|
67.9 |
54.6 |
1.0 |
0.5 |
0.0 |
|
|||
|
|
118.8P |
44.0 |
0.0 |
0.0 |
0.0 |
|
|||
* Including cells carrying exchanges
# Evaluation of 50 metaphases per culture
P Precipitation occurred at the end of treatment
S Aberration frequency statistically significant higher than corresponding control values
1 Ethanol 0.5 % (v/v)
2 EMS825.0 µg/mL
3 EMS770.0
µg/mL
Summary of results of the chromosomal aberration study with CAS 94581-15-4 (Resin acids and rosin acids, fumarated, esters with pentaerythritol)
Exp. |
Preparation |
Test item |
Mitotic indices |
Aberrant cells |
|
|||
|
interval |
concentration |
in % |
in % |
|
|||
|
|
in µg/mL |
of control |
incl. gaps* |
excl. gaps* |
carrying exchanges |
|
|
|
Exposure period 4 hrs with S9 mix |
|||||||
IA |
22 hrs |
Solvent control1 |
100.0 |
2.0 |
1.5 |
0.0 |
|
|
|
|
Positive control2 |
46.3 |
11.0 |
11.0S |
2.5 |
|
|
|
|
38.8 |
104.7 |
1.5 |
1.0 |
0.0 |
|
|
|
|
67.9P |
112.2 |
1.0 |
0.5 |
0.0 |
|
|
|
|
207.9P |
80.8 |
1.0 |
1.0 |
0.0 |
|
|
|
|
363.8P |
67.1 |
1.0 |
1.0 |
0.0 |
|
|
II |
22 hrs |
Solvent control1 |
100.0 |
2.0 |
2.0 |
0.0 |
|
|
|
|
Positive control3 |
73.7 |
10.0 |
9.0S |
2.0 |
|
|
|
|
100.0 |
95.2 |
2.0 |
1.5 |
0.0 |
|
|
|
|
200.0P |
88.4 |
1.5 |
1.5 |
0.0 |
|
|
|
|
400.0P |
98.3 |
1.0 |
1.0 |
0.0 |
|
|
* Including cells carrying exchanges
P Precipitation occurred at the end of treatment
S Aberration frequency statistically significant higher than corresponding control values
1 Ethanol 0.5 % (v/v)
2 CPA 7.5 µg/mL
3 CPA 15.0 µg/mL
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
Test material
- Reference substance name:
- Resin acids and Rosin acids, fumarated, esters with pentaerythritol
- EC Number:
- 305-514-1
- EC Name:
- Resin acids and Rosin acids, fumarated, esters with pentaerythritol
- Cas Number:
- 94581-15-4
- IUPAC Name:
- 94581-15-4
- Details on test material:
- - Name of test material (as cited in study report): CAS 94581-15-4 (Resin acids and rosin acids, fumarated, esters with pentaerythritol)
- Molecular weight (if other than submission substance): Not applicable
- Analytical purity: Not indicated by the sponsor
- Lot/batch No.: 23248
- Expiration date of the lot/batch: May 2010
- Stability under test conditions: Not indicated by the sponsor
- Storage condition of test material: At approx. -20 °C, light protected, under nitrogen
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- lymphocytes: human
- Details on mammalian cell type (if applicable):
- - Type and identity of media: Dulbeccos's modified Eagle's medium/Ham's F12 medium
- Properly maintained: yes
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver S9
- Test concentrations with justification for top dose:
- With metabolic activation:
Experiment IA: 4.1, 7.2, 12.7, 22.2, 38.8, 67.9, 118.8, 207.9, 363.8, 636.7, 1114.3, 1950.0 µg/mL
Experiment II: 25.0, 50.0, 100.0, 200.0, 300.0, 400.0, 500.0, 600.0, 700.0, 800.0 µg/mL
Without metabolic activation:
Experiment IA: 12.7, 22.2, 38.8, 67.9, 118.8, 207.9, 363.8, 636.7, 1114.3, 1950.0 µg/mL
Experiment IB: 40.4, 80.7, 121.1, 161.5, 201.8, 242.2, 282.5, 322.9, 363.3, 403.6, 444.0 µg/mL
Experiment II: 0.8, 1.4, 2.4, 4.1, 7.2, 12.7, 22.2, 38.8, 67.9, 118.8, 207.9, 363.8, 636.7, 1114.3, 1950.0 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Ethanol
- Justification for choice of solvent/vehicle: solubility and relatively low cytotoxicity in accordance to the OECD Guideline 473
Controlsopen allclose all
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Details on test system and experimental conditions:
- Three independent experiments were performed. In Experiment IA and IB, the exposure period was 4 hours with and without S9 mix. In Experiment II, the exposure period was 4 hours with S9 mix and 22 hours without S9 mix. The chromosomes were prepared 22 hours after start of treatment with the test item.
METHOD OF APPLICATION: in culture medium
DURATION
- Exposure duration: 4 hours (+/- S9 mix) and 22 hours (- S9 mix)
- Fixation time (start of exposure up to fixation or harvest of cells): 22 hours
SPINDLE INHIBITOR (cytogenetic assays): Colcemid
STAIN (for cytogenetic assays): Giemsa
NUMBER OF REPLICATIONS: about 1.5
NUMBER OF CELLS EVALUATED: 100 per culture, except for the positive control in Experiment II in the absence of S9 mix, where only 50 metaphases were scored
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index - Evaluation criteria:
- Evaluation of the cultures was performed (according to standard protocol of the "Arbeitsgruppe der Industrie, Cytogenetik") using NIKON microscopes with 100x oil immersion objectives. Breaks, fragments, deletions, exchanges, and chromosome disintegrations were recorded as structural chromosome aberrations. Gaps were recorded as well but not included in the calculation of the aberration rates. 100 well spread metaphases per culture were scored for cytogenetic damage on coded slides, except for the positive control in Experiment II without metabolic activation, where only 50 metaphases were scored.
Only metaphases with characteristic chromosome numbers of 46 ± 1 were included in the analysis. To describe a cytotoxic effect the mitotic index (% cells in mitosis) was determined. - Statistics:
- Statistical significance was confirmed by means of the Fisher´s exact test (p < 0.05).
Results and discussion
Test results
- Species / strain:
- lymphocytes:
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Highest concentration for Experiment IB and II
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- The test item CAS 94581-15-4 (Resin acids and rosin acids, fumarated, esters with pentaerythritol), dissolved in ethanol, was assessed for its potential to induce chromosomal aberrations in human lymphocytes in vitro in the absence and presence of metabolic activation by S9 mix.
Three independent experiments were performed. In Experiment IA and IB, the exposure period was 4 hours with and without S9 mix. In Experiment II, the exposure period was 4 hours with S9 mix and 22 hours without S9 mix. The chromosomes were prepared 22 hours after start of treatment with the test item.
In each experimental group two parallel cultures were analysed. 100 metaphases per culture were scored for structural chromosomal aberrations, except for the positive control in Experiment II in the absence of S9 mix, where only 50 metaphases were scored. 1000 cells were counted per culture for determination of the mitotic index.
The highest treatment concentration in this study, 1950.0 µg/mL was chosen with respect to the OECD Guideline for in vitro mammalian cytogenetic tests considering the solubility properties of the test item in an appropriate solvent (ethanol).
In Experiment IA visible precipitation of the test item in the culture medium was observed at 67.9 µg/mL and above in the absence and presence of S9 mix. In Experiment IB precipitation occurred in the absence of S9 mix at 201.8 µg/mL and above. In Experiment II precipitation occurred at 118.8 µg/mL and above in the absence of S9 mix and at 200.0 µg/mL in the presence of S9 mix. No relevant influence in the osmolarity or pH value was observed (Exp. IA: solvent control: 392 mOsm, pH 7.4 versus 372 mOsm and pH 7.4 at 1950.0 µg/mL; Exp. IB: solvent control: 395 mOsm, pH 7.4 versus 407 mOsm and pH 7.4 at 444.0 µg/mL; Exp. II: solvent control: 411 mOsm, pH 7.5 versus 352 mOsm and pH 7.4 at 1950.0 µg/mL).
In Experiment IA in the absence and presence of S9 mix, concentrations showing clear cytotoxicity were not scorable for cytogenetic damage. In Experiment IB with narrow concentration spacing in the absence of S9 mix and in Experiment II in the absence of S9 mix, clear cytotoxicity was observed at the highest evaluated concentration (44.1 and 44.0 % of control, respectively). In Experiment II in the presence of S9 mix it was not possible to obtain evaluable concentrations in a cytotoxic range.
In all experiments, in the absence and presence of S9 mix, no biologically relevant increase in the number of cells carrying structural chromosome aberrations was observed. The aberration rates of the cells after treatment with the test item (0.0 – 1.5 % aberrant cells, excluding gaps) were close to the range of the solvent control values (0.5 – 2.0 % aberrant cells, excluding gaps) and within the range of the laboratory´s historical solvent control data.
No evidence of an increase in polyploid metaphases was noticed after treatment with the test item as compared to the control cultures.
In both experiments, either EMS (770.0 or 825.0 µg/mL) or CPA (7.5 or 15.0 µg/mL) were used as positive controls and showed distinct increases in cells with structural chromosome aberrations. - Remarks on result:
- other: strain/cell type: human lymphocytes
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
Summary of results of the chromosomal
aberration study with CAS 94581-15-4
(Resin acids and rosin acids, fumarated, esters with pentaerythritol)
Exp. |
Preparation |
Test item |
Mitotic indices |
Aberrant cells |
|
|||||
|
interval |
concentration |
in % |
in % |
|
|||||
|
|
in µg/mL |
of control |
incl. gaps* |
excl. gaps* |
carrying exchanges |
|
|||
|
Exposure period 4 hrs without S9 mix |
|
||||||||
IA |
22 hrs |
Solvent control1 |
100.0 |
0.5 |
0.5 |
0.0 |
|
|||
|
|
Positive control2 |
96.8 |
8.5 |
7.5S |
1.0 |
|
|||
|
|
38.8 |
94.9 |
0.5 |
0.5 |
0.0 |
|
|||
|
|
67.9P |
81.0 |
0.0 |
0.0 |
0.0 |
|
|||
|
|
118.8P |
71.7 |
2.5 |
1.5 |
0.0 |
|
|||
IB |
22 hrs |
Solvent control1 |
100.0 |
2.0 |
2.0 |
0.0 |
|
|||
|
|
Positive control3 |
61.2 |
10.5 |
10.5S |
0.5 |
|
|||
|
|
121.1 |
88.0 |
2.0 |
1.5 |
0.0 |
|
|||
|
|
161.5 |
84.8 |
0.5 |
0.5 |
0.0 |
|
|||
|
|
201.8P |
44.1 |
0.5 |
0.5 |
0.0 |
|
|||
|
Exposure period 22 hrs without S9 mix |
|||||||||
II |
22 hrs |
Solvent control1 |
100.0 |
1.5 |
1.0 |
0.0 |
|
|||
|
|
Positive control#2 |
35.1 |
39.0 |
38.0S |
11.0 |
|
|||
|
|
38.8 |
95.5 |
0.5 |
0.5 |
0.0 |
|
|||
|
|
67.9 |
54.6 |
1.0 |
0.5 |
0.0 |
|
|||
|
|
118.8P |
44.0 |
0.0 |
0.0 |
0.0 |
|
|||
* Including cells carrying exchanges
# Evaluation of 50 metaphases per culture
P Precipitation occurred at the end of treatment
S Aberration frequency statistically significant higher than corresponding control values
1 Ethanol 0.5 % (v/v)
2 EMS825.0 µg/mL
3 EMS770.0
µg/mL
Summary of results of the chromosomal aberration study with CAS 94581-15-4 (Resin acids and rosin acids, fumarated, esters with pentaerythritol)
Exp. |
Preparation |
Test item |
Mitotic indices |
Aberrant cells |
|
|||
|
interval |
concentration |
in % |
in % |
|
|||
|
|
in µg/mL |
of control |
incl. gaps* |
excl. gaps* |
carrying exchanges |
|
|
|
Exposure period 4 hrs with S9 mix |
|||||||
IA |
22 hrs |
Solvent control1 |
100.0 |
2.0 |
1.5 |
0.0 |
|
|
|
|
Positive control2 |
46.3 |
11.0 |
11.0S |
2.5 |
|
|
|
|
38.8 |
104.7 |
1.5 |
1.0 |
0.0 |
|
|
|
|
67.9P |
112.2 |
1.0 |
0.5 |
0.0 |
|
|
|
|
207.9P |
80.8 |
1.0 |
1.0 |
0.0 |
|
|
|
|
363.8P |
67.1 |
1.0 |
1.0 |
0.0 |
|
|
II |
22 hrs |
Solvent control1 |
100.0 |
2.0 |
2.0 |
0.0 |
|
|
|
|
Positive control3 |
73.7 |
10.0 |
9.0S |
2.0 |
|
|
|
|
100.0 |
95.2 |
2.0 |
1.5 |
0.0 |
|
|
|
|
200.0P |
88.4 |
1.5 |
1.5 |
0.0 |
|
|
|
|
400.0P |
98.3 |
1.0 |
1.0 |
0.0 |
|
|
* Including cells carrying exchanges
P Precipitation occurred at the end of treatment
S Aberration frequency statistically significant higher than corresponding control values
1 Ethanol 0.5 % (v/v)
2 CPA 7.5 µg/mL
3 CPA 15.0 µg/mL
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results:
negative with metabolic activation
negative without metabolic activation
CAS 94581-15-4 (Resin acids and rosin acids, fumarated, esters with pentaerythritol) is considered to be non-clastogenic in this chromosome aberration test, when tested up to cytotoxic and/or precipitating concentrations. Therefore, the test material is not classifiable for Germ Cell Mutagenicity according to Directive 67/548/EEC, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. - Executive summary:
The test item CAS 94581-15-4 (Resin acids and rosin acids, fumarated, esters with pentaerythritol), dissolved in ethanol, was assessed for its potential to induce structural chromosomal aberrations in human lymphocytesin vitro in three independent experiments. The following study design was performed:
Without S9 mix
With S9 mix
Exp.& IB
Exp. II
Exp.& II
Exposure period
4 hrs
22 hrs
4 hrs
Recovery
18 hrs
-
18 hrs
Preparation interval
22 hrs
22 hrs
22 hrs
In each experimental group two parallel cultures were analysed. Per culture 100 metaphases were scored for structural chromosomal aberrations, except for the positive control in Experiment II, in the absence of S9 mix, where only 50 metaphases were scored. The highest applied concentration in the pre-test on toxicity (1950.0 µg/mL of the test item) was chosen with regard to the solubility properties of the test item and with respect to the current OECD Guideline 473. Dose selection of the cytogenetic experiment was performed considering the toxicity data and the occurrence of test item precipitation in accordance with OECD Guideline 473.
In the absence and presence of S9 mix, concentrations showing clear cytotoxicity were not scorable for cytogenetic damage. In Experiment IB with narrow concentration spacing in the absence of S9 mix and in Experiment II in the absence of S9 mix, clear cytotoxicity was observed at the highest evaluated concentration. In Experiment II in the presence of S9 mix it was not possible to obtain evaluable concentrations in a cytotoxic range.
In all independent experiments, neither a statistically significant nor a biologically relevant increase in the number of cells carrying structural chromosomal aberrations was observed after treatment with the test item.
No evidence of an increase in polyploid metaphases was noticed after treatment with the test item as compared to the control cultures. Appropriate mutagens were used as positive controls. They induced statistically significant increases (p < 0.05) in cells with structural chromosome aberrations.
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