Registration Dossier
Registration Dossier
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EC number: 947-842-3 | 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
- Study period:
- 1992
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- The concentration used for the test was selected only based on the cytotoxicity, but not based on the precipitation.The results obtained at concentrations with precipiations are not considered as valid.
Cross-reference
- Reason / purpose for cross-reference:
- assessment report
Reference
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1992
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- The concentration used for the test was selected only based on the cytotoxicity, but not based on the precipitation.The results obtained at concentrations with precipiations are not considered as valid.
- Justification for type of information:
- Justification for read-across is provided in chapter 13 as separate statement
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- adpted July 21, 1997
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- other: in-vitro chromosome aberration
- Species / strain / cell type:
- lymphocytes:
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver S9
- Test concentrations with justification for top dose:
- The highest dose selected was the dose causing 50% reduction of mitotic indices of control.
- Vehicle / solvent:
- water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in culture medium. The chromosomes were prepared 22 hours after start of treatment with the test item. Evaluation of two cultures per dose group.
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: At least 100 per culture
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index - Species / strain:
- lymphocytes:
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- lymphocytes:
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: The author of the study evaluated the results obtained as "positive". The registrant performed re-evaluation, taking account the precipitation in the culture medium as the potential artifical factor for false-positive responce.
- Conclusions:
- The genotoxicity of the registration substance is assessed via read-across to N-cocoyl glycinate. The genotoxicity of N-cocoyl glycinate was investigated according to the Guideline OECD 473. No genotoxic activity was observed up to the insoluble concentrations. Likewise, no genotoxicity activity can be assigned in the cytogenetic assay in mammalian cells to the registration substance.
- Executive summary:
The genotoxicity of the registration substance is assessed via read-across to N-cocoyl glycinate.
The genotoxicity of N-cocoyl glycinate was investigated according to the Guideline OECD 473 (version 1997). Human lymphocytes were treated with the test substance with and without metabolic activation up to the concentration associated with 50% reduction of mitotic indices. In general, reduced cytotoxicity was observed with metabolic activation, leading to the use of higher concentrations with metabolic activation for the genotoxicity investigation. These concentrations were associated with enhanced precipitation.
Total five independent experiments were performed. No increase of aberration frequency was observed without metabolic activation. Significant increase of aberration frequency was obtained with metabolic activation at concentrations associated not only with significant cytotoxicity but also with enhanced precipitation. The author of the study evaluated the results obtained as "positive".
The registrant performed re-evaluation in 2018, taking account the precipitation in the culture medium as potential interfering factor responsible for a false-positve response (according to the current OECD Guideline, version 2016). Based on the re-evaluation, no significant genotoxic activity can be assigned up to the insoluble concentrations for N-cocoyl glycinate.
Likewise, no genotoxicity activity can be assigned in the cytogenetic assay in mammalian cells to the registration substance.
Summary of results of the chromosome aberration study: without metabolic activation |
|||||||
Exp |
Preparation Interval |
Test item concentration [µg/mL] |
Mitotic indices in % of control |
Aberrant cells |
Carrying exchange |
Evaluation based on the Guideline adopted July 29, 2016 |
|
Incl. gaps* |
Excl. gaps* |
||||||
Exposure period 4 hrs without S9 mix |
|||||||
IA |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
1.5 |
1.5 |
0.0 |
Negative: Precipitation occurred at 99.5 µg/mL, which should be considered as the valid high dose. The dose 304.6 µg/mL is not compliant to the Guideline adopted in 2016. |
|
|
EMS, 770 µg/mL |
51.7 |
8.5 |
8.5S |
0.5 |
|
|
|
56.8 |
82.1 |
0.0 |
0.0 |
0.0 |
|
|
|
99.5P |
70.3 |
0.0 |
0.0 |
0.0 |
|
|
|
304.6P |
61.8 |
1.0 |
1.0 |
0.0 |
|
IB |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
0.5 |
0.5 |
0.0 |
Negative: Precipitation occurred at 50.0 µg/mL. The doses 200 and 325 µg/mLis not compliant to the Guideline adopted in 2016. |
|
|
EMS, 770 µg/mL |
74.8 |
8.5 |
8.5S |
3.0 |
|
|
|
25.0 |
101.0 |
1.5 |
0.5 |
0.0 |
|
|
|
50.0P |
98.0 |
0.5 |
0.5 |
0.0 |
|
|
|
200.0P |
83.0 |
2.0 |
2.0 |
0.0 |
|
|
|
325.0P |
45.1 |
2.5 |
2.5 |
0.0 |
|
Exposure period 22 hrs without S9 mix |
|||||||
IIA |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
0.0 |
0.0 |
0.0 |
Negative: No Precipitation observed, but the highest dose induced clear cytotoxicity.
|
|
|
EMS, 660 µg/mL |
38.0 |
21.5 |
20.5S |
9.0 |
|
|
|
30.5 |
96.1 |
1.0 |
1.0 |
0.0 |
|
|
|
53.3 |
82.8 |
1.0 |
1.0 |
0.0 |
|
|
|
93.3 |
62.4 |
1.0 |
1.0 |
0.0 |
|
IIB |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
2.5 |
2.0 |
0.0 |
Negative: No Precipitation observed, but the highest dose induced clear cytotoxicity.
|
|
|
EMS, 550 µg/mL |
43.1 |
22.0 |
21.5S |
9.0 |
|
|
|
100.0 |
86.3 |
3.0 |
2.0 |
0.0 |
|
|
|
140.0 |
56.5 |
1.5 |
1.5 |
0.0 |
|
|
|
160.0 |
37.8 |
0.5 |
0.5 |
0.0 |
|
* Including cells carrying exchanges P Precipitation occurred at the end of treatment S Aberration frequency statistically significant higher than corresponding control values |
|||||||
Summary of results of the chromosome aberration study: with metabolic activation |
|||||||
Exp |
Preparation Interval |
Test item concentration [µg/mL] |
Mitotic indices in % of control |
Aberrant cells |
Carrying exchange |
Evaluation based on the Guideline adopted July 29, 2016 |
|
Incl. gaps* |
Excl. gaps* |
||||||
Exposure period 4 hrs with S9 mix |
|||||||
IA |
22 hrs |
Deionised water 10.0 % (v/v) |
100.0 |
1.0 |
1.0 |
0.0 |
Negative: Precipitation occurred at 99.5 µg/mL, which should be considered as the valid high dose. The dose 304.6 µg/mL is not compliant to the Guideline adopted in 2016. |
|
|
CPA, 15.0 µg/mL |
79.6 |
12.5 |
12.0S |
1.0 |
|
|
|
56.8 |
100.0 |
0.0 |
0.0 |
0.0 |
|
|
|
99.5P |
98.9 |
0.5 |
0.5 |
0.0 |
|
|
|
304.6P |
88.9 |
1.0 |
1.0 |
0.0 |
|
IIA |
22 hrs |
Deionised water 10.0 % (v/v) |
100.0 |
2.0 |
2.0 |
0.0 |
Negative: Precipitation occurred at 100 µg/mL. The dose 500 µg/mL is not compliant to the Guideline adopted in 2016. |
|
|
CPA, 15.0 µg/mL |
69.9 |
22.5 |
22.0S |
5.5 |
|
|
|
50.0 |
89.3 |
1.0 |
1.0 |
0.0 |
|
|
|
100.0P |
93.2 |
2.0 |
2.0 |
0.0 |
|
|
|
500.0P |
87.4 |
3.5 |
3.5 |
1.0 |
|
IIB |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
1.5 |
1.5 |
0.0 |
Negative: Precipitation occurred at 100 µg/mL. The dose 520 µg/mL is not compliant to the Guideline adopted in 2016. |
|
|
CPA, 7.5 µg/mL |
78.2 |
9.5 |
8.0S |
2.0 |
|
|
|
50.0 |
72.8 |
2.0 |
1.5 |
0.0 |
|
|
|
100.0P |
87.9 |
1.5 |
1.5 |
0.0 |
|
|
|
520.0P |
56.8 |
8.0 |
8.0S |
2.5 |
|
IIC |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
0.5 |
0.5 |
0.0 |
Negative: Precipitation occurred at 100 µg/mL, and the aberration cells were statistically increased. Taking account the results obtained in other three independent experiments were negative and the incidence is marginally increased, the overall assessment should be negative. The doses 400 and 440 µg/mL are not compliant to the Guideline adopted in 2016. |
|
|
CPA, 7.5 µg/mL |
54.9 |
19.5 |
19.5S |
6.0 |
|
|
|
50.0 |
91.7 |
2.0 |
1.5 |
0.0 |
|
|
|
100.0P# |
99.5 |
2.8 |
2.5S |
0.3 |
|
|
|
400.0P# |
61.1 |
6.3 |
6.0S |
1.0 |
|
|
|
440.0P# |
37.8 |
9.0 |
8.8S |
1.0 |
|
* Including cells carrying exchanges P Precipitation occurred at the end of treatment S Aberration frequency statistically significant higher than corresponding control values # Evaluation of 200 metaphases per culture |
|||||||
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- adpted July 21, 1997
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- other: in-vitro chromosome aberration
Test material
- Reference substance name:
- Sodium cocoyl glycinate (SCG) [INCI]
- IUPAC Name:
- Sodium cocoyl glycinate (SCG) [INCI]
- Details on test material:
- Stability of Test Item: Stable under storage conditions
Stability of Test Item Dilution: Unknown in PEG 300; excluded from the statement of compliance.
Storage Conditions: At room temperature (range of 20 ± 5 °C, provided by Harlan Laboratories Ltd.), light protected.
Safety Precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.
Description: Colorless solid
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- lymphocytes:
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver S9
- Test concentrations with justification for top dose:
- The highest dose selected was the dose causing 50% reduction of mitotic indices of control.
- Vehicle / solvent:
- water
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in culture medium. The chromosomes were prepared 22 hours after start of treatment with the test item. Evaluation of two cultures per dose group.
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: At least 100 per culture
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index
Results and discussion
Test resultsopen allclose all
- Species / strain:
- lymphocytes:
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- lymphocytes:
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: The author of the study evaluated the results obtained as "positive". The registrant performed re-evaluation, taking account the precipitation in the culture medium as the potential artifical factor for false-positive responce.
Any other information on results incl. tables
Summary of results of the chromosome aberration study: without metabolic activation |
|||||||
Exp |
Preparation Interval |
Test item concentration [µg/mL] |
Mitotic indices in % of control |
Aberrant cells |
Carrying exchange |
Evaluation based on the Guideline adopted July 29, 2016 |
|
Incl. gaps* |
Excl. gaps* |
||||||
Exposure period 4 hrs without S9 mix |
|||||||
IA |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
1.5 |
1.5 |
0.0 |
Negative: Precipitation occurred at 99.5 µg/mL, which should be considered as the valid high dose. The dose 304.6 µg/mL is not compliant to the Guideline adopted in 2016. |
|
|
EMS, 770 µg/mL |
51.7 |
8.5 |
8.5S |
0.5 |
|
|
|
56.8 |
82.1 |
0.0 |
0.0 |
0.0 |
|
|
|
99.5P |
70.3 |
0.0 |
0.0 |
0.0 |
|
|
|
304.6P |
61.8 |
1.0 |
1.0 |
0.0 |
|
IB |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
0.5 |
0.5 |
0.0 |
Negative: Precipitation occurred at 50.0 µg/mL. The doses 200 and 325 µg/mLis not compliant to the Guideline adopted in 2016. |
|
|
EMS, 770 µg/mL |
74.8 |
8.5 |
8.5S |
3.0 |
|
|
|
25.0 |
101.0 |
1.5 |
0.5 |
0.0 |
|
|
|
50.0P |
98.0 |
0.5 |
0.5 |
0.0 |
|
|
|
200.0P |
83.0 |
2.0 |
2.0 |
0.0 |
|
|
|
325.0P |
45.1 |
2.5 |
2.5 |
0.0 |
|
Exposure period 22 hrs without S9 mix |
|||||||
IIA |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
0.0 |
0.0 |
0.0 |
Negative: No Precipitation observed, but the highest dose induced clear cytotoxicity.
|
|
|
EMS, 660 µg/mL |
38.0 |
21.5 |
20.5S |
9.0 |
|
|
|
30.5 |
96.1 |
1.0 |
1.0 |
0.0 |
|
|
|
53.3 |
82.8 |
1.0 |
1.0 |
0.0 |
|
|
|
93.3 |
62.4 |
1.0 |
1.0 |
0.0 |
|
IIB |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
2.5 |
2.0 |
0.0 |
Negative: No Precipitation observed, but the highest dose induced clear cytotoxicity.
|
|
|
EMS, 550 µg/mL |
43.1 |
22.0 |
21.5S |
9.0 |
|
|
|
100.0 |
86.3 |
3.0 |
2.0 |
0.0 |
|
|
|
140.0 |
56.5 |
1.5 |
1.5 |
0.0 |
|
|
|
160.0 |
37.8 |
0.5 |
0.5 |
0.0 |
|
* Including cells carrying exchanges P Precipitation occurred at the end of treatment S Aberration frequency statistically significant higher than corresponding control values |
|||||||
Summary of results of the chromosome aberration study: with metabolic activation |
|||||||
Exp |
Preparation Interval |
Test item concentration [µg/mL] |
Mitotic indices in % of control |
Aberrant cells |
Carrying exchange |
Evaluation based on the Guideline adopted July 29, 2016 |
|
Incl. gaps* |
Excl. gaps* |
||||||
Exposure period 4 hrs with S9 mix |
|||||||
IA |
22 hrs |
Deionised water 10.0 % (v/v) |
100.0 |
1.0 |
1.0 |
0.0 |
Negative: Precipitation occurred at 99.5 µg/mL, which should be considered as the valid high dose. The dose 304.6 µg/mL is not compliant to the Guideline adopted in 2016. |
|
|
CPA, 15.0 µg/mL |
79.6 |
12.5 |
12.0S |
1.0 |
|
|
|
56.8 |
100.0 |
0.0 |
0.0 |
0.0 |
|
|
|
99.5P |
98.9 |
0.5 |
0.5 |
0.0 |
|
|
|
304.6P |
88.9 |
1.0 |
1.0 |
0.0 |
|
IIA |
22 hrs |
Deionised water 10.0 % (v/v) |
100.0 |
2.0 |
2.0 |
0.0 |
Negative: Precipitation occurred at 100 µg/mL. The dose 500 µg/mL is not compliant to the Guideline adopted in 2016. |
|
|
CPA, 15.0 µg/mL |
69.9 |
22.5 |
22.0S |
5.5 |
|
|
|
50.0 |
89.3 |
1.0 |
1.0 |
0.0 |
|
|
|
100.0P |
93.2 |
2.0 |
2.0 |
0.0 |
|
|
|
500.0P |
87.4 |
3.5 |
3.5 |
1.0 |
|
IIB |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
1.5 |
1.5 |
0.0 |
Negative: Precipitation occurred at 100 µg/mL. The dose 520 µg/mL is not compliant to the Guideline adopted in 2016. |
|
|
CPA, 7.5 µg/mL |
78.2 |
9.5 |
8.0S |
2.0 |
|
|
|
50.0 |
72.8 |
2.0 |
1.5 |
0.0 |
|
|
|
100.0P |
87.9 |
1.5 |
1.5 |
0.0 |
|
|
|
520.0P |
56.8 |
8.0 |
8.0S |
2.5 |
|
IIC |
22 hrs |
Deionized water, 10% (v/v) |
100.0 |
0.5 |
0.5 |
0.0 |
Negative: Precipitation occurred at 100 µg/mL, and the aberration cells were statistically increased. Taking account the results obtained in other three independent experiments were negative and the incidence is marginally increased, the overall assessment should be negative. The doses 400 and 440 µg/mL are not compliant to the Guideline adopted in 2016. |
|
|
CPA, 7.5 µg/mL |
54.9 |
19.5 |
19.5S |
6.0 |
|
|
|
50.0 |
91.7 |
2.0 |
1.5 |
0.0 |
|
|
|
100.0P# |
99.5 |
2.8 |
2.5S |
0.3 |
|
|
|
400.0P# |
61.1 |
6.3 |
6.0S |
1.0 |
|
|
|
440.0P# |
37.8 |
9.0 |
8.8S |
1.0 |
|
* Including cells carrying exchanges P Precipitation occurred at the end of treatment S Aberration frequency statistically significant higher than corresponding control values # Evaluation of 200 metaphases per culture |
|||||||
Applicant's summary and conclusion
- Conclusions:
- The genotoxicity of N-cocoyl glycinate was investigated according to the Guideline OECD 473. No genotoxic activity was observed up to the insoluble concentrations.
- Executive summary:
The genotoxicity of N-cocoyl glycinate was investigated according to the Guideline OECD 473 (version 1997). Human lymphocytes were treated with the test substance with and without metabolic activation up to the concentration associated with 50% reduction of mitotic indices. In general, reduced cytotoxicity was observed with metabolic activation, leading to the use of higher concentrations with metabolic activation for the genotoxicity investigation. These concentrations were associated with enhanced precipitation.
Total five independent experiments were performed. No increase of aberration frequency was observed without metabolic activation. Significant increase of aberration frequency was obtained with metabolic activation at concentrations associated not only with significant cytotoxicity but also with enhanced precipitation. The author of the study evaluated the results obtained as "positive".
The registrant performed re-evaluation in 2018, taking account the precipitation in the culture medium as potential interfering factor responsible for a false-positve response (according to the current OECD Guideline, version 2016). Based on the re-evaluation, no significant genotoxic activity can be assigned up to the insoluble concentrations for N-cocoyl glycinate.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
