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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

not mutagenic


Ames tests: negative


ivt MLA: negative


ivt MN test: negative


 

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
from 1995-05-24 till 1995-08-07
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP but with deviations; no analytical certificate available for the test item identity
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
(adapted May 26, 1983)
Deviations:
yes
Remarks:
4 strains of S. typhimurium were used.
GLP compliance:
yes
Remarks:
statement
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
other: Histidin mutation
Metabolic activation:
with and without
Metabolic activation system:
S9-mix
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: sodium azide, 9-aminoacridine, daunomycine, methylmethanesulfonate
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:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative

Based on the results of this study it is concluded that the test item is not mutagenic in the Salmonella typhimurium reverse mutation assay with and without S9-mix activation.
Endpoint:
in vitro cytogenicity / micronucleus study
Remarks:
Type of genotoxicity: genome mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2011-07-11 till 2011-11-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP and without any deviations.
Qualifier:
according to guideline
Guideline:
other: OECD guideline 487 for the testing of chemicals: In Vitro Mammalian Cell Micronucleus Test (MNvit); adopted 22 July 2010.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
in vitro mammalian cell micronucleus test
Target gene:
The assay thus has the potential to detect the activity of both clastogenic and aneugenic chemicals.
Species / strain / cell type:
primary culture, other: binucleated human lymphocytes
Details on mammalian cell type (if applicable):
Blood samples were obtained by venapuncture from a young healthy, non-smoking individual (32 years old) with no known recent exposures to genotoxic chemicals or radiation.
Metabolic activation:
with and without
Metabolic activation system:
S9-mix (based on Aroclor 1254-induced rat liver homogenate (03 March 2010) fraction (S9) and cofactors)
Test concentrations with justification for top dose:
final concentration in the culture medium of 1981 μg/ml (10 mmol/l; limit dose) 1000, 500, 250, 125 and 62.5 μg/ml.
Untreated negative controls:
yes
Remarks:
culture medium
Negative solvent / vehicle controls:
no
Remarks:
solvent of technical product is water
Positive controls:
yes
Remarks:
Indirect acting positive control (clastogen): Cyclophosphamide; Direct acting positive control (clastogen): Mitomycin C; Aneugenic positive control substance: Vinblastine s
Details on test system and experimental conditions:
In the presence of PHA-L, aliquots of 0.5 ml of whole blood in 4.5 ml culture medium, were incubated for 48 hours at 37ºC in humidified air containing 5% CO2. The incubation was carried out in sterile screw-capped (loose) centrifuge tubes. After the 48-hour incubation period, the cells were exposed to different concentrations of the test substance, in both the presence and absence of the S9-mix.

In the first test, in both the presence and absence of metabolic activation (S9-mix), the treatment time was 4 hours (pulse treatment) and the recovery time 20 hours after the end of treatment. In the second test, in which metabolic activation was absent, the treatment time was 20 hours (continuous treatment) and the recovery time was 28 hours after the end of treatment. In all treatment groups, the cells were exposed to the test substance at concentrations ranging from 62.5 to 1981 μg/ml. In both the first and second test, the maximum final concentration in the culture medium was 1981 μg/ml, which corresponded to 10 mmol/l (i.e. the limit dose). Cytotoxicity was calculated from the Cytokinesis-Block Proliferation Index (CBPI). Based on cytotoxicity, three dose levels were selected for micronuclei analysis. Cyclophosphamide, a clastogenic compound which requires metabolic activation, was used as positive control in the presence of S9-mix. A known clastogenic compound (Mitomycin C) and a known aneugenic compound (Vinblastine sulphate) were used as positive controls in the absence of S9-mix.
Species / strain:
lymphocytes:
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
MPAAU was neither clastogenic nor aneugenic to cultured human lymphocytes
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
In the 1st test (w/wo S9-mix) and in the 2nd test (wo S9-mix) the test substance was only slightly toxic (10% and 15%, respectively) to the cells at the highest dose level (1981 µg/ml, 10 mmolar, limit concentration) analysed.
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: strain/cell type: binucleated human lymphocytes
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative w/wo metabolic activation

From the results obtained in two in vitro micronucleus tests it is concluded that, under the conditions used in this study, the test substance MPAAU was neither clastogenic nor aneugenic to cultured human lymphocytes.
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:
from 2003-11-29 till 2004-07-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP and without any deviations.
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 Fraction and S9 Mix
Test concentrations with justification for top dose:
dose levels: 0.213, 0.470, 1.033, 2.272, 5.0 µL/plate
Vehicle / solvent:
solvent: water
Untreated negative controls:
yes
Remarks:
equal to solvent control
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 9-Aminoacridine, Sodium azide, 2-Nitrofluorene, Cumene hydroperoxide
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:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative

From the results of this study, it is concluded that the test item, up to 5.0 µlL/plate is non-mutagenic in all the five strains of Salmonella typhimurium TA1537, TA1535, TA98, TA100 and TA102; both in the presence (5% and 10% v/v S9 mix) and absence of metabolic activation under the specified conditions of the OECD 471 test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for selection of genetic toxicity endpoint
No study selected because all three GLP studies were negative.

Short description of key information:
In vitro: Ames-negative (2), MLA-negative, in-vitro MN-negative.
In vivo: not necessary (not tested)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, the substance is non-genotoxic and accordingly a classification according to EC 1272/2008 is deemed to be not necessary.