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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In a Salmonella/microsome test, an in vitro chromosomal aberration study and a forward mutation assay at the hypoxanthine-guanine phosphoribosyl transferase locus in V79 cell cultures no genotoxic effects could be observed. There are no valid data available to characterize the genetic toxicity in vivo.

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Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No OECD study or GLP defined, only 4 Salmonella strains tested.
Principles of method if other than guideline:
other: Ames assay
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
Ames assay: detection of base pair substitutions and frameshift mutations
Species / strain / cell type:
other: Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Test concentrations with justification for top dose:
up to 12500 ug/plate
Untreated negative controls:
yes
Negative solvent / vehicle controls:
not specified
True negative controls:
yes
Positive controls:
yes
Remarks:
s1) Endoxan (only TA 1535 and TA 100); 2) Trypaflavin (only 1537 and TA 98); 3) 2-Aminoanthrazen (only TA 1537 and TA 98)
Positive control substance:
other: Endoxan, Trypaflavin, 2-Aminoanthrazen
Details on test system and experimental conditions:
IUCLID4 Type: Ames test
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 specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: other: Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537
Remarks:
Migrated from field 'Test system'.

No references for a mutagen effect of Mesamoll could be found.

Executive summary:

Mesamoll was tested in an Salmonella/microsome test in doses up to 12500 µg/plate (20; 100; 500; 2500; 12500 µg/plate) with 4 Salmonella typhimurium strains (TA 1535; TA 100; TA 1537 and TA 98).

Doses up to 12500 µg/plate did not lead to bacteriotoxic effects. The positive controls Endoxan, Trypaflavin and 2 -Aminoanthrazen reacted clearly mutagen.

No references for a mutagen effect of Mesamoll could be found.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study according to recent guidelines; full report available.No OECD guideline defined.
Principles of method if other than guideline:
in vitro mammalian chromosome aberration test
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test
Target gene:
other: chromosomal aberrations
Species / strain / cell type:
other: CHL/IU cells derived from female chinese hamsters
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Test concentrations with justification for top dose:
313 ; 625 ; 1250 ; 2500 ; 5000 µ/mL
Untreated negative controls:
yes
Remarks:
(Solvent for the test substance) DMSO
Negative solvent / vehicle controls:
not specified
True negative controls:
yes
Remarks:
DMSO
Positive controls:
yes
Remarks:
Mitomycin (MMC); Benzo[a]pyrene (BP)
Positive control substance:
other: Mitomycin (MMC); Benzo[a]pyrene (BP)
Species / strain:
other: CHL/IU cells derived from female chinese hamsters
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: > 5000 µg/mL
Vehicle controls validity:
not specified
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: other: CHL/IU cells derived from female chinese hamsters
Remarks:
Migrated from field 'Test system'.

RS-Freetext:
Cell growth was not inhibited up to the highest concentration to more  than 50%.
0 to 2 % cells with chromosomal aberrations were detected in the short  term test (6h treatment) and after continuous treatment for 24 or 48  hours at all concentrations. 

In the negative controls the incidence of aberrant cells was also below 0  - 1.5 % and in the positive controls the incidence was 18 to 57 %.

Executive summary:

An in vitro chromosomal aberration study of Mesamoll was conducted using CHL/IU cells derived from the lungs of female Chinese hamsters as the indicator cells.

Based on the result of a preliminary test, the cell growth inhibition test was conducted at 313; 625; 1250; 2500; and 5000 µg/mL in the short-term treatment assay in the absence of S9 mix and in the presence of S9 mix and in the continuous treatment assay for 24 hours and 48 hours. In the cell growth inhibition test, the test substance did not inhibit cell growth by more than 50% under any treatment condition.

From these results, the chromosomal aberration test was conducted at 1250; 2500; and 5000 µg/mL in each treatment condition.

In the chromosomal aberration test, the incidence of cells with structural and numerical chromosome aberrations was less than 5% at each concentration in each assay.

Mesamoll was considered not to have the ability to induce chromosomal aberration.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No OECD guideline defined.
Principles of method if other than guideline:
Method: other
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay
Target gene:
hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus
Species / strain / cell type:
other: V79 cells
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Test concentrations with justification for top dose:
up to 75 ug/ml
Untreated negative controls:
yes
Remarks:
1) untreated cells exposed to the S9 mixture. 2) untreated cells exposed to vehicle alone either with or without metabolic activation.
Negative solvent / vehicle controls:
not specified
True negative controls:
yes
Remarks:
untreated cells
Positive controls:
yes
Remarks:
1) without S9 mix: Ethylmethanesulfonate (EMS); 2) with S9 mix: Dimethylbenzanthracene (DMBA)
Positive control substance:
other: 1) without S9 mix: Ethylmethanesulfonate (EMS); 2) with S9 mix: Dimethylbenzanthracene (DMBA)
Details on test system and experimental conditions:
IUCLID4 Type: HGPRT assay
Species / strain:
other: V79 cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
not specified
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: other: V79 cell cultures
Remarks:
Migrated from field 'Test system'.

The test substance induced no cytotoxic effects.

The test substance was not mutagenic in the V79 -HPRT Forward Mutation Assay, both with and without metabolic activation.

Executive summary:

Mesamoll was evaluated for mutagenic effects at the hypoxynthine-guanine phosphoribosyl transferase locus (forward mutation assay) in V79 cell cultures after in vitro treatment at concentrations up to 75 µg/ml, both with and without S9 mix.

Under both activation conditions the test substance induced no cytotoxic effects. However, Mesamoll was tested up to its limit of solubility under culture conditions.

There was no significant dose-related or reproducible increase in mutant frequency above that of the negative controls. In contrast, the positive controls Ethylmethanesulfonate (without S9 mix) and Dimethylbenzanthracene (with S9 mix) produced a clearly mutagenic effect in the assay.

The test substance was not mutagenic in the V79 -HPRT Forward Mutation Assay, both with and without metabolic activation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In vitro:

Mesamoll was tested in a Salmonella/microsome test in doses up to 12500 µg/plate (20; 100; 500; 2500; 12500 µg/plate) with 4 Salmonella typhimurium strains (TA 1535; TA 100; TA 1537 and TA 98; with and without S9-mix). Doses up to 12500 µg/plate did not lead to bacteriotoxic effects. The positive controls Endoxan, Trypaflavin and 2 -Aminoanthrazen reacted clearly mutagen. No evidence for a mutagenic effect of Mesamoll could be found (Herbold B., Bayer AG, 1981).

According to OECD TG 471 it is known that the above tested bacterial strains may not detect certain oxidising mutagens, cross-linking agents and hydrazines. No data are available for E.coli WP2 strains or S. typhimurium TA102 which have an AT base pair at the primary reversion site and would be sensitive to the mechanism mentioned above. Since Mesamoll has no oxidising properties, is not a cross-linking agents or a hydrazine derivative further testing is not necessary.

An in vitro chromosomal aberration study of Mesamoll was conducted using CHL/IU cells derived from the lungs of female Chinese hamsters as the indicator cells. Based on the result of a preliminary test, the cell growth inhibition test was conducted at 313; 625; 1250; 2500; and 5000 µg/mL in the short-term treatment assay in the absence of S9 mix and in the presence of S9 mix and in the continuous treatment assay for 24 hours and 48 hours. In the cell growth inhibition test, the test substance did not inhibit cell growth by more than 50% under any treatment condition. From these results, the chromosomal aberration test was conducted at 1250; 2500; and 5000 µg/mL in each treatment condition. In the chromosomal aberration test, the incidence of cells with structural and numerical chromosome aberrations was less than 5% at each concentration in each assay. Mesamoll was considered not to have the ability to induce chromosomal aberration (Nakagawa M., Bayer AG, 2003).

Furthermore Mesamoll was evaluated for mutagenic effects at the hypoxanthine-guanine phosphoribosyl transferase locus (forward mutation assay) in V79 cell cultures after in vitro treatment at concentrations up to 75 µg/ml, both with and without S9 mix. Under both activation conditions the test substance induced no cytotoxic effects. However, Mesamoll was tested up to its limit of solubility under culture conditions. There was no significant dose-related or reproducible increase in mutant frequency above that of the negative controls. In contrast, the positive controls Ethylmethanesulfonate (without S9 mix) and Dimethylbenzanthracene (with S9 mix) produced a clearly mutagenic effect in the assay. The test substance was not mutagenic in the V79 -HPRT Forward Mutation Assay, both with and without metabolic activation (Brendler-Schwaab S., Bayer AG, 1996).



Justification for classification or non-classification

Classification is not required.