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Genetic toxicity in vitro

Description of key information

Genetoxicity in vitro;

Data for the reaction mass test chemicals was reviewed to determine the mutagenic nature of Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (911-358-0). The read across substances share high similarity in structure and functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for test substance. Experimental data from target chemical composition and read across chemical have been reviewed to determine the mutagenic nature. The studies are as mentioned below

 

Bacterial gene mutation test was performed to evaluate the mutagenic response for the test chemical. The test was performed using Salmonella typhimurium strainsTA1535, TA100, TA1538, and TA98 in the presence and absence of S9 metabolic activation system. The test chemical was dissolved in DMSO and used at dose levels of 100, 500 or 1000µg/plate. Concurrent positive control chemicals were also included in the study. Test chemical did not induce reversion of mutation when applied to Salmonella typhimurium strainsTA1535, TA100, TA1538, and TA98 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.

Salmonella/microsome mammalian assay was performed to determine the mutagenic nature of test chemical. The study was performed using Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 in the presence and absence of S9 metabolic activation system. The test chemical was dissolved in Aqua distilled and used at dose levels of 0, 10, 50, 500 or 1000µg/plate. The doses for the main study were decided on the basis of preliminary dose range finding study. The plates were incubated for 48 hrs at 37˚C. An investigated compound was judged to have induced a positive response when a dose-related increase in the number of revertants was observed and the number of revertants exceeded the negative control values by at least 2-foId in at least two successive concentrations of the test chemical. Test chemical did not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant.

Genetic toxicity in vitro study was assessed for test chemical. The test chemical was exposed to Salmonella typhimurium TA98, TA100, TAl535, TA1537 and TA1538 in the presence and absence of metabolic activation S9. The concentration of test material used in the presence and absence of metabolic activation were 61 to 5000 mglplate . No mutagenic effect were observed in the presence of S9 in Salmonella typhimurium strains TAl535and TA1538.While metabolic activity was observed in Salmonella typhimurium strains TA98,TA100and TA1537 in the presence of S9 metabolic activation. As this study is not available in descriptive manner. Hence data is insufficient to classify the substance.

The data available for the target chemical based on its read across substance and applying weight of evidence Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (911-358-0) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
experimental data of read across substances
Justification for type of information:
Data for the target chemical is summarized based on the structurally similar read across chemicals.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
WoE derived based on the experimental data from structurally and functionally similar read across chemicals
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
- Name of test material : Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone
- Substance type : Organic
- Physical state : Solid
Target gene:
Histidine
Species / strain / cell type:
S. typhimurium, other: TA1535, TA100, TA1538 and TA98
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium, other: TA98, TA100, TAl535, TA1537 and TA1538
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
No data
Metabolic activation:
with and without
Metabolic activation system:
S9 mix was prepared from liver homogenate of rats treated with Aroclor 1254 plus adequate cofactors
Test concentrations with justification for top dose:
1,100, 500 or 1000 µg/plate
2, 0, 10, 50, 500 or 1000 µg/plate
3,61 to 5000 mglplate
Vehicle / solvent:
1,- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test chemical was soluble in DMSO
2,- Vehicle(s)/solvent(s) used: Aqua distilled
- Justification for choice of solvent/vehicle: The test chemical was soluble in Aqua distilled
3,Not specified
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
methylmethanesulfonate
other: Hycanthone (TA1538 and TA98)
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
Aqua distilled
True negative controls:
not specified
Positive controls:
yes
Remarks:
TA1535, -S9 - Sodium azide TA1537, -S9 - 9-Aminoacridine TA1538, TA98, +S9 - 2-Aminofluorene -S9 - 4-Nitro-o-phcnylenediamine TA100, +S9 - Sodium azide -S9 - 2-Aminofluorene
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Details on test system and experimental conditions:
1,METHOD OF APPLICATION: soft-agar overlay method

DURATION
- Preincubation period: No data
- Exposure duration: No data
- Expression time (cells in growth medium): No data
- Selection time (if incubation with a selection agent): No data available
- Fixation time (start of exposure up to fixation or harvest of cells): No data available

SELECTION AGENT (mutation assays): No data available

SPINDLE INHIBITOR (cytogenetic assays): No data available

STAIN (for cytogenetic assays): No data available

NUMBER OF REPLICATIONS: 4 experiments were performed

NUMBER OF CELLS EVALUATED: No data available

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data available

OTHER EXAMINATIONS:
- Determination of polyploidy: No data available

- Determination of endoreplication: No data available

- Other: No data available

OTHER: No data available
2,Details on test system and conditions
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: No data
- Exposure duration: 48 hrs
- Expression time (cells in growth medium): 48 hrs
3,Details on test system and conditions
METHOD OF APPLICATION: Standard plate method


2,
Rationale for test conditions:
No data
Evaluation criteria:
1,The plates were observed for number of revertants/plate
2,An investigated compound was judged to have induced a positive response when a dose-related increase in the number of revertants was observed and the number of revertants exceeded the negative control values by at least 2-foId in at least two successive concentrations of the test chemical.
3,Histidine revertants per plate’s colonies were observed.
Statistics:
No data
Species / strain:
S. typhimurium, other: TA1535, TA100, TA1538, and TA98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 1538, 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 specified
Positive controls validity:
valid
Species / strain:
S. typhimurium, other: TA98, TA100, TAl535, TA1537 and TA1538
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
S. typhimurium, other: TAl535and TA1538
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
S. typhimurium, other: TA98,TA100and TA1537
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
No data
Remarks on result:
other: No mutagenic potential
Conclusions:
Gene mutation toxicity study for Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino) -4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (911-358-00)as predicted using data from read across chemicals for Salmonella typhimurium bacterial strains in the presence and absence of S9 metabolic activation system is negative and hence the chemical is not likely to classify as a gene mutant in vitro.
Executive summary:

Genetoxicity in vitro;

Data for the reaction mass test chemicals was reviewed to determine the mutagenic nature of Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (911-358-0). The read across substances share high similarity in structure and functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for test substance. Experimental data from target chemical composition and read across chemical have been reviewed to determine the mutagenic nature. The studies are as mentioned below

 

Bacterial gene mutation test was performed to evaluate the mutagenic response for the test chemical. The test was performed using Salmonella typhimurium strainsTA1535, TA100, TA1538, and TA98 in the presence and absence of S9 metabolic activation system. The test chemical was dissolved in DMSO and used at dose levels of 100, 500 or 1000µg/plate. Concurrent positive control chemicals were also included in the study. Test chemical did not induce reversion of mutation when applied to Salmonella typhimurium strainsTA1535, TA100, TA1538, and TA98 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.

Salmonella/microsome mammalian assay was performed to determine the mutagenic nature of test chemical. The study was performed using Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 in the presence and absence of S9 metabolic activation system. The test chemical was dissolved in Aqua distilled and used at dose levels of 0, 10, 50, 500 or 1000µg/plate. The doses for the main study were decided on the basis of preliminary dose range finding study. The plates were incubated for 48 hrs at 37˚C. An investigated compound was judged to have induced a positive response when a dose-related increase in the number of revertants was observed and the number of revertants exceeded the negative control values by at least 2-foId in at least two successive concentrations of the test chemical. Test chemical did not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant.

Genetic toxicity in vitro study was assessed for test chemical. The test chemical was exposed to Salmonella typhimurium TA98, TA100, TAl535, TA1537 and TA1538 in the presence and absence of metabolic activation S9. The concentration of test material used in the presence and absence of metabolic activation were 61 to 5000 mglplate . No mutagenic effect were observed in the presence of S9 in Salmonella typhimurium strains TAl535and TA1538.While metabolic activity was observed in Salmonella typhimurium strains TA98,TA100and TA1537 in the presence of S9 metabolic activation. As this study is not available in descriptive manner. Hence data is insufficient to classify the substance.

The data available for the target chemical based on its read across substance and applying weight of evidence Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (911-358-0) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

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

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Genetoxicity in vitro;

Data for the reaction mass test chemicals was reviewed to determine the mutagenic nature of Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (911-358-0). The read across substances share high similarity in structure and functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for test substance. Experimental data from target chemical composition and read across chemical have been reviewed to determine the mutagenic nature. The studies are as mentioned below

 

Bacterial gene mutation test was performed to evaluate the mutagenic response for the test chemical. The test was performed using Salmonella typhimurium strainsTA1535, TA100, TA1538, and TA98 in the presence and absence of S9 metabolic activation system. The test chemical was dissolved in DMSO and used at dose levels of 100, 500 or 1000µg/plate. Concurrent positive control chemicals were also included in the study. Test chemical did not induce reversion of mutation when applied to Salmonella typhimurium strainsTA1535, TA100, TA1538, and TA98 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.

Salmonella/microsome mammalian assay was performed to determine the mutagenic nature of test chemical. The study was performed using Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 in the presence and absence of S9 metabolic activation system. The test chemical was dissolved in Aqua distilled and used at dose levels of 0, 10, 50, 500 or 1000µg/plate. The doses for the main study were decided on the basis of preliminary dose range finding study. The plates were incubated for 48 hrs at 37˚C. An investigated compound was judged to have induced a positive response when a dose-related increase in the number of revertants was observed and the number of revertants exceeded the negative control values by at least 2-foId in at least two successive concentrations of the test chemical. Test chemical did not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant.

Genetic toxicity in vitro study was assessed for test chemical. The test chemical was exposed to Salmonella typhimurium TA98, TA100, TAl535, TA1537 and TA1538 in the presence and absence of metabolic activation S9. The concentration of test material used in the presence and absence of metabolic activation were 61 to 5000 mglplate . No mutagenic effect were observed in the presence of S9 in Salmonella typhimurium strains TAl535and TA1538.While metabolic activity was observed in Salmonella typhimurium strains TA98,TA100and TA1537 in the presence of S9 metabolic activation. As this study is not available in descriptive manner. Hence data is insufficient to classify the substance.

The data available for the target chemical based on its read across substance and applying weight of evidence Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (911-358-0) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Justification for classification or non-classification

Thus based on the above annotation and CLP criteria for target substance Reaction mass of 1,4-bis(butylamino)anthraquinone and 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-(butylamino)-4-(methylamino)anthraquinone and 1-(butylamino)-4-[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone (911-358-0) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.