Formaldehyde, reaction products with N,N-dimethylbenzenamine and N-methylbenzenamine, oxidized, hydrochlorides

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test compound Formaldehyde, reaction products with N,N-dimethylbenzenamine and N-methylbenzenamine, oxidized, hydrochloridesis not likely to be a gene mutant in vitro.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer reviewed publication

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

To evaluate the genotoxicity of methyl violet in Salmonella typhimurium strain TA1535, TA100, TA1537, TA1538 and TA98.

GLP compliance:

not specified

Type of assay:

bacterial gene mutation assay

Target gene:

No data

Species / strain / cell type:

S. typhimurium, other: TA1535, TA100, TA1537, TA1538 and TA98

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

other: strains are excision-repair deficient and contain the gal and rfa mutations.

Metabolic activation:

not specified

Metabolic activation system:

No data

Test concentrations with justification for top dose:

1, 2 or 4µg/plate

Vehicle / solvent:

No data available

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

METHOD OF APPLICATION: Top agar method was used. {soft agar procedure}

Evaluation criteria:

Revertant colonies per plate were observed.

Statistics:

No data available

Species / strain:

S. typhimurium, other: TA1535, TA100, TA1537, TA1538 and TA98

Metabolic activation:

not specified

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

Additional information on results:

No data available

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative

The test result was observed to be negative for Methyl violet in Salmonella typhimurium Strain- TA1535, TA100, TA1537, TA1538 and TA98 by soft agar procedure.

Executive summary:

Genotoxicity study for Methyl violet (CAS no 8004 -87 -3) was conducted in Salmonella typhimurium strain -TA1535, TA100, TA1537, TA1538 and TA98 bysoft agar procedure. They were exposed at the concentration of1, 2, and 4µg\plate. Revertant colonies per plate were observed. The test result was observed to be negative for Methyl violet in Salmonella typhimurium Strain-TA1535, TA100, TA1537, TA1538 and TA98. Based on the above result ,it can be summarized that Methyl violet is not likely to exhibit genetic toxicity and hence can be classified as 'non-hazardous'.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Genetic toxicity in vitro:

Various peer reviewed publications for the alternate cas (CAS no 8004 -87 -3) and read across were studied to determine the mutagenic nature of the test compound Formaldehyde, reaction products with N,N-dimethylbenzenamine and N-methylbenzenamine, oxidized, hydrochlorides (CAS no 83968 -28 -9). The summary is as mentioned below:

Genotoxicity study for Methyl violet (CAS no 8004 -87 -3) was conducted by Shahin (1978) in Salmonella typhimurium strain-TA1535, TA100, TA1537, TA1538 and TA98 bysoft agar procedure. They were exposed at the concentration of1, 2, and 4µg\plate. Revertant colonies per plate were observed. The test result was observed to be negative for Methyl violet in Salmonella typhimurium Strain-TA1535, TA100, TA1537, TA1538 and TA98.

Gene mutation toxicity study was performed (Ministry of Economy, Trade and Industry, Japan, 2016) for the test chemical C.I. Basic Violet 1 (CAS no 8004 -87 -3) using Salmonella typhimurium strains TA100, TA98, TA1535 and TA1537 in the presence and absence of S9 metabolic activation system as per the OECD guideline 471. Preincubation protocol was followed for the test. The test compound C.I. Basic Violet 1 is not mutagenic in the Salmonella typhimurium strains TA100 and TA1535 but positive in the strains TA98 and TA1537 and in E. coli WP2 uvrA.

Mutagenicity testing of methyl violet 2B (CAS no 8004 -87 -3) was performed by Chung et al (1981) using the Salmonella-microsome mutagenicity test developed by Ames et al. The test compound was tested at five concentrations from either 1 to 1,000 or 5 to 5,000 µg. Plate incorporation and preincubation method were performed to determine the mutagenic effect. The test compound methyl violet 2B is not mutagenic to the Salmonella typhimurium TA1535, TA1537, TA1538, TA98 and TA100 in the presence and absence of S9 activation system.

In a gene toxicity test (Sustainability Support Services, 2015), Chinese Hamster Ovary (CHO) cells were exposed to N,N-diethylaniline (RA CAS no 91-66-7) in the concentration of 0, 1, 2.5, 5 or 10 mM and with and without S9-induced metabolic activation for 3 hours. The results showed that there was evidence of cytotoxicity after treatment with 5 mM or above. Independently of tested N,N-diethylaniline concentration, the results showed no evidence of gene toxicity with S9 metabolic activation system. Therefore, it is considered that N,N-diethylaniline in the concentration of 0, 1, 2.5, 5 or 10 mM does not cause genetic mutation(s) when CHO cells are exposed to the test chemical in the presence of metabolic activation.Treatment with 5 mM of N,N-diethylaniline showed evidence of potential gene toxicity.Therefore, it is considered that N,N-diethylaniline in the concentrations of 2.5 mM or below does not cause genetic mutation(s), while concentrations at 5 mM or above may, when CHO cells are exposed to the test chemical in the absence of metabolic activation.Thus, the results indicate that the test chemical does not give rise to gene mutation at ≤ 2.5 mM while concentrations at ≥ 5 mM could. When the mutation frequency was determined, a frequency of 5.23 x 10^-4was shown after a 3 hour exposure of ENU as the positive control and in the absence of S9 liver microsomal fraction, as well as treatment with 5 mM and in the absence of S9 liver microsomal fraction resulted in a mutation frequency of -7.08 x 10^-5. Since no other tested concentration ofN,N-diethylaniline in the absence of S9 liver microsomal fraction resulted in colonies at ≤ 2.5 mM, or at ≤ 10.0 mM in the presence of S9 liver microsomal fraction, we conclude thatN,N-diethylaniline does not give rise to gene mutations in organisms with fully functioning metabolic activation while organisms with non-present or impared metabolic activation may develop genetic mutation when exposed toN,N-diethylaniline at ≥ 5 mM for 3 hrs or more.

Gene mutation toxicity study was performed by Zeiger et al (1988) to evaluate the mutagenic nature of the test compound N, N-diethylaniline. Salmonella Ames assay was performed by the preincubation method using the Salmonella typhimurium strains TA98, TA100 and TA1535 with and without S9 metabolic activation system. The test compound gave negative result for genetic toxicity in Ames test conducted on to S. typhimurium TA98, TA100 and TA1535 with and without metabolic activation by 10% or 30% HLI/RLI S9 system. Hence, N, N-diethylaniline (RA CAS no 91 -66 -7) is not likely to classify as gene mutant in vitro.

The genotoxicity of N, N diethylaniline (RA CAS no 91 -66 -7) was performed by Yoshima et al (1988) using a DNA repair test with rat hepatocytes. N,N-diethylaniline gave negative results in the rat hepatocytes for induction of DNA repair in vitro (in all strains/cell typres tested). Hence, the test chemical is likely to be "not classified for gene mutation".

Gene mutation toxicity study was performed by Mortelmans et al (1986) to evaluate the mutagenic nature of the test compound N, N-diethylaniline. Salmonella Ames assay was performed by the preincubation method using the Salmonella typhimurium strains TA98, TA100 and TA1535 with and without S9 metabolic activation system. The test compound gave negative result for genetic toxicity in Ames test conducted on to S. typhimurium TA98, TA100 and TA1535 with and without metabolic activation by 10% HLI/RLI S9 system. Hence, N, N-diethylaniline (RA CAS no 121 -69 -7) is not likely to classify as gene mutant in vitro.

N,N-dimethylaniline (RA CAS no 121 -69 -7) was studied by Yoshimi (1988) in a DNA repair test with primary cultured rat hepatocytes to determine the mutagenic nature of the test compound. N, N-dimethylaniline failed to show any mutagenic activity on primary rat hepatocytes in an in vitro DNA repair test.

N,N-dimethyl-p-toluidine (RA CAS no 99 -97 -8) was tested by Taningher et al (1993) for gene mutation ability by performing bacterial reverse mutation assay. The test compound was tested at dose levels of 0 -100 µg/plate. The test compound did not show any reversion of mutation and hence is negative for gene mutation in vitro.

N,N-dimethyl-p-toluidine (RA CAS no 99 -97 -8) was tested (USEPA, 2012) for gene mutation ability by performing bacterial reverse mutation assay. The test compuund was tested at dose levels of 100 -5000 µg/plate using S. typhimurium TA98, TA1537, TA1538 and TA100 with and without S9 metabolic activation sytem. The test compound did not show any reversion of mutation and hence is negative for gene mutation in vitro.

The alternate cas no 8004 -87-3 used to predict the data for mutation showed negative gene mutation effects in the studies summarized. Based on the alternate cas no studies and other weight of evidence data, the result is extrapolated to the target chemical also. On this basis the test chemical Formaldehyde, reaction products with N,N-dimethylbenzenamine and N-methylbenzenamine, oxidized, hydrochlorides (CAS no 83968 -28 -9) is also not likely to classify as a gene mutant in vitro.

Justification for selection of genetic toxicity endpoint

Data is from peer reviewed publication

Justification for classification or non-classification

The alternate cas no 8004 -87-3 used to predict the data for mutation showed negative gene mutation effects in the studies summarized. Based on the alternate cas no studies and other weight of evidence data, the result is extrapolated to the target chemical also. On this basis the test chemical Formaldehyde, reaction products with N,N-dimethylbenzenamine and N-methylbenzenamine, oxidized, hydrochlorides (CAS no 83968 -28 -9) is also not likely to classify as a gene mutant in vitro.