4'-sulphamoylacetanilide

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Experimental study was conducted by Punya Temcharoenet al. (Mutation Research, 1994) for target chemical N4-acetylsulfanilamide (121-61-9) to evaluate its mutagenic potential. N4-acetylsulfanilamide were tested by using preincubation method for their mutagenic potential in the Salmonella typhimurium strains TA98 and TA100at concentration0.00, 1, 4 and 8 mg/plate. The substance was tested, with and without metabolic activation. DMSO was used as negative control. Sodium azide and 4NQO used as positive control for TA100 and TA98 respectively with metabolic activation and AFB (0.003 µ/plate) for both TA100 and TA98 without metabolic activation. A number of revertant colonies in treated cultures greater than 2 times the solvent control revertant colonies is considered a positive response. But there was no increase in revertant colonies in test substance, when compare to solvent control. Therefore, the substanceN4-acetylsulfanilamide was considered to be not mutagenic in S. typhimurium strains TA98 and TA100. Hence the substance cannot be classified as gene mutant in vitro.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication.

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Evaluate mutagenicity effect of substance N4-acetylsulfanilamide in S. typhimurium strains TA98 and TA100 by using Ames test.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of test material : N-(4-sulfamoylphenyl) acetamide
- Molecular formula : C8H10N2O3S
- Molecular weight : 214.244 g/mol
- Smiles notation : c1(ccc(NC(C)=O)cc1)S(N)(=O)=O
- InChl : 1S/C8H10N2O3S/c1-6(11)10-7-2-4-8(5-3-7)14(9,12)13/h2-5H,1H3,(H,10,11)(H2,9,12,13)
- Substance type: Organic
- Physical state: Solid

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium, other: strains TA98 and TA100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 metabolic activation

Test concentrations with justification for top dose:

0.00, 1, 4 and 8 mg/plate

Vehicle / solvent:

DMSO

Untreated negative controls:

yes

Remarks:

DMSO

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: Without metabolic activation: sodium azide (0.5 µg/plate) and 4NQO (0.5 µg/plate) for TA100 and TA98 With metabolic activation: AFB (0.003 µ/plate) for both TA100 and TA98

Details on test system and experimental conditions:

Details on test system and conditions
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: Triplicate

Rationale for test conditions:

Not specified

Evaluation criteria:

A number of revertant colonies in treated cultures greater than 2 times the solvent control revertant colonies is considered a positive response.

Statistics:

Not

Key result

Species / strain:

S. typhimurium, other: strains TA98 and TA100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: No mutagenic effect were observed.

Mutagenic effect of seven newly synthsized sulfa drugs on S. typhimurium TA98 and TA100 using the ames test (preincubation method)

Compound	Amount (mg/ plate)	Number of his revertant colonies / plate
N^4- Acetylsulfanilamide		-S9	+S9	-S9	+S9
		TA 98		TA 100
	0.00	33	43	146	138
	1.00	38	44	133	134
	4.00	36	42	136	134
	8.00	32	39	134	138
Positive control (tz g /plate)
Sodium azide	0.5	ND	ND	942	ND
4NQO	0.5	427	ND	ND	ND
AFB	0.003	NDND254 ND 859	254	ND	859

This concentration is the maximum solubility. ND, not detected; k – Killing effect

Conclusions:

The substance N4-acetylsulfanilamide (121-61-9) was considered to be not mutagenic in S. typhimurium strains TA98 and TA100 by AMES test .

Executive summary:

N4-acetylsulfanilamidewere tested by using preincubation method for their mutagenic potential in theS. typhimurium strains TA98 and TA100at concentration0.00, 1, 4 and 8 mg/plate. The substance was tested , with and without metabolic activation. DMSO was used as negative control.Sodium azide and 4NQO used as positive control for TA100 and TA98 respectively with metabolic activation and AFB (0.003 µ/plate) for both TA100 and TA98 without metabolic activation.A number of revertant coloniesin treated cultures greater than 2 times the solventcontrol revertant colonies is considered apositive response. But there was no increase in revertant colonies in test substance, when compare to solvent control. Therefore, the substanceN4-acetylsulfanilamide was considered to be not mutagenic in S. typhimurium strains TA98 and TA100. Hence the substance cannot be classified as 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

Various publications and prediction model were reviewed to determine the mutagenic nature of N4-acetylsulfanilamide (121-61-9). The studies are as mentioned below:

Experimental study was conducted by Punya Temcharoenet al. (Mutation Research, 1994) for target chemical N4-acetylsulfanilamide (121-61-9) to evaluate its mutagenic potential. N4-acetylsulfanilamide were tested by using preincubation method for their mutagenic potential in the Salmonella typhimurium strains TA98 and TA100at concentration0.00, 1, 4 and 8 mg/plate. The substance was tested, with and without metabolic activation. DMSO was used as negative control. Sodium azide and 4NQO used as positive control for TA100 and TA98 respectively with metabolic activation and AFB (0.003 µ/plate) for both TA100 and TA98 without metabolic activation. A number of revertant colonies in treated cultures greater than 2 times the solvent control revertant colonies is considered a positive response. But there was no increase in revertant colonies in test substance, when compare to solvent control. Therefore, the substanceN4-acetylsulfanilamide was considered to be not mutagenic in S. typhimurium strains TA98 and TA100. Hence the substance cannot be classified as gene mutant in vitro.

Gene mutation toxicity was predicted for N-(4-sulfamoylphenyl)acetamide (121 -61 -9)using the battery approach from Danish QSAR database (2017). The study assumed the use of Salmonella typhimurium bacteria in the Ames test. The end point for gene mutation has been modeled in the Danish QSAR using the three software systems Leadscope, CASE Ultra and SciQSAR. Based on predictions from these three systems, a fourth and overall battery prediction is made. The battery prediction is made using the so called Battery algorithm. With the battery approach it is in many cases possible to reduce “noise” from the individual model estimates and thereby improve accuracy and/or broaden the applicability domain. Gene mutation toxicity study as predicted by Danish QSAR for N-(4-sulfamoylphenyl)acetamide is negative and hence the chemical is predicted to not classify as a gene mutant in vitro.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by Errol Zeiger et al.( Environmental Mutagenesis,1987) to determine the mutagenic nature of pyrazine-2-carboxamide (RA CAS no98-96-4). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Mutagenicity effect of Pyrazinamide was evaluated in Salmonella typhimurium. Salmonella typhimurium strains TA100, TA1535, TA1537, TA98 were used in the study. Mutagenic assay was performed by preincubationmethod. The assay performed in presence and absence pf metabolic activator i.e. Aroclor 1254-induced rat liver S-9 and Aroclor 1254-induced hamster liver S-9.DMSO was used as solvent for test substance.The test chemical, Salmonella culture and S-9 mix or buffer incubated at 37 °C for 20 min without shaking. Agar was added on plate, content of tubes were mixed poured on surface of petri dish that contain Vogel Bonner medium. The mutant colonies on plates were counted after 2 days post incubation. Doses of test substance 0, 100, 333, 1000, 3333, 10000 ug/plate were tested in triplicate. Experiments were repeated 1 week following of initial trial. Sodium azide was used as positive control substance in absence of metabolic activation for strains TA100, TA1535. 9-aminocaridine and 4-nitro-o-phenylenediamine were positive control in absence of metabolic activation for strains TA1537 and TA98 respectively. The positive control with metabolic activation for all strains was 2-aminoanthracene. In results of study, there was no increase in dose related mean number of revertant colonies compared to solvent control across all strains.Therefore, Pyrazinamide was not mutagenic in bacteria Salmonella typhimurium. Hence Pyrazinamide not likely to be classified as gene mutation in vitro.

 

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by Jean-Luc Garrigue et al.( Mutation Research, 2006) to determine the mutagenic nature ofN-(4-acetamidophenyl)acetamide ( 140-50-1). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Gene mutation toxicity study was performed to determine the mutagenic nature of N,N- diacetyl-para-phenylenediamine. The study was performed using Salmonella typhimurium strainsTA98, TA100, TA1535, TA1537 and TA102 in the absence of S9 metabolic activation system. The chemical was dissolved in DMSO as solvent and used at dose levels 1.6 to 5000µg/plate in experiment 1 by the plate incorporation method and at a narrow dose range of 156.3 – 5000µg/plate in experiment 2 by the preincubation method. Concurrent solvent and positive control chemicals were also included in the study. N,N- diacetyl-para-phenylenediaminedid not induce mutation in Salmonella typhimuriumTA98, TA100, TA1535, TA1537 and TA102 in the absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Based on the data available for the target chemical and its read across substance N4-acetylsulfanilamide (121-61-9) 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 on the data available for the target chemical . N4-acetylsulfanilamide (121-61-9) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.