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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
1,2-benzisothiazol-3(2H)-one 1,1-dioxide was found to be non mutagenic.
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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed journal
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
in vitro bacterial gene mutation assay of Saccharin by using Salmonella strains TA1535, TA1537, TA97, TA98, and TA100
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 100
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 1535
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 1537
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 98
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
with 10 % & 30 % HLI = induced male Syrian hamster liver S9 and 10% & 30 % RLI = induced male Sprague Dawley rat liver S9
Test concentrations with justification for top dose:
100-10000 µg/Plate
Vehicle / solvent:
Water
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
Water
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
For strains tested with S9
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
Water
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
For strains TA100 and TA1535 tested in the absence of S9
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
Water
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
For strain TA97 and TA1537 tested in the absence of S9
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
Water
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-phenylenediamin
Remarks:
For strain TA98 tested in the absence of S9
Species / strain:
S. typhimurium 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:
not specified
Positive controls validity:
not specified
Species / strain:
S. typhimurium TA 1535
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:
not specified
Species / strain:
S. typhimurium TA 1537
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:
not specified
Species / strain:
S. typhimurium TA 98
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:
not specified
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'. Remarks: Bacterial

Strain: TA100

Dose No Activation 
(Negative)
No Activation 
(Negative)
10% RLI 
(Negative)
10% RLI 
(Negative)
10% HLI 
(Negative)
10% HLI 
(Negative)
Protocol Preincubation Preincubation Preincubation Preincubation Preincubation Preincubation
ug/Plate Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM
 0         
148 8.9 159 3.2 148 16.9 216 5.7 152 4 156 6.4
100         
120 6.4 167 14.4 125 6.7 201 6.7 141 .7 158 14.3
333         
142 11.9 164 6.7 119 7.8 198 4 138 10.7 161 5.8
1000         
138 6 172 7.9 134 3.8 192 9.2 142 3.7 173 4.6
3333         
133 4.2 170 8.9 129 11.8 189 2 143 6.1 166 7.4
10000         
134 6.7 161 9.8 124 9.5 202 5 149 14.3 162 7
Positive Control 960 80.3 1504 29.3 1048 28.7 1100 61.4 1267 9 1259 30
Strain: TA1535
Dose No Activation 
(Negative)
No Activation 
(Negative)
10% RLI 
(Negative)
10% RLI 
(Negative)
10% HLI 
(Negative)
10% HLI 
(Negative)
Protocol Preincubation Preincubation Preincubation Preincubation Preincubation Preincubation
ug/Plate Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM
 0         
28 3.2 28 3.8 13 2.9 12 4.3 10 1.2 15 2.4
100         
20 2 34 2.2 12 4 14 1.5 10 1.2 19 1.8
333         
23 2.9 31 1.9 11 3 15 .7 8 2 17 1.8
1000         
26 5.8 26 2.4 15 1.2 17 1.9 13 2 22 1.8
3333         
23 0 34 2.3 8 1.5 16 3 9 .9 20 2.9
10000         
25 1.3 27 2.7 9 2.1 18 2.5 9 3.5 18 .6
Positive Control 797 55.8 1114 67.8 91 4.6 111 9 120 16 128 3.5

Conclusions:
Interpretation of results (migrated information):
negative

In an Ames test , 1,2-benzisothiazol-3(2H)-one 1,1-dioxide , in water from doses 100-10000 µg/Plate was not mutagenic in Salmonella typhimurium strains TA100,TA1535,TA1537 and TA98 with and without addition of S9 liver fractions from Aroclor induced hamsters. The same has been observed for rats as well.
Executive summary:

In an Ames test , 1,2-benzisothiazol-3(2H)-one 1,1-dioxide , in water from doses 100-10000 µg/Plate was not mutagenic in Salmonella typhimurium strains TA100,TA1535,TA1537 and TA98 with and without addition of S9 liver fractions from Aroclor induced hamsters. The same has been observed for rats as well.

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

Additional information

Additional information from genetic toxicity in vitro:

Genetic toxicity in vitro

Studies for genetic toxicity from reliable sources having Klimisch rating 1, 2 and 4.

The summary of the results are presented below

Sr.No

Endpoint

Interpretation of Results

Species/Strain

Sources

1.     

Gene mutation

Negative with and without metabolic activation

S. typhimurium TA100,TA1535,TA1537 and TA98

Experimental data for target chemical

2.     

Gene mutation

Negative with metabolic activation

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Experimental data for target chemical

3.     

Chromosome Aberration

Negative with metabolic activation

Chinese hamster Lung (CHL)

Predicted data for target chemical

4.     

Chromosome Aberration

Negative without metabolic activation

Chinese hamster Lung (CHL)

Experimental data for target chemical

5.     

Gene mutation

Negative with and without metabolic activation

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Experimental data for RA chemical: 128-44-9

6.     

DNA damage and/or repair

Negative

WI-38 human diploid fibroblasts

Experimental data for RA chemical: 128-44-9

 

On the basis of the above results, it can be concluded that the substance 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, is non-genotoxic.

Genetic toxicity in vivo:

In an in vivo gene DNA damage and/or repair toxicity study, male ddY mice were exposed to saccharin in the concentration of 100, 1000 or 2000 mg/kg for 3 hours and 2000 mg/kg for 24 hours. The choice of method for analysis was the comet assay. Significant migration of nuclear DNA was observed in colon at 3 hour after treatment with 1000 and 2000 mg/kg at 3 hour, and at 24 hours after treatment with 2000 mg/kg. It was also shown that non-nuclear DNA migrated in glandular stomach, liver, kidney, bladder, lung, brain and bone marrow at 3 and 24 hours. Therefore, saccharin was considered to be positive, i.e. have mutagenic effects, for colon, while being negative for all other investigated organs/tissues in male ddYmale mice after exposure tosaccharin for 3 and/or 24 hours.


Justification for selection of genetic toxicity endpoint
In an Ames test , 1,2-benzisothiazol-3(2H)-one 1,1-dioxide , in water from doses 100-10000 µg/Plate was not mutagenic in Salmonella typhimurium strains TA100,TA1535,TA1537 and TA98 with and without addition of S9 liver fractions from Aroclor induced hamsters. The same has been observed for rats as well. Also the chromosome aberration is based on the prediction for in-vitro mammalian chromosome aberration test on Chinese hamster Lung (CHL) with S9 metabolic activation it was estimated that 1,2-benzisothiazol-3(2H)-one 1,1-dioxide does not exhibit positive chromosomal effect.

Justification for classification or non-classification

1,2-benzisothiazol-3(2H)-one 1,1-dioxide shows negative effect in bacterial mutation studies as well as mammalian chromosome abberation studies.