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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992-01-09 to 1992-02-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to official test guidelines (Japanese Ministry of Labour), and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Guidelines of the Ministry of Labour (Notification No. 77, 1988)
Deviations:
no
GLP compliance:
yes
Remarks:
The study report cites GLP according to Ministry of Labour guidelines, and includes a statement of Quality Assurance.
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Solfit-AC
- State: Colorless transparent liquid
- Analytical purity: 99.49%
- Impurities (identity and concentrations): Water, 0.010 % by weight
- Lot/batch No.: 033224

Method

Target gene:
Histidine operon
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
E. coli WP2 uvr A
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9-Mix (prepared in-house from SD rat livers after treatment at PB and BF ip)
Test concentrations with justification for top dose:
0 (Solvent control), 313, 625, 1250, 2500, 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: Material is soluble in DMSO, and soluble at 6.8% in water.
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
N-ethyl-N-nitro-N-nitrosoguanidine
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene (2-AA)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 Minutes
- Exposure duration: 48 Hours

SELECTION AGENT (mutation assays):

NUMBER OF REPLICATIONS: 2

DETERMINATION OF CYTOTOXICITY
- Method: Not reported
Evaluation criteria:
The increase in the number of revertant colonies reletive to the negative control was determined for each concentration level. A two-fold increase was considered to show positive evidence of mutagenicity.
Statistics:
None

Results and discussion

Test resultsopen allclose all
Key result
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:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
The test material did not induce more than twice increase in the revertant colony count compared with the count of the negative control in any of the tester strains, either with or without metabolic activation.
Remarks on result:
other: all strains/cell types tested

Any other information on results incl. tables

Test Results: main Study Test Material Name: Solfit-AC 
 With or Without S9-Mix   Test substance concentration (µg/plate)   Number of revertants (mean number of colonies perplate) 
 Base-pair substitution type   Frameshift type  
 TA100   TA1535   WP2uvrA-   TA98   TA1537 
 -   0 (Solvent control)  140 146 (143)  26 34 (30)  34 41 (38)  20 30 (25)  4 8 (6)
 313  135 132 (134)  24 25 (25)  38 38 (38)  29 22 (26)  10 3 (7)
 625  122 116 (119)  19 21 (20)  45 32 (39)  37 18 (28)  10 2 (6)
 1250  132 144 (138)  18 32 (25)  49 32 (41)  21 34 (28)  10 7 (9)
 2500  141 145 (143)  21 24 (23)  37 29 (33)  30 33 (32)  9 9 (9)
 5000  154 143 (149)  28 29 (29)  36 25 (31)  33 24 (29)  4 8 (6)
 +   0 (Solvent control)  145 149 (147)  30 32 (31)  33 38 (36)  34 42 (38)  12 11 (12)
 313   153 160 (157)  20 30 (25)  38 58 (48)  43 34 (39)  9 7 (8)
 625   153 113 (133)  27 23 (25)  46 37 (42)  36 44 (40)  7 9 (8)
 1250   143 157 (150)  25 20 (23)  50 46 (48)  42 41 (42)  14 10 (12)
 2500   168 164 (166)  20 22 (21)  41 35 (38)  45 54 (50)  10 12 (11)
 5000   177 165 (171)  19 21 (20)  49 40 (45)  58 59 (59)  6 10 (8)
 Positive controls   S-9 Mix -   Name   AF-2   NaN3   ENNG   AF-2   9-AA 
 Concentration (µg/plate)   0.01   0.5   2   0.1   80 
 No. colonies per plate   403 390 (397)   221 240 (231)   466 400 (433)   367 310 (339)   74 70 (72) 
 S-9 Mix +   Name   BP   2-AA   2-AA   BP   BP 
 Concentration (µg/plate)   5   2   10   5   5 
 No. colonies per plate   470 600 (535)   177 146 (162)   425 462 (444)   244 259 (252)   106 116 (111) 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative With and without metabolic activation

The test material did not induce more than twice increase in the revertant colony count compared with the count of the negative control in any of the tester strains, either with or without metabolic activation.
Therefore, it was not considered that the test material is mutagenic.