Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 217-968-7 | CAS number: 2022-85-7
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2004-05-24 to 2004-06-14
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 004
- Report date:
- 2004
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- 2000
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Flucytosine
- EC Number:
- 217-968-7
- EC Name:
- Flucytosine
- Cas Number:
- 2022-85-7
- Molecular formula:
- C4H4FN3O
- IUPAC Name:
- flucytosine
- Test material form:
- solid: particulate/powder
Constituent 1
Method
- Target gene:
- his-/uvrB- for S. typhimurium and trp-/uvrA- for E. coli
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- Experiment 1:
Salmonella strains: 0.05, 0.15, 0.5, 1.5, 5, 15, 50 µg/plate
E. coli strain: 15, 50, 150, 500, 1500, 5000 µg/plate
Experiment 2:
Salmonella strains: 0.05, 0.15, 0.5, 1.5, 5, 15 µg/plate
E. coli strain: 15, 50, 150, 500, 1500, 5000 µg/plate
Amendment was performed based on the results from Experiment 1.
Highest concentration was determined in a preliminary experiment - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: solvent formed the best dosable suspension
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- N-ethyl-N-nitro-N-nitrosoguanidine
- benzo(a)pyrene
- other: 2-Aminoanthracene, with metabolic acitvation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium; in agar (plate incorporation)
DURATION
- Exposure duration: 48h
NUMBER OF REPLICATIONS: 3 - Rationale for test conditions:
- Test conditions meet the requirements of the OECD test guidelines
- Evaluation criteria:
- The test material may be considered positive in this test system if the following criteria are met:
The test material should have induced a reproducible, dose-related and statistically (Dunnet´s method ef linear regression) significant increase in the revertant count in at least one strain of bacteria.
Results and discussion
Test results
- Key result
- Species / strain:
- other: TA 98, TA100, TA1535; TA1537 and E.coli WP2uvrA-
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: The test material formed a suspension in distilled water, dimethyl-sulphoxide and acetone and was insoluble in dimethyl formamide, ethanol and acetonitrile at 50 mg/mL and tetrahydrofuran at 200 mg/mL.
- Precipitation: non reported
RANGE-FINDING/SCREENING STUDIES: A preliminary test was conducted in TA100 and WP2uvrA- with the following concentrations, 0, 0.15, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: detection of the reduction of the backgraund lawn or reduction in number of revertants
Any other information on results incl. tables
Table 1: Number of revertants per plate (mean of 3 plates) experiment I
|
[TA98] |
[TA100] |
[WP2uvrA-] |
[TA1535] |
[TA1537] |
|||||||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
|
0* |
19 ± 2.5 |
32 ± 4.9 |
no |
100 ± 10.8 |
105 ± 16.5 |
no |
20 ± 2.1 |
20 ± 2.5 |
no |
29 ± 1.2 |
16 ±0.0 |
no |
9 ± 2.6 |
19 ± 2.6 |
no |
|
0.05 |
16 ± 6.4 |
27 ± 9.5 |
no |
111 ± 3.2 |
94 ± 17.8 |
no |
NT |
NT |
|
35 ± 6.9 |
12 ± 1.0 |
no |
11 ± 1.5 |
20 ± 3.2 |
no |
|
0.15 |
11 ± 3.2 |
30 ± 4.4 |
no |
91 ± 11.5 |
113 ± 40.4 |
no |
NT |
NT |
|
27 ± 3.8 |
8 ± 0.6 |
no |
9 ± 6.4 |
19 ± 4.6 |
no |
|
0.5 |
8 ± 2.9 |
31 ± 3.8 |
no |
81 ± 12.4 |
113 ± 41.9 |
no |
NT |
NT |
|
34 ± 6.1 |
13 ± 4.7 |
no |
5 ± 2.3 |
12 ± 4.0 |
no |
|
1.5 |
8 ± 2.5 |
21 ± 3.5 |
no |
77 ± 4.5 |
57 ± 6.7 |
yes |
NT |
NT |
|
28 ± 6.7 |
9 ± 1.2 |
yes |
2 ± 1.5 |
13 ± 7.0 |
no |
|
5 |
5 ± 0.0 |
4 |
yes |
6 ± 3.2 |
0 ± 0.0 |
yes |
NT |
NT |
|
14 ± 7.9 |
0 ± 0.0 |
yes |
0 ± 0.0 |
0 ± 0.0 |
yes |
|
15 |
0 ± 0.0 |
0 ± 0.0 |
yes |
0 ± 0.0 |
0 ± 0.0 |
yes |
11 ± 2.0 |
13 ± 3.8 |
|
0 ± 0.0 |
0 ± 0.0 |
yes |
0 ± 0.0 |
0 ± 0.0 |
yes |
|
50 |
0 ± 0.0 |
0 ± 0.0 |
yes |
0 ± 0.0 |
0 ± 0.0 |
yes |
6 ± 5.0 |
9 ± 1.7 |
no |
0 ± 0.0 |
0 ± 0.0 |
yes |
0 ± 0.0 |
0 ± 0.0 |
yes |
|
150 |
NT |
NT |
|
NT |
NT |
|
8 ± 1.5 |
4 ± 1.2 |
no |
NT |
NT |
|
NT |
NT |
|
|
500 |
NT |
NT |
|
NT |
NT |
|
3 ± 1.5 |
9 ± 2.0 |
no |
NT |
NT |
|
NT |
NT |
|
|
1500 |
NT |
NT |
|
NT |
NT |
|
0 ± 0.6 |
4 ± 2.9 |
yes |
NT |
NT |
|
NT |
NT |
|
|
5000 |
NT |
NT |
|
NT |
NT |
|
0 ± 0.0 |
0 ± 0.6 |
yes |
NT |
NT |
|
NT |
NT |
|
|
Positive control |
116 ± 17.3 |
281 ± 22.7 |
|
725 ± 55.6 |
1232 ± 41.2 |
|
1149 ± 59.5 |
163 ± 58.8 |
|
349 ± 40.0 |
244 ± 25.5
|
|
1082 ± 15.7 |
315 ± 40.5 |
|
|
*solvent control with DMSO
NT = not tested at this dose level
Table 2: Number of revertants per plate (mean of 3 plates) experiment II
|
[TA98] |
[TA100] |
[WP2uvrA-] |
[TA1535] |
[TA1537] |
|||||||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
|
0* |
18 ± |
44 ± 10.0 |
no |
88 ± 4.0 |
95 ± 10.2 |
no |
16 ± 2.6 |
40 ± 3.1 |
no |
20 ± 7.6 |
33 ± 4.6 |
no |
12 ± 2.3 |
17 ± 2.1 |
no |
|
0.05 |
20 ± |
29 ± 1.5 |
no |
83 ± 10.3 |
91 ± 11.1 |
no |
NT |
NT |
|
21 ± 3.6 |
32 ± 8.1 |
no |
7 ± 2.1 |
10 ± 2.6 |
no |
|
0.15 |
19 ± |
23 ± 6.1 |
no |
81 ± 9.5 |
94 ± 4.2 |
no |
NT |
NT |
|
17 ± 1.7 |
14 ± 5.2 |
no |
15 ± 4.0 |
15 ± 2.5 |
no |
|
0.5 |
13 ± |
19 ± 1.5 |
no |
71 ± 5.5 |
90 ± 7.2 |
no |
NT |
NT |
|
17 ± 6.6 |
12 ± 4.6 |
no |
9 ± 2.1 |
10 ± 3.1 |
no |
|
1.5 |
21 ± |
17 ± 7.8 |
no |
66 ± 8.5 |
89 ± 2.6 |
yes |
NT |
NT |
|
18 ± 3.0 |
10 ± 2.5 |
no |
7 ± 3.2 |
13 ± 3.0 |
no |
|
5 |
14 ± |
12 ± 1.7 |
no |
35 ± 3.1 |
52 ± 12.6 |
yes |
NT |
NT |
|
3 ± 1.7 |
4 ± 1.2 |
yes |
0 ± 0.0 |
1 ± 0.6 |
yes |
|
15 |
4 ± |
0 ± 0.0 |
yes |
1 ± 0.6 |
0 ± 0.0 |
yes |
9 ± 2.9 |
9 ± 3.0 |
no |
2 ± 1.2 |
0 ± 0.0 |
yes |
1 ± 1.0 |
1 |
yes |
|
50 |
NT |
NT |
|
NT |
NT |
|
14 ± 4.6 |
11 ± 3.2 |
no |
NT |
NT |
|
NT |
NT |
|
|
150 |
NT |
NT |
|
NT |
NT |
|
10 ± 1.0 |
15 ± 2.3 |
no |
NT |
NT |
|
NT |
NT |
|
|
500 |
NT |
NT |
|
NT |
NT |
|
9 ± 1.0 |
8 ± 3.8 |
no |
NT |
NT |
|
NT |
NT |
|
|
1500 |
NT |
NT |
|
NT |
NT |
|
2 ± 1.2 |
6 ± 2.1 |
no |
NT |
NT |
|
NT |
NT |
|
|
5000 |
NT |
NT |
|
NT |
NT |
|
0 ± 0.0 |
0 ± 0.0 |
yes |
NT |
NT |
|
NT |
NT |
|
|
Positive control |
130 ± 12.9 |
325 ± 21.2 |
|
574 ± 71.8 |
2430 ± 57.7 |
|
705 ± 27.2 |
307 ± 50.5 |
|
373 ± 26.0 |
306 ± 14.0
|
|
655 ± 52.2 |
493 ± 27.2 |
|
|
*solvent control with DMSO
NT = not tested at this dose level
Table 3: Positive control data 2002
Strain S9-Mix |
TA100 |
TA1535 |
WP2uvrA- |
TA 102 |
TA98 |
TA1537 |
||||||
|
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
Mean |
460 |
1880 |
347 |
310 |
621 |
866 |
1126 |
858 |
136 |
239 |
1953 |
453 |
SD |
118.2 |
594.3 |
204.0 |
119.7 |
235.5 |
350.5 |
289.4 |
169.5 |
38.2 |
74.7 |
803.1 |
145.9 |
Min |
235 |
499 |
80 |
91 |
185 |
210 |
686 |
568 |
66 |
91 |
486 |
140 |
Max |
952 |
3397 |
1385 |
810 |
1295 |
3406 |
2456 |
2009 |
323 |
507 |
4622 |
1365 |
Table 4: Positive control data 2003
Strain S9-Mix |
TA100 |
TA1535 |
WP2uvrA- |
TA 102 |
TA98 |
TA1537 |
||||||
|
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
Mean |
429 |
1529 |
297 |
305 |
649 |
656 |
1068 |
911 |
174 |
249 |
1273 |
370 |
SD |
108.1 |
493.1 |
156.8 |
82.6 |
175.7 |
264.4 |
230.0 |
183.8 |
64.6 |
72.2 |
623.1 |
109.9 |
Min |
197 |
485 |
98 |
162 |
273 |
136 |
698 |
559 |
64 |
87 |
262 |
148 |
Max |
849 |
3662 |
1099 |
625 |
1198 |
1373 |
1886 |
1887 |
410 |
465 |
3704 |
759 |
Table 5: Negative (solvent/vehicle) historical control data (2002)
Strain S9-Mix |
TA100 |
TA1535 |
WP2uvrA- |
TA 102 |
TA98 |
TA1537 |
||||||
|
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
Mean |
91 |
100 |
20 |
17 |
23 |
27 |
322 |
349 |
22 |
35 |
12 |
17 |
SD |
16.6 |
18.0 |
5.5 |
4.3 |
4.8 |
5.3 |
47.7 |
34.6 |
5.2 |
6.8 |
4 |
5 |
Min |
61 |
68 |
8 |
8 |
10 |
14 |
183 |
255 |
11 |
13 |
4 |
5 |
Max |
160 |
162 |
38 |
37 |
47 |
45 |
414 |
449 |
44 |
66 |
29 |
38 |
Table 6: Negative (solvent/vehicle) historical control data (2003)
Strain S9-Mix |
TA100 |
TA1535 |
WP2uvrA- |
TA 102 |
TA98 |
TA1537 |
||||||
|
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
Mean |
98 |
106 |
20 |
15 |
23 |
28 |
331 |
365 |
20 |
30 |
10 |
14 |
SD |
20.7 |
23.4 |
8.5 |
3.9 |
5.6 |
7.0 |
38.2 |
29.0 |
5.1 |
7.1 |
3.9 |
5.0 |
Min |
61 |
64 |
8 |
7 |
11 |
13 |
233 |
264 |
10 |
15 |
3 |
3 |
Max |
165 |
191 |
45 |
39 |
44 |
57 |
400 |
422 |
52 |
53 |
26 |
32 |
Applicant's summary and conclusion
- Conclusions:
- In the present study conducted according to OECD guideline 471, 4 Salmonella thypimurium strains and one Escherichia coli strain were exposed to 5-Fluorocytosine at the following concentrations: Salmonella strains: 0.05, 0.15, 0.5, 1.5, 5, 15, 50 µg/plate E. coli strain: 15, 50, 150, 500, 1500, 5000 µg/plate in two independent experiments. Since the validity criteria were fulfilled and there were no doubling of the revertant number, the substance is considered non-mutagenic under the present conditions. Thus, no classification is needed according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) with respect to mutagenicity.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
