Silicic acid, sodium salt

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

yes

Remarks:

RCC-Cytotest Cell Research GmbH

Type of assay:

in vitro mammalian chromosome aberration test

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

CELL CULTURE DETAILS:
- Type and identity of media: Minimal Essential Medium supplemented with  10% fetal calf serum.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital / ß-Naphthoflavone induced  rat liver S9-mix

Test concentrations with justification for top dose:

19.5, 39.1, 78.1 & 156.3 µg active ingredient/ml

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

medium

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 300-400 µg/ml  Ethylmethane sulfonate (-S9), 1.4-2.0 µg/ml Cyclophosphamide (+S9)

Details on test system and experimental conditions:

- Spindle inhibitor: 0.2 µg/ml Colcemid
- Stain: Giemsa
- No. of metaphases analyzed: 100
- Dosing: Cytotoxic concentrations were determined in a range-finder study with and without metabolic activation. 312.5 µg/ml was chosen as  top concentration in the actual experiments.
- Number of replicates: 2

Evaluation criteria:

Breaks, fragments, deletions, exchanges,  and chromosome disintegrations were recorded as structural chromosome  aberrations. Gaps were recorded as well, but not included in the  calculation of aberration rates. Only metaphases with characteristic  chromosome numbers (22+-1) were included in the analysis. The mitotic  index (% cells in mitosis) and the percentage of polyploid cells in 500  metaphase plates/culture were determined.

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: 156.3 - 312.5 µg active ingredient/mL

PRECIPITATION CONCENTRATION:

156.3 µg active ingredient/ml (except experiment II after 18h preparation interval without S9 mix where precipitation occurred at 78.1 µg/ml and above)

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according to OECD 476

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Guideline:

EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)

Guideline:

EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test

Guideline:

other: Japanese Guidelines: Kanpoan No. 287, Environment Protection Agency; Eisei No. 127, Ministry of Health and Welfare; Heisei 09/10/31 Kikyoku No. 2, Ministry of International Trade and Industry

Principles of method if other than guideline:

first experiment 4 hours treatment with and without metabolic activation
second experiment 24 hours treatment without metabolic activation and 4 hours treatment with metabolic activation

GLP compliance:

yes (incl. QA statement)

Remarks:

Harlan Cytotest Cell Research GmbH

Type of assay:

mammalian cell gene mutation assay

Target gene:

HPRT

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

- Type and identity of media: MEM
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S9

Test concentrations with justification for top dose:

Experiment I:
without S9 mix: 28.1; 56.3; 112.5; 225.0; 337.5; 450 µg/mL
with S9 mix: 56.3; 112.5; 225.0; 450.0; 675.0; 900.0 µg/mL
Experiment II:
without S9 mix: 28.1; 56.3; 112.5; 225.0; 450.0; 675.0 µg/mL
with S9 mix: 112.5; 225.0; 450.0; 900.0; 1350.0; 1800 µg/mL

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: solubility properties

Negative solvent / vehicle controls:

yes

Remarks:

water

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

Migrated to IUCLID6: 7,12-dimethylbenz(a)anthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium


DURATION
- Exposure duration: 4 hours with and without metabolic activation in experiment 1, 24 hours without metaoblic activation in experiment 2
- Expression time (cells in growth medium): 72 hours
- Selection time (if incubation with a selection agent): 10 days

SELECTION AGENT (mutation assays): Thioguanine

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: >1,5x10exp.6

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency

Evaluation criteria:

A test item is classified as positive if it induces either a concentration-related increase of the mutant frequency or a reproducible and positive response at one of the test points.
A test item producing neither a concentration- related increase of the mutant frequency nor a reproducible positive response at any of the test points is considered non-mutagenic in this system.
A positive response is described as follows:
A test item is classified as mutagenic if it reproducibly induces a mutation frequency that is three times above the spontaneous mutation fre¬quency at least at one of the concentrations in the experiment.
The test item is classified as mutagenic if there is a reproducible concentration-related increase of the mutation frequency. Such evaluation may be considered also in the case that a threefold increase of the mutant frequency is not observed.

However, in a case by case evaluation this decision depends on the level of the corre-sponding negative control data. If there is by chance a low spontaneous mutation rate in the range normally found (0.5 ¿ 31.8 mutants per 10exp.6 cells) a concentration-related in-crease of the mutations within this range has to be discussed. The variability of the mutation rates of negative and solvent controls within all experiments of this study was also taken into consideration.

Statistics:

Linear regression analysis (least squares) .

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Summary Table

			relative	relative	mutant		relative	relative	mutant
	conc. µg	S9	cloning	cloning	colonies/	induction	cloning	cloning	colonies/	induction
	per mL	mix	efficiency I	efficiency II	10^6 cells	factor	efficiency I	efficiency II	10^6 cells	factor
			%	%			%	%
column	1	2	3	4	5	6	7	8	9	10
Experiment I / 4 h treatment			culture I				culture II
Solvent control with water		-	100.0	100.0	18.4	1.0	100.0	100.0	17.1	1.0
Positive control with	150.0	-	76.2	94.8	137.7	7.5	84.7	86.2	132.3	7.7
Test item	28.1	-	98.4	114.2	15.4	0.8	92.7	104.2	13.0	0.8
Test item	56.3	-	100.0	110.3	12.0	0.7	97.1	98.0	16.8	1.0
Test item	112.5	-	102.8	101.8	16.7	0.9	88.2	96.3	15.5	0.9
Test item	225.0	-	87.2	102.0	21.5	1.2	76.9	95.5	19.9	1.2
Test item	337.5	-	0.2	98.4	14.6	0.8	8.8	89.2	20.5	1.2
Test item	450.0	-	0.0	culture was not continued^#			0.0	culture was not continued^#
Solvent control with water		+	100.0	100.0	24.6	1.0	100.0	100.0	17.9	1.0
Positive control with DMBA	1.1	+	43.9	89.0	636.4	25.9	36.6	99.5	620.9	34.7
Test item	56.3	+	94.4	culture was not continued^##			97.3	culture was not continued^##
Test item	112.5	+	89.5	94.1	16.9	0.7	95.7	105.9	22.3	1.2
Test item	225.0	+	94.1	89.8	17.6	0.7	94.2	85.8	20.6	1.2
Test item	450.0	+	84.7	90.5	16.3	0.7	94.5	81.5	20.9	1.2
Test item	675.0	+	88.5	114.3	13.2	0.5	93.6	92.6	17.9	1.0
Test item	900.0	+	85.0	85.7	27.8	1.1	92.9	96.4	15.5	0.9
Experiment II / 24 h treatment			culture I				culture II
Solvent control with water		-	100.0	100.0	13.7	1.0	100.0	100.0	14.1	1.0
Positive control with	75.0	-	92.5	97.7	132.5	9.7	102.2	93.2	105.6	7.5
Test item	28.1	-	104.7	culture was not continued^##			101.8	culture was not continued^##
Test item	56.3	-	102.5	95.7	16.9	1.2	102.2	69.3	18.8	1.3
Test item	112.5	-	88.0	94.5	17.4	1.3	102.7	97.8	9.0	0.6
Test item	225.0	-	95.1	88.7	23.2	1.7	102.0	71.3	17.4	1.2
Test item	450.0	-	94.1	84.2	23.6	1.7	101.4	65.3	17.7	1.3
Test item	675.0	-	43.3	90.9	16.2	1.2	102.9	63.5	28.4	2.0
Experiment II / 4 h treatment			culture I				culture II
Solvent control with water		+	100.0	100.0	13.7	1.0	100.0	100.0	16.1	1.0
Positive control with DMBA	1.1	+	55.9	73.5	809.9	59.1	51.2	78.8	595.5	36.9
Test item	112.5	+	114.6	78.2	20.1	1.5	95.6	90.4	22.6	1.4
Test item	225.0	+	91.3	101.5	24.6	1.8	107.2	98.0	14.5	0.9
Test item	450.0	+	95.5	109.1	22.9	1.7	99.1	83.9	20.5	1.3
Test item	900.0	+	111.7	99.4	26.1	1.9	112.6	80.5	20.8	1.3
Test item	1350.0	+	10.6	100.7	11.4	0.8	7.4	102.9	8.8	0.5
Test item	1800.0	+	0.0	culture was not continued^#			0.0	culture was not continued^#

#     culture not continued due to exceedingly strong toxic effects

##    culture was not continued since a minimum of only four analysable concentrations is required

Conclusions:

Interpretation of results (migrated information):
negative

In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells.
Therefore, C-SAT 080094 is considered to be non-mutagenic in this HPRT assay.

Executive summary:

The study was performed to investigate the potential of C-SAT 080094 to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster.

The assay was performed in three independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 hours. The experimental part without metabolic activation was terminated prematurely due to exceedingly severe cytotoxic effects even al low concentrations. This part of the first experiment was repeated in experiment IA using a lower concentration range. The data of the repeat experiment IA are included in the first experiment.

The second experiment was performed in the absence of metabolic activation with a treatment period of 24 hours and in the presence of metabolic activation with a treatment period of 4 hours.

The highest applied concentration in the pre-test on toxicity (7300 µg/mL) was based on the purity of the test item (36 % active ingredient). The dose range of the main experiments was limited by toxicity of the test item.

No substantial and reproducible dose dependent increase of the mutation frequency was observed in both main experiments.

Appropriate reference mutagens, used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test item and the activity of the metabolic activation system.

Reference 3

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:

other: see 'Remark'

Remarks:

GLP - Guideline study, tested with the source substance disodium metasilicate nonahydrate. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

his operon (for S. tyhphimurium strains)
trp operon (for E. coli strain)

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

Aroclor-induced rat liver S-9 mix and uninduced hamster liver S-9 mix

Test concentrations with justification for top dose:

standard plate test: 33, 100, 333, 1000, 2500, 5000 µg/plate with and without metabolic activation
preincubation test: 10, 33, 100, 333, 1000, 2500 µg/plate with and without metabolic activation

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: with rat S-9: 2-aminoanthracene: TA tester strains, 2.5 µg; E.coli WP2uvrA, 60 µg

Remarks:

with S9 mix

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-methyl-N'-nitro-N-nitrosoguanidine (TA1535, TA100: 5 µg/plate), 4-nitro-o-phenylendiamine (TA98: 10 µg/plate), 9-aminoacridine (TA1537, 100 µg/plate), 4-nitroquinoline-N-oxide (E. coli WP2 uvrA, 5 µg/plate)

Remarks:

without S9 mix

Details on test system and experimental conditions:

METHOD OF APPLICATION: standard plate test and preincubation test

DETERMINATION OF CYTOTOXICITY
- Method: reduced background growth

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Table 1: Results of tester strains TA1537 and TA98 with and without metabolic activation

(*reduced background growth)

		TA 1537						TA 98
Dose [µg/plate]	S-9 mix	Standard Test			Preincubation Test			Standard Test			Preincubation Test
0	+	9	7	6	8	5	7	28	25	21	21	24	22
10	+	-	-	-	6	8	6	-	-	-	28	21	19
33	+	8	6	9	6	7	8	28	19	27	28	17	26
100	+	8	8	7	9	4	7	25	23	18	24	21	20
333	+	10	5	8	5	8	7	22	25	26	20	15	21
1000	+	8	5	7	4	5	4	21	23	24	17	10	11
2500	+	7	7	5	2*	2*	3*	18	14	17	4*	4*	5*
5000	+	2*	5*	5*	-	-	-	10*	8*	6*	-	-	-
2-aminoanthracene	+	155	129	111	164	119	138	668	634	529	665	578	634
0	-	8	6	6	5	7	7	21	17	19	21	15	18
10	-	-	-	-	7	5	6	-	-	-	17	19	16
33	-	8	5	9	8	5	4	18	23	14	20	18	14
100	-	7	6	5	5	7	4	15	22	21	16	19	21
333	-	8	6	6	6	5	6	17	18	20	21	15	14
1000	-	7	8	5	2*	1*	2*	20	14	18	9*	5*	5*
2500	-	3	5	5	0*	0*	0*	12	13	17	0*	0*	0*
5000	-	2*	4*	1*	-	-	-	8*	5*	5*	-	-	-
AAC(TA1537)/NOPD(TA98)	-	336	378	329	335	412	368	558	534	611	551	539	571

 

Table 2: Results of tester strains TA1535 and TA100 with and without metabolic activation

(*reduced background growth)

		TA 1535						TA 100
Dose [µg/plate]	S-9 mix	Standard Test			Preincubation Test			Standard Test			Preincubation Test
0	+	16	13	14	12	13	10	92	96	100	85	77	86
10	+	-	-	-	11	14	11	-	-	-	89	86	80
33	+	16	13	15	10	12	12	103	102	81	80	74	95
100	+	15	14	12	13	14	13	109	90	113	81	93	83
333	+	20	11	11	14	10	11	100	91	103	71	83	81
1000	+	12	11	15	8	9	9	92	111	90	55	78	65
2500	+	10	10	8	2*	5*	5*	89	80	73	40*	51*	46*
5000	+	8*	5*	8*	-	-	-	46*	48*	40*	-	-	-
2-aminoanthracene	+	126	193	164	178	136	154	882	739	812	-	-	-
0	-	10	13	9	12	10	10	100	85	97	71	69	80
10	-	-	-	-	11	10	12	-	-	-	76	75	88
33	-	13	11	10	13	9	10	88	100	90	68	71	82
100	-	10	13	10	11	10	14	86	93	88	87	79	73
333	-	12	12	9	7	13	13	105	85	87	72	80	71
1000	-	9	10	12	2*	1*	1*	76	79	76	16*	11*	14*
2500	-	11	8	8	0*	0*	0*	70	57	66	0*	0*	0*
5000	-	7*	3*	6*	-	-	-	33*	30*	24*	-	-	-
MNNG(TA1535 +TA100)	-	819	802	915	668	712	731	773	813	761	-	-	-

 

Table 3: Results of E.coli WP2 uvrA with and without metabolic activation (*reduced background growth)

		E. coli WP2 uvrA
Dose [µg/plate]	S-9 mix	Standard Test			Preincubation Test
0	+	44	45	39	40	37	37
10	+	-	-	-	38	38	37
33	+	41	38	51	37	36	34
100	+	45	42	40	38	41	35
333	+	40	41	36	40	39	31
1000	+	47	36	45	17	14	21
2500	+	33	29	32	12*	15*	14*
5000	+	17*	14*	14*	-	-	-
2-aminoanthracene	+	265	228	255	247	258	264
0	-	32	38	41	40	33	35
10	-	-	-	-	40	30	37
33	-	45	39	33	31	44	32
100	-	36	41	42	36	35	37
333	-	41	36	29	31	32	34
1000	-	38	41	45	26	25	20
2500	-	32	28	18	7*	8*	8*
5000	-	12*	14*	14*	-	-	-
4-NQO	-	559	688	634	731	712	644

 

MNNG: N-methyl-N'-nitro-N-nitrosoguanidine

NOPD: 4-nitro-o-phenylendiamine

AAC: 9-aminoacridine

4NQO: 4-nitroquinoline-N-oxide

Conclusions:

Interpretation of results:
negative

Reference 4

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Study seems to be performed according to established test procedures, but report too limited in detail.

Principles of method if other than guideline:

Bacterial reverse mutation assay (e.g. Ames test), plate count

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

other: Salmonella typhimurium TA98, TA100, TA1535, TA1537

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

0.1, 1 and 10 mg/plate

Untreated negative controls:

yes

Remarks:

buffer solution

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 0.01 µg/plate AF2 without metabolic activation was used as a positive control for TA100 and TA 98, 100 µg/plate 9-aminoacridine without metabolic activation was used as a positive control for TA 1537, and 2 µg/plate 2-aminoanthracene with metabolic activa

Details on test system and experimental conditions:

plate incorporation

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 10 mg/plate

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Reference 5

Endpoint:

in vitro DNA damage and/or repair study

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication report which meets basic scientific principles

Principles of method if other than guideline:

Rec assay described by Kada et al. (1972)

GLP compliance:

no

Type of assay:

Bacillus subtilis recombination assay

Species / strain / cell type:

other: Bacillus subtilis H17 and M45

Additional strain / cell type characteristics:

other: H17 is recombination-repair-proficient, trp-deficient and arg-deficient. M45 is recombinant-repair-deficient, trp-deficient and arg-deficient.

Metabolic activation:

without

Test concentrations with justification for top dose:

0.005-0.5 M

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Species / strain:

bacteria, other: Bacillus subtilis H17 and M45

Metabolic activation:

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

Reference 6

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented study, but not according to established guidelines.

Principles of method if other than guideline:

E. coli reverse mutation assay according to Demerec (1951), Bertani (1951).

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

E. coli, other: B/Sd-4/1,3,4,5 and B/Sd-4/3,4 

Additional strain / cell type characteristics:

other: streptomycin-dependant strains

Metabolic activation:

without

Test concentrations with justification for top dose:

0.025 - 0.30%

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

no

Details on test system and experimental conditions:

- Number of replicates: 3 hrs exposure, 5-10 replicates/dose

Species / strain:

E. coli, other: B/Sd-4/1,3,4,5 and B/Sd-4/3,4 

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not examined

mutant frequency (mutants per 10E6 bacteria): 
conc. (%) mut.freq.(treated) mut.freq.(control) survival (%)
0.025      5.9                 6.3                 66
0.100      2.4                 5.3                 33
0.050      8.7                 6.3                 27
0.100      6.6                 6.1                 16
0.100      11.4                6.2                 4.6
0.150      2.0                 6.2                 3
0.300      0.0                 7.0                 0.11

Genetic toxicity in vivo

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study was performed similar to OECD TG 475, with the restriction that no positive controls were used.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

not specified

GLP compliance:

no

Type of assay:

chromosome aberration assay

Species:

mouse

Strain:

other: BDF1

Sex:

male

Details on test animals or test system and environmental conditions:

- Age: 9 weeks

Route of administration:

oral: feed

Duration of treatment / exposure:

24 hours

Frequency of treatment:

once, 4 mg/kg bw  colchicine was  administered intraperitoneally 2 hours before necropsy.

Post exposure period:

sampling time was 24 h after administration

Remarks:

Doses / Concentrations:
740-1340 mg/kg bw (7 graduated  levels)
Basis:
nominal conc.

No. of animals per sex per dose:

4 - 6

Control animals:

yes, concurrent vehicle

Tissues and cell types examined:

femur bone marrow cells

Evaluation criteria:

The chromosomes were examined blind by three persons. Slides from femur  bone marrow cells were prepared according to standard methods, and 100  metaphases per animal analyzed for chromosomal aberrations (including  gaps, breaks, deletions, and exchanges).

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

MUTANT/ABERRATION/mPCE/ POLYPLOIDY FREQUENCY:

No significant increase of chromosomal aberrations compared to negative control even at dosage  levels exceeding the M.T.D. of 940 mg/kg bw.

Additional information

The in-vitro genetic toxicity of disodium metasilicate nonahydrate was investigated in the Ames test (BASF SE, 2012).The standard plate test and the preincubation test were conducted each with S. typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 uvrA in the presence and absence of a metabolic activation system. Concentrations up to 5000 µg/plate were used for the standard plate test and concentrations up to 2500 µg/plate for the preincubation test. The test substance did not induce reversions in any of the S. typhimurium strains or in E. coli WP2 uvrA with or without metabolic activation.

All other in vitro mutagenicity tests with bacteria were negative. Sodium silicate (MR = 3.3) also did not induce chromosomal aberrations and HPRT mutations in V79 mammalian cells in vitro, both in the presence and the absence of metabolic activation. In vivo, sodium metasilicate did not induce chromosome aberrations in the bone marrow of mice. From the available results it can be concluded that there is no evidence of a genotoxic potential for sodium silicate.

Short description of key information:
in vitro: negative
in vivo: negative

Endpoint Conclusion:

Justification for classification or non-classification

The available data is conclusive but not sufficient for classification.