Barium europium strontium silicate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

This study was performed with a structural analogue substance according to GLP and the methods applied are fully compliant with OECD TG 471.

It was concluded that with and without addition of S9 mix as the external metabolizing system, the test material was not mutagenic under the experimental conditions described.

Link to relevant study records

Reference

Reference 1

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:

April 18 - 29, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Target gene:

Salmonella: histidine operon
E coli. tryptophane operon

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

- Type and identity of media:
- Properly maintained: yes
- 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:

S9 mix from Aroclor 1254 pretreated rats

Test concentrations with justification for top dose:

1st series: 5, 1.58, 5, 15.8, 50, 158, 500 µg/plate
2nd series: 15.8, 50, 158, 500, 1580 µg/plate

Vehicle / solvent:

H2O

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Sodium azide, 2-Aminoanthracene, 9-Aminoacridine, Daunomycin, 4-Nitroquinoline-N-oxide

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: 3-5 hours
- Exposure duration: about 2 days


SELECTION AGENT (mutation assays): Histidine, Tryptophane

NUMBER OF REPLICATIONS:
Negative controls 6
Test material 3
Positive controls 3


NUMBER OF CELLS EVALUATED: about 1e9


DETERMINATION OF CYTOTOXICITY
- Method: other: background cytotox

Evaluation criteria:

- valid assay (cf. laboratory historical data)
- no or weak increase in revertant colonies = negative
- clear, dose dependent (over at least two concentrations), and reproducible increase in revertant colonies= positve

Statistics:

not applied

Key result

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:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no
- Effects of osmolality: no
- Evaporation from medium: no
- Water solubility: ok
- Precipitation: yes, at 1580 µg/plate with and without metabolic activation
- Other confounding effects: no

Summary Table 1^stseries

Metabolic Activation	Test Material	Concentr. [µg/plate]		Revertants per plate (Mean ± SD)
				TA 98	TA 100	TA 1535	TA 1537	WP2 uvrA
Without Activation	H2O			31 ± 8	101 ± 12	24 ± 5	26 ± 8	38 ± 2
	Test item	0.500		25 ± 5	115 ± 6	22 ± 3	27 ± 10	38 ± 3
		1.58		27 ± 4	107 ± 16	22 ± 6	31 ± 3	34 ± 7
		5.00		22 ± 8	113 ± 4	29 ± 8	20 ± 2	38 ± 6
		15.8		22 ± 4	116 ± 16	22 ± 1	28 ± 2	34 ± 11
		50.0		18 ± 1	102 ± 13	21 ± 4	32 ± 3	38 ± 5
		158		22 ± 3	110 ± 13	21 ± 2	24 ± 6	31 ± 6
		500		20 ± 1	112 ± 15	20 ± 6	21 ± 8	29 ± 4
	DAUN	1.00		201 ± 19
	NaN3	2.00			1290 ± 94	815 ± 14
	9-AA	50.0					1601 ± 111
	NQO	2.00						2043 ± 102
With Activation	H2O			32 ± 4	131 ± 22	27 ± 9	25 ± 4	34 ± 13
	Test item	0.500		22 ± 2	141 ± 7	23 ± 6	17 ± 6	44 ± 6
		1.58		35 ± 10	156 ± 7	25 ± 5	15 ± 2	36 ± 4
		5.00		19 ± 4	146 ± 7	26 ± 10	19 ± 8	48 ± 5
		15.8		23 ± 8	132 ± 19	29 ± 6	12 ± 5	40 ± 7
		50.0		19 ± 2	124 ± 6	20 ± 3	15 ± 7	41 ± 3
		158		23 ± 9	137 ± 2	23 ± 2	13 ± 5	34 ± 8
		500		18 ± 4	120 ± 7	17 ± 6	14 ± 3	32 ± 9
	2-AA	2.00		252 ± 89	971 ± 105
	2-AA	5.00				274 ± 24	333 ± 114
	2-AA	10.0						314 ± 99

Key to Positive Controls
NaN3 2-AA 9-AA DAUN NQO	Sodium azide 2-Aminoanthracene 9-Aminoacridine Daunomycin 4-Nitroquinoline-N-oxide

Summary Table 2^ndseries

 

Metabolic Activation	Test Material	Concentr. [µg/plate]		Revertants per plate (Mean ± SD)
				TA 98	TA 100	TA 1535	TA 1537	WP2 uvrA
Without Activation	H2O			35 ± 6	119 ± 13	28 ± 2	23 ± 4	26 ± 3
	Test item	15.8		31 ± 5	116 ± 7	34 ± 10	21 ± 2	18 ± 5
		50.0		27 ± 3	125 ± 15	25 ± 7	23 ± 3	19 ± 8
		158		31 ± 6	120 ± 6	20 ± 3	30 ± 1	17 ± 5
		500		26 ± 4	119 ± 7	31 ± 9	22 ± 6	19 ± 3
		1580		27 ± 10^S E	128 ± 5^S E	27 ± 4^S E	25 ± 4^S E	17 ± 2^S E
	DAUN	1.00		373 ± 39
	NaN3	2.00			870 ± 41	648 ± 34
	9-AA	50.0					519 ± 235
	NQO	2.00						724 ± 62
With Activation	H2O			35 ± 9	128 ± 13	28 ± 7	20 ± 7	35 ± 9
	Test item	15.8		36 ± 2	122 ± 17	23 ± 4	21 ± 6	29 ± 3
		50.0		34 ± 6	128 ± 2	25 ± 4	20 ± 3	40 ± 2
		158		31 ± 7	114 ± 6	25 ± 2	19 ± 8	42 ± 9
		500		33 ± 8	139 ± 4	25 ± 2	22 ± 6	38 ± 3
		1580		36 ± 10^S E	126 ± 13^S E	22 ± 6^S E	19 ± 2^S E	40 ± 1^S E
	2-AA	2.00		188 ± 38
	2-AA	5.00			1189 ± 26
	2-AA	10.0				188 ± 11	269 ± 24	132 ± 3

 

Key to Positive Controls		Key to Plate Postfix Codes
NaN3 2-AA 9-AA DAUN NQO	Sodium azide 2-Aminoanthracene 9-Aminoacridine Daunomycin 4-Nitroquinoline-N-oxide	S E	Plated as suspension Precipitation until end of experiment

 

Conclusions:

With and without addition of S9 mix as the external metabolizing system, the test material was not mutagenic under the experimental conditions described.

Executive summary:

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 471. With and without addition of S9 mix as the external metabolizing system, the test material was not mutagenic under the experimental conditions described.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

For this endpoint information from a structural similar compound is available. This study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 471. See chapter 13 report for a more detailed justification.

Reason / purpose for cross-reference:

read-across source

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Based on the data obtained from the structural analogue substance, the test item is not classified for mutagenicity according to Regulation (EC) No 1272/2008.