Dodecaaluminium trimolybdenum dodecaoxide

Genetic toxicity: in vitro

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:

09 Nov - 02 Dec 2011

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study with acceptable restrictions (limited documentation: not specified at which concentration precipitation occurred)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

(adopted July 1997)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Version / remarks:

(adopted May 2008)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht, Kaiser-Friedrich-Straße 7, 55116 Mainz, Germany

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Dodecaaluminium trimolybdenum dodecaoxide

EC Number:

239-183-9

EC Name:

Dodecaaluminium trimolybdenum dodecaoxide

Cas Number:

15123-80-5

Molecular formula:

Al2Mo3O12

IUPAC Name:

dialuminium(3+) tris(dioxomolybdenumbis(olate))

Details on test material:

- Name of test material (as cited in study report): Aluminium molybdate
- Physical state/appearance: solid, odourless
- Analytical purity: > 99%
- Lot/batch No.: GRA 2011-10-13-01
- Expiration date of the lot/batch: Nov 2018
- Storage condition of test material: room temperature

Method

Target gene:

his-operon

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 1535, TA 97a, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254

Test concentrations with justification for top dose:

Experiment I: 4993, 1503, 499, 152, and 51 µg/plate
Experiment II: 5049, 2511, 1262, 621, and 317 µg/plate

Vehicle / solvent:

sterile aqua denim.

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

benzo(a)pyrene

other: 4-Nitro-1,2-phenylene diamine (NPD); 2-amino anthracene (2AA)

Remarks:

NPD (20 µg/plate, DMSO): TA97a, TA98, and TA102 (- S9 mix); sodium azide (1 µg/plate, H2O): TA100 and TA1535 (- S9 mix); 2AA (1 µg/plate, DMSO: TA97a, TA100, TA102, and TA1535 (+ S9 mix); Benzo-a-pyrene (20 µg/plate, DMSO): TA98 (+ S9 mix)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation) (experiment II)

DURATION
- Exposure duration: 48 h at 37 °C

METHOD OF APPLICATION: preincubation (experiment II)
- Preincubation time: 20 min
- Exposure duration: 48 h at 37 °C

NUMBER OF REPLICATIONS: four replicates per condition per experiment

DETERMINATION OF CYTOTOXICITY
- Method: reduction of background lawn
A toxicity control was performed analogously to the titre control with test substance concentrations of 5000 and 1500 µg/plate.

Evaluation criteria:

A test item is considered to have mutagenic potential, if a significant, reproducible increase of revertant colonies per plate (factor >= 2) in at least one strain can be observed. A concentration-related increase over the range tested can also be taken as a sign of mutagenic activity.

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 1535, TA 97a, TA 98, TA 100 and TA 102

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
- Precipitation: No complete dissolution was possible, undissolved particles were visible on the plates. Thus, only the nominal concentration is given. It was not specified in the study report if undissolved particles were seen in all plates or only at higher concentrations.

COMPARISON WITH HISTORICAL CONTROL DATA: Yes; the values for spontaneous revertants and for positive controls were within the range of the historical data. Thus, the study is considered as valid.

ADDITIONAL INFORMATION ON CYTOTOXICITY: No signs of toxicity towards the tested strains were detected. The background lawn was visible and the number of revertant colonies was not reduced.

In both experiments, the sterility control and the determination of the titre did not show any inconsistencies.
 

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1. Test results of experiment 1 (plate incorporation).

With or without S9-Mix	Test substance (μg/plate)	Mean number of revertant colonies per plate (average of 4 plates ± Standard deviation)
		Base-pair substitution type			Frameshift type
		TA 100	TA1535	TA102	TA98	TA97a
	H2O	150 ± 11	15 ± 3.6	166 ± 9.1	10 ± 0.5	121 ± 13.5
–	DMSO	125 ± 6.4	15 ± 3.9	147 ± 22.1	10 ± 0.0	99 ± 6.6
–	51	117 ± 11	16 ± 3	173 ± 6	11 ± 3	116 ± 13
–	152	131 ± 12	17 ± 2	169 ± 13	11 ± 3	97 ± 6
–	499	138 ± 11	19 ± 1	146 ± 19	11 ± 4	128 ± 11
–	1503	118 ± 11	16 ± 1	146 ± 16	9 ± 2	105 ± 11
–	4993	122 ± 18	17 ± 5	158 ± 7	10 ± 0	111 ± 10
Positive controls, –S9	Name	SA	SA	NPD	NPD	NPD
	Concentrations (μg/plate)	1	1	20	20	20
	Mean No. of colonies/plate (average of 4 ± SD)	487 ± 109	124 ± 12	579 ± 86	132 ± 14	414 ± 68
	H2O	126 ± 15.3	17 ± 1.9	148 ± 21.3	10 ± 0.8	126 ± 31.2
+	DMSO	137 ± 17.1	19 ± 1.7	159 ± 8.6	10 ± 0.0	116 ± 7.5
+	51	113 ± 20	14 ± 3	172 ± 38	13 ± 5	111 ± 8
+	152	157 ± 13	19 ± 3	164 ± 21	11 ± 2	112 ± 9
+	499	129 ± 17	17 ± 3	161 ± 26	11 ±3	111 ± 4
+	1503	135± 30	16 ± 1	162 ± 8	13 ± 3	103 ± 13
+	4993	145 ± 11	15 ± 1	184 ± 33	12 ± 4	120 ± 15
Positive controls, +S9	Name	2AA	2AA	2AA	BP	2AA
	Concentrations (μg/plate)	1	1	1	20	1
	Mean No. of colonies/plate (average of 4 ± SD)	444 ± 100	111 ± 11	621 ± 75	117 ± 10	376 ± 49

 

NPD = 4-Nitro-1.2-phenylene diamine

SA = Sodium azide

2AA = 2-Aminoanthracene

BP = Benzo(a)pyrene

 

Table 2. Test results of experiment 2 (pre-incubation).                                                                

With or without S9-Mix	Test substance (μg/plate)	Mean number of revertant colonies per plate (average of 4 plates ± Standard deviation)
		Base-pair substitution type			Frameshift type
		TA 100	TA1535	TA102	TA98	TA97a
	H2O	100 ± 7.5	14 ± 2.9	178 ± 20.3	16 ± 2.8	118 ± 2.2
–	DMSO	92 ± 5.1	12 ± 1.7	147 ±8.3	15 ± 1.7	102 ±4.3
–	317	87 ± 13	13 ± 4	115 ± 4	14 ± 3	106 ±10
–	621	87 ± 9	12 ± 2	119 ± 5	14 ± 1	116 ± 5
–	1262	101 ± 7	14 ± 3	156 ± 6	13 ±1	109 ± 6
–	2511	95 ± 7	11 ± 2	165 ± 19	16 ±1	114 ±7
–	5049	90 ± 11	12 ± 2	165 ± 7	14 ± 3	106 ± 7
Positive controls, –S9	Name	SA	SA	NPD	NPD	NPD
	Concentrations (μg/plate)	1	1	20	20	20
	Mean No. of colonies/plate (average of 4 ± SD)	513 ± 38	230 ± 25	635 ± 51	221 ± 15	475 ± 68
	(Second value*)	294 ± 108		473 ± 175
	H2O	86 ± 8.5	13 ± 2.2	155 ± 8.7	15 ± 3.9	112 ±5.5
+	DMSO	88 ± 11.8	11 ± 2.2	159 ± 8.7	14 ± 2.9	110 ±2.2
+	317	84 ± 8	15 ± 3	111 ± 11	14 ± 2	128 ± 6
+	621	89 ± 13	15 ± 2	111 ± 9	13 ± 3	115 ±4
+	1262	86 ± 9	14 ± 3	170 ± 23	16 ± 2	108 ±7
+	2511	85 ± 9	14 ± 4	154 ± 14	14 ± 2	110 ±6
+	5049	90 ± 10	15 ± 2	148 ± 9	14 ± 2	102 ± 8
Positive controls, +S9	Name	2AA	2AA	2AA	BP	2AA
	Concentrations (μg/plate)	1	1	1	20	1
	Mean No. of colonies/plate (average of 4 ± SD)	472 ± 144	217 ± 15	612 ± 72	242 ± 22	554 ±23

 

NPD = 4-Nitro-1.2-phenylene diamine

SA = Sodium azide

2AA = 2-Aminoanthracene

BP = Benzo(a)pyrene

* Two different values were calculated in these cases, because the raw data were recorded in a way that could be interpreted in different ways.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative