Dimethoxymethyloctadecylsilane

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Mutagenicity in bacteria (OECD 471, Ames): S. typhimurium strains: TA 98, TA 100, TA 102, TA 1535 and TA 1537: Negative with and without metabolic activation

Mutagenicity in mammalian cells: no data

Clastogenicity in mammalian cells: no data

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002-05-13 to 2002-09-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Freie und Hansestadt Hamburg, Behörde für Arbeit, Gesundheit uns SozialesFreie und Hansestadt Hamburg, Behörde für Arbeit, Gesundheit uns Soziales, Germany

Type of assay:

bacterial reverse mutation assay

Target gene:

His operon

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain / cell type:

S. typhimurium TA 102

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

3.16, 10, 31.6, 100 and 316 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Acetone
- Justification for choice of solvent/vehicle: Solubility properties and relative non-toxicity to bacteria

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

- S9: 10 µg/plate in water for strains TA 1535 and TA 100.

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

-S9: 10 µg/plate in DMSO for strain TA 98

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

-S9: 100 µg/plate in ethanol for strain TA 1537

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

-S9: 1300 µg/plate in DMSO for strain TA 102

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-anthracene amide

Remarks:

+S9: 2 µg/plate in DMSO for strains TA 98, TA 102, TA 1537

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

+S9: 1500 µg/plate in aqua ad iniectabilia for stains TA 100 and TA 1535

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

DURATION

- Preincubation period: 60 minutes

- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 3 plates for each test concentration in 2 independent experiments

DETERMINATION OF CYTOTOXICITY

- Method: Background lawn assessment, revertant colony counts

Evaluation criteria:

A result is positive if the number of revertants is significantly increased compared with the solvent control to at least 2-fold of the solvent control for TA 98, TA 100 and TA 102 and 3-fold of the solvent control for TA 1535 and TA 1537 in both experiments.

Positive results have to be reproducible and the histidine independence of the revertants has to be confirmed by streaking on histidine-free agar plates.

Cytotoxicity is defined as a reduction in the number of colonies by >50% compared with the solvent control and/or a sparse background lawn.

Statistics:

MANN and WHITNEY and Spearman’s rank.

Key result

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

316 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

316 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data

Table 2: Dose range-finding study Number of revertants per plate (2 plates)

	TA100
Conc. (µg/plate)	Plate 1	Plate 2	Cytotoxic (yes/no)
0*	148	140	No
0.316	160	151	No
1	148	141	No
3.16	153	149	No
10	138	141	No
31.6	162	149	No
100	132	162	No
316	171	157	Yes
1000	0	0	Yes
3160	0	0	Yes
5000	0	0	Yes

*solvent control with acetone

Table 3: Experiment 1 Plate incorporation Number of revertants per plate (mean of 3 plates)

	TA98			TA100			TA102
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+  MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	30.3	39	No	152.3	164.7	No	273.7	275.7	No
3.16	34.7	38.3	No	152	159.7	No	275.7	278	No
10	26.3	33.3	No	155	164.3	No	274.3	266	No
31.6	26.7	39	No	149	169	No	270	273	No
100	22.7	36.3	No	152	162	No	270.7	262.7	No
316	31.7	36	Yes	150	164.7	Yes	272.3	260.7	Yes
Positive control	726.3	736.3	No	1091.7	1093.3	No	1105.3	1115	No

*solvent control with acetone

Table 3: Experiment 1 Plate incorporation Number of revertants per plate (mean of 3 plates)

	TA1535			TA1537
Conc. µg/plate	— MA	+  MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	17.3	17.7	No	4	5	No
3.16	16	15	No	4	3.7	No
10	17.3	18	No	2.7	4	No
31.6	15.7	12	No	3	3.3	No
100	16	17	No	3.7	4.7	No
316	15.3	18.3	Yes	3	4.3	Yes
Positive control	529.3	530.7	No	518.3	528.3	No

*solvent control with acetone

Table 4: Experiment 2 Preincubation Number of revertants per plate (mean of 3 plates)

	TA98			TA100			TA102
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+  MA	Cytotoxic (yes/no)
0*	32	35.3	No	151.3	176.7	No	271.7	287.7	No
3.16	31	35	No	136.3	162.3	No	285	260.3	No
10	30.7	36	No	146.7	165	No	278	269.3	No
31.6	25.3	26.7	No	161	171	No	278	268.3	No
100	25	27	No	152	170.7	No	274	271.3	No
316	26.7	32.7	Yes	157	173.3	Yes	277	292	Yes
Positive control	876.7	1062.3	No	1300.3	1264	No	1294.3	1267.3	No

*solvent control with acetone

Table 4: Experiment 2 Preincubation Number of revertants per plate (mean of 3 plates)

	TA1535			TA1537
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	15.3	14.7	No	4	3.3	No
3.16	15	12.3	No	3	4	No
10	11.3	12.3	No	2.3	4	No
31.6	12	14.3	No	3.3	4.7	No
100	13.7	12.7	No	3	4	No
316	12	12	Yes	3	4	Yes
Positive control	491.7	451	No	443.3	446.7	No

*solvent control with acetone

MA - Metabolic activation

Conclusions:

Interpretation of results:
negative with metabolic activation
negative without metabolic activation

In a reliable test, conducted under OECD 471, with GLP, no mutagenic effect was observed for the test substance tested up to cytotoxic concentration in any of the test strains in two independent experiments without and with metabolic activation. The test substance is non-mutagenic in test strains used.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

An Ames test is available with dimethoxymethyloctadecylsilane (CAS 70851-50-2).

The mutagenicity of dimethoxymethyloctadecylsilane in bacteria was assessed in a study performed according to OECD Guideline 471 with Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 (LPT, 2002). The tester strains were treated using the plate incorporation and the preincubation method both with and without S9-mix. The concentrations tested were 3.16 – 316 µg/plate for the plate incorporation and preincubation test, respectively. Results achieved with vehicle (acetone) and positive controls were valid. No genotoxicity was observed in the presence and absence of metabolic activation. No precipitation was observed up to the highest dose tested. Cytotoxicity (defined as reduction of colonies by more than 50% and/or by a scarce background lawn) was observed in all strains at 316 µg/plate. In conclusion, dimethoxymethyloctadecylsilane did not induce mutations in bacteria under the test conditions applied.

Justification for classification or non-classification

The available in vitro data are reliable and suitable for classification and fulfil the standard requirements given in Annex VII of Regulation (EC) 1272/2008. Based on the available data, there is no indication that the substance induces genetic toxicity. Nevertheless, no final decision on classification for genetic toxicity according to Regulation (EC) 1272/2008 or Directive 67/548/EEC can be made, as no information on mutagenicity and clastogenicity in mammalian cells/in vivo is available.