Trichloro(octadecyl)silane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2002-05-10 to 2002-09-9

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

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 UND SOZIALES

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Chlorodimethyloctadecylsilane

EC Number:

242-472-2

EC Name:

Chlorodimethyloctadecylsilane

Cas Number:

18643-08-8

Molecular formula:

C20H43ClSi

IUPAC Name:

chloro(dimethyl)octadecylsilane

Test material form:

solid

Method

Target gene:

his operon

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 102

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9-mix

Test concentrations with justification for top dose:

Preliminary toxicity test:
- 0.316, 1, 3.16, 10, 31.6, 100, 316, 1000, 3160 and 5000 μg/plate (without metabolic activation)
Experiment I:
- 100, 316, 1000, 3160 and 5000 μg/plate (with and without metabolic activation)
Experiment II:
- 31.6, 100, 316, 1000 and 3160 μg/plate (with and without metabolic activation)

Vehicle / solvent:

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

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: -S9-mix: sodium azide, 10 µg/plate (TA 100, TA 1535); 2-nitro-fluorene, 10 µg/plate (TA 98); 9-AA, 100 µg/plate (TA 1537); MMS, 1300 µg/plate (TA 102); +S9-mix: 2-AA, 2 µg/plate (TA 98, TA 102, TA 1537); CPA, 1500 µg/plate (TA 100, TA 1535)

Details on test system and experimental conditions:

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

DURATION
- Preincubation period: 60 minutes
- Expression time (cells in growth medium): 48 hours

NUMBER OF REPLICATIONS: 3 plates for each test concentration

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.

Results and discussion

Test results

Test results 1

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:

at 3160 μg/plate for all tester strains (experiment II with and without S9-mix)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 3160 μg/plate (experiment II with and without S9-mix)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

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

Any other information on results incl. tables

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

	TA 100
Conc. (µg/plate)	Plate 1	Plate 2	Cytotoxic (yes/no)
0*	123	131	No
0.316	113	118	No
1	117	106	No
3.16	108	179	No
10	108	116	No
31.6	105	129	No
100	139	149	No
316	140	149	No
1000	130	124	No
3160	159	145	No
5000	192	189	No

*solvent control with Ethylene glycol dimethylether

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

	TA 98			TA 100			TA 102
Conc. µg/plate	—  MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	—  MA	+  MA	Cytotoxic (yes/no)
0*	29.7	28	No	128.3	122.7	No	297.3	297.3	No
100	26.7	24.7	No	130.7	144.7	No	308	274.7	No
316	32	37.3	No	131.7	129.3	No	302	264.7	No
1000	39.3	31.7	No	130.3	142	No	298.7	299	No
3160	34.3	33.7	No	123.3	128	No	290.3	276	No
5000	40	30	No	126	125.7	No	294	273.7	No
Positive control	916	944.3	No	1022.3	1007	No	1051	1027.7	No

*solvent control with Ethylene glycol dimethylether

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

	TA 1535			TA 1537
Conc. µg/plate	— MA	+  MA	Cytotoxic (yes/no)	— MA	+  MA	Cytotoxic (yes/no)
0*	14.3	21.3	No	7	4.7	No
100	14	15.7	No	5	3.3	No
316	15.3	14.7	No	5.7	5.7	No
1000	18.7	14	No	4.3	3.7	No
3160	15.7	14	No	5	7.7	No
5000	18.3	12.7	No	3.7	5.3	No
Positive control	404.7	410.7	No	407.3	414.3	No

*solvent control with Ethylene glycol dimethylether

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

	TA 98			TA 100			TA 102
Conc. µg/plate	— MA	+  MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+  MA	Cytotoxic (yes/no)
0*	34	36.3	No	126.7	147	No	277	280.7	No
31.6	31	38.7	No	138.3	109	No	284	275	No
100	28	29.7	No	126	121.7	No	287.3	269	No
316	31.7	36.3	No	140.7	133.3	No	266	279	No
1000	33.3	32.7	No	132.7	134.7	No	271.3	272.3	No
3160	0	0	Yes	0	0	Yes	0	0	Yes
Positive control	538.7	557.7	No	1122	1195.3	No	1335.3	1240.7	No

*solvent control with Ethylene glycol dimethylether

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

	TA 1535			TA 1537
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	12.7	14	No	5.7	4.3	No
31.6	13.3	14	No	4	4.3	No
100	14	12.3	No	4	5	No
316	11.7	14	No	5	5	No
1000	13.7	12	No	5.7	6.7	No
3160	0	0	Yes	0	0	Yes
Positive control	337	333	No	336.3	339	No

*solvent control with Ethylene glycol dimethylether

Applicant's summary and conclusion

Conclusions:

Interpretation of results:
negative

In a highly 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.