Diethyl sulphide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

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

Adequacy of study:

key study

Study period:

From 15-AUG-1995 to 18-OCT-1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to OECD guidelines and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl sulphide (CAS # 75-18-3)

IUPAC Name:

Dimethyl sulphide (CAS # 75-18-3)

Details on test material:

- Name of test material (as cited in study report): dimethyl sulphide
- Substance type: pure active substance
- Physical state: clear, colorless liquid
- Stability under test conditions: data not available
- Storage condition of test material: at room temperature, protected from light

Method

Target gene:

different mutation in various gene in the histidine operon

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium TA 98, 100, 1535, 1537 and Escherichia coli WP2 uvrA

Metabolic activation:

with and without

Metabolic activation system:

Arochlor 1254-induced rat liver S9

Test concentrations with justification for top dose:

0, 100, 333, 1000, 3333, 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: DMSO was selected as the solvent of choice based on the solubility of the test article and compatibility with the target cells. The test article was soluble in DMSO at approximately 500 mg/L, the maximum concentration test.

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: WITH ACTIVATION: all Salmonella strain = 2 aminoanthracene (1µg/pl), Ecoli = 2 aminoanthracene (10µg/pl) // WITHOUT ACTIVATION: TA98 = 2-nitrofluorene (1µg/pl), TA100 & TA1535 = sodium azide (1µg/pl), TA1537 = 2-aminoacridine (75 µg/pl), WP2 uvrA = methyl

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation


DURATION
- Preincubation period: 60 +/- 2 min at 37 +/-2 °C
- Exposure duration: 48 to 72 hours at 37 +/- 2°C


NUMBER OF REPLICATES: three


DETERMINATION OF CYTOTOXICITY
- Method: the condition of the bacterial background lawn was evaluated for evidence of test article toxicity by using a dissecting microscope


OTHER:
Scoring method: revertant colonies for a given tester strain and activation condition were counted either entirely by automated colony counter or entirely by hand unless the assay was the preliminary toxicity assay or the plate exhibited toxicity. Plates with sufficient test article precipitate to interfere with automated colony counting were counted manually.

Evaluation criteria:

Data sets for strains TA1535 and TA1537 were judged positive if the increase in mean revertants at the peak of the dose response is equal to or greater than three times the mean vehicle control value.
Data sets for strains TA98, TA100 and WP2 uvrA were judged positive if the increase in mean revertants at the peak of the dose response is equal to or greater than two times the mean vehicle control value

Statistics:

not applicable

Results and discussion

Test results

Species / strain:

other: Salmonella typhimurium TA 98, 100, 1535, 1537 and Escherichia coli WP2 uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: no precipitate was observed
- Effects of pH, Effects of osmolality, Evaporation from medium,Other confounding effects: data not available


RANGE-FINDING/SCREENING STUDIES: In the preliminary toxicity assay, the maximum dose level tested was 5000 µg/plate. Neither precipitate nor appreciale toxicity was observed.


COMPARISON WITH HISTORICAL CONTROL DATA: the response of the vehicle control group and of the positive control groups are in the range of historical data

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Average number of revertants per plate (mean of 3 plates) – Experiment B1/B2

	TA98			TA100			TA1535
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	15	29	no	134	134	no	14	10	no
100	17	31	no	143	120	no	7	11	no
333	17	29	no	133	145	no	7	14	no
1000	19	25	no	125	143	no	11	9	no
3333	12	30	no	124	120	no	7	9	no
5000	15	31	no	114	135	no	11	11	no
Positive control	432	1202	no	482	1233	no	500	126	no

*solvent control with DMSO

	TA1537			WP2 uvrA
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	9	7	no	20	15	no
100	7	10	no	24	11	no
333	6	10	no	19	18	no
1000	6	8	no	12	20	no
3333	7	9	no	22	14	no
5000	6	8	no	20	17	no
Positive control	575	124	no	432	246	no

Table 2: Average number of revertants per plate (mean of 3 plates) – Experiment B3

	TA98			TA100			TA1535
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	17	22	no	120	131	no	9	10	no
100	14	17	no	99	123	no	6	11	no
333	14	19	no	109	137	no	8	10	no
1000	20	22	no	113	136	no	7	9	no
3333	14	28	no	116	126	no	8	12	no
5000	17	25	no	96	132	no	7	9	no
Positive control	415	1141	no	468	1011	no	311	108	no

*solvent control with DMSO

	TA1537			WP2 uvrA
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	7	5	no	15	14	no
100	4	4	no	12	16	no
333	6	5	no	13	18	no
1000	3	9	no	13	14	no
3333	5	7	no	12	15	no
5000	2	4	no	9	17	no
Positive control	461	123	no	668	82	no

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Dimethyl sulfide was concluded to be negative in the Salmonella / Escherichi coli closed-phase preincubation mutagenicity assay with an independent repeat assay.

Executive summary:

In a reverse gene mutation assay in bacteria (similar to OECD testing guideline 471 and according to GLP), Salmonella typhimurium TA 98, 100, 1535, 1537 and Escherichia coli WP2 uvrA were exposed to Dimethyl sulfide in DMSO at concentrations of 0, 100, 333, 1000, 3333 and 5000 µg/plate in the presence and absence of mammalian metabolic activation by the preincubation method.

 

Neither precipitate nor appreciable toxicity was observed. With dimethyl sulfide, no positive responses were observed in either in the presence or in the absence of activation. The positive controls induced the appropriate responses in the corresponding strains. Dimethyl sulfide was concluded to be negative in the Salmonella/Escherichi coli closed-phase preincubation mutagenicity assay with an independent repeat assay.

 

This study received a Klimisch score of 1 and is classified as reliable without restriction because the study was performed according to OECD guidelines and followed GLP.