Sulphuryl dichloride

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:

10 Apr - 11 May 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP -Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

only 4 strains tested

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

only 4 strains tested

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: EPA, Title40, F, 1986, The salmonella typhimurium reverse mutation assay

Deviations:

yes

Remarks:

only 4 strains tested

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Sulphuryl dichloride

EC Number:

232-245-6

EC Name:

Sulphuryl dichloride

Cas Number:

7791-25-5

Molecular formula:

Cl2O2S

IUPAC Name:

sulfuroyl dichloride

Details on test material:

- Name of test material (as cited in study report): Sulfurylchloride
- CAS No.: 7791-25-5
- Molecular formula: ClSO2Cl
- Molecular weight: 134.96
- Substance type:
- Physical state: liquid (at room temperature)
- Colour: yellowish
- Analytical purity: according to specification
- Lot/batch No.: 29.08.88
- Expiration date of the lot/batch: Auguts 29, 1989
- Stability under test conditions: stable for at least 4 hours in ethyleneglycoldimethylether
- Storage condition of test material: moisture protected

Method

Target gene:

TA 1537: his C 3076; rfa-; uvrB-;
TA 98: his D 3052; rfa-; uvrB-; R-factor
TA 1535: his G46; rfa-; uvrB-;
TA 100: his G46; rfa-; uvrB-; R-factor

Species / strain

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

- Type and identity of media: Nutrient medium: Difco Nutrient Broth (NaCl added)
- Selective agar: 2.0% Vogel-Bonner-Glucose-Minimal-Agar
- Periodically checked for membrane permeability, ampicillin resistence and spontaneous mutation rates

Additional strain / cell type characteristics:

other: the strains are derived from S.typhimurium strain LT2

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

experiment I and II: 10, 33.3, 100, 333.3 and 1000 µg/plate
experiment IIa: 10, 100, 333.3, 1000 and 5000 µg/plate
experiment IIb: 100, 333.3, 666.6, 1000 and 3333.3 µg/plate (only strains TA 98 and TA 100 without S9 mix)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: on the day of exp. sulfurylchloride was dissolved in ethyleneglycoldimethylether
- Justification for choice of solvent/vehicle: solubility properties and its relative non-toxicity for the bacteria

Controls

Untreated negative controls:

yes

Remarks:

untreated

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: sodium azide (NaN3), 4-nitro-o-phenylene-diamine (4-NOPD), 2-aminoanthracene (2-AA)

Remarks:

without S9 mix: TA 1535 and TA 100: NaN3; TA 1537 and TA 98: 4-NOPD; with S9 mix: all strains: 2-AA

Details on test system and experimental conditions:

METHOD OF APPLICATION: plate incorporation test

DURATION
After solidification the plates were incubated upside down for 72 hours at 37 °C in the dark.

NUMBER OF REPLICATIONS: 3

DETERMINATION OF TOXICITY
- Method: relative total growth (reduced spontaneous revertants, reduced background growth)

Evaluation criteria:

The test substance is considered as mutagen if in strain TA 100 the number of reversions is at least twice higher and in strains TA 1535, TA 1537 and TA 98 it is at least three times higher as compared to the spontaneous reversion rate. Also, a dose-dependent increase in the number of revertants is regarded as an indication of possibly existing mutagenic potential.

Statistics:

no appropriate statistical method is available (at the time of experiment)

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

other: >= 3333 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: >= 3333 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: >= 3333 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Distinct toxic effects, evidenced by a reduction in the number of spontaneous revertants, occured in the following test groups at 5000 µg/plate: TA 1535 (exp. IIa), TA 1537 (exp. IIa), TA98 (exp. IIa, without S9 mix), TA 100 (exp. IIa), and at 3333.3 µg/plate in TA 98 (exp. IIb), and TA 100 (exp. IIb).

Remarks on result:

other: strain/cell type: Salmonella typhimurium TA 100

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Significant and reproducible dose-dependent increase up to the highest investigated concentration only in TA 100
without S9-mix.
Negative in TA 98, TA 1535 and TA 1537 with and without metabolic activation.

Precipitation concentration: 5000 µg/plate

Applicant's summary and conclusion

Executive summary:

In one study sulfuryl chloride induced a significant and reproducible dose-dependent increase in the number of revertants in Salmonella typhimurium TA 100 in the absence of metabolic activation, while no mutagenicity was reported in this strain in the presence of metabolic activation and in tester strains TA 98, TA 1535, and TA 1537 both with and without metabolic activation (concentrations up to 5000 μg/plate, and including cytotoxic exposures) (Bayer AG, 1989). In the second study Salmonella typhimurium TA 100 was tested negative with and without metabolic activation (concentrations up to 4000 μg/plate; 4000 μg/plate were slightly cytotoxic) (Bayer AG, 1993).