Thionyl 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Only 4 strains tested. The hydrolysed products of thionyl chloride were tested.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Only 4 strains tested; test of hydrolysis products due to rapid hydrolysis upon contact with moisture

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Thionyl dichloride

EC Number:

231-748-8

EC Name:

Thionyl dichloride

Cas Number:

7719-09-7

Molecular formula:

Cl2OS

IUPAC Name:

thionyl dichloride

Details on test material:

- Name of test material (as cited in study report): Thionyl chloride (in the form of its hydrolysis products in aqueous solution
- Physical state: clear aqueous liquid
- Analytical purity: 99.8 %
- Composition of test material, percentage of components: 1 liter solution of hydrolysis products contained 115 g thionyl chloride (analysis dated 3 July 1987)
- Purity test date: 12 June 1987
- Lot/batch No.: 5441, produced 11 June 1987
- Expiration date of the lot/batch: aqueous solution of hydrolysis products approved until 31 October 1987
- Stability under test conditions: not applicable, hydrolysis products tested
- Storage condition of test material: refrigerator, hydrolysis products stored under prevention from air using nitrogen
- Other: Source: Bayer AG

Method

Target gene:

His-operon

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

other: rfa, uvrB

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9 mix

Test concentrations with justification for top dose:

first test: 0, 1.8, 9.2, 46.0, 229.0, 1149.4 µg per plate
repeat test 1: 0, 16, 80, 400, 2000, 10000 µg per plate
repeat test 2: 0, 625, 1250, 2500, 5000, 10000 µg per plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO (positive controls); deionised water (hydrolised thionyl chloride)

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

deionized water

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA1535 without S9

Migrated to IUCLID6: 10 µg/plate

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

deionized water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: nitrofurantoin, 0.2 µg/plate

Remarks:

TA100 without S9

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

deionized water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-1,2-phenylenediamine, 10 µg/plate

Remarks:

TA1537 without S9

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

Remarks:

deionized water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-1,2-phenylenediamine, 0.5 µg/plate

Remarks:

TA98 witout S9

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

deionized water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene, 3 µg/plate

Remarks:

all strains with S9 (30 % v/v)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours

SELECTION AGENT (mutation assays): reversion to his prototrophy

NUMBER OF REPLICATIONS: quadruplicates

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth; other: background growth, titer (total bacteria count on 2 plates per concentration with S9 with sufficient histidine; if no S9 was used then the total count on 2 plates per concentration with histidine but without S9 was determined)

Evaluation criteria:

1. Negative controls within expected range (literature and historical data).
2. Positive controls show sufficient effects.
3. Titer determinations must prove sufficient bacterial density in the suspension

A reproducible and dose-related increase (i.e. = twice the negative control count) in mutant counts for at least one strain is considered a positive response. Otherwise, the result is evaluated as negative.
In the case of questionable results, the investigations will continue, probably by the use of modifications, until a final evaluation is possible.

Statistics:

Means and standard deviations were calculated.

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

up to and including 10000 µg per plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

COMPARISON WITH HISTORICAL CONTROL DATA:
The negative control data within this study were comparable with the historical control data. The positive control data were largely comparable with the historical controls or at least within an acceptable range.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Maximum number of revertants(means ± SD):

Trial 1 (1.8 - 1149.4 µg/plate)
	Control		Test Substance (µg/plate)
Strain	-S9	+S9	-S9	+S9
TA1535	12 ± 3	11 ± 3	11 ± 2 (46.0)	16 ± 4 (229.9)
TA100	87 ± 6	131 ± 11	79 ± 5 (1.8)	148 ± 15 (46.0)
TA1537	20 ± 9	19 ± 6	26 ± 6 (1.8)	28 ± 6 (46.0)
TA98	17 ± 6	37 ± 6	24 ± 7 (9.2)	40 ± 4 (46.0)
Trial 2 (16 - 10000 µg/plate)
TA1535	12 ± 1	15 ± 6	15 ± 3 (16)	20 ± 4 (16)
TA100	98 ± 9	139 ± 25	103 ± 7 (16)	139 ± 11 (16)
TA1537	11 ± 2	20 ± 6	11 ± 5 (16)	21 ± 3 (80)
TA98	93 ± 11	90 ± 7	98 ± 17 (10000)	114 ± 14 (2000)
Trial 3 (625 - 10000 µg/plate)
TA1535	16 ± 3	15 ± 2	10 ± 2 (10000)	14 ± 4 (625)
TA100	97 ± 12	160 ± 19	77 ± 9 (2500)	111 ± 19 (625)
TA1537	14 ± 4	12 ± 4	11 ± 4 (625)	12 ± 6 (625)
TA98	18 ± 3	25 ± 8	15 ± 4 (625)	26 ± 4 (625)

 

Conclusion:

The test substance was not genotoxic in bacteria up to a concentration of 10000 µg/plate with and without metabolic activation.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Executive summary:

method: Ames test according OECD 471 (4 strains tested - TA 98, TA 100, TA 1535, TA 1537)

result: negative (substance is not genotoxic, with and without metabolic activation)

reference: Herbold (Bayer AG), 1988