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Toxicological information

Genetic toxicity: in vitro

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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

Constituent 1
Chemical structure
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)
Controlsopen allclose all
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
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
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
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
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

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