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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
8th August 1981 to 11th September 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
Reason / purpose for cross-reference:
other: read-across target
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted on read-across material
Justification for type of information:
Read Across to Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) (EC Number 248-227-6 and CAS No 27107-89-7) based on structural similarity and hydrolytical behaviour, see attached justification.
Reason / purpose for cross-reference:
read-across source
Key result
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
Octyltin tris(2-EHMA) [CAS No. 27107-89-7]:Dioctyltin bis(2-EHMA) [CAS No. 15571-58-1] (67%:33% mixture); liquid, >=96 wt% purity
IUPAC Name:
Octyltin tris(2-EHMA) [CAS No. 27107-89-7]:Dioctyltin bis(2-EHMA) [CAS No. 15571-58-1] (67%:33% mixture); liquid, >=96 wt% purity
Details on test material:
Octyltin tris(2-EHMA) [CAS No. 27107-89-7]:Dioctyltin bis(2-EHMA) [CAS No. 15571-58-1] (67%:33% mixture); liquid,
>=96 wt% purity,

Method

Target gene:
S. typhimurium: histidine locus
E. coli: tryptophan locus
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell type (if applicable):
N/A
Species / strain / cell type:
S. typhimurium TA 1538
Details on mammalian cell type (if applicable):
N/A
Species / strain / cell type:
E. coli WP2 uvr A
Details on mammalian cell type (if applicable):
N/A
Metabolic activation:
with and without
Metabolic activation system:
S9 fraction of rat livers
Test concentrations with justification for top dose:
5, 10, 50, 100, 500, 1000, 5000 µg/0.1 mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Acetone for test substance, DMSO for positve controls
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
Acetone
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: see remarks section.
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar (plate incorporation)


DURATION
- Preincubation period: NDA
- Exposure duration: 48 hours
- Expression time (cells in growth medium): NDA
- Selection time (if incubation with a selection agent): NDA
- Fixation time (start of exposure up to fixation or harvest of cells): NDA


SELECTION AGENT (mutation assays): NDA
SPINDLE INHIBITOR (cytogenetic assays): NDA
STAIN (for cytogenetic assays): NDA


NUMBER OF REPLICATIONS: 3


NUMBER OF CELLS EVALUATED: NDA


DETERMINATION OF CYTOTOXICITY
- Method: relative total growth
Evaluation criteria:
These tests permit the detection of point mutations in bacteria induced by chemical substances. Any mutagenic effects of the substances are demonstrable on comparison of the number of bacteria in the treated and control cultures that have undergone back-mutation to histidine- or tryptophan-prototrophism. To ensure that mutagenic effects of metabolites of the test substance formed in mammals would also be detected, experiments were performed in which the cultures were additionally treated with an activation . mixture (rat liver microsomes and co-factors)
Statistics:
no

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

Table 1. Results of tests - mean colony counts.

Material Concentration of testing sample (µg/plate) Presence of S9 mix Back mutation - Number of colonies/plate (mean)
Base conversion type Frame shift type
TA100 TA1535 WP2UVrA TA98 TA1537 TA1538
Vehicle control N/A - 148 15 22 22 6 12
Test material 5 - 133 13 25 25 5 6
10 - 136 12 26 17 5 12
50 - 134 17 21 23 7 17
100 - 139 15 18 25 6 12
500 - 122 11 17 20 5 15
1000 - 132 13 23 16 5 11
5000 - 117 15 23 16 8 8
Vehicle control N/A + 132 14 23 34 5 54
Test material 5 + 116 8 22 45 11 53
10 + 135 7 22 40 7 50
50 + 128 7 28 36 8 55
100 + 122 11 29 41 8 43
500 + 138 9 21 39 6 40
1000 + 107 10 23 33 5 38
5000 + 110 8 26 27 4 24

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, the test material was determined to be non-mutagenic in both the presence and absence of metabolic activation.
Executive summary:

The test material was evaluated for mutagenic effects on histidine-auxotrophic strains of Salmonella typhimurium and on a tryptophan auxotrophic strain of E. coll. The investigations were performed with the following concentrations of the test material without and with microsomal activation: 5, 10, 50, 100, 500, 1000 and 5000 µg/0.l mL.

In the experiments performed without and with microsomal activation, comparison of the number of back-mutant colonies in the controls and the cultures treated with the various concentrations of the test material revealed no marked deviations.

No evidence of the induction of point mutations by the test material or by the metabolites of the substance formed as a result of microsomal activation was detectable in the strains of S. typhimurium and E. coli used in these experiments.

Under the conditions of this study, the test material was determined to be non-mutagenic in both the presence and absence of metabolic activation.

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