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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: Guideline study with restrictions. Restrictions : Test was not conducted using an E. coli strain. Positive controls for strains TA98, TA100, and TA1537 were not included in the test with metabolic activation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
Missing TA102 strain and E.coli strains
Principles of method if other than guideline:
Study conducts prior to implementation of corresponding guideline. Study performed in accordance to the publications od Ames. The later implemented guideline based to a great extent on these publications.
-Ames, B.N., W.E. Durston, E. Yamasaki, and F.D. Lee. 1973. Carcinogens are mutagens: A simple test system combining liver homogenates for activation and bacteria for detection. Proc. Natl. Acad. Sci. USA. 70:2281-2285.
-Ames, B.N., F.D. Lee, and W.E. Durston. 1973b. An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc. Natl. Acad. Sci. USA. 70:782-786.
-Ames, B.N., J. McCann, and E. Yamasaki. 1975. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutation Res. 31:347-364.
GLP compliance:
no
Remarks:
Study predates GLP.
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Dioctyltin bis(2-EHMA) [CAS No. 15571-58-1]:Octyltin tris(2-EHMA) [CAS No. 27107-89-7] (70:30% mixture)

Method

Target gene:
his
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
TiF:RAIF (SPF) rat liver induced with Aroclor 1254. One ml  of the activation mixture contained 0.3 ml S9 fraction and 0.7 ml of the  co-factor solution.
Test concentrations with justification for top dose:
15, 45, 135, 405, and 1215 µg/0.1 ml
Vehicle / solvent:
The test substance was dissolved in acetone.
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
acetone
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: see Details on test system and conditions
Details on test system and experimental conditions:
The test was conducted with triplicate replications. Positive and negative controls were tested concurrently.
Positive controls (without metabolic activation): Daunorubicin-HCl at 5 and 10 ug/0.1 ml phosphate buffer for TA98. 4-Nitroquinoline-n-oxide at 0.125 and 0.25 ug/0.1 ml phosphate buffer for TA100. n-Methyl-n'-nitro-n-nitrosoguanidine at 3 and 5 ug/0.1 ml phosphate buffer for TA1535. 9(5)aminoacridine hydrochloride monohydrate at 50 and 100 ug/0.1 ml DMSO for TA1537.
Positive control (with metabolic activation): Cyclophosphamide at 250 ug/0.1 ml phosphate buffer for TA1535.
Negative (vehicle) control (with and without activation): Acetone
The plates were incubated at 37 +/- 1.5 deg. C in the absence of light for 48 hours.
Evaluation criteria:
The test substance was considered to be non-mutagenic if the colony count in relation to the negative control was not doubled in any 
concentration.
Statistics:
The colonies were counted and the arithmetic mean was 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:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
The test substance precipitated in the soft agar at 1215 ug/0.1 ml. Solvent and positive controls produced the expected mutant colony counts. Under the experimental conditions, a mixture of 70% dioctyltin bis(2-ethylhexylmercaptoacetate) and 30% mono-octyltin tris(2-ethylhexylmercaptoacetate) displayed no mutagenic activity.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Under the experimental conditions, a mixture of 70% dioctyltin bis(2-ethylhexylmercaptoacetate) and 30% mono-octyltin tris(2-ethylhexylmercaptoacetate) displayed no mutagenic activity.
Executive summary:

An Ames test was carried out with a mixture of 70% dioctyltin bis(2-ethylhexylmercaptoacetate) and 30% mono-octyltin tris(2-ethylhexylmercaptoacetate). The relatively old test was considered less reliable, because the test was not conducted using an E. coli strain and no positive controls for strains TA98, TA100, and TA1537 were included in the test with metabolic activation. No mutagenic activity was observed.