Zinc O,O,O',O'-tetrakis(1,3-dimethylbutyl) bis(phosphorodithioate)

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:

1980/10/13-1980/10/31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This non-GLP study was conducted similar to OECD guideline and has significant deviations to warrant restriction.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Only 4/5 recommended strains of bacteria tested and no information regarding cytotoxicity

GLP compliance:

no

Remarks:

Quality Assurance signed off on 1980/10/31

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Zinc O,O,O',O'-tetrakis(1,3-dimethylbutyl) bis(phosphorodithioate)

EC Number:

218-679-9

EC Name:

Zinc O,O,O',O'-tetrakis(1,3-dimethylbutyl) bis(phosphorodithioate)

Cas Number:

2215-35-2

Molecular formula:

Too complex

IUPAC Name:

zinc O,O,O',O'-tetrakis(1,3-dimethylbutyl) bis(phosphorodithioate)

Details on test material:

Test material from lot EC24303 was described as clear, colourless, viscous liquid. Expiration date was listed as 1981/05/06. The test article was stored in glass in the dark at room temperature.

Method

Target gene:

Point (reverse) mutations in selected histidine requiring mutant strains of Salmonella typhimurium. Tester strains have a deletion through uvrB to remove DNA excision repair function and rfa to remove the lipopolysaccharide coat. TA1535 is a missense mutant which is reverted by agents which cause base pair substitutions. TA98, TA1538, TA1537 are frame shift mutants. TA98 is TA1538 and TA100 is TA1535 with the additions of pKM101 plasmid.

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1538

Species / strain 2

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

0.03, 0.01, 0.006, 0.003, 0.001 ul/plate

Vehicle / solvent:

All dilutions were made with acetone due to solubility and lack of reactivity with test article.

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

bacteria only

Negative solvent / vehicle controls:

yes

Remarks:

acetone

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene 5 ug/plate

Remarks:

For all strains +S9

Controls 2

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 98 and TA 1538-S9

Migrated to IUCLID6: 5 ug/plate

Controls 3

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA 1537-S9

Migrated to IUCLID6: 10 ug/plate

Details on test system and experimental conditions:

The assay was performed by plate incorporation and the method of Ames et al with modification. The assay was performed in duplicate, with (+S9) or without (-S9) metabolic activation. Each of the tester strains was dosed with 5 concentrations of test substance, solvent controls, and a positive control. Three plates/dose group/strain/treatment set were evaluated. 100 ul of test substance, positive control or vehicle control were added to each plate along with 100 ul of tester strain, S9 mix (if required) and 2.0 ml of molten top agar. This was overlaid onto the surface of bottom agar in a petri dish and plates were incubated for 48 h at 37 C. The number of revertant colonies were counted on a Biotran II automatic colony counter.

Evaluation criteria:

All sterility controls must be negative for bacterial growth. The average number of revertant colonies representing spontaneous mutation must be within the following acceptable range: TA1535, 6-60; TA1537, 3-16; TA1538, 6-35; TA100, 80-250; TA98, 10-60. The average number of revertant colonies in the positive control plates must be at least 5 times those of the solvent control.

Statistics:

Mean revertant colony count and standard deciation were calculated for each dose level and compared to solvent controls.

Results and discussion

Test results

Test results 1

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

Test results 2

Species / strain:

S. typhimurium TA 1538

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:

A range finder was not included in this report.

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

No detectable mutagenic activity for this test substance was found under the conditions of this study.

Executive summary:

In a bacterial reverse mutation assay in the presence and absence of exogenous metabolic activation, Salmonella strains TA1535, TA1537, TA1538, TA98, and TA100 were treated with test substance at concentrations of 0.03, 0.01, 0.006, 0.003, 0.001 ul/plate. The negative and positive controls fulfilled the requirements for determination of a valid test. None of the test substance treatment conditions produced a statistically significant increase in the number of revertants. Based on the results of this study, the test substance would not be classified based on weight of evidence for the chemical class in accordance with the classification system of GHS.

This toxicity study is classified as acceptable and satisfies the guideline requirement for in vitro mutagenicity test.