2,2-dimethyl-1,3-dioxane-4,6-dione

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test item was found to be not mutagenic in this bacterial reverse mutation assay.

Link to relevant study records

Reference

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:

22 August - 29 September 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study performed in accordance with the corresponding OECD-/EU-testing guidelines

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

- Type and identity of media: The strains were obtained from Professor B.N. Ames, University of California, California, USA
- Properly maintained: yes

Additional strain / cell type characteristics:

DNA polymerase A deficient

Species / strain / cell type:

S. typhimurium TA 1538

Details on mammalian cell type (if applicable):

- Type and identity of media: The strain was obtained from Professor B.N. Ames, University of California, California, USA
- Properly maintained: yes

Additional strain / cell type characteristics:

DNA polymerase A deficient

Metabolic activation:

with and without

Metabolic activation system:

S9-liver fractions of rats treated with Aroclor 1254

Test concentrations with justification for top dose:

- Pretest: 5, 50, 500, 5000 ug/ml & solvent control
- Main test: 5, 50, 150, 500, 1500, 5000 ug/ml & solvent control

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: At 50 mg/ml, P5096 was soluble in water, and therefore this was the chosen solvent for use in subsequent tests.

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

N-ethyl-N-nitro-N-nitrosoguanidine

other: 2-Aminoanthracene

Evaluation criteria:

The mutagenic activity of a test substance is assessed by applying the following criteria:

1.
If treatment with a test substance produces an increase in revertant colony numbers of at least twice the concurrent solvent controls, with some evidence of a positive dose-relationship, in two separate experiments, with any bacterial strain either in the presence or absence of S-9 mix, it is considered to show evidence of mutagenic activity in this test system.

2.
If treatment with a test substance does not produce reproducible increases of at least 1.5 times the concurrent solvent controls, at any dose level with any bacterial strain, it is considered to show no evidence of mutagenic activity in this test system. No statistical analysis is performed.

3.
If the results obtained fail to satisfy the criteria for a clear "positive" or "negative" response given in paragraphs (a) and (b), the following approach is taken in order to resolve the issue of the substance's mutagenic activity in this test system.

(i) Repeat tests may be performed using modifications of the experimental method. These modifications include (but are not restricted to), the use of a narrower dose range than that already tested; the use of different levels of liver homogenate S-9 fraction in the S-9 mix. Should an increase in revertant colony numbers be observed which satisfies paragraph (a) the substance is considered to show evidence of mutagenic activity in this test system.

Statistics:

No statistical analysis performed.

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

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The negative controls, positive controls, and sterility controls all fulfilled requirements for determination of a valid test.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

No substantial increases in revertant colony numbers of any of the tester strains were observed following treatment with P5096 at any dose level, in the presence or absence of S-9 mix, in either mutation test.

Executive summary:

This reverse mutation assay was performed in 1980 in accordance with OECD-guidelines without GLP. Five Salm. typh. strains (TA1535, TA1537, TA1538, TA98 and TA100) were tested with and without metabolic activation. Test concentrations ranged from 5 ug/plate up to 5000 ug/plate.

No detectable mutagenic activity was found for test article when the Salmonella/microsomal assay was performed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Justification for selection of genetic toxicity endpoint
Klimisch 1 study

Justification for classification or non-classification

Based on the data available the substance is not classified or labeled according to Directive 67/548/EEC (DSD) or Regulation 1272/2008/EC (CLP).