1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol

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:

1988-02-18 to 1988-03-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

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:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol

EC Number:

402-950-5

EC Name:

1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol

Cas Number:

87826-41-3

Molecular formula:

C22 H26 O6

IUPAC Name:

(1R)-1-[(4R,4aR,8aS)-2,6-bis(4-methylphenyl)-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol

Details on test material:

- Name of test material (as cited in study report): Technical GEL-ALL-MD
- Substance type: White powder
- Physical state: solid
- Analytical reference: T00335
- Analytical purity: 98.6% w/w
- Purity test date: 1988-01-26 to 1988-01-27
- Batch No: 4140626
- Expiration date of the lot/batch: 1993-01
- Storage condition of test material: Stored at room temperature in the dark
- Other: Test material was analysed by the Analytical Development Department at Schering Agrochemicals Ltd, Hauxton, Cambridge, United Kingdom

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

bacteria, other: S. typhimurium TA 1535, 1537, 1538, 98, 100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix prepared from Aroclor 1254-induced rat liver.

Test concentrations with justification for top dose:

Dose range-finding test: 5000, 500, 50 and 5 µg per plate
Mutation test: 5000, 1500, 500, 150 and 50 µg per plate.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: acetone (fine suspension)

Controls

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates

Negative solvent / vehicle controls:

yes

Remarks:

acetone

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

N-ethyl-N-nitro-N-nitrosoguanidine

other: 2-Aminoanthracene

Remarks:

2-Aminoantracene used with S9 mix. ENNG, 9-AC, , 2-NF used without S( mix

Migrated to IUCLID6: 5 µg/plate for TA 1535 and 3 µg/plate for TA 100 without metabolic activation.

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: 10 hours
- Exposure duration: 72 hr

NUMBER OF REPLICATIONS:
- 3 replications per concentration per strain per test; test performed twice.

DETERMINATION OF CYTOTOXICITY
- Method: plates were assessed for the reduction of the bacterial background lawn and number of revertant colonies.

Evaluation criteria:

The mean number of revertant colonies for all treatment groups is compared with those obtained for negative and positive control groups. The effect of metabolic activation is assessed by comparing the results obtained both in the presence and absence of the liver microsomal fraction for each treatment group.

A compound is deemed to provide evidence of mutagenic potential if a statistically significant dose-related increase in the number of revertant colonies of at least twice the concurrent solvent control is obtained in two separate experiments.

Results and discussion

Test results

Species / strain:

bacteria, other: S. typhimurium TA 1535, 1537, 1538, 98, 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

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Observed at 5000 μg per plate

RANGE-FINDING/SCREENING STUDIES:
No toxicity was observed in the preliminary dose range-finding study.

MUTATION TEST:
Responses of the positive and negative control groups were within the normal ranges experienced in the laboratory. Concurrent positive controls demonstrated the sensitivity of the assay and the metabolising activity of the metabolic activation system.

No significant increases in the revertant colony numbers of any of the five strains were observed following treatment at any dose level, in either the presence or absence of S9 mix.

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

It is concluded that, when tested to the limits of solubility in acetone, the test substance was not mutagenic to the bacteria in either the presence or absence of metabolic activation.

Executive summary:

In this in vitro assessment of the mutagenic potential of technical GEL-ALL-MD, histidine-dependent auxotrophic mutants of Salmonella typhirium (strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100) were exposed to test material diluted in acetone which was also used as a negative control.

Two independent mutation tests were performed using agar plates, in the presence and absence of liver preparations from Aroclor 1254-induced rats.

In the preliminary dose range-finding study no toxicity was observed. A top dose level of 5000 micrograms per plate was chosen for the subsequent mutation study. Other dose levels used in the mutation assays were: 1500, 500, 150, 50 µg/plate.

The concurrent positive control compounds demonstrated the sensitivity of the assay and the metabolising activity of the metabolic activation system.

No evidence of mutagenic activity was seen at any dose level of technical GEL-ALL-MD in either mutation test. Precipitation was observed at the highest dose level tested, 5000 µg/plate.

It is concluded that, when tested to the limits of solubility in acetone, technical GEL-ALL-MD was not mutagenic in either the presence or absence of metabolic activation.