2,3-epoxypropyl isopropyl ether

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

other: publication

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted equivalent to OECD guideline 471 on the registered substance itself with minor deficiencies. There were only four strains tested, however, this deficiency is considered to be minor as the fifth strain was added to the guideline because the former common four strains may not detect certain oxidising mutagens, cross-linking agents and hydrazines. Based on the chemical structure, this mode of action is not to be expected from the test item. There are also only minor deficiencies in documentation, but the given data indicate that the study was well-performed.

Data source

Reference

Reference Type:

review article or handbook

Title:

Comparative mutagenicity of aliphatic epoxides in Salmonella

Author:

DA Canter , E Zeiger, S Haworth, T Lawlor, K Mortelmans and W Speck

Year:

1986

Bibliographic source:

Mutat Res. 1986 Nov;172(2):105-38.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not applicable

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2,3-epoxypropyl isopropyl ether

EC Number:

223-672-9

EC Name:

2,3-epoxypropyl isopropyl ether

Cas Number:

4016-14-2

Molecular formula:

C6H12O2

IUPAC Name:

2-[(propan-2-yloxy)methyl]oxirane

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Isopropyl glycidyl ether, CAS 4016-14-2
- Analytical purity: 97.2%
- Other: manufactured by Pfaltz and Bauer, Div. Aceto Chemicals

Method

Target gene:

his

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 100

Additional strain / cell type characteristics:

not specified

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1535

Additional strain / cell type characteristics:

not specified

Species / strain 3

Species / strain / cell type:

S. typhimurium TA 98

Additional strain / cell type characteristics:

not specified

Species / strain 4

Species / strain / cell type:

S. typhimurium TA 1537

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

HAMSTER, LIVER, S-9, AROCLOR 1254 (10% / 30%)

Test concentrations with justification for top dose:

0, 100, 333, 1000, 3333, 10000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h
- Selection time (if incubation with a selection agent): ≙ exposure duration

SELECTION AGENT (mutation assays): minimal Histidine

NUMBER OF REPLICATIONS: three plates per dose, experiment was repeated no less than 1 week after initial test

DETERMINATION OF CYTOTOXICITY
- Method: One or more parameters were used as an indication of toxicity: reduced numbers of revertant colonies per plate and/or thinning or absence of the bacterial lawn.

OTHER: Testing was performed as set out in Haworth et al., Environmental Mutagenesis Supplement 1:3 -142 (1983), "Salmonella Mutagenicity Test Results for 250 Chemicals", at Case Western Reserve University

Evaluation criteria:

Testing was performed at 5 doses, using triplicate plates. Tests were repeated at least once; a chemical was not designated positive or negative unless the results were reproducible. A positive response was defined as a reproducible, dose-related increase in his+ revertants over the solvent control level; it was not necessary for the increase to equal 2-fold over background. A response was considered equivocal ("?") if a test was not reproducible; when a low-level, non-dose-related response was obtained; or when an increased response was seen at only one dose.
A chemical was considered mutagenic if at least one strain/activation combination yielded a reproducible positive response.

Statistics:

Mean of three replicates and SEM was calculated

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 10 mg/plate, there was complete clearing of background lawn

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with

Genotoxicity:

ambiguous

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

Since the mutagens were all positive in TA100, and most were mutagenic in TA1535 as well, only the data from those strains are presented in detail, whereas data on all four strains is given in short summary.

Remarks on result:

other: all strains/cell types tested

Applicant's summary and conclusion

Conclusions:

The available literature was assessed as Klimisch 2. Data was gathered within an interlaboratory comparison aiming to assess the mutagenicity of aliphatic epoxides in Salmonella. A good intra- and interlaboratory reproducibility was seen in the results. Hence, the results are considered sufficiently reliable to assess the mutagenicity of Isopropyl glycidyl ether in Salmonella typhimurium. The substance was tested positive in two out of four tester strains, both with and without metabolic activation. Hence, Isopropyl glycidyl ether must be considered mutagenic in bacteria.

Executive summary:

In a reverse gene mutation assay in bacteria equivalent to OECD 471, strains TA98, TA100, TA1535, and TA 1537 of S. typhimurium were exposed to Isopropyl glycidyl ether in water at concentrations of 0, 100, 333, 1000, 3333, 10000 µg/plate in the presence and absence of mammalian metabolic activation (hamster and rat liver S9 mix) in the preincubation method.

 

Isopropyl glycidyl ether was tested up to limit concentration 10000 µg/plate. There was a dose-related increase of induced mutant colonies over background in strains TA100 and TA1535 with and without metabolic activation, whereas the test item was negative in strains TA98 and TA1537. The positive controls induced the appropriate responses in the corresponding strains.

 

This study is classified as acceptable and satisfies in principle the requirement for Test Guideline OECD 471 (version of 1983) for in vitro mutagenicity (bacterial reverse gene mutation) data.