Ethyl vinyl ether

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Guideline study. with acceptable restrictions (not tested in TA102 or E. coli WP2; no data about historical negative control [but number of revertants within literature range]) The study report does address the problem of the high volatility of the test substance (in contrast to the study BASF 1992). The incubation temperature of 37°C is well above the boiling point of the test substance (EVE, bp=35.5°C). Therefore incubation was conducted in desiccators in order to ensure saturation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Principles of method if other than guideline:

adopted 1983

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl vinyl ether

EC Number:

203-718-4

EC Name:

Ethyl vinyl ether

Cas Number:

109-92-2

Molecular formula:

C4H8O

IUPAC Name:

ethoxyethene

Details on test material:

ethyl vinyl ether (EVE)
purity 99.8%
Batch: B 157
Test substance no.: 91/410
stored in refrigerator
manufactured Oct 1991 (test performed August 1992)

Method

Target gene:

His-

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

S9-mix; S9-fraction from Aroclor 1254-induced (i.p. 500 mg/kg bw 5 days prior to sacrifice) male Sprague-Dawley rat liver

Test concentrations with justification for top dose:

0, 2500, or 5000 µg/plate (desiccator test, 6 ml of test substance in the desiccator)

Vehicle / solvent:

aqua dest.

Controls

Negative solvent / vehicle controls:

yes

Remarks:

plus sterility control

Positive controls:

yes

Positive control substance:

other: With S9: 2.5 µg/plate 2-aminoanthracene (all tester strains). Without S9: 5 µg/plate N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; for TA100 and TA1535), 10 µg/plate 4-nitro-o-phenylendiamine (TA98), 100 µg/plate 9-aminoacridine (TA1537)

Details on test system and experimental conditions:

Standard plate test conducted in desiccators with and without metabolic activation. Desiccators contained an additional petri dish with 6 ml of TS in order to ensure a saturated atmosphere during the 4-hrs incubation period at 37°C in the dark. Subsequently, the agar plates are taken out of the desiccators and incubated for another 44 hours at 37°C in the dark and than the bacterial colonies (his + revertants) are counted.

Evaluation criteria:

(i) doubling of the spontaneous mutation rate, (ii) dose-response relationship, (iii) reproducibility of results

Statistics:

means +- standard deviation of 3 test plates per dose or per control

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:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

EVE did not increase the number of revertants in the standard plate test in saturated atmosphere, with or without metabolic activation. No cytotoxicity was noted.
Positive control substances gave results as expected.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Ames test with EVE
(conditions: additional exposure to saturated vapour at 37°C in desiccators)

Dose level in µg/plate	TA1535	TA100	TA1537	TA98
Without metabolic activation
0	12+-2	64+-5	11+-4	28+-7
2500	13+-3	78+-6	11+-2	38+-1
Pos. control	1703+-76	1157+-32	556+-30	982+-52
0	16+-3	77+-4	12+-2	28+-4
5000	16+-4	71+-8	13+-5	34+-7
Pos. control	2163+-129	1397+-158	704+-93	1443+-70
With metabolic activation
0	11+-4	97+-1	12+-6	48+-6
2500	13+-2	99+-7	11+-1	52+-6
Pos. control	172+-31	828+-64	80+-8	453+-26
0	16+-5	86+-4	12+-2	50+-2
5000	16+-5	68+-9	16+-2	47+-5
Pos. control	118+-23	930+-93	111+-21	588+-64

Revertants +- standard deviation of 3 plates

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

EVE gave negative results in the standard plate test on S. typhimurium TA1535, TA100, TA1537, and TA98 both in the absence and in the presence of a metabolic activation system at concentrations up to 5000 µg/plate and saturated atmosphere (additional petri dishes with EVE) during the 4-hrs exposure period at 37°C in desiccators to account for the high volatiliy of the test material.