2-ethyl-3-hydroxy-4-pyrone

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Intraperitoneal administration of test substance (not justified), only 4 animals per dose, no toxicity measurements in the bone marrow included.

Data source

Reference

Reference Type:

publication

Title:

Study of artificial flavouring substances for mutagenicity in the Salmonella/microsome, Basc and micronucleus tests.

Author:

Wild D, King MT, Gocke E, Eckhardt K.

Year:

1983

Bibliographic source:

Food Chem Toxicol. 1983 Dec;21(6):707-19.

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

Intraperitoneal administration of test substance, sampling at different time intervals after single exposure (24, 48 and 72 hours)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: M. Salamone et al. Towards an improved micronucleus test Studies on 3 model agents. In Mutation Research/Environmental Mutagenesis and Related Subjects, Volume 74, Issue 5, 1980, Pages 347-356, ISSN 0165-1161.

GLP compliance:

no

Type of assay:

other: Micronucleus test

Test material

Test material information

1

Reference substance name:

2-ethyl-3-hydroxy-4-pyrone

EC Number:

225-582-5

EC Name:

2-ethyl-3-hydroxy-4-pyrone

Cas Number:

4940-11-8

Molecular formula:

C7H8O3

IUPAC Name:

2-ethyl-3-hydroxy-4H-pyran-4-one

Test material form:

solid

Test animals

Species:

mouse

Strain:

NMRI

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ivanovas GmbH, Kisslegg
- Age at study initiation: 10-14 weeks
- Diet: Altromin standard chow ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: olive oil

Frequency of treatment:

Two doses (at 0h and 24h) or single dose (at 0h)

Post exposure period:

Groups exposed twice: 30h
Groups exposed once: 24h, 48h, 72h

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

980 mg/kg bw (total dose)

Remarks:

Administered as single dose (0h) or dosed twice (0h and 24h)

Doses / concentrations 2

Dose / conc.:

700 mg/kg bw (total dose)

Remarks:

Administered twice (0h and 24h)

Doses / concentrations 3

Dose / conc.:

420 mg/kg bw (total dose)

Remarks:

Administered twice (0h and 24h)

No. of animals per sex per dose:

4

Control animals:

yes, concurrent vehicle

Positive control(s):

none

Examinations

Tissues and cell types examined:

polychromatic erythrocytes in the bone marrow

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
Bone-marrow smears were prepared 24h, 30h, 48h or 72h after treatment. The smears were stained according to the method of Schmid (1976).

METHOD OF ANALYSIS:
Slides were scored as previously described (Wild, King & Eckhardt, 1980).

Evaluation criteria:

no data

Statistics:

Statistical significance was determined according to the methods of Kastenbaum & Bowman (1970)

Results and discussion

Test results

Key result

Sex:

female

Genotoxicity:

negative

Toxicity:

not examined

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Additional information on results:

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no effect
- Ratio of PCE/NCE (for Micronucleus assay) was not examined

Any other information on results incl. tables

Results of micronucleus tests on mouse bone marrow after exposure to Ethyl Maltol

Dose (mg/kg)	Surviving/treated mice	Mean no. of micronucleated PE/1000 PE
0	4/4	1.3
2*980	4/4	3.0
2*700	4/4	3.2
2*420	4/4	2.3
0	4/4	2.7
1* 980 (24 hr)	4/4	1.3
1* 980 (48 hr)	4/4	3.5
1* 980 (72 hr)	4/4	1.8

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study, Ethyl Maltol did not induce any increase in micronucleated erythrocytes after peritoneal injection in mice.

Executive summary:

In an NMRI mouse mammalian erythrocyte micronucleus test (Wild et al., 1983), groups of 4 female mice were treated intraperitoneally with Ethyl Maltol in olive oil at doses of 980 mg/kg bw (one dose) or 480, 700, 980 mg/kg bw (two doses 0hrs, 24hrs). Animals were sacrificed 24, 48 or 72 hrs after single treatment, or 30 hours after the second treatment.

Slides were scored for the mean number of micronucleated PE/1000PE (Polychromatic Erythrocytes). After two exposures to 980, 700, 420 or 0 mg/kg bw, the mean numbers of micronucleated PE/100PE were 3.0, 3.2, 2.3 and 1.3 respectively. After a single exposure to 980 mg/kg bw (24, 48, 72 hrs), the number of micronucleated PE/1000PEs were 1.3, 3.5 and 1.8 respectively, with a control value of 2.7. No statistically significant differences were observed. The results of these tests therefore indicate no mutagenic potential of the test substance.