2-ethyl-2-oxazoline

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Peer reviewed article

Data source

Reference

Reference Type:

publication

Title:

Screening of the food additive propionic acid for genotoxic properties

Author:

Basler, A., v.d. Hude, W., & M. Scheutwinkel

Year:

1987

Bibliographic source:

Food Chem. Toxicol, 25(4): 287-290

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

(only one dose group)

GLP compliance:

not specified

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Propionic acid

EC Number:

201-176-3

EC Name:

Propionic acid

Cas Number:

79-09-4

IUPAC Name:

propionic acid

Specific details on test material used for the study:

- purity: 99%
- source: E. Merck AG (Darmstadt)

Test animals

Species:

hamster, Chinese

Strain:

other: Cricetulus griseus

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-12 wks (no further details on test animals)
- number of animals/dose: 6 male and 6 females

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Vehicle(s)/solvent(s) used: physiol. saline

Details on exposure:

Exposure volume: 5 mL/ kg body weight

Duration of treatment / exposure:

Single dose injection (maximum tolerated dose)

Frequency of treatment:

Once

Doses / concentrations

Dose / conc.:

2.5 other: %

Remarks:

Equivalent to 125 mg/kg bw

No. of animals per sex per dose:

6/sex/dose

Control animals:

yes

Positive control(s):

- cyclophosphamide
- Route of administration: intraperitoneal, in normal saline
- Doses / concentrations: 80 mg/kg bw

Examinations

Tissues and cell types examined:

Bone marrow, micronucleated polychromatic erythrocytes

Details of tissue and slide preparation:

Prepared and stained according to the method of Schmid (1975)

Statistics:

The number of micronucleated polychromatic erythrocytes was recorded in each group, and the standard tables of Kastenbaum & Bowman (1970) were used to test for significance.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

4 of 36 hamsters died within a few hours of the injection of propionic acid

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The mean percentage of micronucleated polychromatic erythrocytes in animals treated with propionic acid were not significantly different from those in the animals treated with saline, even though high doses were given. A clastogenic effect was not observed: the mean percentage of micronucleated polychromatic erythrocytes were 0.06, 0.16 and 0.14 in animals killed at 12, 24 and 48 hr after injection, respectively.

Applicant's summary and conclusion

Conclusions:

In an in vivo Chinese hamster (Cricetulus griseus) bone marrow micronucleus assay, 6 animals/sex/dose were treated once with propionic acid (99% pure) by means of intra-peritoneal injection at doses of 0 and 2.5% in normal saline (5 mL/kg bw; approx 125 mg/kg bw; maximum tolerated dose). Bone marrow cells were harvested at 12, 24 and 48 hours post-treatment. Four hamsters died within a few hours of dosing. The positive control elicited the appropriate response. There was no significant increase in the incidence or frequency of micro-nucleated polychromatic erythrocytes in the bone marrow of male or female hamsters treated with propionic acid as compared to concurrent controls. The study design is comparable to the recommendations of the OECD TG 474 for in vivo cytogenetic mutagenicity data.