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Diss Factsheets

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

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.