Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline without detailed documentation

Data source

Reference
Reference Type:
publication
Title:
Screening of the food additive propionic acid for genotoxic properties
Author:
Basler E.D., Hude v.d, Scheutwinkel
Year:
1987
Bibliographic source:
Food Chem. Toxicol, 25: 287-290

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
(only one dose group)
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): propionic acid
- Source: E. Merck AG (Darmstadt)
- Analytical purity: 99%

Test animals

Species:
hamster, Chinese
Strain:
other: Cricetulus griseus
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: 8-12 wks (no further details on test animals)
- number of animals/dose: 6 male and 6 females


ENVIRONMENTAL CONDITIONS
- no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
physiol. saline
Details on exposure:
Exposure volume: 5 ml/ kg bw
Duration of treatment / exposure:
single dose injection
Frequency of treatment:
once
Post exposure period:
no
Doses / concentrations
Remarks:
Doses / Concentrations:
2,5% propionic acid/kg bw. (= 125 mg/kg)
Basis:
other: actually injected
No. of animals per sex per dose:
6/sex/dose/sacrifice time. Total = 36
Control animals:
yes
Positive control(s):
cyclophosphamide

Examinations

Tissues and cell types examined:
Bone marrow prepared according to the method of schmid (1975)
Details of tissue and slide preparation:
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
- The animals in both control groups were killed 24 hr after injection. The hamsters treated with propionic acid were killed 12, 24 or 48 hr after treatment. Five males and five females from each group were examined.
- number of polychromatic erythrocytes scored: 5000

Evaluation criteria:
no data
Statistics:
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:
4/36 of mortality was observed. No further information
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): The mean percentage of micronucleated polychromatic erythrocytes was 7.9 in the positive control group and 0.13 in the hamsters treated with saline only (a significant difference, P < 0.05). The numbers of MN-PCEs in animals treated with propionic acid were not significantly different from those the control animals.
- Ratio of PCE/NCE (for Micronucleus assay): no data
- Appropriateness of dose levels and route: appropriate
- Mortality: 4 of 36 treated animals died

Any other information on results incl. tables

Table 1: Numbers of micronucleated polychromatic erythrocytes in the bone marrow cells of Chinese hamster after intraperitoneal injection of propionic acid

 

Compound

Dose/kg bw

Lenth of exposure (hr)

No./sex/

% PE with MN

Control (physiol. Saline)

5 ml

24

5F

0.14

5M

0.12

Propionic acid

5 ml

12

5F

0.06

5M

0.06

24

5F

0.18

5M

0.14

48

5F

0.12

5M

0.16

Cyclophosphamid

80 mg

24

5F

7.78*

5M

8.02*

 

* values differ significantly (p< 0.05) from saline control

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative