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Toxicological information

Genetic toxicity: in vivo

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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data are given.

Data source

Reference
Reference Type:
publication
Title:
Micronucleus test in mice on 39 food additives and eight miscellaneous chemicals
Author:
Hayashi, M. et al.:
Year:
1988
Bibliographic source:
Fd. Chem. Toxic. 26 (6), 487-500

Materials and methods

Principles of method if other than guideline:
No guideline mentioned, method according to Hayashi et al. (1983, 1984)
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance: Vitamin A fatty acid ester in oil
Cas: 79-81-2
No further data



Vitamin A fatty acid ester in oil; no further data

Test animals

Species:
mouse
Strain:
other: ddY
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Shizuoka Agricultural Cooperative Association for Laboratorie Animals Shizuoka
- Age at study initiation: 8 week

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
olive oil
Duration of treatment / exposure:
single dose or 4 doses; see freetext
Frequency of treatment:
single dose or 4 doses, divided by 24-hour intervals
Post exposure period:
18 h after the single injection and 24 h after the 4th injection following
repeated application.
Doses / concentrations
Remarks:
Doses / Concentrations:
37.5, 75, 150, 300 mg/kg bw
Basis:

No. of animals per sex per dose:
6
Control animals:
yes
Positive control(s):
Mitomycin C (MMC): 2 mg/kg bw/day i.p.

Examinations

Tissues and cell types examined:
Bone marrow: polychromatic and total erythrocytes
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
Maximum dose was determined by pilot experiments using the multisampling at multi-dose levels method, described by Hayashi et al.). No further data given.

DETAILS OF SLIDE PREPARATION:
Cells were fixed with methanol. Staining with Giemsa.

METHOD OF ANALYSIS:
1000 PCE /mouse were scored
Proportion of PCE/total erythrocytes was determined by evaluating 1000 erythrocytes on the same slide.
Evaluation criteria:
Positive result, if one or more treatment groups showed a statistically difference from spontaneous levels of MNPCEs and the trend test indicated a positive dose response
Statistics:
The frequency of MNPCEs in each treatment group was compared with the binominal distribution specified by the historical control data. Dose response relationship was tested by the Cochran-Armitage trend test.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
No substance-related mortality occurred.

Any other information on results incl. tables

Mice treated intraperitoneally with the test substance showed no increase in the incidence of micronucleated erythrocytes at any dose level after single

or 4 consecutive applications.
Result presented only in tabular form; no further data.

Applicant's summary and conclusion