Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study and basic data given
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
secondary source
Title:
Unnamed
Year:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
Remarks:
adopted 1983
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Reference substance name:
64519-82-0
Cas Number:
64519-82-0
IUPAC Name:
64519-82-0
Details on test material:
- Name of test material (as cited in study report): isomalt (mixture of α-D-glucopyranosyl-1,6-D-sorbitol and α-D-glucopyranosyl-1,1-D-mannitol; SZ-i-rH 5093)
- Analytical purity: no data
- Impurities (identity and concentrations): minor saccharides and saccharide alcohols (main components: sorbitol, mannitol) (not further specified)
- Lot/batch No.: SZ-i-rH 5093

A special batch was produced for the conducted study in which the content of minor components occuring during the production process was greatly exagerated to the maximum feasible content.
Composition of the test material (batch SZ-i-rH 5093):
α-D-glucopyranosyl-1,1-D-mannitol (52.5%), α-D-glucopyranosyl-1,6-D-sorbitol (36%), α-D-glucopyranosyl-1,1-D-sorbitol (2.1%), sorbitol + mannitol (7.5%), (glucosyl)2-fructose (isomelezitose) (0.4%) and (glucosyl)2-sorbitol or (glucosyl)2-mannitol (0.5%) (as provided in TNO report V 95.660)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily, 7 days/week
Post exposure period:
no data
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2.5, 5 and 10%
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
1.25, 2.5 and 5 mg/kg bw/day
Basis:
nominal in diet
calculated based on the average daily food consumption of 5 g/100 g bw (WHO, 1987)
No. of animals per sex per dose:
10
Control animals:
other: 10% starch ... (see attached file)
Positive control(s):
mitomycin C
- Justification for choice of positive control(s): due to the known properties of inducing micronuclei, mitomycin C was selected as the appropriate positive control
- Route of administration: intraperitoneal
- Doses / concentrations: 1.5 mg/kg bw

Examinations

Tissues and cell types examined:
Tissue: bone marrow
Cell type: bone marrow cells
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: The highest dose group represented an overall intake of isomalt of more than 5 times the maximum limit dose that needs to be investigated in the micronucleus test according to the OECD Guideline 474 (1 mg/kg bw for treatments longer than 14 days).

METHOD OF ANALYSIS:
GENOTOXICITY: The incidence of micronucleated polychromatic erythrocytes per 1000 polychromatic erythrocytes was determined in test and control groups.
CYTOTOXICITY: The incidence of polychromatic erythrocytes per 1000 erythrocytes was compared in control and test groups.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
not specified
Negative controls validity:
not specified
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative

Categories Display