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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented peer-reviewed report.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
no
Remarks:
the study was conducted prior to adoption of guidelines (in 1974).
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):
Glucono-delta-lactone: CAS 90-80-2

Purity (%) of :

Glucono-delta-lactone: 99-101%


Test animals

Species:
mouse
Strain:
C57BL
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12 or 13 weeks

Administration / exposure

Route of administration:
oral: feed
Vehicle:
- Vehicle(s)/solvent(s) used: physiol. saline;
- Amount of vehicle (if gavage or dermal): 1 mL/mouse
Duration of treatment / exposure:
single dose and 4 days
Frequency of treatment:
not specified
Post exposure period:
The animals were sacrified at 24 hours (single dose) and 27 hours after last administration (4-days repeated dose).
Doses / concentrationsopen allclose all
Dose / conc.:
2 000 mg/kg bw/day
Remarks:
single dose administration
Dose / conc.:
4 000 mg/kg bw/day
Remarks:
single dose administration
Dose / conc.:
8 000 mg/kg bw/day
Remarks:
single dose administration
Dose / conc.:
2 000 mg/kg bw/day
Remarks:
4-day repeated dose administration
Dose / conc.:
4 000 mg/kg bw/day
Remarks:
4-day repeated dose administration
No. of animals per sex per dose:
Single dose administration: 3 (vehicle control and test groups); 2 (positive control);
4-day repeated dose administration: 2 (vehicle control); 3 (test group 1: 4 g/kg); 2 (test group 2: 2 g/kg); 2 (positive control).
Control animals:
yes, concurrent vehicle
Positive control(s):
MMC (mitomycin C) dissolved with 0.9% physiological saline solution and administered intraperitoneally at a dose of 0.5 mL/mouse (= 5 mg/kg bw).

Examinations

Tissues and cell types examined:
At least 200 metaphase cells per mouse were examined for the presence or absence of chromosomal aberrations (gaps, breaks, translocation, fragments, ring chromosomes and minutes chromosomes).
Details of tissue and slide preparation:
TREATMENT AND SAMPLING TIMES: After receiving the single dose and the repeated dose test substance, the animals were sacrified at 24 hours (single dose) and 27 hours after last administration (4-days repeated dose). 0.3 mL of 500 μg/mL colchicine was intraperitoneally injected to each mouse at one hour before sacrifice so that the metaphase cells could be observed.

DETAILS OF SLIDE PREPARATION: After the bone marrow cells were washed, treated and fixed with a fixing solution (1:3 acetic acid:ethanol solution), the cells were suspended and dripped on a slide glass and stained with Giemsa solution and examined.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Remarks:
in both experiments: single administration and 4-d repeated dose administration.
Toxicity:
yes
Remarks:
At 8 g/kg, all mice died (single dose administration experiment)
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Single dose administration:

At 8 g/kg, all mice died.

MMC induced chromosomal aberrations in at least 20% of bone marrow cells.

GDL induced chromosomal aberrations in the cells at a frequency of about 0.5% comparable to the control.

4-day repeated dose administration:

MMC induced chromosomal aberrations at about 30% cells.

The frequency of cells with chromosomal aberrations was 1 % or less in the test groups which is comparable to the control group. Induction of chromosomal aberration by GDL was not detected after in vivo single and repeated dose treatment.

Applicant's summary and conclusion

Conclusions:
The frequency of cells with chromosomal aberrations in the test groups was comparable to the control group in both experiments: single administartion and 4-d repeat administration. Thus, D-Glucono-1,5-Lactone is not clastogenic.