Reaction products of sodium glucoheptonate with copper sulfate and ammonium hydroxide

Genetic toxicity: in vivo

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

Test material information

Constituent 1

Reference substance name:

D-glucono-1,5-lactone

EC Number:

202-016-5

EC Name:

D-glucono-1,5-lactone

Cas Number:

90-80-2

Molecular formula:

C6H10O6

IUPAC Name:

3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-one (non-preferred name)

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 or test system 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 / concentrations

Doses / concentrations 1

Dose / conc.:

2 000 mg/kg bw/day

Remarks:

single dose administration

Doses / concentrations 2

Dose / conc.:

4 000 mg/kg bw/day

Remarks:

single dose administration

Doses / concentrations 3

Dose / conc.:

8 000 mg/kg bw/day

Remarks:

single dose administration

Doses / concentrations 4

Dose / conc.:

2 000 mg/kg bw/day

Remarks:

4-day repeated dose administration

Doses / concentrations 5

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.