Aluminium trilactate

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:

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: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Effects of aluminium salts on bone marrow chromosomes in rats in vivo

Author:

Roy, AK et al.

Year:

1991

Bibliographic source:

Cytobios 66: 105-111

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Aluminium sulphate was orally administered to rats daily for 7, 14 or 21 days. Bone marrow chromosomes were analysed for aberrations.

GLP compliance:

no

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

7784-31-8 (Aluminium sulphate)

IUPAC Name:

7784-31-8 (Aluminium sulphate)

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Aluminium sulphate Al2(SO4)3 x 18H2O
- Analytical purity: no data

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

- Vehicle(s)/solvent(s) used: deionised water

Duration of treatment / exposure:

7, 14 or 21 d

Frequency of treatment:

once daily

Post exposure period:

24 h

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 212, 265, 353, 530, 1060, 2120 mg Al2(SO4)3x18H2O/kg bw/d
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 17, 22, 28, 43, 85, 172 mg Al/kg bw/d
Basis:
nominal conc.

No. of animals per sex per dose:

5 for each time point

Control animals:

yes, concurrent vehicle

Positive control(s):

no

Examinations

Tissues and cell types examined:

bone marrow chromosomes

Details of tissue and slide preparation:

Colchicine (0.04%) was injected intraperitoneally, 90 min before sacrifice.
From each animal, 2000 cells were scored for the mitotic index and 60 well scattered metaphase plates for chromosomal aberration, making a total of 10000 cells and 300 metaphases per set, respectively. For the calculation of breaks/cell, chromatid breaks were taken as a single break, dicentrics and translocations as two breaks. Gaps, polyploid and pulverised cells were recorded separately and not included in the calculation of breaks per cell.

Statistics:

The data were analysed statistically by comparing each group with controls by Student´s t-test and further using the Cochran-Armitage trend test (dose response).

Results and discussion

Test results

Sex:

male

Genotoxicity:

positive

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): positive
Oral administration of Aluminium sulphate to rats for 7, 14 or 21 d induced a dose dependent inhibition of dividing bone marrow cells and an increase in chromosomal aberrations. The effect was not influenced by the duration of exposure.

Executive summary:

In a rat bone marrow micronucleus assay, 5 male rats/dose were treated orally with Aluminium sulphate ( Al2(SO4)3 x 18H2O) at doses of

0, 212, 265, 353, 530, 1060, 2120 mg Al2(SO4)3x18H2O/kg bw/d, corresponding to 0, 17, 22, 28, 43, 85, 172 mg Al/kg bw/d

daily for 7, 14 or 21 days.  Bone marrow cells were harvested at 24 h post-treatment.  The vehicle was deionised water.

In the bone marrow cells, the mitotic index decreased in direct proportion to the dose used. The decrease was highly pronounced in animals treted with the two higher doses.

The frequency of abnormal cells increased with dose and duration of exposure to Aluminium sulphate. During all three sampling times the trend test p value was found to be highly significant. A duration dependent effect was not found with the lowest (7 mg Al/kg bw/d) dose. Most aberrations were chromatid breaks. Translocations were recorded in higher doses.

 

There was a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time.