Zeolite, silica and sodium and titanium based, crystalline, synthetic, non fibrous

Genetic toxicity: in vivo

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:

key study

Study period:

1999-09-21 to 1999-11-12

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

- Name of test material (as cited in study report): Zeostop X (silver alumino-silikate)
- Chemical name: Zeolite, cuboidal, crystalline, synthetic, non-fibrous
- Framework: cuboidal
- Related CAS number: 1318-02-1
- Analytical purity: approx. 100%
- Lot/batch No.: MR 453 136
- Physical state: white powder
- Composition of test material, percentage of components (surface modified with Ag): Si/Al molarity 1.24
Al2O3: 25.6%
CaO 0.08%
Fe2O3 0.00%
K2O 00.08%
MgO 00.00%
Na2O 11.71%
SiO2 37.33%
Ag2O 02.80%
loss resulting from combustion (900°C)
- Expiry date: May 2000
- Storage: in dark and at room temperature

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male/female

Details on test animals or test system and environmental conditions:

Swiss Ico: OF1 (IOPS Caw) mice

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

0.5% aqueous methylcellulose

Details on exposure:

In the main study, three groups of five male and five female Swiss Ico: OF1 (IOPS Caw) mice received four oral treatments of ZEOSTOP X at dose-levels of 1250, 2500 and 5000 mg/kg/day, at a 24-hour interval. Due the low number of available animals in the female vehicle control group, the experiment was repeated for females only, at the same dose-levels.
One group of five males and five females received the vehicle (0.5% aqueous methylcellulose) under the same experimental conditions, and acted as control group.
One group of five males and five females received the positive control test substance (cyclophosphamide) once by oral route at the dose-level of 50 mg/kg.

Duration of treatment / exposure:

four treatments separated by 24 hours (volume: 10 mL/kg)

Frequency of treatment:

four treatments separated by 24 hours

Post exposure period:

24 h

Doses / concentrations

Remarks:

Doses / Concentrations:
0 (vehicle), 1250, 2500 and 5000 mg/kg/day
Basis:
nominal conc.

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide, 50 mg/kg

Examinations

Tissues and cell types examined:

bone marrow, micronucleated polychromatic erythrocytes (MPE), polychromatic (PE) and normochromatic erythrocyte (NE) ratio

Details of tissue and slide preparation:

The animals of the treated and vehicle control groups were killed 24 hours after the last treatment and the animals of the positive control group were killed 24 hours after the single treatment. Bone marrow smears were then prepared.

Evaluation criteria:

For each animal, the number of the micronucleated polychromatic erythrocytes (MPE) was counted in 2000 polychromatic erythrocytes. The polychromatic (PE) and normochromatic erythrocyte (NE) ratio was established by scoring a total of 1000 erythrocytes (PE + NE).

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

The test substance was non-toxic in the preliminary test at 5000 mg/kg/day, this dose-level was selected as the highest one for treatment in the main test.
In the main test, for males the mean values of MPE in the groups treated with the test substance, were equivalent to those of the vehicle control group. The PE/NE ratio was significantly lower (p < 0.05) when compared to that of the vehicle group, in the group given 5000 mg/kg/day,
showing that the bone marrow cells were effectively exposed to the test substance.
For females the mean values of MPE as well as the PE/NE ratio in the groups treated with the test substance, were equivalent to those of the vehicle control group and no significant difference was noted.

The mean values of MPE as well as the PE/NE ratio for the vehicle and positive controls were consistent with historical data of the laboratory. Cyclophosphamide induced a highly significant increase (p < 0.001) in the frequency of MPE, indicating the sensitivity of the test system under the experimental conditions.

Group MPE/1000PE PE/NE ratio
[mg/kg/d] mean mean
--------------------------------------------------
Males
Vehic. 1.1 0.8
1250 0.7 0.7
2500 1.3 0.7
5000 1.0 0.6*
Cyclo. 20.8*** 0.9


Group MPE/1000PE PE/NE ratio
[mg/kg/d] mean mean
--------------------------------------------------
Females
Vehic. 0.4 0.7
1250 0.8 0.9
2500 0.7 0.8
5000 1.1 0.7
Cyclo. 38.9*** 0.7

*p<0.05
***p<0.001

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative