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Administrative data

Key value for chemical safety assessment

Additional information

7.6 GENETIC TOXICITY

Synthetic amorphous aluminum sodium silicate (NAS) showed no mutagenic or clastogenic activity in standard test systems under valid test conditions, in vitro and in vivo. Gene mutation in mammalian cells in vitro has been bridged by making use of a study conducted with synthetic amorphous silica (SAS). The result was negative.

In one non-standard test using SAS, the mutagenic potential was investigated following inhalation exposure to rats, as inhalation has to be considered to be the exposure route of highest toxicological significance for humans. For that purpose, the test design had to be modified and adjusted such as to meet relevant physiological needs: Therefore, the target cells were isolated after in-vivo exposure and cultivated ex vivo. Selection of possible mutants followed the standard method of the HPRT assay (see for details under 7.6.2: Johnston et al. 2000). This study gave no evidence of a mutagenic potential for Aerosil 200 (SAS) when inhaled at a high exposure concentration of 50 mg/m3 for 13 weeks. The study is also reviewed under Chapter 7.5. It is considered to be relevant for aluminum sodium silicate, too.

Overview of the most relevant studies

Test

Test system

Substance/ Result

Reference

Evaluation

         In-Vitro Assays

Ames

S. typh. TA 98, TA100, TA1535, and TA 1537

NAS :

negative with and without metabolic

Zeiger et al. 1987

Rel. 2,

key study

Chromosomal

aberrations

Human embryonic lung cells (Wi-38)

NAS:

negative

without metabolic activation

Litton Bionetics, Inc. 1974

Rel 2,

key study

Gene mutations (mammalian cell)

Chinese hamster ovary cells  / HPRT assay

Read-across, SAS

Cab-O-Sil EH5 (pyrogenic): negative with and without metabolic activation

Sigler and Harbell 1990 (Microbiol.Associates)

Rel 1,

key study

         In-Vivo Assays

Chromosomal

aberrations

Rat, bone marrow

NAS:

negative

Litton Bionetics, Inc. 1974

Rel 2,

key study

Dominant Lethal Assay

Rat, fertility and implantation

NAS

negative

Litton Bionetics, Inc. 1974

Rel 2,

key study

Gene mutations

Alveolar type-II cells after 13-wk inhalation exposure of rats / ex-vivo/in-vivo HPRT assay

Read-across, SAS:

Aerosil 200 (pyrogenic):

negative

Johnston et al. 2000

Rel 2

 



Short description of key information:
The REACH data profile for this endpoint has been covered for synthetic amorphous aluminum sodium silicate (NAS) in combination with read-across for gene mutation inmammalian cells with synthetic amorphous silica (SAS):
Result: not mutagenic and clastogenic in various valid in-vitro tests and in-vivo studies.
In addition, by making readacross to synthetic amorphous silica (SAS), the parent substance of NAS, no mutagenic/genotoxic effects observed after 13-wk inhalation of SAS by rats (see 7.6.2 - Johnston 2000_Aerosil 200_ex-vivo/in-vitro HPRT, rat).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on experimental evidence, no classification as to genotoxic potential is required.