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7.6 GENETIC TOXICITY

Calcium silicate (CS) showed no mutagenic or clastogenic activity in standard test systems under valid test conditions, in vitro and in vivo. Gene mutation in bacterial and mammalian cells is bridged by making use of studies conducted with synthetic amorphous silica (SAS). The results were 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 forsynthetic amorphouscalcium silicate, too.

Overview of the relevant studies

Test

Test system

Substance/ Result

Reference

Evaluation

         In-Vitro Assays

Ames

S. typh. (strains TA98, TA100, TA1535, TA1537, TA 1538)

Read-across, SAS:

Cab-O-Sil EH5

(pyrogenic): negative with and without metabolic activation

San and Springfield 1989
(Microbiol. Associates)

Rel 1

Chromosomal

aberrations

Human embryonic lung cells (WI-38) / cytogenetic assay

CS, calcium silicate:

negative
without metabolic activation

Litton Bionetics, Inc. 1974

Rel 2

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

         In-Vivo Assays

Chromosomal

aberrations

Rat, bone marrow

CS, calcium silicate:

negative

Litton Bionetics, Inc. 1974                

Rel 2

Dominant Lethal Assay

Rat, fertility and implantation

CS, calcium silicate:

negative

Litton Bionetics, Inc. 1974

Rel 2

Gene mutation

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

Host-mediated assay

S. typh. TA1530 + G-46, mouse, i.p.

CS, calcium silicate:

negative

Litton Bionetics, Inc. 1974

Rel 2

 



Short description of key information:
The REACH data profile for this endpoint has been covered for calcium silicate (CS) in combination with read-across for gene mutation
in bacterial and mammalian cells with synthetic amorphous silica (SAS):
Result: not mutagenic and clastogenic in valid in-vitro and in-vivo tests that cover all genetic endpoints.
In addtion, no mutagenic/genotoxic effects observed after 13-wk inhalation in rats with SAS, the parent substance to CS.
(see 7.6.2 - READACTROSS_ Johnston 2000_Aero_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.