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Description of key information

Available 14-d range-finding feeding studies with synthetic amorphous aluminum sodium silicate (NAS) do not provide sufficient information for complete assessment. Because a 90-d study with NAS is not available, studies from structure analogous substances (CS, SAS) were taken.
No significant adverse effects were observed in a 2y feeding study in rats receiving synthetic amorphous calcium silicate (CS): NOAEL = approx. 3000 mg/(kg bw*d). Oral exposure (13 wks, 6 mon, rats) to structure-analogous silica (SAS) showed no adverse effects at high doses in the feed of 4000 mg/(kg bw*d). Additionally, there were no adverse effects in a lifetime feeding study in rat and mouse receiving a structure-analogous silica (SAS).
The target organ to inhalation exposure to NAS is the lung. Because studies with NAS are not available, inhalation studies from structure analogous substances (SAS) were taken into account. Inhalation exposure to SAS showed that low exposure concentration of respirable dust particles provokes an inflammation response, which is reversible. No histopathological manifestations following exposure of 13 weeks to 1.3 mg/m3 of parent substance SAS. An experimental NOAEC (acute to subchronic) of 1 mg/m3 (respirable) was established for silica aerosol.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
3 000 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
1 mg/m³

Additional information

Summary/overview on target-organ effects

Available 14d dose-range finding feeding studies with synthetic amorphous aluminum sodium silicate (NAS) do not provide the comprehensive data base required for complete assessment (Cannon 1979a,b). A 90-d study has not been located for NAS.

However, based on the inherent substance properties along with experimental evidence from structure-analogous silica and silicate, dermal and oral exposure are not relevant toxicological issues: In a 2-y feeding study, a structure-analogous calcium silicate produced no significant adverse effects in rats, the NOAEL(24 mon) is considered to be approx. 3000 mg/kg bw [Columbia 1956]. The high tolerance of this substance class is consistent with findings obtained with parent silica (SAS): Oral exposure (13 wks, 6 months, rats) to SAS: No adverse effects resulted from high doses of >= 4000 mg/(kg bw*d) administered to rats in the feed for 13 weeks [Degussa 1981]. No adverse effects were observed in a lifetime feeding study in rat [NOAEL = approx. 2000 mg SAS/(kg bw*d)] and mouse [NOAEL = approx. 5000 mg SAS/(kg bw*d)] [Takizawa et al. 1988].

No experimental data about inhalation toxicity is available for the target compound, NAS. Therefore, the analogy approach will be adopted, using data obtained with SAS:

The inhalation of respirable particles of synthetic amorphous silica (SAS) produces a time- and dose-related inflammation response of the lung tissue in animal studies. Progressive events following excess exposure are characterised as “interstitial fibrosis/early nodular fibrosis/incipient fibrosis”. However, a progression process of any lesion has not been observed like that seen after quartz exposure, i.e. all observations suggest reversibility. There are no signs of classical nodular silicosis or a lymphatic-type pneumoconiosis. On the other hand, crystalline silica produces persistent lung inflammation even at much lower exposure levels [Johnston et al. 2000].

Thirteen-weeks inhalation exposure to an average concentration of 1.3 mg/m3of a pyrogenic SAS resulted in mild reversible pro-inflammatory cell proliferation rather than a pathologically relevant tissue change. Given the low-grade severity of this common lung-tissue response, 1 mg/m3can be established as NOAEC and LOEC (sub-chronic, 13 weeks). The LOAEC was 5.9 mg/m3, the mid concentration, which produced clear signs of histopathological adverse effects (stimulation of collagen production, increase in lung weight, incipient interstitial fibrosis in the lung, slight focal atrophy in the olfactory epithelium). All these effects were reversible following discontinuation of exposure [Degussa 1987].

No lung-tissue effects were observed following exposure of 5 days to 1 mg/m3of the same silica [NOEC (short-term)]; the LOAEC (5 d) was 5.4 mg/m3[ASASP 2003 a,b,c]. Measurements of the particle-size distributions under experimental conditions revealed that the exposure aerosol was practically fully respirable.

Based on the pathological relevance of effects after inhalation, 1 mg/m3(respirable) could be established as NOEC(short-term) and NOAEC(sub-chronic). This appears to be justified also in light of the fact that the sub-chronic study was conducted with a pyrogenic synthetic amorphous silica (SAS) which appears to induce more marked tissue responses than the precipitated SAS type.

The low exposure level did not provide any evidence of an accumulation of adverse effects over time.

Therefore, the NOAEC of SAS of 1 mg/m3 is considered to apply also for prolonged/chronic exposure.

Based on the structural similarity as well as properties between synthetic amorphous silica (SAS) and synthetic amorphous silicates, the NOAEC of SAS is also adopted for synthetic amorphous aluminum sodium silicate.

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: lung

Justification for classification or non-classification