Synthetic amorphous magnesium silicate, with molar ratio (SiO2:MgO) range of 1.4-4

Endpoint summary

Description of key information

Oral exposure (13 wks, 6 months, rats and mice): There were no adverse toxic effects apparent at high doses administered in the feed. NOAEL values of approximately 4000 and 9000 mg/kg bw/day were identified for the two rodent species.  There were also no adverse effects in lifetime feeding studies in rat and mouse.  The reports do not indicate any carcinogenic hazard in rats or mice.

Repeated dermal administration was not investigated - a high acute tolerance was identified and silicates are inert inorganics by nature with little if any potential for dermal absorption or systemic exposure following topical application.  It is therefore not justified to use vertebrate studies to confirm the predictions from physico-chemical properties.  

Inhalation exposure: Target organ is the lung. Low exposure concentration of respirable dust particles provokes an inflammation response, which is reversible. No histopathological manifestations following exposure of 13 weeks to 31 mg/m³. An experimental NOAEC (acute to subchronic) of 1 mg/m³(respirable) was established for silica aerosol based on pyrogenic synthetic amorphous silica data as a worst case.  

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

9 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

1 mg/m³

Study duration:

chronic

Species:

rat

Additional information

Repeated dermal and oral exposure are not relevant toxicological issues, based on the inherent substance properties and experimental evidence.

Subacute, 13 week, dietary administration of inert Sipernat (synthetic amorphous silica) resulted in no adverse signs of toxicity in rats. No target organs or macroscopic/microscopic abnormalities were identified.

In a six month sub chronic oral administration study, synthetic amorphous silicon dioxide was given to male and female rats, at nominal doses of 7950 or 8980 mg/kg bw/day respectively. There were no treatment-related findings: General constitution and behaviour were normal, body weights not affected.  Isolated pathological findings were unrelated to dosing and common in untreated rats. No histopathological changes in kidneys were identified. Overall there were no signs of adverse toxicological effects at the high dietary inclusion rates administered.

Two-year chronic toxicity investigations in rats and mice to determine the toxicology and carcinogenicity endpoints for silicon dioxide (SAS) resulted in no significant toxicologically relevant findings. Rats dosed at circa 2000 mg/kg bw/day showed no notable changes in any of the parameters evaluated. For mice the same dietary inclusion level (5%) resulted in actual intake of between 4000 and 13000 mg/kg bw/day. These high dose levels resulted in transient changes in bodyweight gain but had no adverse toxicological effects over the two year exposure period. No evidence of carcinogenicity was seen in either rats or mice.

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/m³is considered to apply also for prolonged/chronic exposure. The inhalation studies gave no evidence of systemic adverse effects at high pulmonary and/or lymphoid deposition of SAS.

Read-across/surrogate data

For the repeated administration toxicology investigations the use of data derived for silicon dioxide are justified for read-across due to the similarities in the toxicity profile and physico-chemical properties for synthetic amorphous magnesium silicate and synthetic amorphous silicon dioxide. Refer to read-across justification prepared in Section 13.

Justification for classification or non-classification

No adverse effects were apparent following oral administration of silicon dioxide for up to 2 -years to rats or mice. No indication of any toxic response was seen in any of the parameters evaluated.

For the repeated administration toxicology investigations the use of data derived for silicon dioxide are justified for read-across to magnesium silicate. Refer to read-across justification prepared in Section 13.

Given the completely inert, innocuous response there are no reasons to classify magnesium silicate for long term or repeat administration effects