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

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

194 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

72

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 166 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

12

Modified dose descriptor starting point:

NOAEC

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

56 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

72

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

333 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

12

Modified dose descriptor starting point:

NOAEL

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

Local effects identified after acute or chronic exposure to crystalline forms of silica (ultimately potential silicosis) are not evident for amorphous synthetic silicas nor for the analogous metal salts such as magnesium silicate.  Local effects following inhalation exposure to respirable forms of amorphous silica do not indicate any potential local hazards for workers, who can be assumed to be further protected from any significant exposure by routine mandatory use of protective clothing or equipment and by access to protective equipment including LEV.

In the absence of any other identified local effects it is not necessary to set DNELs for dermal or inhalation local effects. The key available data for magnesium silicate are derived from repeated oral toxicity studies with silicon dioxide. The study durations varied from 13 weeks to two years and were completed in rats and mice. The NOAEL values were consistently high - no effects observed at 2000 up to 13000 mg/kg bw/day. Conservatively the value for a thirteen week subchronic investigation was used as the starting point for deriving DNELs based on the data quality. Dermal and inhalation values were derived by route-to-route extrapolation from the sub-chronic starting point.

 

DNEL derivation

Systemic DNEL values for long-term dermal and inhalation risk assessment are derived from the NOAEL of 4000 mg/kg bw/day in the 13-week oral study in rats. 

For workers, the ECETOC recommended assessment factor is 4 for interspecies effects. {The ECETOC position in relation to factors for the remaining interspecies differences was set out in an evaluation by ECETOC 2003 and 2010. ECETOC considered that routine application of the factor of 2.5 is scientifically unjustified as a default factor and so the interspecies factor has been reduced to 4 from 4 x 2.5. This view is supported by data generated by the ERASM project (Batke et al, 2010)}.

An assessment factor of 3 for intraspecies effects was used (in accordance with ECETOC recommendations), in conjunction with a factor of 2*3 to adjust for differences in exposure period between the chronic value used for DNEL setting and the sub-acute study result used as the starting point. The overall assessment factor was therefore of 12 (4 *3) for short term and 72 (4*3*2*3) for long term calculations. No additional factors, other than ECHA defaults of 1, were used for data quality or dose response.

The acute/short term systemic dermal DNEL value, was derived from the oral DNEL (333 mg/kg bw). No adjustment was included for relative absorption, it was assumed that the low oral absorption value would be reflected in a similarly low dermal absorption. These absorption values were not quantified but qualitative assessment in the toxicokinetics section indicates low uptake from the GI tract. The dermal systemic short term DNEL value was 333 mg/kg bw/day for workers. Systemic toxicity is not predicted by the dermal route. For long term systemic exposure the oral DNEL value was again used as the basis for the calculation but the AF included an additional adjustment for exposure period and consequently the long term DNEL was 333/6 or 56 mg/kg bw/day.

The acute/short term systemic inhalation DNEL was derived by route to route extrapolation based on the oral subacute starting point.

The oral NOAEL was adjusted for inhalation absorption which is assumed to exceed the oral absorption. The starting point was therefore 2000 mg/kg bw/day. The allometric scaling factor used was 4 (rat), giving an NAEL human of 500 mg/kg bw/day which was adjusted for a standard human bodyweight (70 kg) and for the breathing rate of workers on an 8 h shift (10 m3/person). No factor for remaining intraspecies differences was used - this had been accounted for in the route-to-route extrapolation. An interspecies factor of 3 was used by default. NAEC = 2000 / 4 *70 /10 divided by 3 gives an inhalation DNEL of 1166 mg/m3.

For the long term systemic inhalation DNEL the short term value was adjusted for exposure period using a standard factor of 3*2 yielding a DNEL of 194 mg/m3.

The existing OEL for dust (UK WEL EH40/2005) is 4 mg/m³(respirable fraction) and 10 mg/m³(inhalable fraction), and in France is 5 mg/m³(respirable fraction) and 10 mg/m³(inhalable fraction). The derived DNEL for inhalation is higher than the existing OEL for dust, therefore long-term systemic effects caused by synthetic amorphous magnesium silicate are not expected to occur as long as the OEL is complied with.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

Inhalation exposure of the general population is considered negligible. Synthetic amorphous magnesium silicate is essentially non-toxic by oral ingestion. Since there are no envisaged uses or scenarios that are likely to result in quantifiable consumer or general population exposure, it is not appropriate to set limits such as DNELs for general population exposures.