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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 August 2000 to 31 August 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

In accordance with REACH Annex XI, testing is not scientifically necessary since studies on synthetic amorphous magnesium silicate have been conducted by Dallas Group of America and show no acute toxicity via any route. The particle size analysis performed on the Dallas and PQ corporation material show that they are sufficiently similar. The only difference between the materials are the molar ratios. The molar ratio of the tested Dallas material is within the range of the PQ Corporation registered substance. No additional testing is therefore required.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: FHSA/CPSC 16 CFR 1500

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

701-065-4

Molecular formula:

MgO.xSiO2, the molar ratio SiO2:MgO typically ranges from 1.4-4

IUPAC Name:

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

Specific details on test material used for the study:

The test material was identified as Magnesol, Grade HMR-LS, S.R. 000-21-1, a synthetic amorphous magnesium silicate. This grade is within the identifiers of the registered substance.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley, Indianapolis, Indiana.
- Age at study initiation: 6-10 weeks old
- Weight at study initiation: 208-293 grams
- Housing: individually in stainless steel wire bottom cages
- Diet: Purina Laboratory Chow available ad libitum
- Water: available ad libitum

The rats were housed in a temperature, humidity and light controlled room - standard laboratory conditions, compliant with current animal welfare considerations applied.

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

The test material was administered neat and was generated as a dust using an oscillating dust generator and compressed air. The generator dispersed dust from the reservoir utilizing compressed air operated at 8 psi of air during the 1 hour exposure period. The exposure was conducted in a stainless steel chamber and room air entered the top of the chamber and exited through the bottom. The dust entered the chamber through a hole in a rear of the chamber and passed immediately through an atomisation plenum. The plenum was used to improve the distribution of the dust within the chamber and to reduce the size dispersity.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

1 h

Concentrations:

20 mg/L of air

No. of animals per sex per dose:

Ten animals (five female/five male) per dose

Control animals:

no

Details on study design:

The rats were exposed to the test atmosphere for a period of 1 hour. The rats were observed for mortality and pharmacotoxic signs frequently during the day of exposure and daily thereafter for 14 days. Gross necropsy examinations were performed on all test subjects at the end of the 14 day observation period. Body weights were obtained at study initiation and at 14 days post-administration.

Statistics:

Not applicable for single dose study

Results and discussion

Preliminary study:

No preliminary study performed.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 20 mg/L air (nominal)

Mortality:

There was no mortalities during the test period.

Clinical signs:

other: All animals appeared normal and healthy.

Body weight:

The result show an increase in body weight was observed over the 14 day period.

Gross pathology:

No gross changes observed.

Other findings:

No other findings to report.

Any other information on results incl. tables

The findings of the study are tabulated below:

Rat No.	Sex	Initial BWT (g)	Final BWT (g)	Necropsy findings	Fate
690	M	286	361	No gross changes observed.	Survived
691	M	276	350	No gross changes observed.	Survived
692	M	293	369	No gross changes observed.	Survived
693	M	292	372	No gross changes observed.	Survived
694	M	290	372	No gross changes observed.	Survived
695	F	228	252	No gross changes observed.	Survived
696	F	214	241	No gross changes observed.	Survived
697	F	233	258	No gross changes observed.	Survived
698	F	239	248	No gross changes observed.	Survived
699	F	208	227	No gross changes observed.	Survived

Applicant's summary and conclusion

Interpretation of results:

not classified

Conclusions:

Inhalation of the test article at a nominal concentration dose level of at least 20 mg/L of air produced no mortality in any of the ten test subjects indicating that the LC50 of the test article is greater than a minimum nominal concentration of 20 mg/L of air for a one hour period.

Executive summary:

Magnesol, Grade HMR-LS was tested for acute inhalation toxicity at a targeted level of 20 mg/L of air by exposing five males and five females rats for a one hour period.

Inhalation of the test article at a nominal concentration dose level of at least 20 mg/L of air produced no mortality in any of the ten test subjects indicating that the LC50 of the test article is greater than a minimum nominal concentration of 20 mg/L of air for a one hour period. Based on this study the Dallas sample was found to be not toxic by inhalation.

Information from Dallas indicates five grades of magnesol (magnesium silicate).  Four of the samples had circa 10% of the particles within the respirable range. The respirable range is generally <10 micron.

For the PQ grades of magnesium silicate, the respirable range is approximately 10% of the particles and therefore is comparable with the Magnesol. It can therefore be concluded that grades of magnesium silicates known as Ambosol, Macrosorb and Mg trisilicate are also not toxic by inhalation.

Similar results were obtained for the acute toxicity by inhalation of synthetic amorphous silica.

Inhalation data in the CSR for synthetic amorphous silica indicates the particle size distribution was typically 1-250 µm , the MMAD was >100 µm and the synthetic material tends to agglomerate forming high MMAD clumps that are non-respirable, MMAD >10 µm.  The granulometry test for synthetic amorphous silica indicates <1% by weight of particles with <10 um diameter.  However the respirable portion can increase to >80% (<10 µm) under high shear stress or experimental conditions.

SAS with this granulometry was administered acutely by inhalation to rats (MMAD = 0.76 um) without causing death or adverse effect at circa 2 g/L.  Higher exposure levels were precluded by technical difficulties encountered when attempting to create a sustainable atmosphere, with precipitation onto chamber surfaces affecting the nominal exposure concentrations.

Justification for read-across is warranted given the similarities in toxicity profile and physico-chemical properties for silicon dioxide and magnesium silicate. The read -across justification will be expanded in Section 13.