Magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2)

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Final report on the safety assessment of aluminium silicate, calcium silicate, magnesium aluminium silicate, magnesium silicate, magnesium trisilicate, sodium magnesium silicate, zirconium silicate, attapulgite, bentonite, [...], and zeolite.

Author:

Elmore AR (for the Cosmetic Ingredient Review Expert Panel)

Year:

2003

Bibliographic source:

International Journal of Toxicology 22 (Suppl. 1), 37-102.

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1958

Report date:

1958

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: 90-day feeding study using rats.

- Short description of test conditions: Albino rats (10/sex/test group, 25/sex/control group) were fed commercial diet supplemented with 2%, 5%, 10% or 20% VEEGUM (magnesium aluminium silicate), or unmodified (control group) for 90 days.

- Parameters analysed / observed: Body weight and feed intake were recorded daily. Haematological examinations were made at 6 and 12 weeks on half of the test group. Blood sugar and non-protein nitrogen determinations and urinalysis were also completed. Liver, kidneys, spleen, heart and adrenal gland weights were determined post-mortem. Microscopic examination of the liver, kidneys, spleen, and portions of the GI tract of four rats/sex in the control, 10% and 20% groups was carried out.

GLP compliance:

no

Remarks:

Study pre-dates introduction of GLP.

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium magnesium silicate(2:1:2)

EC Number:

235-682-0

EC Name:

Aluminium magnesium silicate(2:1:2)

Cas Number:

12511-31-8

Molecular formula:

Al.H4O4Si.1/2Mg

IUPAC Name:

aluminium magnesium silicate(2:1:2)

Test material form:

solid: flakes

Remarks:

Off-white to creamy white small flakes or micronized powder.

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

20 000 ppm

Remarks:

Reported as 2%

Doses / concentrations 2

Dose / conc.:

50 000 ppm

Remarks:

Reported as 5%

Doses / concentrations 3

Dose / conc.:

100 000 ppm

Remarks:

Reported as 10%

Doses / concentrations 4

Dose / conc.:

200 000 ppm

Remarks:

Reported as 20%

No. of animals per sex per dose:

10/sex/treated group.
25/sex/control group.

Control animals:

yes, plain diet

Examinations

Observations and examinations performed and frequency:

Body weight and feed intake recorded daily and efficiency of feed utilisation (EFU, g bw gained/100 g feed consumed) calculated.
Haematological examinations, blood sugar, non-protein nitrogen and urinalysis at 6 and 12 weeks in half of the test group.

Sacrifice and pathology:

All animals were killed at the end of the 90-day period.
Liver, kidneys, spleen, heart and adrenal weights were recorded from all animals.
Microscopic examination of the liver, kidneys, spleen and portions of the GI tract were carried out on 4 animals/sex in the control, 10% and 20% groups.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

mortality observed, non-treatment-related

Description (incidence):

One (male) in the 2% group and one/sex in the 10% group died during the study. "These rats had fibrinous exudates in the thorax, haemorrhagic lungs, and evidence of respiratory infection at necropsy."

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Average body weights and net body weight gains were not adversely affected up to 10%. "Growth was diminished slightly but with statistical significance when 20% VEEGUM was fed to both sexes"

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

effects observed, treatment-related

Description (incidence and severity):

Only the 20% dose significantly lowered the observed EFU value.

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not specified

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Other effects:

no effects observed

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

100 000 ppm

Based on:

test mat.

Remarks:

Nominal concentration in the diet; reported as 10%

Sex:

male/female

Basis for effect level:

body weight and weight gain

2

Dose descriptor:

NOAEL

Effect level:

5 000 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

Assuming that 1 ppm in the diet corresponds to an average 0.05 mg/kg bw/day consumption of the test material.

Sex:

male/female

Basis for effect level:

body weight and weight gain

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

In a 90-day study, rats were fed a diet supplemented with up to 20% VEEGUM (magnesium aluminium silicate). Animals in the high-dose group displayed a slightly (but statistically significantly) reduced body weight gain. No other adverse effects were reported. The NOAEL was determined to be 10% in the diet (100,000 ppm or 5000 mg/kg bw/day).

Executive summary:

The repeated-dose oral toxicity of VEEGUM (magnesium aluminium silicate) was assessed in albino rats fed a diet supplemented with 2%, 5%, 10% or 20% of the test material for 90 days. Growth was diminished slightly, but with statistical significance, in animals of both sexes at the highest dose. There were no gross pathological or histopathological findings reported, and the haematological and biochemical parameters measured were within normal levels. The NOAEL for VEEGUM (magnesium aluminium silicate) was determined to be 10% in the diet (100,000 ppm, equating to approximately 5000 mg/kg bw/day).