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Description of key information

Studies of the sub-chronic oral toxicity of the structurally-similar substance, magnesium aluminium silicate, are available in two species: rats and dogs.


Albino rats were fed a diet supplemented with 2%, 5%, 10% or 20% of VEEGUM (magnesium aluminium silicate) 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).


The repeated-dose oral toxicity of the same substance was also assessed in mongrel dogs fed a diet supplemented with 10% of the test material for 90 days. No adverse effects were reported. The NOAEL for VEEGUM (magnesium aluminium silicate) was determined to be 10% in the diet (100,000 ppm, equating to approximately 2500 mg/kg bw/day).

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
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
Justification for type of information:
A full justification for the use of data on magnesium aluminium silicate as read-across for this substance, magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2), is attached to Section 13 of this dossier.
Reason / purpose for cross-reference:
read-across source
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
Species:
rat
Strain:
not specified
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Dose / conc.:
20 000 ppm
Remarks:
Reported as 2%
Dose / conc.:
50 000 ppm
Remarks:
Reported as 5%
Dose / conc.:
100 000 ppm
Remarks:
Reported as 10%
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
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.
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
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
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
Key result
Critical effects observed:
no
Conclusions:
In a 90-day study, rats were fed a diet supplemented with up to 20% VEEGUM (magnesium aluminium silicate), a substance closely structurally-related to magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2). 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), a substance closely structurally-related to magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2), 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). Consequently, the target substance magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2) is considered to be non-toxic with regard to its repeated-dose oral toxicity.

Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
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
Justification for type of information:
A full justification for the use of data on magnesium aluminium silicate as read-across for this substance, magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2), is attached to Section 13 of this dossier.
Reason / purpose for cross-reference:
read-across source
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: Mongrel dogs (2/sex/group) were fed commercial diet supplemented with 10% VEEGUM (magnesium aluminium silicate), or unmodified (control group) for 90 days.
GLP compliance:
no
Remarks:
Study pre-dates introduction of GLP.
Limit test:
no
Species:
dog
Strain:
other: Mongrel
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Dose / conc.:
100 000 ppm
Remarks:
Reported as 10%
No. of animals per sex per dose:
2/sex/group.
Control animals:
yes, plain diet
Observations and examinations performed and frequency:
Complete blood counts, blood sugar and non-protein nitrogen were analysed at 6 and 12 weeks. Urine specimens were examined at 12 weeks for acidity, sugar, albumin, and microscopic elements in the sediment.
Sacrifice and pathology:
All animals were killed at the end of the 90-day period and subjected to necropsy. [extent of examination not specified]
Clinical signs:
not specified
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
"Body weight did not change despite a depression of appetite with the addition of VEEGUM"
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
Two of the test animals had slightly increased blood sugar at the end of the testing period.
Urinalysis findings:
no effects observed
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
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
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOAEL
Effect level:
2 500 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
Assuming that 1 ppm in the diet corresponds to an average 0.025 mg/kg bw/day consumption of the test material.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Critical effects observed:
no
Conclusions:
In a 90-day study, dogs were fed a diet supplemented with 10% VEEGUM (magnesium aluminium silicate), a substance closely structurally-related to magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2). No adverse effects were reported. The NOAEL was therefore determined to be 10% in the diet (100,000 ppm or 2500 mg/kg bw/day).
Executive summary:

The repeated-dose oral toxicity of VEEGUM (magnesium aluminium silicate), a substance closely structurally-related to magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2), was assessed in mongrel dogs fed a diet supplemented with 10% of the test material for 90 days. No adverse effects were reported. The NOAEL for VEEGUM (magnesium aluminium silicate) was determined to be 10% in the diet (100,000 ppm, equating to approximately 2500 mg/kg bw/day). Consequently, the target substance magnesium potassium fluoride silicate (Mg2.7K0.7Si4O10F2) is considered to be non-toxic with regard to its repeated-dose oral toxicity.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
5 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

Justification for classification or non-classification

The only adverse effect observed, a slight (but statistically-significant) reduction in body weight gain, occurred only at a dose far above the threshold for classification. Thus, no classification for repeated-dose systemic toxicity is required.