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Repeated dose toxicity: oral

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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

Referenceopen allclose all

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 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

Constituent 1
Chemical structure
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 / concentrationsopen allclose all
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

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

open allclose all
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

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).