Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1958
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is cited in a monograph. Not all study details are available. GLP was not yet available at the time of the study period.

Data source

Reference
Reference Type:
publication
Title:
Final Report on the Safety Assessment of Aluminum Silicate, Calcium Silicate, Magnesium Aluminum Silicate etc.
Author:
Elmore A.R, CIR Expert panel
Year:
2003
Bibliographic source:
Int. J. Toxicol., 2003, 22 Suppl. 1, 37-102 (Cosmetic Ingredient Review)

Materials and methods

Test guideline
Deviations:
not applicable
Remarks:
- no information provided
Principles of method if other than guideline:
Information on a guideline followed are not available.
GLP compliance:
no
Remarks:
GLP regulations didn't exist in 1958
Limit test:
no

Test material

Constituent 1
Reference substance name:
Magnesium Aluminum Silicate
IUPAC Name:
Magnesium Aluminum Silicate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Name: Magnesium Aluminum Silicate
Commercial Name: VEEGUM

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
no information provided

Administration / exposure

Route of administration:
oral: feed
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
2%; 5%; 10%; and 20% = 20,000 ppm; 50,000 ppm, 100,000 ppm; and 200,000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
control group: 25 males + 25 females
Dose groups: 10 males + 10 females
Control animals:
yes, plain diet

Examinations

Observations and examinations performed and frequency:
Body weight and feed intake were recorded daily. Hematological examinations were made at 6 and 12 weeks on half of the test group. Blood sugar and nonprotein nitrogen determinations and urine analyses were also completed.
Sacrifice and pathology:
All animals were killed at the end of the 90-day period. Liver, kidneys, spleen, heart, and adrenal glands weights were determined. Microscopic examination of the liver, kidneys, spleen, and portions of the gastrointestinal tract of four rats of each sex and control, 10% and 20% groups were carried out.
Other examinations:
The efficiency of feed utilization was calculated.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
Mortalities observed are not test item-related
Mortality:
no mortality observed
Description (incidence):
Mortalities observed are not test item-related
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
No effects up to 10%. Gowth was diminished slightly but with statistical significance (p=0.05) when 20% VEEGUM was fed to both sexes.
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
effects observed, treatment-related
Description (incidence and severity):
Only the 20% VEEGUM dose significantly lowered the food efficiency
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
Blood sugar and nonprotein nitrogen were within normal limits.
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
100 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Nominal conc. in the diet
Dose descriptor:
NOAEL
Effect level:
5 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Calculated from the NOAEL of 100000 ppm (assuming that 10 ppm in food equals 0.5 - 0.6 mg/kg bw/day).

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Based on a 90-day feeding study in rats, no adverse effects have been observed up to a test item concentration of 10% in the diet. The highest dose administered (= 200000 ppm) interfered with normal nutrition balance and, thus, can't be used to assess the toxicity of the test item.
Executive summary:

The toxicity of magnesium aluminum silicate, a compound very similar to Fluorphlogopite, has been investigated in a 90 -day feeding study in rats. 4 Groups of animals (10 males and 10 females) received feed supplemented with the test material at 2% (20000 ppm), 5% (50000 ppm), 10% (100000 ppm) and 20% (200000 ppm), respectively. Control animals (25 males and 25 females) received the unmodified diet.

No effects on the body weight and feed uptake were observed up to 10% test material. In the high dose animals (20%), body weight development was slightly diminished, however, the high test material content in the feed interfered with normal nutritional balance. Therefore, the body weight changes are considered of no toxicological relevance. Mortalities observed during the studies are considered not test item-related. No effects have been observed on organ weights, hematology, clinical chemistry and urinalysis. Histopathological examination revealed no abnormalities.

Based on the results of this study, a NOAEL of 100000 ppm can be deduced (assuming that 10 ppm in food equals 0.5 - 0.6 mg/kg bw/day, the NOAEL can be calculated to be 5000 - 6000 mg/kg bw/day).

Categories Display