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

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 October 1980 - 27 January 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Justification for read-across is warranted given the similarities in toxicity profile and physico-chemical properties for silicon dioxide and magnesium silicate.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Silicon dioxide

EC Number:

231-545-4

EC Name:

Silicon dioxide

Cas Number:

7631-86-9

Molecular formula:

O2Si

IUPAC Name:

dioxosilane

Details on test material:

SIPERNAT 22, 97-98 % (SiO2): CAS-Name: Silica, precipitated, cryst.-free; CAS-No.: 112926-00-8

Specific details on test material used for the study:

SIPERNAT 22, 97-98 % (SiO2): CAS-Name: Silica, precipitated,
cryst.-free; CAS-No.: 112926-00-8

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No details available

Administration / exposure

Route of administration:

oral: feed

Details on oral exposure:

DIET PREPARATION
Treated feed: 6-kg batches mixed with the test material for 2 min, freshly prepared on five occasions during 13 weeks and stored at 15 °C until use

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Mean effective (analytical) silica levels in the diet were about 0.4-0.7, 1.7-1.9, 6.5-7.0 % (Tab. 1, p. 17). 
These dietary levels resulted in indicated doses of Sipernat, based on specified mean food intake and body weights

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily, continuous by dietary admixture

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
approx. 0.5, 2 and 6.7 % Si
Basis:
other: based on Si analysis in the diet (i.e. Si concentration) Mean effective (analytical) silica levels in the diet were about 0.4-0.7, 1.7-1.9, 6.5-7.0 % .  These dietary levels result in indicated doses of Sipernat, based on specified mean.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
mean estimated doses: 300-330, 1200-1400, 4000-4500 mg Sipernat/kg/day
Basis:
nominal in diet

No. of animals per sex per dose:

10,
5 per sex and cage

Control animals:

yes, concurrent no treatment

Details on study design:

Post-exposure period: no

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes

CLINICAL CHEMISTRY: Yes

URINALYSIS: Yes

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

No available information

Other examinations:

No available information

Statistics:

No available information

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

no effects observed

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

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Mean food intake was slightly increased in the female top-dose group (some +5 % after 4 wks) with no corresponding body-weight gain, 
but barely seen in males (Tab. 5, p. 23).

FOOD EFFICIENCY
In females (high dose): The apparently reduced food efficiency may be due to the rather high amount of inert Sipernat.

Effect levels

1

Dose descriptor:

NOEL

Effect level:

6.7 other: % in feed

Sex:

male/female

Basis for effect level:

other: overall effects clinical signs; mortality; body weight; food consumption; food efficiency; water consumption and compound intake; haematology; clinical chemistry; urinalysis; gross pathology; organ weights; histopathology

2

Dose descriptor:

NOEL

Remarks:

highest dose

Effect level:

ca. 4 000 - <= 4 500 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: see above

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No clinical symptoms or other findings including haematological, blood-chemical and urinary parameters.
 
Mean food intake was slightly increased in the female top-dose group (some +5 % after 4 wks) with no corresponding body-weight gain, but barely seen in males (Tab. 5, p. 23). The reduced food efficiency may be due to the rather high amount of inert Sipernat. Water consumption was normal throughout. 
  
Gross and microscopical examinations did not reveal any (histo-)pathological changes that could be attributed to the feeding of SIPERNAT 22. 
   

Applicant's summary and conclusion

Conclusions:

Mean food intake was slightly increased in the female top-dose group (some +5 % after 4 wks) with no corresponding body-weight gain, but barely seen in males. The reduced food efficiency may be due to the rather high amount of inert Sipernat. Water consumption was normal throughout.  There were no effects on  behaviour or clinical signs of systemic toxicity. Clinical pathology revealed no treatment related changes. Gross and microscopical examinations did not reveal any (histo-)pathological changes that could be attributed to the feeding of SIPERNAT 22. 

Executive summary:

A 13 -week repeated dose toxicity study was conducted using SIPERNAT 22 Wistar rats. The test substance was administered by oral feed with mean effective (analytical) silica levels in the diet of about 0.4-0.7, 1.7-1.9, 6.5-7.0 %. This equated to mean estimated  doses of 300-330, 1200-1400, 4000-4500 mg Sipernat/kg/day based on the diet.

Five animals were treated per sex per group.

Mean food intake was slightly increased in the female top-dose group (some +5 % after 4 wks) with no corresponding body-weight gain, but barely seen in males. The reduced food efficiency may be due to the rather high amount of inert Sipernat.   Water consumption was normal throughout.  There were no effects on  behaviour or clinical signs of systemic toxicity.  Clinical pathology revealed no treatment related changes.  Gross and microscopical examinations did not reveal any (histo-)pathological changes that could be attributed to the feeding of SIPERNAT 22. 

The NOEL was the highest concentration tested (ca. 6.5 -7%; 4000 -4500 mg Sipernat/kg/d).