Silicon orthophosphate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

27 Oct. 1980 - 27 Jan. 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Comparable to guideline study, performed under GLP conditions. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

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

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

IUPAC Name:

dioxosilane

Details on test material:

- Name of test material (as cited in study report): SIPERNAT 22, 97-98 % (SiO2): CAS-Name: Silica, precipitated, cryst.-free; CAS-No.: 112926-00-8
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

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 5x/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%. 
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

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 bw/d
Basis:
nominal in diet

No. of animals per sex per dose:

10

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

WATER CONSUMPTION: Yes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes

CLINICAL CHEMISTRY: Yes

URINALYSIS: Yes

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

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

Description (incidence and severity):

highest dose group: mean food intake was slightly increased in the females

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):

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

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS
No effects.

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.

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

HAEMATOLOGY
No effects.

CLINICAL CHEMISTRY
No effects.

URINALYSIS
No effects.

GROSS PATHOLOGY
No effects.

HISTOPATHOLOGY: NON-NEOPLASTIC
No effects.

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 4 000 - 4 500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: corresponding to 6.7% in feed; NOAEL corresponding to the highest dose tested.

Target system / organ toxicity

Critical effects observed:

not specified