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Toxicological information

Repeated dose toxicity: oral

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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented (some parts are not available, however basic data given). Study meets generally accepted scientific principles and is acceptable for assessment.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Henkel-method "Subchronic oral toxicity"
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Sasil (HAB)
- Related CAS number: 1318-02-1
- Physical state: white powder
- Analytical purity: no data
- Lot/batch No.: HAB 325
- Molar ratio: Na2O:Al2O:SiO2 = 1.02:1:1.95
- Mean diameter: 9.2 um
- Water content: 20%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: diet
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
90 d
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 1000, 5000 or 10000 ppm (corresponding to approximately 0, 50-60, 250-300 and 500-600 mg/kb bw/day)
Basis:

No. of animals per sex per dose:
20
Control animals:
yes, plain diet

Examinations

Observations and examinations performed and frequency:
Animals were observed daily for signs of toxicity and mortality. Body weight was recorded weekly as well as food consumption; urinalyses were performed at study start and at study term (urine volume, pH, protein, specific gravity, occult blood, ketone bodies, glucose, urobilinogen, and microscopic examination).
Blood chemistry and hematology were performed: alkaline phosphatase, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, total protein, urea as well as hemoglobin, red blood cell count, white blood cell count, glucose.
Sacrifice and pathology:
At study term all rats were sacrificed and necropsied. Following organs were histopathologically examined: stomach, lung, intestine, cerebrum, cervical lymph nodes, heart, testes, liver, mesenteric lymph nodes, spleen, adrenal gland, kidney, ovaries, pancreas, thyroid, salivary gland, thymus, trachea, and uterus.
Following elements were determined in the highest treatment and control group:
Fe-content (blood) and Si (kidney); Zn (kidney), Al (kidney), and Co (liver) were determined via neutron activation analysis except for Fe.
The Cu content of treated and control livers was determined as follows: the dried liver were homogenized and ashed at 550°C. The Cu content was determined spectrophotometrically (yellow copper complex with N,N,N,N, tetraethyl-thiuramdisulfide).
Statistics:
For statistical analysis the U-test and t-test were used.

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):
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
effects observed, treatment-related
Details on results:
All test animals survived the subchronic oral test and no test substance related abnormal behaviour was observed. Feed consumption and body weight gain was comparable to control. Hematology and blood chemistry was not significant different from control. Data of the urinalysis of the 1000 and 5000 ppm test group was similar to control. The only differences between test and control groups were found in the group fed 10000 ppm of the test substance. This group showed diminished urine secretion, haematuria, and ketone bodies in the urine and in 12 of the 20 male animals urinary calculi of varying number and size (mainly composed of Si and in traces S, K, Cl) were observed in the bladder, as well as a thickening of the wall.
The histological examination showed a hyperplastic reaction of the transitional epithelium in rats with calculi.
The determined elements Fe, Zn, and Al of the 10000 ppm group were not significantly different from control. In contrast, the silicon content of the kidneys was considerably higher than the controls, especially in the males of the group fed the highest dose level. The cobalt content of the liver was significantly decreased in treated female rats when statistically analyzed with the t-test, but not statistically decreased in the U-test (the t-test can be regarded as reliable since the values were actually re-evaluated by Sigma Stat for its distribution on normality and passed the test). The copper content of the female rats treated with 10000 ppm Sasil was comparable to control; in both the t-test and U-test, the copper values for the treated male rats were significantly increased compared to the control.

NOAEL = 5000 ppm (assuming that 10 ppm in food equals 0.5-0.6 mg/kg/day, the NOAEL can be calculated to be 250-300 mg/kg/day)

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
5 000 ppm
Sex:
male
Dose descriptor:
LOAEL
Effect level:
10 000 ppm
Sex:
male
Basis for effect level:
other: kidney, urinary bladder
Dose descriptor:
NOAEL
Effect level:
10 000 ppm
Sex:
female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion