Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

Endpoint:
carcinogenicity: 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 meets generally accepted scientific principles; basic data given.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Zeolite A - a phosphate substitute for detergents: toxicological investigation
Author:
Gloxhuber C, Potokar M, Pittermann W, Wallat S, Bartnik F, Reuter H and Braig S
Year:
1983
Bibliographic source:
Fd. Chem. Toxic. 21 (2), 209-220
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Henkel KGaA "Chronic Toxicity and Carcinogenicity"
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Sasil
- Chemical name: Zeolite, cuboidal, crystalline, synthetic, non-fibrous
- Framework: cuboidal
- Related CAS number: 1318-02-1
- Analytical purity: no data
- Lot/batch No.: F 117
- Molar ratio Na2O:Al2O:SiO2 = 1.07:1:1.94
- Mean diameter: 8.3 µm
- Water content: 20.1%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Wistar Mu Ra Han. 67 SPF; 5 - 6 weeks old; 131 - 141 g body weight
food and water was available ad libitum

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: diet
Details on exposure:
- admixed to the diet at corresponding levels
- additional satellite groups of 15 animals/sex/group for starting and intermediate examinations were allocated.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Analyses of the test substance concentrations in the diet were difficult due to the relatively high concentrations of aluminium and silicon naturally occurring in the rat diets. Low zeolite levels were not distinguishable from the controls and even the highest dose concentration was not distinguishable from control due to the naturally occurring variations of Si and Al contents in rat diets.
Duration of treatment / exposure:
104 w
Frequency of treatment:
continuous
Post exposure period:
none
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 10, 100, or 1000 ppm (approx. equivalent to 0.6, 6.0, and 60 mg/kg/day)
Basis:
nominal in diet
No. of animals per sex per dose:
50
Control animals:
yes, plain diet

Examinations

Observations and examinations performed and frequency:
During the study mortality, general state and behaviour were recorded daily. Food consumption was recorded weekly for the first year, thereafter every fourth week. Water consumption was estimated weekly in the control and high dose group, measurements were performed daily in week 6, 12, and 26. Body weights were measured weekly for the first two months, thereafter bi-weekly until week 18, and every 4 weeks until study term.
Following parameters was assayed:
Haematology (satellite groups; prior to exposure, week 6, 26 and 78; 10 rats/sex of control and highest dose level
Biochemistry (satellite group; week 6, 26, and 78; urea, glucose, protein; alkaline phosphatase, serum glutamic-oxaloacetic transaminase (SGOT), Serum-Glutamat-Pyruvat-Transaminase (SGPT), sodium, potassium, calcium, and iron were examined in week 78; 5 animals/sex of control and highest dose level.
Urinalysis including determination of Al und Si content were performed in week 6, 26, and 78 (5 rats/sex/group; control and highest dose level) comprising urine volume, pH, protein, urobilinogen, ketone bodies, spec. gravity, glucose, blood and microscopic examination. Urinary Al and Si content was determined on week 6, 26, and 78 in the satellite groups and on week 104 in the main groups.
Haematology (haematocrit, haemoglobin concentration, erythrocyte count, total and differential leukocyte count, platelet count, blood clotting) and biochemistry, were performed on week 104 in the main groups.
Sacrifice and pathology:
Additional satellite groups were sacrificed at week 78, necropsied and macroscopically investigation, tissues of the satellite groups were fixed but not directly histologically examined. Main groups were sacrificed on week 104, macroscopically examined and histopathologically examined (all dose levels).
Following organ weights of all animals were determined: brain, pituitary, thyroid, thymus, lung and trachea, heart liver, kidneys, adrenals, testes, ovaries, spleen.
Following tissues were histopathologically examined: Liver, kidneys, adrenals, testes, prostate, uterus, ovaries, thymus, spleen, brain, heart, urinary bladder, lungs, cervical and mesenteric lymph nodes, skin, eyes, salivary glands, trachea, aorta, small and large intestines, female mammary gland, tongue, thyroid, sciatic nerve, pituitary, skeletal muscles, bone marrow, stomach.
The content of Si, Al and Zn were determined in kidneys and Co in liver.

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:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
During the study course abnormal behaviour was recorded neither in the treatment nor in the control groups. Body weight development varied within the treatment groups as well as in the control groups, however was not significantly different from control in the main groups, whereas the female satellite groups revealed a significant decrease in body weight in all treatment groups. This decrease was attributed to the small number of investigated animals in the satellite groups and not treatment related.
Food consumption was especially in females conspicuously decreased from study week 50 onwards, whereas the highest dose group revealed a reversibility of this decrease in week 90. Decreased food consumption was also observed in the control groups and therefore was not treatment-related.

Survival rate was as follows [in %]:
-------------------------------------
group males females
control 64 84
10 ppm 84 66
100 ppm 74 70
1000 ppm 86 66

No carcinogenic or toxicologic effects observed.
In animals dying during the test or killed because of their poor condition, the main causes were basophilic adenoma and adenocarcinoma of the pituitary gland, adenoma and fibroadenoma of the mammary glands, subcutaneous fibroma and some tumours of the genital tract. No significant incidence of a particular type of tumour or of spontaneous mortality was evident in any group. No treatment-related findings were seen in any of the organs examined histologically, and there was no indication of any treatment-related induction of neoplasms.
Comparison of the separate sums of the tumour changes observed in the 1000-ppm Zeolite A and control groups by the statistical method of Kastenbaum & Bowman (1970) showed no significant difference between the groups in the frequency of tumours.

Haematology: No significant effects observed, except leukopenia in the highest dose group. When compared to control the lower dose levels revealed also a decrease in leukocytes

Biochemistry, significant findings (no dose-response relationship):
10 ppm: males: GOT, sodium; females: sodium, calcium, potassium, total protein
100 ppm: females: GPT, sodium, urea, calcium, potassium, total protein
1000 ppm: males: GOT, calcium, females: GPT, GOT, calcium

The kidneys of males treated the highest dose level revealed increased Si content, whereas females showed an increase in urinary Al content. These findings were statistically not significant.

Urinalysis: No significant effects observed
Relative organ weights: No treatment-related significant effects observed
Time to tumours: No indications of tumours.

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 60 mg/kg bw/day (nominal)
Sex:
male/female
Remarks on result:
other: Effect type: carcinogenicity (migrated information)

Applicant's summary and conclusion