Sodium sulphate

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Literature data

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Enhancement of Azo fe Carcinogenesis by Dietary Sodium Sulphate.

Author:

Blunck Jill M.and Crowther Carol E.

Year:

1975

Bibliographic source:

Europ. J. Cancer Vol. 11, pp. 23-31. Pergamon Press 1975. Printed in Great Britain

Materials and methods

Principles of method if other than guideline:

Male Sprague-Dawley rats were fed diets containing 0.84% Na2SO4. Two groups were tested for 24 and 44 weeks, daily.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Sodium sulphate

EC Number:

231-820-9

EC Name:

Sodium sulphate

Cas Number:

7757-82-6

Molecular formula:

H2O4S.2Na

IUPAC Name:

disodium sulfate

Test animals

Species:

rabbit

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: random-bred departmental stock.
- No. of animals: ninety
- Weight at study initiation: 211.6 g
- Housing: housed 5 to a cage and allowed free access to tap water.
- Diet: rats were pair-fed by a modified method whereby the total food consumption of each cage of rats was restricted to that of the cage of rats consumi

Administration / exposure

Route of administration:

oral: feed

Vehicle:

maize oil

Details on exposure:

EXPOSURE
Rats from each experimental group were started on the test diets at two different times (Series A and Series B).
The rats were pair-fed one of the test diets for 16 consecutive weeks, then returned to the basal diet for 8 weeks. At this time one rat from each of the control, Na2SO4-containing diets in Series A were killed and the livers examined.
The remaining rats were then returned to the various experimental diets for several 4-week periods, with a week between each period during which they were fed basal diet.

DIET
Basal diet
- Source: IRM; Victorian Wheatgrowers Corporation Ltd., North Melbourne
- Administration: as pellets which were crushed prior to mixing the diets
- Composition being:
protein 15-16%
fat 6-8%
fibre 8-9%.
- Additives:
Control diet: 30 ml maize oil/kg; 0.8%
Na2SO4 diet: 30 ml maize oil plus 8.4 g Na2SO4/kg

Diets were freshly prepared every 3-4 weeks and were stored in polythene containers with lids.

Duration of treatment / exposure:

27 and 44 weeks

Frequency of treatment:

Series A: the approximate rate of diet consumption was 10 g/rat per day during the first 2 weeks; this was then gradually increased to 17 g/rat per day by week 27 and remained at this level for the duration of the experiment.
Series B: rats received 14 g/rat per day of diet initially; this was increased to 17 g/rat per day after 15 weeks and continued at this level until the experiment was concluded.

Doses / concentrations

Remarks:

Doses / Concentrations:
0.84 % in diet, 320- 400 mg/kg/day
Basis:
nominal in diet

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

Rats were killed when they became moribund or when there was gross abdominal distension and any found dead during the course of the experiment were autopsied whenever possible.
Some rats from each group in Series A were killed at 33 weeks: 3 rats; control and Na2SO4-fed groups, one rat from each.
Series A was concluded after 41 weeks and Series B after 27 weeks. Rats were killed by exsanguination under light ether anaesthesia.

Examinations

Observations and examinations performed and frequency:

LIVER LESIONS
Samples of all liver lesions greater than 0.2 cm in diameter were fixed in acetic acid: formalin: ethanol (5:10:85) for 24hr, then transferred to 70% (v/v) ethanol prior to processing to paraffin.
Liver and spleen weights were recorded.

HAEMOGLOBIN
In some instances haemoglobin estimations were performed.

MACROSCOPOC LESIONS
Samples of the livers and any macroscopic lesions in other organs were fixed and processed.

Liver and lung sections were routinely stained with haematoxylin and eosin and by the periodic acid-Schiff (PAS) method; in some instances alcian blue or toluidine blue stains were also used.

Statistics:

The progression with time of the cumulative probability of observing liver tumours of 1 cm or more in diameter, evidence of metastatic spread or multiple tumours at death was calculated by an actuarial method similar to that of Pilgrim and Dowd (1963).

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No significant differences in overall body weight gain or in liver weight were noted.

Details on results:

No dead occurred.
No carcinogenic effects (tumors) were observed and no significant differences in overall body weight gain were observed during the study. Liver weight was not changed, no evidence of hyperplastic and/or dysplastic change and no cholangiofibrosis or mild cirrhosis were observed as compared to controls.

Relevance of carcinogenic effects / potential:

Non carcigogen

Effect levels

Dose descriptor:

NOAEC

Effect level:

>= 320 mg/kg bw/day

Based on:

test mat.

Sex:

male

Remarks on result:

not determinable

Remarks:

no NOAEC identified. Effect type:carcinogenicity (migrated information)

Applicant's summary and conclusion

Conclusions:

No carcinogen; no adverse effects were detected and a NOAEL of >= 320 mg.kg may be deduced.

Executive summary:

Male Sprague-Dawley rats were fed diets containing 0.84% Na2SO4. The actual additional dose could be calculated around 320-400 mg/kg /day.

Two groups were tested for 24 and 44 weeks, daily.

Conclusion

No adverse effects were detected; a NOAEL of >= 320 mg.kg may be deduced.

No carcinogenic effects (tumors) were observed and no significant differences in overall body weight gain were observed during the study. Liver weight was not changed, no evidence of hyperplastic and/or dysplastic change and no cholangiofibrosis or mild cirrhosis were observed as compared to controls.