Sodium sulphate

Endpoint summary

Description of key information

In a sub-acute oral toxicity study with sodium sulfate no adverse effects were noted. A recent study was to set the NOAEL. This NOAEL (oral, rat) is set at 1000 mg/kg bw/day.

 

ORAL

Ceccatelli R., 2010 OECD 421 Main Study C79103: The NOAEL 28 d (rat ,oral ) is 1000 mg/kg/day

Moinuddin & Wing-tsit Lee, 1960: the NOAEL 28 d (rat, oral) from this study is 2000 mg/kg/day

 

DERMAL

Data with respect to repeated dermal toxicity show effects. Male and female New Zealand White Rabbits were treated with the test substance (2 ml/kg/day; 16 % w/w) percutaneously 65 times in 91 days. The only test related effect, which was observed for all groups, was subacute dermatitis that varied from mild to moderate in nature. All other findings were normal or related to spontaneous disease. Some lesions were incidental in nature. LOAEL for the test substance was 2 ml/kg/day (16 % w/w), is 320 mg/kg/day sodium sulphate.  

 

INHALATION

In the available repeated dose study the description of the experiment is insufficient and no actual data are presented. No NOAEL or LOAEL.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Dose descriptor:

LOAEL

320 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

ORAL, RAT - 28 d

Ceccatelli R., 2010 OECD 421 Main Study C79103: The NOAEL 28 d (rat,oral) is 1000 mg/kg/day

This study is a valid investigation of the toxicological effects resulting from repeated oral-gavage administration of the test item Sodium Sulphate to rats. Sodium Sulphate was administered in highly purified water as vehicle at dosages of 100, 300, and 1000 mg/kg body weight/day, and controls received the vehicle only. Sodium Sulphate was administered to male rats for at least 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. In absence of any effect the general NOEL (No Observed Effect Level) was established at 1000 mg/kg/day.

 

Moinuddin & Wing-tstit Lee, 1960: the NOAEL 28 d (rat, oral) from this study is 2000 mg/kg/day

NOAEL (NOEL:) The oral administration of sodium sulfate to rats by dietary admixture for a period of 4 weeks at a dose level of 0.88 mmol/kg feed did not result in any effects. A dosing regime of 8.64 mmol/kg feed on days 1-8, 17.28 mmol/kg feed on days 9-16, 34.56 mmol/kg feed on days 17-24 and 65.12 mmol/kg feed from day 25 for 4-6 days resulted in two slight cases of diarrhea that lasted for a day. At a dose level of 138 mmol/kg feed one rat showed diarrhea on 4 different days (3 consecutive days) in the middle of the feeding period. At the top dose the food contained around 2% sodium sulfate based on which the NOAEL was calculated to be around 2000 mg/kg bw/day.

 

ORAL, RAT - 28 d and 27/44 week

A clear NOAEL cannot be derived from the available data. In the study of Blunck and Crowter (1975), refer to Carcinogenicity [7757 -82 -6 Carcinogenicity, Blunck, J.M. et al., (1975)] two groups of 5 male rats were fed 21% sodium sulphate in the diet for 27 and 44 weeks respectively. No adverse effects were detected with respect to the limited number of endpoints reported from this study. Obviously, group size is too limited to draw firm conclusions but tentatively a chronic NOAEL of >= 320 mg/kg/day may be deduced from a 27 / 44-week study and a sub-chronic NOAEL of 2000 mg/kg from a 28 day study in rats. Ruminating animals are at risk at much lower levels because of the potential formation of sulfide in the rumen. Since this substance has no discernable systemic toxicity, the tentative chronic NOAEL of >= 320 mg/kg in rats would seem to provide a reasonable margin of safety compared to the estimated daily intake of 453 mg/person/day or around 6.5 to 7.5 mg/kg/day.

 

DERMAL

In a 91-Day Percutaneous Toxicity Study (1977) the rabbit skin appeared normal in all groups. A statistically significant (P0.05) increase in MCV and MCH values was noted for the females in the test substance group as compared to the vehicle control females. This increase did not appear to be biologically significant since all individual values were within a normal range for rabbits. The only test-related lesion observed was a subacute dermatitis. 3 animals in the vehicle control group had mild subacute dermatitis. 8 animals in the test substance group had subacute dermatitis that varied from mild to moderate in nature. All other findings were normal or related to spontaneous disease. Some lesions were incidental in nature.

Based on the results of the study, the LOAEL for the test substance was 2 ml/kg/day (16 % w/w) = 320 mg/kg/day sodium sulphate.

 

INHALATION

In a 90 -day study of Denisov et al (1989, 1990) in which rats were exposed to 1 mg/m3 sodium sulfate together with 500 mg/l in drinking water, i.e an estimated dose of 60 mg/kg/d orally and 0.6 mg/kg/day by inhalation. Apart from the neuro-physiological and biochemical parameters described, body weight was also depressed, relative liver weight was decreased, histopathological evidence of serious lung damage and testicular damage was described. The description of the experiment is insufficient, and no actual data are presented. No NOAEL or LOAEL.

Based on the results of several acute toxicity inhalation studies it is unlikely that inhalation of respirable sodium sulfate particles causes pulmonary irritation or systemic effects

Justification for classification or non-classification

Sodium sulphate is not classified based on the test results obtained from the two subacute toxicity studies (28 day, oral, rat), a sub-chronic toxicity study (27/44 week, oral, rat).

Based on the LOAEL of a dermal sub-chronic toxicity study (90 day, dermal, rat) sodium sulphate should not be classified.

 

Based on the results of the oral and dermal repeated dose toxicity study, sodium sulfate does not need to be classified for repeated dose toxicity according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.