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Description of key information

A reliable subacute oral toxicity study available on potasium sulphate shows a NOAEL of 1500 mg/kg bw/day, the highest dose tested. The study was performed according to OECD 422. In addition, repeated dose toxicity data on ammonium sulphate are considered. The 90-day oral study in rats showing a NOAEL of 886 mg/kg bw/day (LOAEL 1792 mg/kg bw/day) and the chronic oral toxicity study in rats showing a NOAEL of 256 mg/kg bw/day (LOAEL 1527 mg/kg bw/day). 
Based on these reliable studies with potassium sulphate and ammonium sulphate for oral repeated dose toxicity, the rat oral NOAEL for the sulphate category is 1500 mg/kg bw/day for subacute toxicity. For chronic toxicity the NOAEL for the sulphate category is 256 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
256 mg/kg bw/day
Study duration:
chronic
Species:
rat

Additional information

Oral

A 28-day oral OECD 422 study has been performed in rats (5 rats/sex/dose) via gavage, containing 50, 750 or 1500 mg/kg bw/day potassium sulphate. There were no treatment-related deaths and no signs of overt clinical toxicity. There were no effects on body weight, food consumption, or food efficiency. Functional observational battery (FOB) and motor activity tests identified no treatment-related changes in behavior, function, or motor activity. Dams at 1,500 mg/kg/day experienced slightly lower food consumption and body weight than the controls during the gestation period only. Because of their moderate and transient nature, these observable effects were considered a LOEL rather than a LOAEL. No treatment-related histopathological changes were reported. Therefore, it was concluded that the NOAEL is 1500 mg/kg bw/day (or higher, highest dose tested).

Further repeated dose toxicity studies were present with ammonium sulfate.

In a 13-week study rats (10/sex/dose) were exposed to diet containing 0, 0.38, 0.75, 1.5 or 3 % ammonium sulfate (corresponding to 0, 222, 441, 886, 1792 mg/kg bw/day in males and to 0, 239, 484, 961, 1975 mg/kg bw/day in females). No substance-related changes were found in body weights, haematology and serum parameters, or in the histological examinations (brain, heart, lung, liver, kidney, adrenal gland, spleen, testes, thymus). The relative testes weight was significantly increased at all doses, but no histological effects were found, not considered to be treatment related. Male animals of the highest dose group exhibited diarrhea during the administration period. According to the authors the NOAEL (male) was 886 mg/kg bw/day and the NOAEL (female)was 1975 mg/kg bw/day. 

A chronic oral toxicity and carcinogenicity study was conducted in rats, similar to the requirements of OECD TG 453. In the subchronic part of the study, groups of 10 rats/sex were fed a diet containing the ammonium sulfate (purity not given) at concentrations of 0, 0.1, 0.6, or 3% for 1 year. These concentrations corresponded to average daily intakes of 0, 42, 256, and 1527 mg/kg bw/d for males and 0, 48, 248, and 1490 mg/kg bw/d for females, respectively. For investigation of the carcinogenic potential, groups of 50 rats/sex were fed a diet containing the test substance (purity not given) at concentrations of 0, 1.5, or 3% for 2 years. These concentrations corresponded to average daily intakes of 0, 465.1, and 1288.2 mg/kg bw/d for males and 0, 649.9, and 1371.4 mg/kg bw/d for females respectively. Absolute and relative kidney weights were increased at the high dose level for both sexes. Absolute spleen weights were decreased and relative liver weights were increased in high dose males. No macroscopic changes were recorded by gross pathology, except for massive nodular or focal lesions suggesting neoplastic changes. At histopathological examination, non-neoplastic and neoplastic lesions were noted in the control and treatment groups, with no significant inter-group difference in their incidences or severity.The authors concluded that the no observed adverse effect level of ammonium sulfate was the 0.6% diet, which is equivalent to 256 and 284 mg/kg bw/d in males and females, respectively, and the compound is noncarcinogenic under the conditions of the study. There was no evidence of a long-term carcinogenic activity of the test substance.

Dermal

No dermal studies are present.

Inhalation

No inhalation studies are present.

Justification for classification or non-classification

The high NOAELs found in the subacute oral toxicity study with potassium sulphate in rats and in a chronic oral toxicity study with ammonium sulphate, indicate that no classification is required for potassium sulphate according to Directive 67/548/EC and the CLP directive.