Reaction mass of calcium sulfate and potassium sulfate and sodium sulphate

Endpoint summary

Description of key information

potassium sulfate: NOAEL: 1500 mg/kg bw/day ( highest dose tested) (according to OECD 422)
calcium sulfate, dihydrate : NOAEL: 100 mg/kg bw/day and LOAEL: 300 mg/kg bw /day for male rats. NOAEL: 1,000 mg/kg bw/day for female rats. (according to OECD 422)
ammonium sulfate:  NOAEL of 886 mg/kg bw/day (LOAEL 1792 mg/kg bw/day) (90-day oral study in rats) 
NOAEL of 256 mg/kg bw/day (LOAEL 1527 mg/kg bw/day) (chronic oral toxicity study in rats). 
Based on these reliable studies with potassium sulfate, calcium sulfate and ammonium sulfate for oral repeated dose toxicity, the rat oral NOAEL for the sulfate category is 100 mg/kg bw/day for subacute toxicity. For chronic toxicity the NOAEL for the sulfate 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 sulfate. 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 as a LOEL rather than a LOAEL. No treatment-related histopathological changes were reported. Therefore, it was concluded that the NOAEL is higher than1500 mg/kg bw/day.

In a combined repeated dose and reproduction/developmental toxicity screening test in rats (OECD Guideline 422), calcium sulfate, dihydrate was administered by gavage at the dose levels of 0, 100, 300 and 1,000 mg/kg bw/day for more than 35 days and 41 -45 days for male and female, respectively. Calcium sulfate, dihydrate had no critical influence on test items such as mortality, body weights (organ weight), food consumption, necropsy, reflex action, grip strength and behaviour of the animals. However, the values of total protein, albumin, blood urea nitrogen, aspartate aminotransferase, alanine aminotransferase and creatinine were decreased at 300 mg/kg bw/ day and 1,000 mg/kg bw/day treatment for male animals showing that the test substance might affect the excretion process, distribution or metabolism of test substance in relation to the kidney. Based on these results, the LOAEL and NOAEL were determined to be 300 mg/kg bw/day and 100 mg/kg bw/day for males rats. In case of females rats, no effects were observed at the top dose tested (1,000 mg/kg bw/day).

Further repeated dose toxicity studies were available 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. No changes indicating obvious ammonium sulfate toxicity were observed in the body weights, organ weights, hematological, serum biochemical, or histopathological examinations. Based on these results, the NOEL (no-observed-effect level) of ammonium sulfate for F344 rats was judged to be 1.5 % in males (886 mg/kg/day) and 3 % in females (1975 mg/kg/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.

The tested category members were used to provide estimates of similar properties for the untested members and to provide estimates for potassic extracts. There was no evidence of adverse toxicity in all the studies available and therefore no clasification is justified according to EU criteria.

Dermal:

No dermal studies are available.

Inhalation

No inhalation studies are present.

Justification for classification or non-classification

The high NOAELs found in the sub-acute oral toxicity study with potassium sulfate and calcium sulfate, dihydrate in rats and in a chronic oral toxicity study with ammonium sulfate, indicate that no classification is required for potassic extracts according to Directive 67/548/EC and the CLP Regulation.