Reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate

Carcinogenicity

Description of key information

No evidence of a carcinogenic potential was observed in a combined chronic toxicity/carcinogenicity study with rats exposed to ammonium sulphate following closely the requirements of OECD TG 453. Additionally, there are no indications that the substance may cause carcinogenicity by a direct genotoxic mechanism as the results of all genotoxicity studies (mutagenicity and cytogenicity) were negative.
Similarly to other salts, high doses of ammonium sulphate may have the capability of tumour promotion in the rat stomach. It is, however, much less potent than sodium chloride when tested under identical conditions. However, these data need careful evaluation as high salt concentrations were given as a bolus dose directly into the stomach. It is known that high salt concentrations can denature proteins leading to cell injury or cell death. Subsequently cell proliferation might occur as a repair mechanism causing an increase in ornithine decarboxylase in the glandular stomach.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Dose descriptor:

NOAEL

1 288 mg/kg bw/day

Justification for classification or non-classification

Based on read-across, the available data on carcinogenicity are conclusive but not sufficient for classification according to the criteria of Directives 67/548/EEC (DSD) and Regulation 1272/2008/EC (CLP).

Additional information

Based on the available information on absorption, distribution, metabolism and excretion properties as well as the available toxicological data of all three components of the reaction mass, it can be concluded, that ammonium sulphate is the most critical substance within the reaction mass. Thus, available data on ammonium sulphate will be used for hazard assessment of the toxicological properties of the reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate:

A chronic oral toxicity and carcinogenicity study was conducted in Fischer 344 rats, similar to the requirements of OECD 453 (Ota et al., 2006). In the chronic part of the study, groups of 10 rats/sex were fed a diet containing ammonium sulphate at concentrations of 0.1, 0.6, or 3% for 1 year, corresponding to average daily intakes of 42, 256, and 1527 mg/kg bw/d for males and 48, 284, 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 at concentrations of 1.5, or 3% for 2 years. These concentrations corresponded to average daily intakes of 564.1, and 1288.2 mg/kg bw/d for males and 649.9, and 1371.4 mg/kg bw/d for females, respectively. The examinations revealed that the 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, while no macroscopic changes different from that found in controls were recorded. 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. Based on the results it can be concluded that ammonium sulphate is non-carcinogenic under the conditions of the study. Thus, the no observed adverse effect level (NOAEL) of ammonium sulphate regarding carcinogenicity is the highest dose given, which is equivalent to 1288.2 and 1371.4 mg/kg bw/d in males and females, respectively.

In addition, there is no evidence that the substance may cause carcinogenicity by a direct genotoxic mechanism as the results of all genotoxicity studies (mutagenicity and cytogenicity) were negative.